Neuro-Ophthalmology & Neuro-Otology

Axial T1-weighted MRI of the brain showing post-gadolinium enhancement of the left optic nerve. (Contributed by Dr. Josephe Honorat.)

Axial STIR MRI of the brain shows longitudinally extensive increased signal of the left optic nerve and mild atrophy of the right optic nerve. (Contributed by Dr. Josephe Honorat.)

The image identifies the location of the striate cortex (V1), early occipital visual regions (V2, V3), and two parallel pathways. One that leads dorsally to the posterior parietal regions for the "where and visually-guided action" pathway and one that leads ventrally to posterior and inferior temporal regions for the "what" pathway. (Contributed by Dr. Victoria Pelak. Modified with permission from: Pelak VS. The clinical approach to the identification of higher-order visual dysfunction in neurodegenerative disease. Curr Neurol Neurosci Rep 2022;22[4]:229-42.)

(A) Macular OCT of central retinal vein occlusion shows thickening of the foveal region in cystoid macular edema. Small cystic spaces are evident in the outer plexiform layer, with loss of the normal foveal depression. The hyperreflectivity of the inner retina is due to ischemia. (B) Normal macular OCT. (Contributed by Dr. Prin Hantrakul.)

Dilated and tortuous retinal veins are seen along with scattered flame-shaped hemorrhages. The white patch temporal to the optic disc suggests secondary cilioretinal artery occlusion that occurred after the central retinal vein occlusion. (Contributed by Dr. Parin Hantrakul.)

The central retinal arteries and veins emerge from the optic nerve head. The normal ratio of artery and vein is 2:3. The fovea, seen as a yellow spot, is located between the superior and inferior temporal vascular arcades. (Contributed by Dr. Prin Hantrakul.)

Axial delayed gadolinium-enhanced 3D FLAIR images at the level of the inner ear in a 77-year-old woman with unilateral left-sided definite Meniere disease. There is cochlear hydrops grade 1 (small arrowhead) and vestibular hydrops grade 2 according to a four-stage grading system (large arrowhead). Note increased vestibular (small arrow) and cochlear (large arrow) perilymphatic enhancement on the symptomatic side compared with the normal right labyrinth. This is the signature of blood-perilymph barrier impairment. (Source: Bernaerts A, Vanspauwen R, Blaivie C, et al. The value of four-stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI. Neuroradiology 2019;61[4]:421-429. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Cropped axial delayed gadolinium-enhanced 3D FLAIR images at the inferior part of the vestibulum and correlated axial cryosections with hematoxylin and eosin staining (magnification, × 7) and color overlay. (a) Normal vestibule (grade 0). The saccule (small arrowhead) and utricle (large arrowhead) are visibly separate and take less than half of the surface of the vestibule. (b) Vestibular hydrops grade I: The saccule (small arrowhead), normally the smallest of the two vestibular sacs, has become equal or larger than the utricle (large arrowhead) but is not yet confluent with the utricle. (c) Vestibular hydrops grade 2: There is a confluence of the saccule and utricle (arrowhead) with still a peripheral rim enhancement of the perilymphatic space (arrow). (d) Vestibular hydrops grade 3: The perilymphatic enhancement is no longer visible (arrowhead). There is a full obliteration of the bony vestibule. Also notice in this case, the beginning utricular protrusion in the non-ampullated part of the lateral (horizontal) semicircular canal (arrow). (Source: Bernaerts A, Vanspauwen R, Blaivie C, et al. The value of four-stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI. Neuroradiology 2019;61[4]:421-429. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Cropped axial delayed gadolinium-enhanced 3D FLAIR images at the mid-modiolar area of the cochlea and correlated axial cryosections with hematoxylin and eosin staining (magnification, × 7) and color overlay. (a) Normal cochlea (grade 0); in the normal cochlea, one can recognize the interscalar septum (arrow), the scala tympani, and scala vestibuli. The scala media is normally minimally visible. (b) Cochlear hydrops grade 1; the scala media becomes indirect visible as a nodular black cut-out of the scala vestibuli (arrow). (c) Cochlear hydrops grade 2; the scala vestibuli (arrow) is fully obliterated due to the distended cochlear duct. (Source: Bernaerts A, Vanspauwen R, Blaivie C, et al. The value of four-stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI. Neuroradiology 2019;61[4]:421-429. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(a) Large-cell pneumatization (arrow) in the vicinity of the aqueduct. (b) Small-cell pneumatization (arrow) in the vicinity of the aqueduct. (c) Absence of air cell. (Source: Xia K, Lei P, Liu Y, et al. Comparison of vestibular aqueduct visualization on computed tomography and magnetic resonance imaging in patients with Ménière's disease. BMC Med Imaging 2024;24[1]:93. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(a) Funnel type. (b) Tubular type. (c) Filiform type. (d) Hollow type. (e) Obliterated type. (Source: Xia K, Lei P, Liu Y, et al. Comparison of vestibular aqueduct visualization on computed tomography and magnetic resonance imaging in patients with Ménière's disease. BMC Med Imaging 2024;24[1]:93. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Vestibular aqueduct grading on the Pöschl planes on 3D sampling perfection with application-optimized contrasts using different flip angle evolutions (3D-SPACE). (a) Grade A with a continuous vestibular aqueduct (arrow). (b) Grade B with a discontinuous vestibular aqueduct (arrow). (c) Grade C with a no visible vestibular aqueduct. Note: The Pöschl projection is used in imaging the temporal bone; the plane of projection is perpendicular to the long axis of the temporal bone. (Source: Xia K, Lei P, Liu Y, et al. Comparison of vestibular aqueduct visualization on computed tomography and magnetic resonance imaging in patients with Ménière's disease. BMC Med Imaging 2024;24[1]:93. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(a) Grade 0 with a continuous vestibular aqueduct (arrow). (b) Grade I with a discontinuous vestibular aqueduct (arrow). (c) Grade II with a complete ossification of vestibular aqueduct. Note: The Pöschl projection is used in imaging the temporal bone: the plane of projection is perpendicular to the long axis of the temporal bone. (Source: Xia K, Lei P, Liu Y, et al. Comparison of vestibular aqueduct visualization on computed tomography and magnetic resonance imaging in patients with Ménière's disease. BMC Med Imaging 2024;24[1]:93. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Proteins and their coding genes are listed for the stereocilia links (tip links, horizontal top connectors, shaft connectors, and ankle links) and between the stereocilia and the tectorial membrane. In addition, proteins that are part of the mechanoelectrical transduction (MET complex; the tectorial membrane), and some of the most relevant proteins that constitute the stereocilium are indicated. Mutated structural proteins in familial Meniere disease are indicated in bold. Ankle links and shaft connectors are not found in mature hair cells, although they are found during hair cell development. Abbreviations: ADGRV1: adhesion G-protein coupled receptor V1; CAPZA1: capping actin protein of muscle Z-line subunit alpha 1; CAPZB2: capping actin protein of muscle Z-line subunit beta 2; CEACAM16: carcinoembryonic antigen-related cell adhesion molecule 16; CIB2: calcium and integrin-binding family member 2; Clic5: chloride intracellular channel protein 5; EPS8: epidermal growth factor receptor kinase substrate 8; EPS8L2: epidermal growth factor receptor kinase substrate 8-like protein 2; LHFPL5: LHFPL (lipoma HMGIC fusion partner-like) tetraspan subfamily member 5 protein; MAGI-1: membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1; PDZD7: PDZ domain-containing protein 7; PMCA2: plasma membrane calcium-transporting ATPase 2; PTPRQ protein tyrosine phosphatase receptor type Q; RIPOR2: RHO family interacting cell polarization regulator 2; SANS: pre-mRNA splicing regulator USH1G; TMIE: transmembrane inner ear expressed protein; TMC1/2: transmembrane channel-like protein 1 and 2 dimer; TRIOBP: TRIO And F-Actin Binding Protein; TUB: tubby protein homolog; XIRP2: Xin actin-binding repeat-containing protein 2. (Source: Parra-Perez AM, Lopez-Escamez JA. Types of inheritance and genes associated with familial Meniere disease. J Assoc Res Otolaryngol 2023;24[3]:269-79. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Mohseni-Dargah M, Falahati Z, Pastras C, et al. Meniere's disease: Pathogenesis, treatments, and emerging approaches for an idiopathic bioenvironmental disorder. Environ Res. 2023;238[Pt 1]:116972. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Structural images of the inner ear showing no, mild, and significant endolymphatic hydrops, after intravenous injection of an ordinary dose of gadolinium (Gd) contrast agent with a 3T MRI. Arrows and arrowheads indicate endolymphatic hydrops in the cochlea and in the vestibule, respectively. (Source: Mohseni-Dargah M, Falahati Z, Pastras C, et al. Meniere's disease: Pathogenesis, treatments, and emerging approaches for an idiopathic bioenvironmental disorder. Environ Res. 2023;238[Pt 1]:116972. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 62-year-old woman with left Meniere disease and posterior semicircular canal dysplasia. 3D-FLAIR (a) and 3D-T2WI (b) showed left posterior semicircular canal dysplasia (arrowheads). The endolymph compartment occupies more than 50% of the short and enlarged posterior semicircular canal. (Source: Li J, Li L, Jin X, et al. MRI can help differentiate Ménière's disease from other menieriform diseases. Sci Rep 2023b;13[1]:21527. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Comparison of MRI from a 50-year-old woman with left vestibular schwannoma (a, b) and a 49-year-old man with right vestibular schwannoma (c) in the internal auditory canal. The inner auditory canal schwannoma presented (a, c) relatively equal hyperintense (long arrows) on intravenous gadolinium-enhanced 3D-FLAIR and (b) asymmetric hypointense (long arrows) on 3D-T2WI compared with the contralateral side, and the nerves in the internal auditory canal were unclear. (c) Axial 3D-FLAIR image showed vestibular hydrops grade III (short arrow). Note: abnormal cochlear (arrowhead) or vestibular (arrowhead) perilymphatic enhancement was shown on the same side compared with the contralateral side (a, c). (Source: Li J, Li L, Jin X, et al. MRI can help differentiate Ménière's disease from other menieriform diseases. Sci Rep 2023b;13[1]:21527. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

High-resolution 3D-FLAIR images were obtained 6 hours after intravenous gadolinium injection. (a) Cochlear hydrops grade II: a 45-year-old man with right Meniere disease. Axial 3D-FLAIR image showed that the scala vestibuli was fully obliterated due to the dilated cochlear duct (arrow). (b) Vestibular hydrops grade II: a 49-year-old man with right Meniere disease. Axial 3D-FLAIR image showed a confluence of the saccule and utricle (long arrow) with continuous peripheral rim enhancement of the perilymphatic space (short arrows) Note: abnormal cochlear perilymphatic enhancement (arrowhead) was shown on the same side. (c) Vestibular hydrops grade III: a 48-year-old woman with right Meniere disease. Axial 3D-FLAIR image showed that the perilymphatic enhancement was no longer continuous. There was a full obliteration of the bony vestibule, and the perilymphatic enhancement was no longer visible (short arrow). (Source: Li J, Li L, Jin X, et al. MRI can help differentiate Ménière's disease from other menieriform diseases. Sci Rep 2023b;13[1]:21527. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

According to grading criteria of the 1997 World Health Group, the pure tone average hearing threshold was calculated as the average pure tone audiometry thresholds of binaural air conduction at 500, 1000, 2000, and 4000 Hz (PTA 500 to 4000 Hz). The degree of cochlear endolymphatic hydrops in the affected ear was significantly positively correlated with the PTA 500 to 4000 Hz value. (Source: Huang Y, Zhao P, Han Z, et al. Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere's disease based on three-dimensional real inversion recovery sequence. Braz J Otorhinolaryngol 2023;89[5]:101314. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Meniere disease staging was obtained by calculating the pure tone average hearing thresholds at 500, 1000, 2000, and 3000 Hz (Committee on Hearing and Equilibrium, American Academy of Otolaryngology-Head and Neck Foundation. Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Menière's disease. American Academy of Otolaryngology-Head and Neck Foundation, Inc. Otolaryngol Head Neck Surg 1995;113[3]:181-5). Both ears were evaluated separately for patients with bilateral Meniere disease. The average hearing thresholds for stages 1, 2, 3, and 4 were 25 or lower, 26 to 40, 41 to 70, and higher than 70 dB HL, respectively. (Source: Huang Y, Zhao P, Han Z, et al. Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere's disease based on three-dimensional real inversion recovery sequence. Braz J Otorhinolaryngol 2023;89[5]:101314. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(2a) Right vestibular endolymphatic hydrops grade 0. (2b) Right vestibular endolymphatic hydrops grade 1. (2c) Right vestibular endolymphatic hydrops grade 2. Orange arrow shows the area of endolymphatic hydrops. (Source: Huang Y, Zhao P, Han Z, et al. Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere's disease based on three-dimensional real inversion recovery sequence. Braz J Otorhinolaryngol 2023;89[5]:101314. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(1a) Right cochlear endolymphatic hydrops grade 0. (1b) Right cochlear endolymphatic hydrops grade 1. (1c) Right cochlear endolymphatic hydrops grade 2. (1d) Right cochlear endolymphatic hydrops grade 3. Orange arrow shows the area of endolymphatic hydrops. (Source: Huang Y, Zhao P, Han Z, et al. Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere's disease based on three-dimensional real inversion recovery sequence. Braz J Otorhinolaryngol 2023;89[5]:101314. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Inducing the secretion of inflammatory cytokines or interferon (IFN) through the Toll-like receptor (TLR) signaling pathway (left, middle) or the IG-I-like receptor (RLR) signaling pathway (right). In the TLR signaling pathway, TLR2 recognizes signals induced by HSV-1 envelope proteins, such as gB or gD. The signal is transmitted to the cytoplasm, where MyD88 binds to the cytoplasmic domain of TLR2, leading to the activation of transcription factors like NF-kappaB. This activation promotes the translocation of P50/P65 into the nucleus and increases the expression of inflammatory cytokines and IFN-1. Additionally, TLR3, TLR7/8, and TLR9 signaling are activated by dsRNA, ssRNA, or CpG DNA, respectively, in endosomes. These signals activate IRF-3, IRF-7, and NF-kappaB, ultimately resulting in increased expression in endosomes and increased inflammatory cytokines, IFN-1, IFN-III, and interferon-stimulated genes (ISGs). In the RLR signaling pathway, RIG-I and MDA5, which contain N-terminal caspase activation and recruitment domains, recruit and activate the mitochondrial antiviral signaling (MAVS) protein to mediate signal transduction. The activated MAVS protein further activates downstream signaling, promoting the expression of inflammatory cytokines and IFN. Both pathways contribute to the immune response against HSV-1 infection by triggering the production of inflammatory cytokines and interferons, which play crucial roles in controlling viral replication and coordinating innate and adaptive immune responses. (Source: Zhao Z, Liu X, Zong Y, Shi X, Sun Y. Cellular processes induced by HSV-1 infections in vestibular neuritis. Viruses 2023;16[1]:12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Zhao Z, Liu X, Zong Y, Shi X, Sun Y. Cellular processes induced by HSV-1 infections in vestibular neuritis. Viruses 2023;16[1]:12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Although the types and composition of envelope proteins may vary among different viruses in the sporozoan virus family, the fusion of the viral envelope with the host cell membrane and the entry of the nucleocapsid rely on the binding of multiple envelope proteins to receptors on the host cell membrane and conformational changes. (Source: Zhao Z, Liu X, Zong Y, Shi X, Sun Y. Cellular processes induced by HSV-1 infections in vestibular neuritis. Viruses 2023;16[1]:12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

HSV-1 is composed of double-stranded DNA, nucleocapsid, tegument, envelope proteins, and a lipid envelope. (Source: Zhao Z, Liu X, Zong Y, Shi X, Sun Y. Cellular processes induced by HSV-1 infections in vestibular neuritis. Viruses 2023;16[1]:12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The Nystagmocatcher can be coupled to any commercially available smartphone. It is placed in front of the eye, and a video recording can be made with the smartphone. (Source: Melliti A, van de Berg M, van de Berg R. Capturing nystagmus during vertigo attacks using a smartphone: adherence, characteristics, pearls and pitfalls. J Neurol 2023;270[12]:6044-56. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Comparison of lesion morphology of “iron dot” lesions in Susac syndrome (bottom) and multiple sclerosis (top). The figure illustrates differences in morphology on 7T T2*w images between “iron dots” in Susac syndrome (red arrows) and the central vein sign (white and black arrow) as well as T2*w hypointense core lesions (blue arrows with zoom) in multiple sclerosis. T2*-weighted imaging is an MRI sequence to quantify observable or effective T2 (T2* or "T2-star"); in this sequence, hemorrhages and hemosiderin deposits become hypointense (Chavhan GB, Babyn PS, Thomas B, Shroff MM, Haacke EM. Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics 2009;29[5]:1433-49). All exemplary T2*w images in the bottom are from different patients with Susac syndrome. Note that the “iron dots” in Susac syndrome (red arrows) appear punctate and sharply delineated on T2*w. In contrast, the T2*w hypointense core lesions (blue arrows with zoom) in multiple sclerosis often appear just slightly less hyperintense on T2*w in comparison to other multiple sclerosis lesions. Only when the lesion is viewed on strongly susceptibility-weighted sequences (right) does a rather diffuse signal loss become apparent. The central vein sign in multiple sclerosis also appears as a point-like, pronounced hypointensity on T2*w images when the slice plane is perpendicular to the long axis of the multiple sclerosis lesion (white arrow). However, if the slice plane is parallel to the long axis of the lesion, the central vein sign can be recognized as a straight line running through the center of multiple sclerosis lesions (black arrow). (Source: Strunk D, Sinnecker T, Kleffner I, et al. Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome: an exploratory study. BMC Med Imaging 2024;24[1]:4. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Callosal “iron dot” lesions (indicated by red arrows) on 7T quantitative T1 maps (left) and 3D T2* weighted (right) sequences. (Source: Strunk D, Sinnecker T, Kleffner I, et al. Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome: an exploratory study. BMC Med Imaging 2024;24[1]:4. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

"Iron dot” lesion in the left frontal lobe on 3D T2*-weighted (T2*w) coronal (top left), sagittal (lower left), and axial (right) 7 Tesla MRI sequences. T2*-weighted imaging is an MRI sequence to quantify observable or effective T2 (T2* or "T2-star"); in this sequence, hemorrhages and hemosiderin deposits become hypointense (Chavhan GB, Babyn PS, Thomas B, Shroff MM, Haacke EM. Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics 2009;29[5]:1433-49). Note the strong but punctate and sharply delineated intralesional signal loss. This type of intralesional T2*w signal loss differs from that of more recent multiple sclerosis lesions where central T2*w hypointensities appear larger and are more diffuse. They are also distinct from (enlarged) venules present in multiple sclerosis lesions as “iron dot” lesions do not show a tubular appearance following the course of a vessel. (Source: Strunk D, Sinnecker T, Kleffner I, et al. Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome: an exploratory study. BMC Med Imaging 2024;24[1]:4. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(A) Optical coherence tomography infrared image of the right eye shows inferior retinal branch involvement (black arrows); the black arrows on the right of the image show occlusion, whereas on the left there is incomplete occlusion. (B) Fundus fluorescein angiography, late phase of the left eye in the same patient seen in A. There is arteriolar wall hyper-fluorescence seen along with frank leakage. (C) Late phase of fundus fluorescein angiography of the left eye demonstrates the requirement for peripheral views to gauge the extent of the retinal vascular involvement. (D) Late phase of fundus fluorescein angiography of the right eye shows superior arterial tree involvement in the same patient. (Source: Bose S, Papathanasiou A, Karkhanis S, et al. Susac syndrome: neurological update [clinical features, long-term observational follow-up and management of sixteen patients]. J Neurol 2023;270[12]:6193-206. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Algorithm for diagnosis, treatment, and monitoring of Susac syndrome. (Source: Bose S, Papathanasiou A, Karkhanis S, et al. Susac syndrome: neurological update [clinical features, long-term observational follow-up and management of sixteen patients]. J Neurol 2023;270[12]:6193-206. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Brain histology at higher magnification shows microangiopathy with thickening of arteriolar wall and a sparse perivascular lymphocytic infiltrate (arrow). (Source: Bose S, Papathanasiou A, Karkhanis S, et al. Susac syndrome: neurological update [clinical features, long-term observational follow-up and management of sixteen patients]. J Neurol 2023;270[12]:6193-206. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Brain histology shows multiple microinfarcts (arrows) in the cerebral cortex. Abbreviation: H&E, hematoxylin and eosin staining. (Source: Bose S, Papathanasiou A, Karkhanis S, et al. Susac syndrome: neurological update [clinical features, long-term observational follow-up and management of sixteen patients]. J Neurol 2023;270[12]:6193-206. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T2-weighted MRI shows central callosal lesions. (Source: Bose S, Papathanasiou A, Karkhanis S, et al. Susac syndrome: neurological update [clinical features, long-term observational follow-up and management of sixteen patients]. J Neurol 2023;270[12]:6193-206. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Coronal FLAIR MRI sequence shows callosal, periventricular, and thalamic lesions. (Source: Bose S, Papathanasiou A, Karkhanis S, et al. Susac syndrome: neurological update [clinical features, long-term observational follow-up and management of sixteen patients]. J Neurol 2023;270[12]:6193-206. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Auger CA, Perosa V, Greenberg SM, van Veluw SJ, Kozberg MG. Cortical superficial siderosis is associated with reactive astrogliosis in cerebral amyloid angiopathy. J Neuroinflammation 2023;20[1]:195. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Comparison of axial MRI on days 0 and 14 in a 74-year-old, right-handed man, with no past medical history or vascular comorbidities and no prior head trauma, who presented with sudden left arm weakness, paresthesias, word-finding difficulties, and involuntary movements of the fingers. (A) Susceptibility-weighted imaging and (B) T2*-weighted imaging on days 0 and 14, respectively. On A there is very faint superficial siderosis in the central sulcus, which is much more pronounced at the last examination (B). Both MRIs were performed on the same 3 Tesla scanner. (Source: Andersen NH, Blauenfeldt RA, Mikkelsen R, Simonsen CZ. Preceding symptoms and temporal development of cortical superficial siderosis in cerebral amyloid angiopathy: a case report. BMC Neurol. 2023;23[1]:252. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Comparison of axial MRI on days 0 and 14 in a 74-year-old, right-handed man, with no past medical history or vascular comorbidities and no prior head trauma, who presented with sudden left arm weakness, paresthesias, word-finding difficulties, and involuntary movements of the fingers. MRI on days 0 (A-C) and 14 (D-F). (A and D) Diffusion-weighted imaging shows a hyperintense lesion in relation to the right lateral ventricle (dotted circle). (B and F) FLAIR. (C and F) Susceptibility-weighted imaging reveals multiple cortical microbleeds in the same area (solid circle). Both MRIs were performed on the same 3 Tesla scanner. (Source: Andersen NH, Blauenfeldt RA, Mikkelsen R, Simonsen CZ. Preceding symptoms and temporal development of cortical superficial siderosis in cerebral amyloid angiopathy: a case report. BMC Neurol. 2023;23[1]:252. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 27-year-old woman with right-sided headache and sensory Jacksonian seizures demonstrates a hyperintense cortical lesion in the right postcentral parietal area on (a) axial T2-weighted and (b) axial FLAIR images (arrow), with (c) signal loss and “blooming” of the central vein on axial T2*-weighted image (arrow) without cortical superficial siderosis. (d,e) Circumscribed peripheral contrast enhancement in an axial post-contrast T1-weighted image (arrow) and (f) restricted diffusion of the thrombus on axial diffusion-weighted imaging. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Acute cortical subarachnoid hemorrhage on (b) axial FLAIR, (c) axial susceptibility-weighted, and (d) axial diffusion-weighted images (arrow). (a, e) Enlarged perivascular spaces on axial T2-weighted images (arrow). (b, f) Focal gliosis on axial FLAIR (arrowhead). (c, g) Multiple microbleeds, cortical superficial siderosis, and residual atypical intracerebral bleeding in the left frontal area (arrowhead) on axial susceptibility-weighted images. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

CT and MRI in a 74-year-old woman suffering from recurrent cortical subarachnoid hemorrhage in cerebral amyloid angiopathy. (a-d) The first cortical subarachnoid hemorrhage in the right frontal area on (a) axial CT (arrow) with (b) sulcal hyperintense signal changes on FLAIR image (arrow) and (c, d) sulcal signal loss on T2*-weighted images (arrow) with additional cortical superficial siderosis on the left (arrowhead). (e-g) The second cortical subarachnoid hemorrhage in the paramedian left frontal area on (e) axial FLAIR and (g) axial T2*-weighted image (arrowhead). (f, g) Note the characteristic bilinear track-line appearance of cortical superficial siderosis in the chronic stage on T2*-weighted images (arrow). (h-k) The third cortical subarachnoid hemorrhage in the left frontodorsal area on (h) axial CT (arrow) with (i-k) signal loss on susceptibility-weighted imaging (arrow) and progressive cortical superficial siderosis bilaterally. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial post-contrast T1-weighted MRI in the lower cervical area showing inhomogeneous contrast enhancement (arrow) in a 59-year-old man suffering from progressive gait ataxia within 6 months and traumatic nerve root injury C7 and C8 30 years previously. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Enlarged empty nerve root pouches (arrows) in the lower cervical area on the left on sagittal T2*-weighted MRI in a 59-year-old man suffering from progressive gait ataxia within 6 months and traumatic nerve root injury C7 and C8 30 years previously. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Enlarged empty nerve root pouches (arrows) on the left at C7 and C8 on sagittal T2*-weighted MRI in a 59-year-old man suffering from progressive gait ataxia within 6 months and traumatic nerve root injury C7 and C8 30 years previously. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal susceptibility-weighted imaging of the spinal cord in a 73-year-old woman with a ventral dural defect at the level of the second thoracic vertebra with spontaneous intracranial hypotension and recurrent subarachnoid bleeding over more than 10 years. Extensive spinal superficial siderosis (arrows) and ventral epidural fluid collection at the upper thoracic level (arrowheads). (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial siderosis of the spinal cord on sagittal T2*-weighted images (arrows) in a 59-year-old man suffering from progressive gait ataxia within 6 months and traumatic nerve root injury C7 and C8 30 years previously. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 77-year-old woman with progressive hearing loss, gait ataxia, visual disturbances, and visual hallucinations over 6 months due to classical infratentorial superficial siderosis. Axial T2*-GRE (a-f) showing superficial siderosis of the upper cervical spinal cord (a, arrow), cranial nerve VIII but sparing cranial nerve VII (b; arrowhead, arrow), the cerebellum and mesencephalon (c, d; arrow), the medial Sylvian fissure (e, arrow) and of the medial occipital lobes (f, arrow).

Abbreviation: T2*-GRE multi-echo gradient recalled echo T2*-weighted imaging (Tang MY, Chen TW, Zhang XM, Huang XH. GRE T2∗-weighted MRI: principles and clinical applications. Biomed Res Int 2014;2014:312142).

(Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI sequences from a 61-year-old man with superficial siderosis due to ongoing hemorrhage from a melanoma metastasis in the right frontal cortex. In T2*-GRE (f) and susceptibility-weighted imaging (b, g), superficial siderosis is revealed by dark rims on the surface of affected structures, eg, the mesencephalon (arrow), with susceptibility-weighted imaging being more sensitive. Minimum intensity projections of susceptibility-weighted images (c, h) further enhance the conspicuousness of superficial siderosis. In addition, a filtered phase image of susceptibility-weighted imaging (a) can be used to distinguish paramagnetic (hemorrhage/iron, dark here) from diamagnetic substances (calcification, bright here), as they have opposite signal intensities. In general, susceptibility effects are more pronounced on images acquired at 3T (f-j) than on images acquired at 1.5T (a-e). Whereas at 3T a hypointense rim around the mesencephalon is seen in T2-weighted and FLAIR images (i, j; arrow), superficial siderosis is almost undetectable at 1.5T in T2-weighted and FLAIR images (d, e; arrow). (a-e) 1.5T; (a-c) susceptibility-weighted imaging, TR/alpha 52ms/20°, 4 echoes TE1 = 12 ms, deltaTE = 11 ms; (d) T2, TR/TE/alpha = 5762 ms/110 ms/90°; (e) FLAIR, TR/TE/TI/alpha = 11000 ms/140 ms/2800 ms/90°; (f-j) 3 T; (f) T2*-GRE, TR/TE/alpha=631ms/20ms/20°; (g, h) susceptibility-weighted imaging, TR/TE/alpha=27ms/20ms/15°; (i) T2, TR/TE/alpha=4980ms/92ms/150°, (j) FLAIR: TR/TE/TI/alpha = 8500 ms/81 ms/2440 ms/150°. TR repetition time, TE echo time, TI inversion time, α flip angle.

Abbreviation: T2*-GRE multi-echo gradient recalled echo T2*-weighted imaging (Tang MY, Chen TW, Zhang XM, Huang XH. GRE T2∗-weighted MRI: principles and clinical applications. Biomed Res Int 2014;2014:312142).

(Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Microscopic examination of CSF in a 59-year-old man suffering from progressive gait ataxia within 6 months and traumatic nerve root injury C7 and C8 30 years previously. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

CSF is from a 73-year-old woman with a ventral dural defect at the level of the second thoracic vertebra with spontaneous intracranial hypotension and recurrent subarachnoid bleeding over more than 10 years. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Auburn-colored CSF from a 73-year-old woman with a ventral dural defect at the level of the second thoracic vertebra with spontaneous intracranial hypotension and recurrent subarachnoid bleeding over more than 10 years. (Source: Weidauer S, Neuhaus E, Hattingen E. Cerebral superficial siderosis: etiology, neuroradiological features and clinical findings. Clin Neuroradiol 2023;33[2]:293-306. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Significantly altered functional connections featured highly connected nodes of presbycusis in HOFC networks. Spheres represent regions (nodes) and lines indicate connections (edges). Abbreviations: ANG, angular gyrus; CAL, calcarine fissure and surrounding cortex; IFGoperc, inferior frontal gyrus, opercular part; IFGtriang, inferior frontal gyrus, triangular part; IOG, inferior occipital gyrus; ITG, inferior temporal gyrus; L, left; LING, lingual gyrus; PreCG, precental gyrus; R, right; SFGdor, superior frontal gyrus, dorsolateral; SFGmed, superior frontal gyrus, medial; SMA, supplementary motor area; ORBsupmed, superior frontal gyrus, medial orbital; PAL, lenticular nucleus, pallidum; PCL, paracentral lobule; PCUN, precuneus; PHG, parahippocampal gyrus; PoCG, postcentral gyrus; SMG, supramarginal gyrus; SOG, superior occipital gyrus; TPOsup, temporal pole: superior temporal gyrus. (Source: Xu Y, Li X, Yan Q, et al. Topological disruption of low- and high-order functional networks in presbycusis. Brain Commun 2024;6[2]:fcae119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The mean strength of the three connections between patients with presbycusis and healthy controls were compared using a two-sample t-test. (A) In LOFC networks, no significant intergroup differences were observed in the mean strength of the three connections. (B) In HOFC networks, the mean strength of rich-club connections in patients with presbycusis was significantly higher than in healthy controls (p < 0.05). *indicates significant intergroup difference with P < 0.05. Abbreviations: LOFC, low-order functional connectivity; HCs, healthy controls; HOFC, high-order functional connectivity. (Source: Xu Y, Li X, Yan Q, et al. Topological disruption of low- and high-order functional networks in presbycusis. Brain Commun 2024;6[2]:fcae119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Classification performance of low-order functional connectivity and high-order functional connectivity networks in patients with presbycusis. (Source: Xu Y, Li X, Yan Q, et al. Topological disruption of low- and high-order functional networks in presbycusis. Brain Commun 2024;6[2]:fcae119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Significantly altered inter-modular functional connectivity between groups was observed in LOFC (A) and HOFC (C) networks. Significant changes were observed in intramodular functional connectivity in LOFC (B) and HOFC networks (D). * indicates significant intergroup difference (p < 0.05). Abbreviations: DMN, default mode network; LOFC, low-order functional connectivity; FPN, fronto-parietal network; HCs, healthy controls; HOFC, high-order functional connectivity; SMN, sensorimotor network; SN, subcortical network; VN, visual network. (Source: Xu Y, Li X, Yan Q, et al. Topological disruption of low- and high-order functional networks in presbycusis. Brain Commun 2024;6[2]:fcae119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Following its entry into the cochlea and uptake by cells via either simple or facilitated diffusion, cisplatin induces an inflammatory response through various signaling pathways, including TLR4-NF-kappaB activation, TLR4-NF-κB-NLRP3 inflammasome activation, NOX3-NF-kappaB activation, NOX3-STAT1 activation, XO-NF-kappaB/STAT1 activation, reductions in antioxidant enzyme levels, STAT3 inhibition, and mast cell degranulation. The upregulation of proinflammatory mediators in the cochlea leads to the infiltration and activation of macrophages.

Abbreviations: COX-2, cyclooxygenase 2; CTR1, copper-like transporter-1; CXCL1, chemokine (C-X-C motif) ligand 1; IL-1β, interleukin-1β; IL-18, interleukin-18; IL-6, interleukin-6; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B; NLRP3, NOD-like receptor protein 3; NOX3, NADPH oxidase 3; OCT2, organic cation transporter-2; ROS, reactive oxygen species; STAT1, signal transducer and activator of transcription-1; STAT3, signal transducer and activator of transcription-3; TNF-α, tumor necrosis factor-alpha; TLR4, Toll-like receptor 4; TMC1, transmembrane channel-like protein 1; XO, xanthine oxidase.

(Source: Tan WJ, Vlajkovic SM. Molecular characteristics of cisplatin-induced ototoxicity and therapeutic interventions. Int J Mol Sci 2023;24[22]:16545. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

This illustration depicts the anatomical structure of the cochlea, highlighting the various cell types vulnerable to cisplatin-induced damage. The cochlea consists of three fluid-filled compartments: the scala vestibuli and scala tympani, filled with Na⁺-rich perilymph, and the scala media, filled with K⁺-rich endolymph. The scala media houses the organ of Corti, which comprises the inner hair cells (responsible for auditory transduction), outer hair cells (critical for cochlear amplification), and surrounding supporting cells. Adjacent to the organ of Corti sits the lateral wall, comprising the stria vascularis (responsible for generating and maintaining the endocochlear potential, the driving force for sensory transduction) and spiral ligament (supporting the stria vascularis and cochlear fluid homeostasis). Spiral ganglion neurons innervate the sensory hair cells and transmit auditory signals to the auditory nuclei in the brainstem. Cisplatin enters the endolymph in the scala media through capillaries in the stria vascularis and is subsequently absorbed by the sensory hair cells in the organ of Corti (red dashed arrows). (Source: Tan WJ, Vlajkovic SM. Molecular characteristics of cisplatin-induced ototoxicity and therapeutic interventions. Int J Mol Sci 2023;24[22]:16545. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Audiograms of a 55-year-old man with a prosthetic shoulder infection who reported hearing loss (a) after four doses of dalbavancin and (b) at the 1-year follow-up visit. Circles represent the right ear, and crosses represent the left ear. X-axis: sound frequencies (Hz); Y-axis: volume (dB). Pure tone average (PTA) is the mean of frequencies 0.5, 1, 2, and 4 kHz. PTA < 20 dB is regarded as normal hearing, PTA 20 to 34 dB as mild hearing loss, and PTA 35 to 48 dB as moderate hearing loss. (Source: Lange A, Thunberg U, Söderquist B. Ototoxicity associated with extended dalbavancin treatment for a shoulder prosthetic joint infection. BMC Infect Dis 2023;23[1]:706. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Abbreviations: CCA: common cochlear artery; CNS: central neural system; IHCs: inner hair cells; OC: organ of Corti; OHCs: outer hair cells; OW: oval window; RW: round window; SM: scala media; SP: spiral prominence; ST: scala tympani; SV: scala vestibuli. (Source: Xu K, Xu B, Gu J, Wang X, Yu D, Chen Y. Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss. Theranostics 2023;13[11]:3524-9. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Signaling pathways involved in (A) inflammation, (B) energy metabolism, (C) oxidative stress, (D) programmed cell death, and (E) excitotoxicity and autophagy are illustrated in separated regions. Protective responses are shown in green. Adverse cellular events are shown in red. Pharmacological interventions are shown in purple. (Source: Xu K, Xu B, Gu J, Wang X, Yu D, Chen Y. Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss. Theranostics 2023;13[11]:3524-9. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Noise-related dysfunction of the stria vascularis leads to ischemia-reperfusion injury, which increases the level of reactive oxygen species (ROS) in the cochlea. The overproduction of ROS and cochlear inflammation are two biochemical events that promote each other. With excessive calcium influx triggering glutamate neurotoxicity at the ribbon synapses, both hair cells and synaptic structures are damaged, triggering intrinsic or extrinsic pathways of apoptosis. Abbreviations: ROS: reactive oxygen species; GluR: glutamate receptor. (Source: Xu K, Xu B, Gu J, Wang X, Yu D, Chen Y. Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss. Theranostics 2023;13[11]:3524-9. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(A) Schematic representation of ear anatomy. The ear consists of three parts: the outer, middle, and inner ear. The outer and middle ear are separated by the tympanic membrane. Sound waves are transduced through the tympanic membrane to the chain of three tiny bones (the ossicles) in the middle ear cavity, which is attached to the oval window membrane, leading to fluid vibrations in the inner ear. The inner ear is responsible for hearing (cochlea) and balance (vestibule). (B) The cochlea is divided into three fluid-filled membranous tubes coiling around the modiolus: the scala tympani, scala vestibuli, and scala media. The fluid vibrations create a traveling wave along the basilar membrane, in which hair cells generate the electrical signals and pass them to the spiral ganglion cells. (C) High-intensity sound waves travel through the cochlear duct, causing damage to three key functional areas: the organ of Corti, the spiral ganglion neurons, and the stria vascularis. Hair cells, supporting cells, and spiral ganglion neurons go through morphological changes and eventual apoptosis in extreme cases. Loss of tight junctions, malfunction of endothelial cells, and surrounding cell types contribute to the blood-labyrinth barrier disruption. Abbreviations: BLB, blood-labyrinth barrier; IHC, inner hair cell; OHCs, outer hair cells; SCs, supporting cells; SM, scala media; ST, scala tympani; SV, scala vestibuli. (Source: Xu K, Xu B, Gu J, Wang X, Yu D, Chen Y. Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss. Theranostics 2023;13[11]:3524-9. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Radial diffusivity maps show significant differences between patients with mild noise‐induced hearing loss, relatively severe noise‐induced hearing loss, and healthy controls. The red-yellow highlighted areas indicate higher radial diffusivity values in the left inferior longitudinal fasciculus and left inferior fronto-occipital fasciculus. The background image consists of the standard MNI T1-weighted template at 1 mm thickness and the fractional anisotropy skeleton (green). (The red-yellow scale represents regions of significant difference, with red representing regions of greatest difference.) The right-hand column is the corresponding section sagittal/coronal position. (Source: Huang R, Wang A, Zhang Y, et al. Alterations of the cerebral microstructure in patients with noise-induced hearing loss: a diffusion tensor imaging study. Brain Behav 2024;14[4]:e3479. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Mean diffusivity maps show significant differences between patients with mild noise‐induced hearing loss, relatively severe noise‐induced hearing loss, and healthy controls. The red-yellow highlighted areas indicate higher mean diffusivity values in the left inferior longitudinal fasciculus and left inferior fronto-occipital fasciculus. The background image consists of the standard MNI T1-weighted template at 1 mm thickness and the fractional anisotropy skeleton (green). (The red-yellow scale represents regions of significant difference, with red representing regions of greatest difference.) The right-hand column is the corresponding section sagittal/coronal position. (Source: Huang R, Wang A, Zhang Y, et al. Alterations of the cerebral microstructure in patients with noise-induced hearing loss: a diffusion tensor imaging study. Brain Behav 2024;14[4]:e3479. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial diffusivity maps show significant differences between patients with mild noise‐induced hearing loss, relatively severe noise‐induced hearing loss, and healthy controls. The red-yellow highlighted areas indicate higher axial diffusivity values in the left inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, right corticospinal tract, right external capsule, and right superior longitudinal fasciculus; they are significantly lower in the left corticospinal tract, right anterior thalamic radiation, and right superior cerebellar peduncle. The background image consists of the standard MNI T1-weighted template at 1 mm thickness and the fractional anisotropy skeleton (green). (The red-yellow scale represents regions of significant difference, with red representing regions of greatest difference.) The right-hand column is the corresponding section sagittal/coronal position. (Source: Huang R, Wang A, Zhang Y, et al. Alterations of the cerebral microstructure in patients with noise-induced hearing loss: a diffusion tensor imaging study. Brain Behav 2024;14[4]:e3479. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Fractional anisotropy maps show significant differences between patients with mild noise‐induced hearing loss, relatively severe noise‐induced hearing loss, and healthy controls. The red-yellow highlighted areas indicate lower fractional anisotropy values in the left inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, bilateral corticospinal tract, right fronto-pontine tract, right forceps major, left superior longitudinal fasciculus (temporal part), and left cingulum (hippocampus). The background image consists of the standard MNI T1-weighted template at 1 mm thickness and the fractional anisotropy skeleton (green). The right-hand column is the corresponding section sagittal/coronal position. (Source: Huang R, Wang A, Zhang Y, et al. Alterations of the cerebral microstructure in patients with noise-induced hearing loss: a diffusion tensor imaging study. Brain Behav 2024;14[4]:e3479. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Legend: arrow: insula; arrowhead: right superior temporal gyrus. (Source: Shin S, Nam HY. Characteristics of brain glucose metabolism and metabolic connectivity in noise-induced hearing loss. Sci Rep 2023;13[1]:21889. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Italian physician Bernardino Ramazzini described noise-related hearing loss (and possibly tinnitus) in corn millers and coppersmiths in the pre-industrial era. (Public domain.)

MRI of the head/ internal auditory canal with gadolinium demonstrated asymmetrical enhancement of the tympanic and mastoid segments of the left facial nerve and both internal auditory canals. (Source: Sheik-Ali S, Jiang Y, Nasef H, Sproson E, Tuohy O. Bilateral sequential Ramsay Hunt syndrome in an immunocompromised adult: a rare entity. Ann R Coll Surg Engl 2024;106[2]:197-9 Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Extensive vesicular eruption involving the left pinna and external auditory canal, with an associated necrotic focus in the conchal bowl and subsequent blistering. (Source: Sheik-Ali S, Jiang Y, Nasef H, Sproson E, Tuohy O. Bilateral sequential Ramsay Hunt syndrome in an immunocompromised adult: a rare entity. Ann R Coll Surg Engl 2024;106[2]:197-9 Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Data presented as overall prevalence. All patients with CANVAS experienced more than one symptom. *Based on nerve conduction studies. (Source: Turner RD, Hirons B, Cortese A, Birring SS. Chronic cough as a genetic neurological disorder? Insights from cerebellar ataxia with neuropathy and vestibular areflexia syndrome [CANVAS]. Lung 2023;201[6]:511-19. Adapted from: Cortese A, Tozza S, Yau WY, et al. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. Brain 2020;143[2]:480-90. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

CA, crista ampullaris. (Source: Stultiens JJ, Lewis RF, Phillips JO, et al. The next challenges of vestibular implantation in humans. J Assoc Res Otolaryngol 2023;24[4]:401-12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image sharpened by Dr. Douglas Lanska.)

Retraction (double arrow) of the electrode ending is evident (E‐endolymph). (Source: Stultiens JJ, Lewis RF, Phillips JO, et al. The next challenges of vestibular implantation in humans. J Assoc Res Otolaryngol 2023;24[4]:401-12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image sharpened by Dr. Douglas Lanska.)

The endolymphatic compartment (E) is completely preserved. A vibratome is an instrument used to cut thin slices of material. It is similar to a microtome but uses a vibrating blade to cut through tissue. (Source: Stultiens JJ, Lewis RF, Phillips JO, et al. The next challenges of vestibular implantation in humans. J Assoc Res Otolaryngol 2023;24[4]:401-12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image sharpened by Dr. Douglas Lanska.)

The xy, yz, and xz planes are resolved at 20 μm/voxel. Lateral, anterior, and posterior semicircular canals are shown with metal wires of vestibular electrodes colored blue. The crosshair intersection represents the tip of the lateral canal electrode. Highlighted slice within orange lines represents the 3D view in the lower right image. (Source: Stultiens JJ, Lewis RF, Phillips JO, et al. The next challenges of vestibular implantation in humans. J Assoc Res Otolaryngol 2023;24[4]:401-12. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image sharpened by Dr. Douglas Lanska.)

Frequency of individual phenotypic features in 17 GAA-FGF14-positive patients. Numbers in brackets indicate the number of affected patients over the total number of patients assessed for this feature. FGF14, fibroblast growth factor 14 gene. (Source: Pellerin D, Wilke C, Traschütz A, et al. Intronic FGF14 GAA repeat expansions are a common cause of ataxia syndromes with neuropathy and bilateral vestibulopathy. J Neurol Neurosurg Psychiatry 2024;95[2]:175-179. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Vestibular implant, combined with a cochlear lead (ie, a vestibulocochlear implant), in relation to the bony and membranous labyrinth of the inner ear. The electrodes implanted through fenestrations in the bony semicircular canals stimulate the terminal afferent nerve fibers from the ampullae. Abbreviations: SCC, semicircular canal; A, ampulla; U, utricle; S, saccule. (Source: Stultiens JJ, Lewis RF, Phillips JO, et al. The next challenges of vestibular implantation in humans. J Assoc Res Otolaryngol 2023;24[4]:401-12. Illustration made by Ruoning Qin. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image sharpened by Dr. Douglas Lanska.)

Negative correlation between the size of the FGF14 repeat expansion and age at disease onset in 17 patients (Pearson’s r, −0.67; R2=0.45; p=0.0031). The grey area displays the 95% confidence interval. Simple linear regression fitting (slope, -0.079 and intercept, 89.84) suggests that age at onset decreases by about 3.96 years (95% CI: 1.56 to 6.37 years) for every increment of 50 GAA repeats above the pathogenic threshold of 250 repeat units. (Source: Pellerin D, Wilke C, Traschütz A, et al. Intronic FGF14 GAA repeat expansions are a common cause of ataxia syndromes with neuropathy and bilateral vestibulopathy. J Neurol Neurosurg Psychiatry 2024;95[2]:175-179. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Percentage of patients who carried an FGF14 (GAA) 250 or greater repeat expansion in the subgroups with (1) cerebellar ataxia plus polyneuropathy (CA+PN) (5 of 13 patients), (2) cerebellar ataxia plus bilateral vestibulopathy (CA+BVP) (9 of 21), and (3) cerebellar ataxia plus polyneuropathy and bilateral vestibulopathy (CA+PN+ BVP) (3 of 11). (Source: Pellerin D, Wilke C, Traschütz A, et al. Intronic FGF14 GAA repeat expansions are a common cause of ataxia syndromes with neuropathy and bilateral vestibulopathy. J Neurol Neurosurg Psychiatry 2024;95[2]:175-179. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Electron microscopic image of sural nerve biopsy findings in a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Electron microscopic image of a sural nerve biopsy shows membranous material between myelin sheaths (white arrow) or between a myelin sheath and an axon (white arrowhead). Biopsy findings are from a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Electron microscopic image of a sural nerve biopsy shows a Schwann cell with a cytoplasmic inclusion (yellow arrow). Biopsy findings are from a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Electron microscopic image of a sural nerve biopsy shows a Schwann cell with a cytoplasmic inclusion (yellow arrow). Biopsy findings are from a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Electron microscopic image of a sural nerve biopsy shows a Schwann cell with cytoplasmic dense material (blue arrow). Biopsy findings are from a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Electron microscopic image of a sural nerve biopsy shows many collagen pockets (black arrow), reflecting unmyelinated fiber damage. Biopsy findings are from a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Light microscopic image of a sural nerve biopsy in a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Light microscopic image of a sural nerve biopsy in a woman in her late 70s with an RFC1 mutation (biallelic ACAGG) and slowly progressive sensory autonomic neuropathy with mild motor deficit, moderate sensory impairment, and severe autonomic disturbance. (Source: Hirano M, Kuwahara M, Yamagishi Y, et al. CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. Sci Rep 2023;13[1]:17801. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The functional mechanism under deafferentation (ie, blindness in this context) is that false sensory data become overly influential, overriding the results of data comparison and expectancies to become incorporated into a hallucinatory perception. The hallucinated perception is replaced by a veridical one when the strength of the false sensory evidence reduces, or expectancies and data comparison override it. False sensory data results from hyperexcitability and spontaneous activation of the primary visual cortex caused by chronic loss of visual input. Green shading indicates which aspects of the framework are mapped to in each model, with the green text indicating the specific effects on functions. (Source: Collerton D, Barnes J, Diederich NJ, et al. Understanding visual hallucinations: a new synthesis. Neurosci Biobehav Rev 2023;150:105208. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Descending influences are shown in blue, and ascending are shown in red. Horizontal influences are in green. The grey blur over memory, context, emotion, and intention indicates that these factors interact to create complex expectancies. Linking arrows show the specific relationships between concepts while recognizing that the influence of these varies dynamically. The level of detail for each function reflects the need to incorporate distinctions in existing theories; thus, perception and attention are much more fractionated than memory or context. Expectancies act to bias perception and can be conceptualized as brain states that reflect prior information about what is possible or probable in the forthcoming sensory environment, ie, what is expected to be seen in that context (Parr T, Rees G, Friston KJ. Computational neuropsychology and Bayesian inference. Front Hum Neurosci 2018;12:61.). Predictions of sensory-level data are central to state models; in contrast, trait models emphasize higher-order expectances that develop from an interaction between (1) memories of past similar visual environments (memory expectancies), (2) the current visual context (context expectancies), (3) future intentions and motivations (intentional and motivational expectancies), and (4) emotions (emotional expectancies). Emphasizing the circular interactions between these functions, the visual context is created from inputs arising from current visual (and other sensory) perceptions. In addition to their direct role in modifying predicted data, expectancies also indirectly affect sensory data gathering and processing via attention. (Source: Collerton D, Barnes J, Diederich NJ, et al. Understanding visual hallucinations: a new synthesis. Neurosci Biobehav Rev 2023;150:105208. Creative Commons Attribution [CC BY] license.)

Ten-second EEG epoch tracing with longitudinal bipolar montage and central leads showing focal slowing over the left temporal region (encased in the blue box). (Source: Sy AJ, Gochioco DC. Charles Bonnet syndrome as sequelae of occipital lobe infarct with hemorrhagic conversion: a case report. Cureus 2023;15[12]:e50472. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Cranial T2 FLAIR MRI showing a subacute hemorrhagic infarct involving the left posteromedial temporal and left occipital lobes and, to a lesser extent, the left posterior thalamus. (Source: Sy AJ, Gochioco DC. Charles Bonnet syndrome as sequelae of occipital lobe infarct with hemorrhagic conversion: a case report. Cureus 2023;15[12]:e50472. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

OS (left eye) showing right visual field loss (area in black); OD (right eye) showing right visual field loss (area in black). (Source: Sy AJ, Gochioco DC. Charles Bonnet syndrome as sequelae of occipital lobe infarct with hemorrhagic conversion: a case report. Cureus 2023;15[12]:e50472. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Cranial gradient echo (GRE) MRI showing a subacute hemorrhagic infarct involving the left posteromedial temporal and left occipital lobes and, to a lesser extent, the left posterior thalamus. (Source: Sy AJ, Gochioco DC. Charles Bonnet syndrome as sequelae of occipital lobe infarct with hemorrhagic conversion: a case report. Cureus 2023;15[12]:e50472. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A model of a perception process in the predictive processing framework in which a prediction is sent to the model of perception, which, in turn, passes down an expected perception that is contrasted with sensory input to generate a prediction error. This prediction error goes up to the perceptual model and, in turn, changes predictions about environmental states. (Source: Schmid FR, Kriegleder MF. Explanatory power by vagueness. Challenges to the strong prior hypothesis on hallucinations exemplified by the Charles-Bonnet-Syndrome. Conscious Cogn 2024;117:103620. Creative Commons Attribution [CC BY] license.)

A model of a perception process in the predictive processing framework in which a prediction is sent to the model of perception, which, in turn, passes down an expected perception that is contrasted with sensory input to generate a prediction error. This prediction error goes up to the perceptual model and, in turn, changes predictions about environmental states. (Source: Schmid FR, Kriegleder MF. Explanatory power by vagueness. Challenges to the strong prior hypothesis on hallucinations exemplified by the Charles-Bonnet-Syndrome. Conscious Cogn 2024;117:103620. Creative Commons Attribution [CC BY] license.)

T2 FLAIR-weighted sagittal image 7 months after metastasis resection shows the resection cavity, with slight enhancement at the margins, and the adjacent sub-/epidural collection. (Source: Ovchinnikov A, Andereggen L, Rogers S, Gschwind M. Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images. Strahlenther Onkol 2024. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

T1-weighted contrast-enhanced axial MRI 7 months after metastasis resection shows the resection cavity, with slight enhancement at the margins. (Source: Ovchinnikov A, Andereggen L, Rogers S, Gschwind M. Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images. Strahlenther Onkol 2024. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

T2 FLAIR-weighted axial image 7 months after metastasis resection shows the resection cavity, with slight enhancement at the margins, and the adjacent sub-/epidural collection. (Source: Ovchinnikov A, Andereggen L, Rogers S, Gschwind M. Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images. Strahlenther Onkol 2024. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T1-weighted contrast-enhanced MRI at time of diagnosis shows a slightly hypointense, ring-enhancing, and partially cystic mass with marked perilesional edema. There was a minor midline shift. (Source: Ovchinnikov A, Andereggen L, Rogers S, Gschwind M. Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images. Strahlenther Onkol 2024. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T2 fluid-attenuated inversion recovery (FLAIR)-weighted MRI sequence at time of diagnosis depicts a left occipital paramedian iso- to hypointense lesion. (Source: Ovchinnikov A, Andereggen L, Rogers S, Gschwind M. Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images. Strahlenther Onkol 2024. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T2 fluid-attenuated inversion recovery (FLAIR)-weighted MRI sequence at time of diagnosis depicts a left occipital paramedian iso- to hypointense lesion. (Source: Ovchinnikov A, Andereggen L, Rogers S, Gschwind M. Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images. Strahlenther Onkol 2024. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Case timeline for a 74-year-old man who presented with a right homonymous hemianopia and persistent left-temporal headache. (Source: Ovchinnikov A, Andereggen L, Rogers S, Gschwind M. Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images. Strahlenther Onkol 2024. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Public domain.)

(Public domain.)

Pictured is Dr. Anton as a professor in Graz, Austria, circa 1890. (Public domain.)

Diagram illustrating the time course of the disease. Abbreviations: PTA, pure-tone average; R, right; L, left; MRI, magnetic resonance imaging; MCP, middle cerebellar peduncle. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Brain and neck computed tomography angiography revealed occlusion of the bilateral vertebral artery V3 segment, proximal V4 segment, and anterior inferior cerebellar artery bilaterally, as well as severe stenosis of the distal left vertebral artery V4 segment. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Brain and neck computed tomography angiography revealed occlusion of the bilateral vertebral artery V3 segment, proximal V4 segment, and anterior inferior cerebellar artery bilaterally, as well as severe stenosis of the distal left vertebral artery V4 segment. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Ten days after hospitalization, diffusion-weighted MRI showed new hyperintense foci at the middle cerebellar peduncle bilaterally. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Third day, diffusion-weighted MRI showed hyperintense foci in the cerebellum bilaterally. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Ten days after hospitalization, diffusion-weighted MRI showed new hyperintense foci at the middle cerebellar peduncle bilaterally. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Third day, diffusion-weighted MRI showed hyperintense foci in the cerebellum bilaterally. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The electrocochleogram showed the binaural SP/AP (summating potential/action potential) ratio in the normal range at 90 dBnHL (decibel normal hearing level), with the left ear SP/AP ratio 0.33 and the right ear SP/AP ratio 0.25. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Pure tone audiogram after 3-month follow-up showing moderately severe to severe hearing loss in both ears with pure tone averages (PTA) of 67 dB on the right and 73 dB on the left. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Pure-tone audiogram on admission showing profound sensorineural hearing loss in both ears with pure-tone averages (PTA) of 112 dB on the right and 115 on the left. (Source: Yuan Z, Xiang L, Liu R, Yue W. Case report: bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral? Front Med [Lausanne] 2023;10:1174512. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Combined activation map of auditory processing in a 29-year-old right-handed man with bihemispheric cardioembolic infarcts in the middle cerebral artery territories. Activation map contrasting language conditions relative to rest for the two "spoken narrative" and "slow spoken narrative" paradigms, where only activation in a given voxel across all three paradigms is shown. The activation maps are overlain on coronal slices in two-slice increments from T1-weighted structural imaging spanning the length of Heschl's gyri bilaterally. Slices with activation of Heschl's gyri in a given hemisphere are denoted with arrows. The lesion mask (unsmoothed to allow for fine-grained interpretation of the activation patterns relative to structural damage) is depicted in blue. Left is left. Abbreviation: HG = Heschl's gyri. (Source: Casilio M, Kasdan AV, Schneck SM, et al. Situating word deafness within aphasia recovery: a case report. Cortex 2024;173:96-119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Activation maps for the narrative paradigms in a 29-year-old right-handed man with bihemispheric cardioembolic infarcts in the middle cerebral artery territories. (A-B) Activation maps contrasting language conditions relative to matched perceptual conditions for the written narrative and slow written narrative paradigms. (C-D) Activation maps contrasting language conditions relative to matched perceptual conditions for the spoken narrative and slow spoken paradigms. The activation map from the repeated spoken narrative paradigm obtained during the second scanning session is not depicted because it is identical to the one obtained during the first scanning session. The smoothed lesion mask is depicted in blue. The color bar reflects the percentile range a t statistic fell within for a given voxel (lower % indicates greater statistical significance). Left is left. (Source: Casilio M, Kasdan AV, Schneck SM, et al. Situating word deafness within aphasia recovery: a case report. Cortex 2024;173:96-119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Activation maps for the adaptive word paradigms in a 29-year-old right-handed man with bihemispheric cardioembolic infarcts in the middle cerebral artery territories. (A-C) Activation maps contrasting language conditions relative to matched perceptual conditions. The color bar reflects the percentile range a thresholded t statistic fell within for a given voxel (lower % indicates greater statistical significance). The smoothed lesion mask is depicted in blue. Left is left. (Source: Casilio M, Kasdan AV, Schneck SM, et al. Situating word deafness within aphasia recovery: a case report. Cortex 2024;173:96-119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Lesion-delineated structural scan in a 29-year-old right-handed man with bihemispheric cardioembolic infarcts in the middle cerebral artery territories. Axial slices are presented at five-slice intervals from T1-weighted scans spanning the extent of his lesions, which are delineated in blue (unsmoothed to allow for fine-grained review of structural damage). Left is left. (Source: Casilio M, Kasdan AV, Schneck SM, et al. Situating word deafness within aphasia recovery: a case report. Cortex 2024;173:96-119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Model of hypothesized processes that underly spoken language comprehension. Boxes and connecting arrows in blue depict linguistic processes, whereas boxes and arrows in gray show auditory processes. This model is a simplified modification of the model proposed by Whitworth in 2013 and is designed to also express interaction among processes (Dell et al 1997; Levelt et al 1999; Whitworth et al 2013). Components of this model were ultimately derived from German neurologist and psychiatrist Karl Kleist (1879-1960) (Kleist 1962), a student of German neurologist, psychiatrist, and neuropathologist Carl Wernicke (1848-1905). Kleist's work can be understood within the historical connectionist model of language processing (Wernicke 1874; Lichtheim 1885). To show this direct comparison, lettering in the top-right corner of the boxes corresponds to those used by German physician and pioneering aphasiologist Ludwig Lichtheim (1845-1928) in 1885, as does the color-coding of the boxes and connecting arrows described above (ie, those outlined in blue represent centers and pathways that result in select aphasia syndromes if damaged). (Source: Casilio M, Kasdan AV, Schneck SM, et al. Situating word deafness within aphasia recovery: a case report. Cortex 2024;173:96-119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

References cited:
Dell GS, Schwartz MF, Martin N, Saffran EM, Gagnon DA. Lexical access in aphasic and nonaphasic speakers. Psychol Rev 1997;104[4]:801-38.
Kleist K. Sensory aphasia and amusia: the myeloarchitectonic basis. Oxford: Pergamon Press, 1962.
Levelt WJ, Roelofs A, Meyer AS. A theory of lexical access in speech production. Behav Brain Sci 1999;22[1]:1-38; discussion 38-75.
Lichtheim L. On aphasia. Brain 1885;7:433-84. Wernicke C. Der aphasische symptomencomplex. Breslau: Cohn and Weigert, 1874.
Whitworth A, Webster J, Howard D. A Cognitive Neuropsychological Approach To Assessment And Intervention In Aphasia: A Clinician's Guide. 2nd ed. Hove [England]: Psychology Press, 2013.

Normal pure-tone audiogram results from an audiological evaluation approximately 1 month after stroke onset. (Source: Casilio M, Kasdan AV, Schneck SM, et al. Situating word deafness within aphasia recovery: a case report. Cortex 2024;173:96-119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Representative axial slices from diffusion-weighted MRI obtained approximately 3 days after stroke onset show bilateral middle cerebral artery infarcts, most likely from a cardioembolic source. Images were warped to standardized space. Left is left. (Source: Casilio M, Kasdan AV, Schneck SM, et al. Situating word deafness within aphasia recovery: a case report. Cortex 2024;173:96-119. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 19-year-old patient developed cardiac arrest. When extubated, she was noted to be cortically blind. Diffusion-weighted MRI and corresponding ADC map (6 days after cardiac arrest) showed evidence for extensive predominantly cortical diffusion restriction most prominent in the right occipital cortex and bilateral basal ganglia. (Contributed by Dr.Sangeeta Khanna.)

Enhancement of the left oculomotor nerve during an attack of recurrent painful ophthalmoplegic neuropathy. (Contributed by Dr. Aubrey L Gilbert.)

A 10-year-old girl had infrequent attacks of recurrent painful ophthalmoplegia affecting the right sixth nerve. She also experienced migraine headaches without ophthalmoparesis, and her mother had migraines without aura. There is a right lateral rectus palsy and enhancement of the prepontine right abducens nerve during an attack, which resolved when symptoms remitted. (Contributed by Vivek Lal MD.)

(Contributed by Dr. Jonathan Trobe.)

The patient also had abnormally low scores in speech audiometry (not shown). (Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Wide-field fluorescein angiogram demonstrating right eye peripheral (superior, temporal, and inferior) branch artery occlusions and focal arterial leakage in an inferior branch artery. (Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Fundoscopic examination revealed fluffy white patches along the inferotemporal arcade in a 22-year-old man diagnosed with Susac syndrome. Fluorescein angiography confirmed 14 branch artery occlusions and arterial wall hyperfluorescence with leakage of dye (not shown). (Source: Gertner E, Rosenbloom MH. Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report. J Med Case Rep 2016;10[1]:137. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial brain DWI in a 22-year-old man diagnosed with Susac syndrome, showing multifocal subacute punctate supratentorial white matter lesions (black arrows) with the most prominent lesion affecting the posterior corpus callosum (red arrowhead). The study also showed T2/FLAIR hyperintensities involving the deep gray nuclei as well as leptomeningeal enhancement (not shown). (Source: Gertner E, Rosenbloom MH. Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report. J Med Case Rep 2016;10[1]:137. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Livedo reticularis-like skin manifestation occurring on both arms, but nowhere else, one week before presentation and resolving with treatment, in a 22-year-old man diagnosed with Susac syndrome. (Source: Gertner E, Rosenbloom MH. Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report. J Med Case Rep 2016;10[1]:137. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Large ischemic area in the lower half of the left retina (arrow) and smaller infarct in the top left quadrant (tailed arrow), representing branch retinal artery occlusions in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Axial contrast-enhanced T1-weighted MRI showing multiple small contrast-enhancing lesions (arrows) in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Near-median sagittal T2 MRI demonstrating atrophy of the corpus callosum in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Sagittal T2 MRI showing centrally located corpus callosum lesions (arrow) and one lesion with spoke-like morphology (tailed arrow) in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Diffusion-weighted image from a 32-year-old woman with Susac syndrome; the image shows multiple small lesions exhibiting diffusion restriction (arrows) and correspondingly decreased ADC values (not shown). (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Axial FLAIR image from a 32-year-old woman with Susac syndrome, showing multiple small white matter lesions. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the deep layer, left eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the superficial layer, left eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the deep layer, right eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the superficial layer, right eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Color fundus photography revealing a glass plaque (white arrow) as yellowish lipid sediments at the mid-segment of the retinal arterioles in the left eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Sagittal MRI of a 33-year-old man with Susac syndrome. The red arrow shows an ellipsoid focal lesion involving the corpus callosum. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Transverse MRI of a 33-year-old man with Susac syndrome. The red arrows show various round and ellipsoid focal lesions involving the cerebellum. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Transverse MRI of a 33-year-old man with Susac syndrome. The red arrows show various round and ellipsoid focal lesions involving the corpus callosum, periventricular and subcortical white matter, and deep grey matter (basal ganglia and thalami). (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

On follow-up 18 months after the initial FLAIR sequence, there was generalized brain atrophy with stable white matter lesions. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

On follow-up 2 weeks after the initial brain MRI, FLAIR sequence showed an area of increased T2 signal without diffusion restriction over the left side of the pontine tegmentum. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

On follow-up 2 weeks after the initial brain MRI, diffusion-weighted images showed a new area of diffusion restriction in the left corona radiata, corpus callosum, and right middle cerebral peduncle. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Initial brain MRI in a 56-year-old man with Susac syndrome. Transverse FLAIR images showed increased T2 signal in the areas corresponding to areas of restricted diffusion on diffusion-weighted images. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Initial brain MRI in a 56-year-old man with Susac syndrome. Diffusion-weighted images showed areas of restricted diffusion over the central/left aspect of the splenium of the corpus callosum, left parietal white matter, left basal ganglia, and anterior right cingulate gyrus. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal FLAIR sequence on brain MRI from the patient’s last follow-up, showing improvement of the radiological findings. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Transverse FLAIR sequence on brain MRI from the patient’s last follow-up, showing improvement of the radiological findings. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal FLAIR sequence on brain MRI showing hyperintense white matter lesions with "snowball"-like lesions in the corpus callosum. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Transverse FLAIR sequence on brain MRI showing hyperintense white matter lesions with "snowball"-like lesions in the corpus callosum. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T1 MRI showing the pathognomonic central callosal "holes" (microinfarcts) of Susac syndrome. These residual "holes" (and sometimes, "spokes") develop as the acute callosal changes resolve. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Legend: C, cyclophosphamide; IVIg, intravenous immunoglobulin; MM, mycophenolate mofetil. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Audiogram showing bilateral low-frequency sensorineural hearing loss, rising to normal at higher frequencies. This is the typical cochlear hearing loss pattern seen in Susac syndrome, likely reflecting microinfarction of the striae vascularis at the apex of the cochlea. Legend: X = left ear; O = right ear. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Axial T2 image showing multiple white matter lesions, especially in the corpus callosum. The arrows point to 2 of several callosal lesions. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

These scores are derived by adding disease activity (0-100) for each domain (brain, ears, eyes). (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Admission MRI revealed multifocal T1 hypointensity and T2 hyperintensity lesions in the periventricular and supraventricular cerebral and cerebellar white matter, including extensive involvement of the corpus callosum. (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

These scores are derived by adding disease activity (0-100) for each domain (brain, ears, eyes). (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI on admission showing several “snowball” lesions in the corpus callosum. (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Bilateral severe visual field defects. Foveal threshold is also reduced at 16 dB in the right eye and 15 dB in the left eye. (Contributed by Dr. Allison Liu.)

Larger and brighter isopters (II4e to V4e) are relatively preserved. However, the smaller and dimmer isopters (I3e and I2e) show moderately to severely constricted visual fields. (Contributed by Dr. Allison Liu.)

(Contributed by Dr. Allison Liu.)

Optical coherence tomography retina nerve fiber layer measurements and ganglion cell complex measurements show thinning in both eyes. (Contributed by Dr. Allison Liu.)

(Contributed by Dr. Allison Liu.)

The first (shown in green) and last (shown in brown) pure-tone audiograms. Legend: left ear (x) and right ear (o). (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Postoperative resolution of the large ventral epidural fluid collection. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Subsequent tracking of contrast to the right posterior thoracic cord delineating the site of the dural defect, T9-10. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Reverse dynamic CT myelogram demonstrating contrast injection into the ventral epidural collection. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal spine T2-weighted SPC MRI revealed a large ventral epidural fluid collection extending from C3 to L3. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the frontal horns (black arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the third ventricle (yellow arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the mesencephalon, suprasellar pons cistern (white arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the peripontine cistern, pons, aqueduct of Sylvius, tentorium, temporal horn of the left lateral ventricle (red arrows). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted axial image shows hemosiderin deposits around the mesencephalon) (blue arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted axial image shows hemosiderin deposits along the cerebellar peduncles, around the fourth ventricle (green arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Dorsolateral view of spinal cord after laminectomy and opening of dura--rotated up to show the ventral dural defect. Legend: A. branch of anterior spinal artery; B. rostral and caudal margins of ventral dural defect with anterior pseudomeningocoele (*) in the depths; C. xanthochromia on spinal cord; D. dentate ligament divided; E. Adhesions to the dural defect, the probable source of chronic subarachnoid hemorrhage. (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

T2-weighted spine MRI in axial (a) and sagittal (b) section shows a longitudinally extensive epidural CSF collection from T2 to T8 (E) with a large spike-like osteophyte at T5/T6 impinging on the dura (G). The CT myelogram (c) shows contrast in the epidural collection from a CSF leak adjacent to the osteophyte (G). Legend: (A) spinal cord coated with hemosiderin; (B) epidural fat, bright on T2; (C) dura posterior to cord; (D) intradural CSF surrounding cord; (E) epidural CSF collection; (F) dura anterior to cord; (G) osteophyte; (H) CSF pulsation artifact. (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Susceptibility-weighted brain MRI (SWI) shows extensive leptomeningeal low signal intensity around the cerebellar folia (a), the basis pontis and vestibulocochlear nerves (b) and Sylvian fissures (c) due to hemosiderin deposition. (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (CD68 immunohistochemistry). Superficially located within the cortex, CD68-positive macrophages can be observed (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (GFAP immunohistochemistry). Within the superficial cortex area, iron deposits are accompanied by reactive astrocytes (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (Perls Prussian blue stain). Covering the superficial layers of the cortex, ribbon-like iron deposits are appreciable (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (H&E). Apart from recent bleeding constituents within the leptomeningeal compartment (arrow), hemosiderin deposits can be seen within the molecular layer of the cortex (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T2-weighted images show intramedullary hyperintense edema and hypointense hemosiderin deposition along the spinal cord surface. The thecal sac shows hypointense blood-fluid levels (left image). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Image shows abnormal linear enhancement along the cord surface and diffuse enhancement of the nerve roots of the cauda equina (-->). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sequential transverse susceptibility-weighted imaging (SWI) of the brain at the level of the medulla and cerebellum that were acquired over a 64-day period. The progression of the superficial sideroses is visible as a black coating of the brain surface most pronounced on the top of the cerebellum and around the brainstem. (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sequential transverse susceptibility-weighted imaging (SWI) of the brain at the level of the pons, 4th ventricle, and cerebellum that was acquired over a 64-day period. The progression of the superficial sideroses is visible as a black coating of the brain surface most pronounced on the top of the cerebellum and around the brainstem. (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sequential transverse susceptibility-weighted imaging (SWI) of the cerebrum acquired over a 64-day period. The progression of the superficial sideroses is visible as a black coating of the brain surface most pronounced on the top of the cerebellum and around the brainstem. (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up T2-weighted gradient echo (GRE) sagittal image of cervical spinal cord shows severe spinal superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up susceptibility-weighted (SW) transverse image of mesencephalic structures shows severe spinal superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up susceptibility-weighted (SW) transverse image shows severe cortical and periventricular superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

T2-weighted images of cerebellum and brainstem show superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T2-weighted imaging using spectral attenuated inversion recovery (SPAIR) of a myxopapillary ependymoma near the conus terminalis (L3/4). (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Coronal T2-weighted MRI shows left parietal meningioma. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Supratentorial superficial siderosis (yellow arrowhead) along the interhemispheric and Sylvian fissures and within temporal and occipital sulci is well demonstrated by the axial susceptibility-weighted (SW) sequence. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Superficial siderosis along the eighth cranial nerves on both sides is clearly seen on an axial gradient echo (GRE) image magnification. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Superficial siderosis along the eighth cranial nerves on both sides is clearly seen on a sagittal TSE T2 image magnification. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Apparent diffusion coefficient (ADC) image shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast susceptibility-weighted image (SWI) shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast gradient echo (GRE) image shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast axial TSE T2 image shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast coronal T2 Fluid-attenuated inversion recovery (FLAIR) image shows superior cerebellar atrophy (yellow crooked arrow). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast sagittal 3D T1 MRI shows superior cerebellar atrophy (yellow crooked arrow). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Sagittal gradient echo (GRE) T2 MRI of the thoracic spine shows extensive superficial siderosis around the spinal cord, from below a dural defect up to the medullary cone. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Axial CT image through the T6-T7 disc shows a dural defect just to the right of midline at the level of the spur and further delineates the associated ventral epidural fluid collection. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Axial T1-weighted MRI through the T6-T7 disc shows a dural defect just to the right of midline at the level of the spur and further delineates the associated ventral epidural fluid collection. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Axial turbo-spin echo (TSE) T2 MRI through the T6-T7 disc shows a dural defect just to the right of midline at the level of the spur and further delineates the associated ventral epidural fluid collection. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

CT in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. The noncontrast sagittal spinal CT image shows a partially calcified disc extrusion also recognizable by noncontrast sagittal spinal CT images. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Sagittal T1-weighted MRI of the cervical and upper thoracic spine shows an anterior wedge degenerative deformation of the T6 vertebral body with a superimposed prominent central disc extrusion characterized by osteo-calcific signal (yellow arrow) causing a dural tear at the T6-T7 level. Above the disc extrusion, note the “sentinel” epidural fluid collection (red asterisk) stretching along the ventral aspect of the spinal canal and displacing the dura posteriorly. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Sagittal turbo-spin echo (TSE) T2 MRI of the cervical and upper thoracic spine shows an anterior wedge degenerative deformation of the T6 vertebral body with a superimposed prominent central disc extrusion characterized by osteo-calcific signal (yellow arrow) causing a dural tear at the T6-T7 level. Above the disc extrusion, note the “sentinel” epidural fluid collection (red asterisk) stretching along the ventral aspect of the spinal canal and displacing the dura posteriorly. TSE T2 MRI shows low signal intensity along the surface of the spinal cord consistent with superficial siderosis (yellow arrowhead). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast sagittal constructive interference in steady state (CISS) MRI of the cervical and upper thoracic spine shows an anterior wedge degenerative deformation of the T6 vertebral body with a superimposed prominent central disc extrusion characterized by osteo-calcific signal (yellow arrow) causing a dural tear at the T6-T7 level. Above the disc extrusion, note the “sentinel” epidural fluid collection (red asterisk) stretching along the ventral aspect of the spinal canal and displacing the dura posteriorly. CISS MRI shows low signal intensity along the surface of the spinal cord consistent with superficial siderosis (yellow arrowhead). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

C and D are the left and right sides, respectively, of the same patient. (Source: Artukarslan E, Matin F, Donnerstag F, Gärtner L, Lenarz T, Lesinski-Schiedat A. Cochlea implantation in patients with superficial hemosiderosis. Eur Arch Otorhinolaryngol 2022;279[9]:4363-70. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial T2-weighted MRI indicates siderosis of the quadrigeminal plate (double white arrows) and the upper cerebral vermis (white arrowheads) with sparing of the cortex of both temporal lobes (curved white). (Source: Artukarslan E, Matin F, Donnerstag F, Gärtner L, Lenarz T, Lesinski-Schiedat A. Cochlea implantation in patients with superficial hemosiderosis. Eur Arch Otorhinolaryngol 2022;279[9]:4363-70. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial T2-weighted MRI indicates siderosis of the cranial nerves VII, VIII, and IX from their pontine emergence up to the entry in the inner auditory canal (white arrows) and the cerebellar cortex (white arrowheads). (Source: Artukarslan E, Matin F, Donnerstag F, Gärtner L, Lenarz T, Lesinski-Schiedat A. Cochlea implantation in patients with superficial hemosiderosis. Eur Arch Otorhinolaryngol 2022;279[9]:4363-70. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Functional connectivity networks of the right- and left-sided lesions of the posterior insula that did not lead to vertigo/dizziness (n=10 cases). The functional connectivity network observed in these lesions was remarkably similar, involving the vestibulo-cerebellum and the cortical vestibular and ocular motor networks. The color bar shows t score intensities. Abbreviations: IX, X cerebellar lobules IX, X, MT+ motion-sensitive temporal area, PIVC parieto-opercular (retro-) insular vestibular cortex, PIC posterior insular cortex, FEF frontal eye field, CEF cingulate eye field, LIP/VIP lateral/ventral intraparietal area, CsV cingulate visual sulcus. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Overlap of functional connectivity networks of the individual lesions in published case reports on hemispheric infarcts accompanied by vertigo (positive correlations with the lesion site). The figure shows an overlap of eight or more cases. Common vestibular network hubs to all lesions include the cerebellar vestibular and ocular motor representations in lobules IX (nodulus, uvula); lobule X (flocculus/paraflocculus); the vestibular nuclei (VN); the thalamus; the parieto-insular vestibular cortex (PIVC), which includes insular gyri IV, V (anterior and posterior long insular gyri), area OP2, and retro-insular cortex; the posterior insular cortex (area PIC); motion-sensitive temporal and cingulate areas MT + and CSv (cingulate visual area); ocular motor and vestibular intraparietal areas LIP and VIP (lateral and ventral intraparietal area); and the frontal and cingulate eye fields (FEF, CEF). The color bar gives the number of overlapping lesion functional connectivity networks. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Disconnectome map of all 10 lesions that manifested with vertigo from published case reports on hemispheric infarcts. Disconnectome results are shown with a threshold at 0.5 (greater than 50% probability of disconnection). Disconnection was observed for the posterior fronto-insular tracts (IV, V) that connect the posterior insula with the opercula. Intra-hemispheric disconnection affected the arcuate fascicle and the superior longitudinal fascicle (SLF, mostly third branch). (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

In rare cases, the lesions (from published case reports on hemispheric infarcts accompanied by vertigo) involved vestibular structures in the parietal operculum (OP2), the intraparietal sulcus (area VIP), and the temporal lobe (MT+). None of the lesions directly affected the posterior insular cortex (PIC) although lesion 5 is close to this structure. Abbreviations: OP2 parietal operculum 2; MT+, motion-sensitive middle temporal area; VIP ventral intraparietal area; PIC posterior insular cortex, IV anterior long insular gyrus, V posterior long insular gyrus. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Overlap image of ischemic infarcts involving the insula (overlap of at least two lesions is depicted) from published case reports on hemispheric infarcts accompanied by vertigo: the ischemic lesions were mainly located in the posterior parts of the insula (anterior long insular gyrus and posterior long insular gyrus--IV, V). (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Representative axial slices for each lesion of published case reports on hemispheric infarcts accompanied by vertigo (lesions 1-10) and infarcts that did not present with vertigo (lesion overlap of 10 cases; 11-12). Left-sided lesions with vertigo are shown in the top row. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Perfusion CT showed that the perfusion deficits remained in the left cerebellum along the PICA and AICA territories (red arrow). (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Pure-tone audiogram documented persistent left sensorineural hearing loss with a pure-tone average of 53 dB on follow-up 2 months after treatment for sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up diffusion-weighted imaging and apparent diffusion coefficient mapping performed 3 days after onset of sudden unilateral hearing loss and vertigo demonstrated multifocal infarctions along the posterior circulation involving the upper cerebellum and occipital lobe. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Brain CT angiography revealed occlusion of the left intracranial vertebral artery distal to the posterior inferior cerebellar artery (PICA) and multifocal stenosis of the right intracranial vertebral artery, suspicious for bilateral vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Perfusion-weighted imaging revealed left posterior inferior cerebellar artery and anterior inferior cerebellar artery territorial perfusion deficits without infarction in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Normal apparent diffusion coefficient map in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Normal diffusion-weighted imaging in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Pure tone audiogram showing mild left sensorineural hearing loss in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Cooperrider J, Kriegler J, Yunus S, Wilson R. A survey-based study examining differences in perception of postural orthostatic tachycardia syndrome between patients and primary care physicians. Cureus 2022;14[10]:e30167. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Coronal CT scan showing involvement of the petrous part of the left temporal bone. The superior semicircular canal is surrounded by dysplasia. (Source: Sbai AA, Es-Salhi F, Tsen AA, Fahd Elayoubi. Otalgia revealing McCune-Albright syndrome: a case report. Ann Med Surg (Lond) 2022;82:104706. Creative Commons Attribution [CC-BY] license, creativecommons.org/licenses/by/4.0)

Transverse CT image, showing an extensive, homogeneous, "ground glass" appearance of the left temporal area. (Source: Sbai AA, Es-Salhi F, Tsen AA, Fahd Elayoubi. Otalgia revealing McCune-Albright syndrome: a case report. Ann Med Surg (Lond) 2022;82:104706. Creative Commons Attribution [CC-BY] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemically, these cells are immunoreactive toward MUM1 (multiple myeloma 1) antibodies. MUM1 is a member of the IRF family of transcriptional factors, is induced by antigen receptor-mediated stimuli, and plays a crucial role in cell proliferation, differentiation, and survival. (Source: Jumaat AF, Gendeh H, Mohd Mustapha AW, Tan GC, Goh BS. Otalgia and facial nerve palsy: common symptoms revealing the uncommon pathology of middle ear lymphoma. Cureus 2022;14(5):e25023. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemically, these cells are immunoreactive toward CD20, a common B cell marker. (Source: Jumaat AF, Gendeh H, Mohd Mustapha AW, Tan GC, Goh BS. Otalgia and facial nerve palsy: common symptoms revealing the uncommon pathology of middle ear lymphoma. Cureus 2022;14(5):e25023. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Histology of the right temporalis muscle (H&E) demonstrating malignant lymphoid cells with markedly pleomorphic and enlarged nuclei, small nucleoli, and scanty cytoplasm (white arrows). There are many mitoses and apoptotic bodies (white arrow heads). (Source: Jumaat AF, Gendeh H, Mohd Mustapha AW, Tan GC, Goh BS. Otalgia and facial nerve palsy: common symptoms revealing the uncommon pathology of middle ear lymphoma. Cureus 2022;14(5):e25023. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0)

Coronal MRI (A) showing thickening of the right temporalis muscle (white arrow) and masseter muscle (black arrow). On the axial view (B), the right temporalis muscle (white arrow) is thickened with clear plane surrounding the muscle. (Source: Jumaat AF, Gendeh H, Mohd Mustapha AW, Tan GC, Goh BS. Otalgia and facial nerve palsy: common symptoms revealing the uncommon pathology of middle ear lymphoma. Cureus 2022;14(5):e25023. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial high-resolution computed tomography of the temporal bone. On a coronal cut, there is a rim-enhancing intramuscular hypodensity within the bulky and thickened right temporalis muscle with enhancement of the right temporalis muscle (white arrows). (Source: Jumaat AF, Gendeh H, Mohd Mustapha AW, Tan GC, Goh BS. Otalgia and facial nerve palsy: common symptoms revealing the uncommon pathology of middle ear lymphoma. Cureus 2022;14(5):e25023. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial high-resolution computed tomography of the temporal bone showing a soft tissue density in right middle ear occupying the epitympanum (black arrow), bony erosion at the anterior the wall of the right mastoid air cells, and fluid-filled right mastoid air cells (white arrow). (Source: Jumaat AF, Gendeh H, Mohd Mustapha AW, Tan GC, Goh BS. Otalgia and facial nerve palsy: common symptoms revealing the uncommon pathology of middle ear lymphoma. Cureus 2022;14(5):e25023. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI of the brain in axial cut showing enlarged right trigeminal nerve (white arrow). (Source: Jumaat AF, Gendeh H, Mohd Mustapha AW, Tan GC, Goh BS. Otalgia and facial nerve palsy: common symptoms revealing the uncommon pathology of middle ear lymphoma. Cureus 2022;14(5):e25023. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing high-uptake lesions with osteolytic bone destruction of a vertebral body and the ilium (arrows). Transverse image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing high-uptake lesions with osteolytic bone destruction of the right parietal skull bone (arrows). Transverse image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing a lung nodule (arrow). Transverse image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing multiple high-uptake lesions in the liver. Frontal image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing multiple high-uptake lesions in the liver. Transverse image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Cystoscopy shows a pedunculated, cauliflower-like mass in the right lateral wall of the bladder with a diameter of about 0.8cm. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal MRI shows an approximately circular lesion of high signal intensity on T2-weighted imaging (4.9cm×3.8cm) in the right anterior wall of the bladder. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Plot of vanillylmandelic acid levels in 24-hour urine samples over the perioperative and chemotherapeutic period. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The size of metastases in the ilium did not significantly change with two courses (far left), four courses (left center), and six courses of chemotherapy (right center), and 6-month follow-up (far right). (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The size of metastases in the skull did not significantly change with two courses (far left), four courses (left center), and six courses of chemotherapy (right center), and 6-month follow-up (far right). (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The size of metastases in the liver did not significantly change with two courses (far left), four courses (left center), and six courses of chemotherapy (right center), and 6-month follow-up (far right). (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The size of metastases in the lung did not significantly change with two courses (far left), four courses (left center), and six courses of chemotherapy (right center), and 6-month follow-up (far right). (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paraganglioma, showing high-uptake localizations with osteolytic bone destruction of the ilium. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paraganglioma, showing high-uptake localizations with osteolytic bone destruction of right parietal skull bone. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paraganglioma, showing multiple high-uptake localizations in the lung. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paragangliomas, showing multiple high-uptake localizations in the liver. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paraganglioma, showing multiple high-uptake localizations in the liver. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemical staining of a bladder paraganglioma with SSTR2 (somatostatin receptor 2), a marker of neuroendocrine neoplasias. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemical staining of a bladder paraganglioma with CgA (chromogranin A), a widely used immunohistochemical marker for neuroendocrine cells and their tumors. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemical staining of the bladder paraganglioma with SDHB, one of four protein subunits forming succinate dehydrogenase. Immunohistochemical evaluation of SDHB is a tool pathologists use to screen paragangliomas for possible mutations in SDHx genes. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemical staining of the bladder paraganglioma with Ki-67 (15%), widely used as a proliferation marker for human tumor cells. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(H&E staining) (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Intraoperative condition of the bladder paraganglioma during laparoscopy-assisted partial cystectomy. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Cystoscopy shows inward bulging of the right anterior wall of the bladder. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI shows an approximately circular mass with high T2 signal (4.9 cm × 3.8 cm) in the right anterior wall of the bladder with heterogeneous enhancement of arterial phase. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI shows an approximately circular mass with high T2 signal (4.9 cm × 3.8 cm) in the right anterior wall of the bladder. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Computed tomography urography (CTU) scan shows a roundish soft tissue lesion (4.8 cm × 3.7 cm) in the right anterior wall of bladder with heterogeneous enhancement during the arterial phase. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Jailani M, Barbarawi M, Tigadi S. Post total thyroidectomy deglutition syncope. Cureus 2022;14[12]:e32836. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Jailani M, Barbarawi M, Tigadi S. Post total thyroidectomy deglutition syncope. Cureus 2022;14[12]:e32836. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The blink reflex test reveals absent responses of ipsilateral R1 and R2 and contralateral R2 at stimulation of the right supraorbital nerve. (Source: Hwang YS, Kim YS, Shin BS, Kang HG. Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports. BMC Neurol 2023;23[1]:43. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The blink reflex test reveals absent responses of ipsilateral R1 and R2 and contralateral R2 at stimulation of the right supraorbital nerve. (Source: Hwang YS, Kim YS, Shin BS, Kang HG. Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports. BMC Neurol 2023;23[1]:43. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Internal auditory canal (IAC) MRI image of a patient with herpes zoster oticus. The post-contrast 3D T1-weighted image shows contrast enhancement in the left vestibulocochlear nerve (small arrow) and the dura of the left IAC (large arrow). (Source: Lee J, Choi JW, Kim CH. Features of audio-vestibular deficit and 3D-FLAIR temporal bone MRI in patients with herpes zoster oticus. Viruses 2022;14[11]:2568. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Internal auditory canal MRI image of a patient with herpes zoster oticus. The post-contrast 3D T1-weighted image shows that the labyrinthine segment of the left facial nerve is enhanced (arrow). (Source: Lee J, Choi JW, Kim CH. Features of audio-vestibular deficit and 3D-FLAIR temporal bone MRI in patients with herpes zoster oticus. Viruses 2022;14[11]:2568. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Contrast‐enhanced T1‐weighted MRI of the brain showing enhancement in the right facial nerve (white arrows). (Source: Hwang YS, Kim YS, Shin BS, Kang HG. Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports. BMC Neurol 2023;23[1]:43. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The facial nerve conduction study reveals a prolonged terminal latency and reduced compound muscle action potential amplitude upon direct stimulation of the right facial nerve. NCV = nerve conduction velocity. (Source: Hwang YS, Kim YS, Shin BS, Kang HG. Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports. BMC Neurol 2023;23[1]:43. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Pure-tone audiometry revealing both increased air and bone conduction thresholds without an air-bone gap in the right ear, consistent with predominantly high-frequency sensorineural hearing loss. (Source: Hwang YS, Kim YS, Shin BS, Kang HG. Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports. BMC Neurol 2023;23[1]:43. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Vesicles noted along the medial aspect of the antihelix of the right ear (arrow). (Source: Gillette BT, Heilbronn CM. A rare case of vocal cord paralysis in the setting of Ramsay Hunt syndrome. Cureus 2023;15[3]:e36027. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Initial onset of Ramsay Hunt syndrome. Right facial palsy presented as an asymmetric mouth and incomplete closure of the right eye. The patient received a Grade V score on the House-Brackmann Facial Paralysis Scale. (Source: Chou CC, Lo YT, Su HC, Chang CM. Fear of falling as a potential complication of Ramsay Hunt syndrome in older adults: a case report. BMC Geriatr 2022;22[1]:901. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image was cropped from the original.)

Pure-tone audiogram showing right-sided sensorineural hearing loss of 43 dB PTA (pure-tone average) in a 42-year-old woman with herpes zoster oticus, delayed facial nerve palsy, and cranial polyneuropathy. (Source: Al-Ani RM. Ramsay Hunt syndrome with cranial polyneuropathy and delayed facial nerve palsy: a case report. Cureus 2022;14[7]:e27434. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Right peripheral facial nerve paralysis with flattening of the nasolabial fold, drop of the oral angle, and reduced wrinkles on the forehead in a 42-year-old woman with herpes zoster oticus, delayed facial nerve palsy, and cranial polyneuropathy. (Source: Al-Ani RM. Ramsay Hunt syndrome with cranial polyneuropathy and delayed facial nerve palsy: a case report. Cureus 2022;14[7]:e27434. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Vesicular eruption of the right auricle (A), external auditory canal, and tympanic membrane (B) in a 42-year-old woman with herpes zoster oticus, delayed facial nerve palsy, and cranial polyneuropathy. (Source: Al-Ani RM. Ramsay Hunt syndrome with cranial polyneuropathy and delayed facial nerve palsy: a case report. Cureus 2022;14[7]:e27434. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Autofluorescence of optic nerve head demonstrating hyperautofluorescent optic disc drusen in a patient. (Contributed by Dr. Randall Brown.)

Left-right difference in beating of the brachial artery in an 82-year-old man with left subclavian artery stenosis and subclavian steal phenomenon. The right brachial artery can be seen beating whereas the left has no visible pulsation. (Source: Amano Y, Watari T. "Asymptomatic" subclavian steal syndrome. Cureus 2021;13[10]:e19109. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Color-flow imaging (triplex ultrasound) ultrasound examination after balloon angioplasty of the right subclavian artery shows normal, antegrade flow in the right vertebral artery.

Abbreviations: RVA=right vertebral artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Color-flow imaging (triplex ultrasound) ultrasound examination after balloon angioplasty of the right subclavian artery shows a normal triphasic subclavian waveform.

Abbreviations: RSCA=right subclavian artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

B-mode (brightness mode) ultrasound examination after balloon angioplasty of the right subclavian artery reveals significantly reduced stenosis.

Abbreviations: RSCA=right subclavian artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Color-flow imaging (triplex ultrasound) of the right vertebral artery after release of a blood pressure cuff shows complete flow inversion for the entire cardiac cycle during reactive hyperemia of the arm in a 43-year-old man evaluated for repeated transient ischemic attacks in the vertebrobasilar territory.

Abbreviations: RVA=right vertebral artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Color-flow imaging (triplex ultrasound) of the right vertebral artery during compression of the right arm with a blood pressure cuff (a "cuff test") shows the appearance of a minimal positive diastolic flow in a 43-year-old man evaluated for repeated transient ischemic attacks in the vertebrobasilar territory.

Abbreviations: RVA=right vertebral artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Color-flow imaging (triplex ultrasound) of the right vertebral artery reveals retrograde midsystolic and no diastolic flow in a 43-year-old man evaluated for repeated transient ischemic attacks in the vertebrobasilar territory.

Abbreviations: RVA=right vertebral artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Color-flow imaging (triplex ultrasound) shows severely elevated peak systolic flow velocities in the right subclavian artery of a 43-year-old man evaluated for repeated transient ischemic attacks in the vertebrobasilar territory.

Abbreviations: RSCA=right subclavian artery, BRA=brachiocephalic artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Duplex scan (color mode) shows a hypoechoic atherosclerotic plaque at the origin of the right subclavian artery causing severe stenosis with turbulent flow in a 43-year-old man evaluated for repeated transient ischemic attacks in the vertebrobasilar territory.

Abbreviations: RCCA=right common carotid artery, RSCA=right subclavian artery, BRA=brachiocephalic artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

B-mode (brightness mode) ultrasound examination shows a hypoechoic atherosclerotic plaque at the origin of the right subclavian artery causing severe stenosis in a 43-year-old man evaluated for repeated transient ischemic attacks in the vertebrobasilar territory.

Abbreviations: RCCA=right common carotid artery, RSCA=right subclavian artery, BRA=brachiocephalic artery.

(Source: Bajko Z, Motataianu A, Stoian A, et al. Prevalence and clinical characteristics of subclavian steal phenomenon/syndrome in patients with acute ischemic stroke. J Clin Med 2021;10[22]:5237. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The proximal part of left subclavian is blocked on the left side. Blood flow is antegrade in the right vertebral artery but retrograde in the left vertebral artery, which supplies the distal left subclavian artery. (Courtesy of Wikimedia Commons. Illustration by User:Rajtheja on July 5, 2013. Creative Commons Attribution 3.0 Unported [CC BY 3.0] license, creativecommons.org/licenses/by/3.0.)

Chest CT with subclavian artery plaque (red circle) and no contrast in left vertebral artery suggests reversal of flow. (Courtesy of Jason Robert Young MD. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Left subclavian artery stent placed (green circle) with improved distal blood flow (red arrow) and contrast extending into the left vertebral artery (green arrow). (Courtesy of Jason Robert Young MD. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Angiogram of the aortic arch shows plaque in the left subclavian artery (red circle) with decreased blood flow distally (purple arrow) and no contrast extending into the left vertebral artery. (Courtesy of Jason Robert Young MD. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Postoperative follow-up duplex imaging of the right vertebral artery shows oscillation of flow after bypass with stenting in a 72-year-old woman with innominate artery occlusion and subclavian steal syndrome. (Source: George JM, Cooke PV, Ilonzo N, Tadros RO, Grossi RJ. Management of innominate artery occlusion with severe left common carotid artery stenosis. Cureus 2021;13[11]:e19592. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Postoperative follow-up duplex imaging shows a patent left carotid to right carotid artery bypass graft in a 72-year-old woman with innominate artery occlusion and subclavian steal syndrome. (Source: George JM, Cooke PV, Ilonzo N, Tadros RO, Grossi RJ. Management of innominate artery occlusion with severe left common carotid artery stenosis. Cureus 2021;13[11]:e19592. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Carotid angiogram after stenting in a 72-year-old woman with innominate artery occlusion and subclavian steal syndrome demonstrates resolution of the left carotid stenosis. The sheath is within the left common carotid artery in a retrograde fashion after carotid cutdown. (Source: George JM, Cooke PV, Ilonzo N, Tadros RO, Grossi RJ. Management of innominate artery occlusion with severe left common carotid artery stenosis. Cureus 2021;13[11]:e19592. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Arch aortogram in a 72-year-old woman reveals complete occlusion of the innominate artery (black arrow) with delayed filling and severe stenosis of the left common carotid artery (white arrow). (Source: George JM, Cooke PV, Ilonzo N, Tadros RO, Grossi RJ. Management of innominate artery occlusion with severe left common carotid artery stenosis. Cureus 2021;13[11]:e19592. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Right transradial angiogram in a 72-year-old woman demonstrates innominate occlusion with filling of the right subclavian (black arrow) and the right common carotid (white arrow) arteries. (Source: George JM, Cooke PV, Ilonzo N, Tadros RO, Grossi RJ. Management of innominate artery occlusion with severe left common carotid artery stenosis. Cureus 2021;13[11]:e19592. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Right transradial angiogram in a 72-year-old woman demonstrates innominate occlusion with filling of the right subclavian (black arrow) and the right common carotid (white arrow) arteries. (Source: George JM, Cooke PV, Ilonzo N, Tadros RO, Grossi RJ. Management of innominate artery occlusion with severe left common carotid artery stenosis. Cureus 2021;13[11]:e19592. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Carotid duplex imaging shows sustained reversed flow in the right vertebral artery in a 72-year-old woman with innominate artery occlusion and subclavian steal syndrome. (Source: George JM, Cooke PV, Ilonzo N, Tadros RO, Grossi RJ. Management of innominate artery occlusion with severe left common carotid artery stenosis. Cureus 2021;13[11]:e19592. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

CT reconstruction shows almost complete occlusion at the origin of the subclavian artery in an 82-year-old man with left subclavian artery stenosis and subclavian steal phenomenon. (Source: Amano Y, Watari T. "Asymptomatic" subclavian steal syndrome. Cureus 2021;13[10]:e19109. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Audiogram showing a low-frequency trough pattern of sensorineural hearing loss, commonly seen in Meniere disease. The left ear is shown. (Contributed by James Lanska.)

Air travels in a retrograde fashion due to severe tricuspid regurgitation forcing air back into the superior vena cava where it ascends into the jugular veins and intracranial venous structures. (Source: Santucci J, Mullaguri N, Battineni A, Guddeti RR, Newey CR. Paradoxical and retrograde air embolism from pressurized peripheral bolus. Case Rep Neurol Med 2021;2021:1063264. Copyright 2020 Cleveland Clinic Foundation. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Pathway of air emboli paradoxically traveling from the right atrium across an intracardiac shunt (eg, patent foramen ovale) into the left atrium and subsequently into the left ventricle and aorta before entering the carotid and then intracranial arteries. (Source: Santucci J, Mullaguri N, Battineni A, Guddeti RR, Newey CR. Paradoxical and retrograde air embolism from pressurized peripheral bolus. Case Rep Neurol Med 2021;2021:1063264. Copyright 2020 Cleveland Clinic Foundation. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

CT angiography of the head and neck shows a small right apical pneumothorax (solid arrow) and pneumomediastinum (nonsolid arrows). (Source: Morales G, Fiero M, Albert J, Di Gennaro J, Gerbino A. Cerebral arterial gas embolism due to helium inhalation from a high-pressure gas cylinder. Case Rep Emerg Med 2022;2022. Creative Commons Attribution 4.0 International License [CC BY 4.0].)

Chest x-ray upon admission to the emergency department demonstrates pneumomediastinum without pneumothorax (solid arrows). (Source: Morales G, Fiero M, Albert J, Di Gennaro J, Gerbino A. Cerebral arterial gas embolism due to helium inhalation from a high-pressure gas cylinder. Case Rep Emerg Med 2022;2022. Creative Commons Attribution 4.0 International License [CC BY 4.0].)

EEG showing focal spikes and diffuse slow waves in a patient with lung cancer and spontaneous cerebral gas emboli. (Source: Inatomi S, Izumi T, Eura N, et al. Electroencephalographic findings after convulsive seizures due to cerebral arterial air embolism secondary to lung cancer: a case report. J Med Case Rep 2022;16[1]:137. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Findings on susceptibility-weighted imaging from a head MRI in a patient with lung cancer and spontaneous cerebral gas emboli. Small dot-like low signal (circles) in the right frontal cortex (left image) and the left parietal subcortex (right image) on susceptibility-weighted imaging. (TR/TE). (Source: Inatomi S, Izumi T, Eura N, et al. Electroencephalographic findings after convulsive seizures due to cerebral arterial air embolism secondary to lung cancer: a case report. J Med Case Rep 2022;16[1]:137. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Findings on diffusion-weighted images from a head MRI in a patient with lung cancer and spontaneous cerebral gas emboli. Head MRI showing faint hyperintensity (circle) along the right parietal cortex and subcortex and the left frontal cortex on diffusion-weighted images. (Source: Inatomi S, Izumi T, Eura N, et al. Electroencephalographic findings after convulsive seizures due to cerebral arterial air embolism secondary to lung cancer: a case report. J Med Case Rep 2022;16[1]:137. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Findings on head CT in a patient with lung cancer and spontaneous cerebral gas emboli. Head CT image taken on day 1 showing multiple air-densities (circles) in the right cortex and the subcortex bilaterally. (Source: Inatomi S, Izumi T, Eura N, et al. Electroencephalographic findings after convulsive seizures due to cerebral arterial air embolism secondary to lung cancer: a case report. J Med Case Rep 2022;16[1]:137. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Findings on chest and abdominal CT in a patient with lung cancer and spontaneous cerebral gas emboli. (A) Chest CT image showing a left pulmonary hilar mass invading the left atrium and the left main bronchus. (B) Air densities (arrow) inside the tumor. (C) Abdominal CT image showing air densities (arrow) around the intestinal wall. (Source: Inatomi S, Izumi T, Eura N, et al. Electroencephalographic findings after convulsive seizures due to cerebral arterial air embolism secondary to lung cancer: a case report. J Med Case Rep 2022;16[1]:137. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Diffusion-weighted sequence of a brain MRI showing findings consistent with diffuse bilateral cortical anoxic injury. (Source: Santucci J, Mullaguri N, Battineni A, Guddeti RR, Newey CR. Paradoxical and retrograde air embolism from pressurized peripheral bolus. Case Rep Neurol Med 2021;2021:1063264. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

(Source: Santucci J, Mullaguri N, Battineni A, Guddeti RR, Newey CR. Paradoxical and retrograde air embolism from pressurized peripheral bolus. Case Rep Neurol Med 2021;2021:1063264. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Axial brain CT showing air emboli in the cortical branches of the posterior cerebral, middle, and anterior cerebral arteries (left and center, white arrows), and air in the superior sagittal sinus and cortical veins (right, black arrow). (Source: Santucci J, Mullaguri N, Battineni A, Guddeti RR, Newey CR. Paradoxical and retrograde air embolism from pressurized peripheral bolus. Case Rep Neurol Med 2021;2021:1063264. Creative Commons Attribution 4.0 International license [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Transthoracic echocardiography showing tricuspid valve vegetation (left, white arrow) and location of interatrial septum and patent foramen ovale (right, white arrowhead). There was a large right-to-left shunt through the patent foramen ovale on bubble study with spontaneous opacification of the left atrium and ventricle (right). (Source: Santucci J, Mullaguri N, Battineni A, Guddeti RR, Newey CR. Paradoxical and retrograde air embolism from pressurized peripheral bolus. Case Rep Neurol Med 2021;2021:1063264. Creative Commons Attribution 4.0 International license [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Brain CT without contrast showed multiple low densities in the right occipital lobe (red arrow). (Source: Chen Y, Zheng C, Zeng Q, Zhang F, Tu S, Wu Z. Cerebral air embolism after pigtail catheter drainage for pneumothorax: a case report and review of the literature. Front Surg 2021;8:743051. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

A pigtail catheter (small-bore chest tube) was inserted into chest for relief of a pneumothorax (red arrow). (Source: Chen Y, Zheng C, Zeng Q, Zhang F, Tu S, Wu Z. Cerebral air embolism after pigtail catheter drainage for pneumothorax: a case report and review of the literature. Front Surg 2021;8:743051. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Chest x-ray shows evidence of a pneumothorax after removal of a chest tube (red arrows). (Source: Chen Y, Zheng C, Zeng Q, Zhang F, Tu S, Wu Z. Cerebral air embolism after pigtail catheter drainage for pneumothorax: a case report and review of the literature. Front Surg 2021;8:743051. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

A chest CT scan showed a 3.7 × 3.0 cm mass in the right lower lung (red arrow). (Source: Chen Y, Zheng C, Zeng Q, Zhang F, Tu S, Wu Z. Cerebral air embolism after pigtail catheter drainage for pneumothorax: a case report and review of the literature. Front Surg 2021;8:743051. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Follow-up brain CT 2 days after percutaneous transhepatic biliary drainage shows a marked increase in the extent of cerebral edema in the right cerebral hemisphere with a midline shift to the left. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Magnetic resonance angiography shows no demonstrable steno-occlusive lesions. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Arterial spin-labeling perfusion imaging shows that the cerebral blood flow is markedly decreased in the right cerebral hemisphere and mildly decreased in the left frontal lobe. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Gradient-echo sequence shows multifocal hypointense "blooming dots" (arrows) in the right frontal and temporal lobes, consistent with residual air bubbles. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Fluid-attenuated inversion recovery shows areas of increased signal intensity and cortical swelling, suggestive of acute infarctions. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Apparent diffusion coefficient map shows the corresponding low-signal-intensity areas. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Brain diffusion-weighted MRI revealed multiple high signal intensities in the right frontal, right parietal, and left frontal (ie, superior frontal gyrus) lobes. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Axial abdominopelvic CT shows air bubbles around the biliary stent and percutaneous transhepatic biliary drainage tube (small white arrows). (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Coronal abdominopelvic CT shows a ruptured hepatic mass with free air and fluid in the perihepatic space (white arrow in upper left). (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Pulmonary CT angiography reveals large filling defects in the left main and left lobar (upper and lower) pulmonary arteries (arrows), consistent with pulmonary thromboembolism. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

Initial noncontrast brain CT in a in a 50-year-old woman with recurrent gall bladder cancer shows extensive pneumocephali in the sulci of the right cerebral hemisphere with air densities in the superior frontal sulcus of the left frontal lobe. (Source: Lee JH, Lee HY, Lim MK, Kang YH. Massive cerebral air embolism following percutaneous transhepatic biliary drainage: a case report. Medicine [Baltimore]. 2021;100[52]:e28389. Creative Commons Attribution 4.0 International License [CC BY 4.0], https://creativecommons.org/licenses/by/4.0.)

(July 12, 2019) At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 60 crewmembers Luca Parmitano (b 1976), an Italian astronaut of the European Space Agency (foreground), and Andrew ("Drew") Morgan (b 1976) of NASA test out their vestibular systems on tilt tables as part of prelaunch activities. Along with cosmonaut Alexander Aleksandrovich Skvortsov (b 1966) of Roscosmos, they launched July 20, 2019, on a Soyuz MS-13 spacecraft from the Baikonur Cosmodrome in Kazakhstan for a mission to the International Space Station. (Photo credit: Andrey Shelepin/GCTC. Source: NASA/Johnson Space Center [Houston]. NASA ID: jsc2019e039266. Public domain.)

(March 15, 2018) At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 55 crewmembers Andrew ("Drew") Feustel (b 1965) of NASA (top) and Richard ("Ricky") Arnold (b 1963) of NASA (bottom) conduct tests of their vestibular systems on tilt tables as part of prelaunch activities. Along with cosmonaut Oleg Germanovich Artemyev (b 1970) of Roscosmos, they launched March 21, 2018, on the Soyuz MS-08 spacecraft from the Baikonur Cosmodrome for a 5-month mission to the International Space Station. (Photo credit: NASA/Victor Zelentsov. Source: NASA/Johnson Space Center [Houston]. NASA ID: jsc2018e025556. Public domain.)

(May 29, 2018) At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 56 prime crewmember Alexander Gerst (b 1976), a German astronaut of the European Space Agency, "takes a spin" in a rotating chair to test his vestibular system as part of prelaunch activities. Gerst, astronaut and physician Serena Auñón-Chancellor (b 1976) of NASA, and cosmonaut Sergey Prokopyev (b 1975) of Roscosmos launched June 6, 2018, from the Baikonur Cosmodrome in Kazakhstan on a Soyuz MS-09 spacecraft for a 6-month mission on the International Space Station. (Photo credit: NASA/Victor Zelentsov. Source: NASA/Johnson Space Center [Houston]. NASA ID: jsc2018e050828. Public domain.)

(December 11, 2017) At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 54-55 prime crewmember Scott Tingle (b 1965) of NASA tests his vestibular skills on a rotating chair as part of his prelaunch training. Tingle, astronaut and physician Norishige Kanai (b 1976) of the Japan Aerospace Exploration Agency (JAXA), and cosmonaut Anton Nikolaevich Shkaplerov (b 1976) of the Russian Federal Space Agency (Roscosmos) launched December 17, 2017, on a Soyuz MS-07 spacecraft from the Baikonur Cosmodrome for a 5-month mission on the International Space Station. Photo credit: Andrey Shelepin/Gagarin Cosmonaut Training Center. (Source: NASA/Johnson Space Center [Houston]. NASA ID: jsc2017e137339. Public domain.)

(May 24, 2017) European Space Agency astronaut and French aerospace engineer Thomas Pesquet (b 1978) performs the commissioning of the Gravitational References for Sensorimotor Performance (GRASP) experiment. (Source: NASA/Johnson Space Center [Houston]. NASA ID: ISS051e049152. Public domain.)

(May 24, 2017) European Space Agency astronaut and French aerospace engineer Thomas Pesquet (b 1978) performs the commissioning of the Gravitational References for Sensorimotor Performance (GRASP) experiment on the International Space Station to better understand how the central nervous system integrates information from different sensations. The objective is to better understand the human vestibular system and how it connects to the other sensory organs. (Source: NASA/Johnson Space Center [Houston]. NASA ID: ISS051e049147. Public domain.)

(January 12, 2003) The short-arm centrifuge subjects an astronaut to conflicting sensory input and is used to study the astronaut's perception of motion. It was part of the Spatial Reorientation Following Space Flight investigation conducted on crewmembers. During space flight, the vestibular organs no longer respond in a familiar way. In particular, when astronauts undergo a linear acceleration (eg, bending their heads forward) while in space, their otoliths are not properly stimulated. This creates a sensory conflict, which must be resolved by the brain to maintain orientation. When they first return to Earth, astronauts are again disoriented because of sensory conflict. They undergo a period of spatial reorientation as their brains reconcile what their eyes see and what their vestibular system senses. Recovery can take anywhere from hours to days depending on the length of the mission. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 0300115. Public domain.)

(November 1, 1993) Astronaut and surgeon Rhea Seddon (b 1947), STS-58 Payload Commander, spins the Spacelab Life Sciences (SLS-2) rotating chair as Payload Specialist and pathologist Martin J Fettman (b 1956) serves as test subject. The two joined five NASA astronauts for 14 days of medical research aboard the Earth-orbiting Space Shuttle Columbia. (Source: NASA/Johnson Space Center [Houston]. NASA ID: sts058-202-002. Public domain.)

(November 1, 1993) In the Spacelab onboard the Space Shuttle Columbia, STS-58 Commander John Blaha (b 1942) is positioned at the rotating dome vestibular experiment as Payload Commander, and surgeon Rhea Seddon (b 1947) sets up the experiment. (Source: NASA/Johnson Space Center [Houston]. NASA ID: STS058-03-020. Public domain.)

(September 29, 1993) Astronaut and surgeon Rhea Seddon (b 1947), STS-58 Payload Commander, is in a piloting simulator as part of a preflight data collection project concerning neurovestibular function. The seven Spacelab Life Sciences (SLS-2) crew members devoted a full day to miscellaneous biomedical data collection in preparation for a 2-week mission aboard Space Shuttle Columbia. (Source: NASA/Johnson Space Center [Houston]. NASA ID: S93-45373. Public domain.)

(May 6, 1993) Terence T (Tom) Henricks (b 1952), STS-55 pilot, wears a special collar for a space adaptation experiment in the science module onboard the Earth-orbiting Space Shuttle Columbia
(OV-102). The Baroreflex experiment was designed to investigate the theory that lightheadedness and a reduction in blood pressures on standing after landing may arise because the normal reflex system regulating blood pressure behaves differently after having adapted to a microgravity environment. These space-based measurements of the baroreflex were compared to ground measurements to determine how microgravity affects the reflex. (Source: NASA/Johnson Space Center [Houston]. NASA ID: STS055-233-019. Public domain.)

(Jan 30, 1992) Astronaut and physician David C Hilmers (b 1950), STS-42 mission specialist, wearing a helmet assembly, sits in the Microgravity Vestibular Investigation (MVI) rotating chair. The scene is in the International Microgravity Laboratory (IML-1) science module aboard Space Shuttle Discovery. Hilmers, a mission specialist, and six other crewmembers spent more than 8 days in Earth’s orbit conducting experiments. Hilmer's helmet assembly is outfitted with accelerometers to measure head movements and with visors that fit over each eye independently to provide visual stimuli. The chair system has three movement patterns: (1) "sinusoidal," or traveling predictably back and forth over the same distance at a constant speed; (2) "pseudorandom," or moving back and forth over varying distances; and (3) "stepped," or varying speeds beginning and stopping suddenly. (Source: NASA/Johnson Space Center [Houston]. NASA ID: STS042-27-037. Public domain.)

(Jan 30, 1992) Canadian astronaut and neurologist Roberta L Bondar (b 1945), STS-42 Payload Specialist, gets into the Microgravity Vestibular Investigations (MVI) rotator chair to begin an experiment. The chair is mounted in the center aisle of the International Microgravity Laboratory 1 (IML-1) Spacelab module. Just above Bondar's head is the helmet assembly, which is outfitted with accelerometers to measure head movements, and with visors that fit over each eye independently to provide visual stimuli. The chair system has three movement patterns: (1) "sinusoidal" or traveling predictably back and forth over the same distance at a constant speed; (2) "pseudorandom" or moving back and forth over varying distances; and (3) "stepped" or varying speeds beginning and stopping suddenly. (Source: NASA/Johnson Space Center [Houston]. NASA ID: STS042-06-031. Public domain.)

(June 14, 1991) Vestibular experiment activities were captured onboard Columbia's Spacelab Life Sciences (SLS-1) module in this 35 mm scene. Astronaut and physician-engineer James P Bagian (b 1952), STS-40 mission specialist, is in a rotating chair while wearing an accelerometer and electrodes to record head motion and horizontal and vertical eye movements during the rotations. Payload Specialist and molecular biologist Millie Hughes-Fulford (1945-2021), lower left, assisted with the test. She also has electronystagmography contacts on her head, so she was also a participant in some of the experiments. (Source: NASA/Johnson Space Center [Houston]. NASA ID: STS040-211-020. Public domain.)

(June 5, 1991) The laboratory module in the cargo bay of the Space Shuttle Orbiter Columbia was photographed during the Spacelab Life Science-1 (SLS-1) mission. SLS-1 was the first Spacelab mission dedicated solely to life sciences. The main purposes of the SLS-1 mission were (1) to study the mechanisms, magnitudes, and time courses of certain physiological changes that occur during space flight and (2) to investigate the consequences of the body's adaptation to microgravity and readjustment to Earth's gravity. The mission was designed to study the neurovestibular system (ie, involving the interactions of the vestibular system, eyes, and brain) and, particularly, to examine the causes of space motion sickness. The SLS-1 was launched aboard the Space Shuttle Orbiter Columbia
(STS-40) on June 5, 1991. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 9135505. Public domain.)

(June 17, 1985) Saudi astronaut and Payload Specialist Sultan Salman Abdelazize Al-Saud (b 1956) participates in the French Postural Experiment on the mid-deck of the Earth-orbiting Space Shuttle Discovery. (Source: NASA/Johnson Space Center [Houston]. NASA ID: 51g-105-030. Public domain.)

(June 17, 1985) The two Payload Specialists for the week-long flight share a mid-deck scene on the Earth-orbiting Space Shuttle Discovery. On the left, Saudi astronaut Sultan Salman Abdelazize Al-Saud (b 1956) is eating a meal, while on the right, French astronaut Patrick Baudry (b 1946) conducts a phase of the French Postural Experiment on himself. Note the electronystagmography electrodes attached at both temples and above and below his right eye. Sleep restraints are in the background. (Source: NASA/Johnson Space Center [Houston]. NASA ID: 51G-102-035. Public domain. Note: based on the NASA description of this image, it was inadvertently inverted by a NASA technician. This has been corrected.)

(November 1, 1983) In this Spacelab-1 mission onboard photograph, astronaut, fighter pilot, and engineer Byron Lichtenberg (b 1948) performs a drop experiment, one of the Vestibular Experiments in Space investigations. The experiment examined spinal reflexes to determine whether they changed in microgravity. In Earth's environment, the otoliths signal the muscles to prepare for jolts associated with falling. During the flight, the normal reflex between the otoliths and the muscles was partially inhibited early in flight, declined further as the flight progressed, and returned to normal after landing, suggesting that the brain ignored or reinterpreted otolith signals during space flight. Crewmembers reported a lack of awareness of position and location of feet, difficulty in maintaining balance, and a perception that falls were more sudden, faster, and harder than similar drops experienced in preflight. Crewmembers experienced illusions as they performed prescribed movement tests. When crew members viewed various targets and then pointed at them while blindfolded, their perception of target location and position of their own limbs was inaccurate in flight compared with similar tests on the ground. Spacelab-1 was launched aboard the Space Shuttle Orbiter Columbia for the STS-9 mission on November 28, 1983. The Marshall Space Flight Center had management responsibilities for the mission. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 8440350. Public domain.)

(November 1, 1983) In this photograph, scientist-astronaut and electrical engineer Owen K Garriott (1930-2019) on the body restraint system and astronaut, fighter pilot, and engineer Byron Lichtenberg (b 1948) prepare for a vestibular experiment during the Spacelab-1 mission. The Vestibular Experiments in Space studied the interaction among the otoliths, semicircular canals, vision, and spinal reflexes in humans. The main objective was to determine how the body, which receives redundant information for several sensory sources, interprets this information in microgravity. Another objective was to record and characterize the symptoms of space sickness experienced by crewmembers. The body restraint system was a rotating chair with a harness to hold the test subject in place. The crewmember wore an accelerometer and electrodes to record head motion and horizontal and vertical eye movement as the body rotated. The first Spacelab mission, Spacelab-1, was sponsored jointly and shared equally by NASA and the European Space Agency. Spacelab-1 was launched aboard the Space Shuttle Orbiter Columbia for the STS-9 mission on November 28, 1983. The Marshall Space Flight Center had management responsibilities for the mission. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 8440005. Public domain.)

(November 16, 1982) Astronaut Joseph P Allen IV (b 1937), one of two mission specialist astronauts for STS-5, participates in a biomedical test in the middeck area of the Earth-orbiting space shuttle Columbia. A series of electrodes have been connected to his face to monitor his responses in zero-g. He was assisted in the test by astronaut William B Lenoir, the flight’s other mission specialist. Dr. Allen is wearing the multi-pieced constant wear garment for space shuttle astronauts. This frame was exposed with a 35 mm camera. (Source: NASA/Johnson Space Center [Houston]. NASA ID: s05-04-141. Public domain.)

(August 9, 1973) Scientist-astronaut and electrical engineer Owen K Garriott (1930-2019), Skylab 3 science pilot, serves as a test subject for the Skylab Human Vestibular Function M131 experiment, as seen in this image from a television transmission made by a color TV camera aboard the Skylab space station in Earth’s orbit. (Source: NASA/Johnson Space Center [Houston]. NASA ID: S73-32113. Public domain.)

(August 9, 1973) Scientist-astronaut and electrical engineer Owen K Garriott (1930-2019), Skylab 3 science pilot, serves as a test subject for the Skylab Human Vestibular Function M131 experiment in this image from a television transmission made by a color TV camera aboard the Skylab space station in Earth’s orbit. The objectives of the M131 experiment were: (1) assess specific behavioral or physiological responses influenced by vestibular activity under 1-g and zero-g conditions; (2) determine man's adaptability to unusual vestibular conditions and predict habitability of future spacecraft conditions involving reduced gravity and Coriollis forces; and (3) measure the accuracy and variability in man's judgment of spatial coordinates based on atypical gravity receptor cues and inadequate visual cues. Dr. Garriott is seated in the experiment's "litter chair," which can rotate the test subject at predetermined rotational velocity or a programmed acceleration/deceleration profile. (Source: NASA/Johnson Space Center [Houston]. NASA ID: S73-34171. Public domain.)

(March 1,1973) Astronaut Charles Conrad Jr (1930-1999), commander of the first manned Skylab mission, serves as a subject in Human Vestibular Function Experiment M131 during Skylab training at Johnson Space Center. Conrad is in the work-and-experiments compartment of the crew quarters of the Skylab Orbital Workshop (OWS) trainer at Johnson Space Center in Houston. The reference sphere with a magnetic rod is used by the astronaut to indicate body orientation non-visually. The "litter chair" in which he is seated can be rotated by a motor at its base or, when not being rotated, can tilt forward, backward, or to either side. (Source: NASA/Johnson Space Center [Houston]. NASA ID: S73-20695. Public domain.)

(March 1, 1973) Astronaut Charles Conrad Jr (1930-1999), commander of the first manned Skylab mission, serves as a subject in Human Vestibular Function Experiment M131 during Skylab training at Johnson Space Center. Scientist-astronaut and physician Joseph P Kerwin (b 1932), science pilot of the mission, goes over a checklist. The two men are in the work-and-experiments compartment of the crew quarters of the Skylab Orbital Workshop (OWS) trainer at Johnson Space Center in Houston. (Source: NASA/Johnson Space Center [Houston]. NASA ID: S73-20678. Public domain.)

(January 1,1972) The base houses the motor for the rotary chair. Skylab's Human Vestibular Function experiment (M131) was a set of medical studies designed to determine the effect of long-duration space missions on astronauts' coordination abilities. This experiment tested the astronauts' susceptibility to motion sickness in the Skylab environment, acquired data fundamental to an understanding of the functions of human gravity reception under prolonged absence of gravity, and tested for changes in the sensitivity of the semicircular canals. Data from this experiment were collected before, during, and after flight. The Marshall Space Flight Center in Redstone Arsenal, Alabama, had program management responsibility for the development of Skylab experiments. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 0102036b. Public domain.)

(January 1, 1972) The control panel is at the upper left. The base houses the motor for the rotary chair. Skylab's Human Vestibular Function experiment (M131) was a set of medical studies designed to determine the effect of long-duration space missions on astronauts' coordination abilities. This experiment tested the astronauts' susceptibility to motion sickness in the Skylab environment, acquired data fundamental to an understanding of the functions of human gravity reception under prolonged absence of gravity, and tested for changes in the sensitivity of the semicircular canals. Data from this experiment were collected before, during, and after flight. The Marshall Space Flight Center in Redstone Arsenal, Alabama, had program management responsibility for the development of Skylab experiments. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 0102036b. Public domain.)

(January 1, 1972) Skylab's Human Vestibular Function experiment (M131) was a set of medical studies designed to determine the effect of long-duration space missions on astronauts' coordination abilities. This experiment tested the astronauts' susceptibility to motion sickness in the Skylab environment, acquired data fundamental to an understanding of the functions of human gravity reception under prolonged absence of gravity, and tested for changes in the sensitivity of the semicircular canals. Data from this experiment were collected before, during, and after flight. The Marshall Space Flight Center in Redstone Arsenal, Alabama, had program management responsibility for the development of Skylab experiments. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 0102036a. Public domain.)

(January 1, 1970) The Rotating "Litter Chair" was a major component of Skylab's Human Vestibular Function experiment (M131). The experiment was a set of medical studies designed to determine the effect of long-duration space missions on astronauts' coordination abilities. The M131 experiment tested the astronauts' susceptibility to motion sickness in the Skylab environment, acquired data fundamental to an understanding of the functions of human gravity reception under prolonged absence of gravity, and tested for changes in the sensitivity of the semicircular canals. Data from this experiment were collected before, during, and after flight. The Marshall Space Flight Center had program management responsibility for the development of Skylab hardware and experiments. (Source: NASA/Marshall Space Flight Center [Redstone Arsenal, Alabama]. NASA ID: 7026007. Public domain.)

Astronauts and Canadian space medicine researcher and physiologist Douglas Watt (top left) acclimating themselves to space adaptation syndrome in a KC-135 airplane that flies parabolic arcs to create short periods of weightlessness. In 2001 and 2002, Watt of McGill University in Montreal studied how the human body adapts to weightlessness through his H-Reflex experiment. This was the first medical experiment completed on the International Space Station (ISS). (Source: NASA's Marshall Space Flight Center. Public domain.)

Garn did acceptably well in training, including his stint on the KC-135 "Vomit Comet." However, while one of the crew (in green flight suit) is moving about in the zero-g environment and clearly enjoying himself, Garn (at left in orange flight suit) is holding on tensely with both hands and appearing apprehensive. (Source: NASA/Johnson Space Center [Houston]. NASA ID: S85-25619. Public domain. Cropped by Dr. Douglas J Lanska.)

Beginning in 1981, United States Senator Edwin Jacob "Jake" Garn (b 1932), from Utah, pressured NASA to let him fly on a Space Shuttle mission, and in 1985 he was included on the STS-51-D mission of Space Shuttle Discovery. Garn's role was as a congressional observer and as a subject for medical experiments on space motion sickness. Despite having flown more than 10,000 hours as a Navy combat pilot, the space sickness Garn experienced was so severe that a scale for space sickness was jokingly based on him, where "1 Garn" is the highest possible level of sickness. (Source: NASA. Public domain.)

(Source: Post of Moldova. Not subject to copyright.)

Cosmonaut German Titov (right) appears with NASA astronaut John Glenn (left) and President John Kennedy (center) at the White House on May 3, 1962. Titov was in Washington to give his account of the Vostok 2 spaceflight to the Committee on Space Research (COSPAR). (Credit: NASA image from the files of Asif Siddiqi. Source: Siddiqi AA. Challenge to Apollo: The Soviet Union and the Space Race, 1945-1974 [NASA SP-2000-4408]. Washington, DC: NASA History Division, National Aeronautics and Space Administration, 2000. Public domain.)

From left to right: Soviet cosmonaut Gherman Stepanovich Titov (1935-2000); Nikita Sergeyevich Khrushchev (1894-1971), First Secretary of the Communist Party of the Soviet Union; and Soviet cosmonaut Yuri Alekseyevich Gagarin (1934-1968). Gagarin had been the first human to journey into outer space: traveling in the Vostok 1 capsule, Gagarin completed one orbit of Earth on April 12, 1961. Titov became the second human to orbit Earth on August 6, 1961, aboard Vostok 2. Titov is also remembered as the first person to suffer significant space sickness (space orientation syndrome). (Source: Dutch National Archives, The Hague, Fotocollectie Algemeen Nederlands Persbureau (ANEFO), 1945-1989. Creative Commons Attribution-Share Alike 3.0 Netherlands License, creativecommons.org/licenses/by-sa/3.0/nl/deed.en.)

Space shuttle “Teacher in Space” astronaut Christa McAuliffe (at top), her backup crew member, Barbara Morgan (bottom), and Payload Specialist Greg Jarvis (top right) training on the KC-135 zero-g aircraft. STS-51-L was the 25th mission of the NASA Space Shuttle program and the final flight of Space Shuttle Challenger. Planned as the first "Teacher in Space" Project, in addition to observing Halley's Comet for 6 days, the mission never achieved orbit; a structural failure during ascent 73 seconds after launch from Kennedy Space Center on January 28, 1986, killed all seven crew members and destroyed the orbiter. Morgan was not onboard the ill-fated STS-51-L mission of the Space Shuttle Challenger; she later trained as a Mission Specialist and flew on the STS-118 mission of Space Shuttle Endeavor in August 2007, more than 20 years after the Challenger disaster. (Source: NASA [S85-44833]. Public domain.)

This August 1995 photo aboard a KC-135 zero-g aircraft carrying that year's class of NASA astronaut candidates depicts the kind of training required to prepare astronauts for flights on assigned missions in space. Those pictured are (from the left, top row) Frederick W Sturckow, Rick D Husband, Dafydd R (Dave) Williams Jr, Stephen K Robinson, Kalpana C Chawla, and Takao Doi and (bottom row, left to right) Michel Tognini, Carlos I Noriega, Susan L Still, Janet L Kavandi, Michael P Anderson, and Joe F Edwards. Doi is representing the National Space Development Agency (NASDA) of Japan; Williams, the Canadian Space Agency (CSA); and Tognini, France's Centre National d'Etudes Spatiales (CNES). Williams joined four other first-time fliers (not pictured) on Space Shuttle Columbia for the April 1998 Neurolab mission. (Source: NASA [S95-09698]. Public domain.)

In this photo from 1978, six astronauts who had been in training at the Johnson Space Center for almost a year are experiencing weightlessness. They are onboard the NASA KC-135, which uses a special parabolic pattern to create brief periods of microgravity, affording astronauts and astronaut candidates a preview of spaceflight. The photo should be viewed with feet at the top. The three astronauts in the foreground are (left to right): Richard O Covey, Steven R Nagal, and George D Nelson. In the center background is Robert L Stewart. Obscured in the background are Norman E Thagard and Ellison S Onizuka. (Source: NASA. Public domain.)

Note the approximate 45-degree angle of ascent. (Source: NASA Image and Video Library [GRC-2001-C-00614]. Public domain.)

Parabolic flight trajectory of the NASA KC-135A 9 from the aircraft nose of "Weightless Wonder IV," Johnson Space Center. (Source: NASA/Glenn Research Center. The present image was created from a photograph of the aircraft nose by Dr. Douglas J Lanska.)

NASA/U.S. Air Force KC-135 aircrew below the aircraft nose, 1995: "Weightless Wonder IV," Johnson Space Center. Note the parabolic flight trajectory painted on the aircraft's nose. (Source: NASA/Glenn Research Center [C-1995-716]. Public domain.)

The KC-135 provided NASA's Reduced Gravity Program with a zero-g environment for testing and training of human reactions (1968). (Source: NASA [NAS-9-9-59279-163125]. Public domain.)

Mercury astronauts in simulated weightless flight in C-131 aircraft flying zero-g trajectory (the "vomit comet") at Wright Air Development Center, 1959. Weightless flights were a new form of training for the Mercury astronauts. These flights were nicknamed the "vomit comet" because of the nausea that is often induced. (Source: NASA. Public domain.)

NASA's Reduced Gravity Research Program made it possible for scientists to study human responses to simulated weightlessness. The reduced-gravity aircraft flies an up-and-down parabolic pattern. This provides about 30 seconds of hypergravity (1.8 to 2.0 g) as the plane climbs to the top of the parabola. Once the aircraft starts to tip over the top of the parabola to descend toward Earth, the aircraft experiences about 25 seconds of microgravity (zero-g). A typical flight conducted 30 to 40 parabolic maneuvers over the Gulf of Mexico. KIAS = knots indicated air speed. (Source: NASA Reduced Gravity Research Program. Because of the poor quality of the original, the figure has been recreated with modified labeling by Dr. Douglas J Lanska.)

Harry Larson, one of the “Gallaudet Eleven" research subjects in the 1950s, inside a 20-foot slow rotation room, rotating at 10 revolutions per minute. (Credits: Gallaudet University Archives/Harry Larson Collection and NASA. Source: Hotovy/NASA 2017.)

John Zakutney, one of the “Gallaudet Eleven" research subjects in the 1950s, being lowered into a centrifuge pool. (Credits: NASA/U.S. Navy/Personal collection of David Myers. Source: Hotovy/NASA 2017.)

The central auditory deficits shown in orange constitute an ensemble of indirect effects presumably common to all forms of congenital peripheral deafness. Other central deficits in blue denote deficits that may be combined in specific genetic forms of congenital deafness. Except for genes playing intrinsic roles in both the central and peripheral auditory systems, all central auditory deficits shown here are indirect consequences of peripheral hearing impairment. The time scale is based on the development of the human auditory system. (Source: Michalski N, Petit C. Central auditory deficits associated with genetic forms of peripheral deafness. Hum Genet 2022;141(3-4):335-45. Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0.)

Atrioventricular block 10 seconds after swallowing cold water. (Source: Malone K, Modi M, Koripalli S, Amorn A, Stevens CM. Swallow syncope associated with intermittent sinus pause and high-degree atrioventricular block: a case report. Cureus 2022;14(3):e22915. Creative Commons Attribution License [CC-BY 4.0].)

Sinus arrest 5 seconds after the initiation of drinking cold water. (Source: Malone K, Modi M, Koripalli S, Amorn A, Stevens CM. Swallow syncope associated with intermittent sinus pause and high-degree atrioventricular block: a case report. Cureus 2022;14(3):e22915. Creative Commons Attribution License [CC-BY 4.0].)

Overnight ECG showing transient high-grade, second-degree atrioventricular block on a background of 2:1 second-degree atrioventricular block. (Source: Malone K, Modi M, Koripalli S, Amorn A, Stevens CM. Swallow syncope associated with intermittent sinus pause and high-degree atrioventricular block: a case report. Cureus 2022;14(3):e22915. Creative Commons Attribution License [CC-BY 4.0].)

Initial 12-lead ECG on presentation while the patient was at rest. New bifascicular block compared with previous ECG 7 months earlier, which showed only a right bundle branch block. (Source: Malone K, Modi M, Koripalli S, Amorn A, Stevens CM. Swallow syncope associated with intermittent sinus pause and high-degree atrioventricular block: a case report. Cureus 2022;14[3]:e22915. Creative Commons Attribution License [CC-BY 4.0].)

Pendred syndrome is characterized by severe-to-profound congenital deafness and is associated with a large vestibular aqueduct. There may also be a cochlear malformation (Mondini displasia). (Figure prepared by the National Institutes of Health. Public domain. Figure edited by Dr. Douglas J Lanska.)

(Illustration by C Burnett, March 25, 2007. Creative Commons Attribution-Share Alike 3.0 Unported License, https://creativecommons.org/licenses/by-sa/3.0/deed.en. Figure edited by Dr. Douglas J Lanska.)

C-shaped halo of disc edema with normal temporal disc margin and disrupted radial nerve fiber layer striation. (Contributed by Dr. Yue Li.)

Circumferential halo with nasal elevation. No major vessel obscuration. (Contributed by Dr. Yue Li.)

Circumferential halo with general elevation of the optic nerve head. Obscuration of at least one segment of major vessels leaving the disc. (Contributed by Dr. Yue Li.)

Circumferential obscuration of the disc margin with complete elevation of the optic nerve head. Obscuration of more than one major vessel on the disc. (Contributed by Dr. Yue Li.)

The optic disc is elevated with circumferential halo. But all the vessels are not obscured. The disc has a mild refractile appearance. (Contributed by Dr. Yue Li.)

High swelling of the optic nerve head with partial or total obscuration of all vessels on the disc and leaving the disc. (Contributed by Dr. Yue Li.)

(A, C) Enhanced depth imaging OCT scan of the optic nerve with green line corresponding to the cross-sections in (B) and (D), which are showing the visible optic disc drusen (blue arrow). The drusen always has a signal-poor, hyporeflective core and fragments of hyperreflective margins. (Contributed by Dr. Yue Li.)

A 59-year-old woman had severe bilateral vision loss as well as altered sensorium, headaches, and seizures. The blood pressure was 203/180 mmHg. MRI revealed signal abnormality in the bilateral parieto-occipital areas, predominantly in the white matter, without infarction, which is consistent with posterior reversible encephalopathic syndrome. Visual acuity improved following treatment of hypertension. (Contributed by Dr. Sangeeta Khanna.)

A 49-year-old female developed sudden bilateral vision loss after an interventional procedure for embolization for uterine leiomyoma due to thromboembolism. CT revealed hypoattenuating ill-defined areas of low attenuation seen in the occipital lobes bilaterally, more extensive on the right side than the left. MRI showed areas of restricted diffusion with loss of gray-white matter differentiation seen predominantly involving the bilateral occipital lobes. She slowly improved to 20/100 in both eyes with conservative measures. (Contributed by Dr. Sangeeta Khanna.)

MRI demonstrates cerebral edema in affected areas, typically the posterior hemispheres best seen in T2-FLAIR sequence, generally in the absence of restricted diffusion, a sign that would be more characteristic of ischemic infarction. (Contributed by Dr. Sangeeta Khanna.)

Coronal T2-weighted MRI image of a left inferior occipital stroke in a patient with pure alexia and right hemianopia. (Contributed by Dr. Jason J S Barton.)

(Contributed by Dr. Jason J S Barton.)

Medieval carving of Saint David, sea-sick during his journey to the holy land, as depicted on a misericord in Saint David's Cathedral in the county of Pembrokeshire, near the most westerly point of Wales. A misericord (or mercy seat) is a small wooden structure on the underside of a folding seat in a church which, when the seat is folded up, is intended to support a person in a partially standing position during long periods of prayer. (Courtesy of the Wellcome Collection, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image edited by Dr. Douglas Lanska to correct perspective distortion and to repair small areas of damage to the image.)

Audiogram showing a “4 kHz notch” (or colloquially, a “4K notch”) pattern of sensorineural hearing loss, commonly seen in noise-induced hearing loss. Both ears are shown. (Contributed by James Lanska.)

Audiogram showing symmetric, gradually sloping, high-frequency sensorineural hearing loss. (Contributed by James Lanska.)

Audiogram showing a low-frequency trough pattern of sensorineural hearing loss, commonly seen in Meniere disease. The left ear is shown. (Contributed by James Lanska.)

Note the reversal of anisocoria after topical instillation of apraclonidine 0.5%. (Contributed by Dr. Jonathan Trobe from: Neuro-ophthalmology At Your Fingertips, //fingertips.neuro-ophthalmology.med.umich.edu.)

(Contributed by Dr. Rosa Ana Tang.)

(Contributed by Dr. Rosa Ana Tang.)

Comparing ERG responses in dark (scotopic) and light (photopic) conditions. (Contributed by Dr. Rosa Ana Tang.)

Comparison of A- and B-wave ratios in a normal ERG versus abnormal ERG under scotopic (dark) conditions. (Contributed by Dr. Rosa Ana Tang.)

Normal electroretinogram showing the anatomical correlates of the B wave, oscillatory potential, and A wave. (Contributed by Dr. Rosa Ana Tang.)

(A) Multifocal visual evoked potential stimulus contains 60 sectors of black and white checks (one sector shown in red). (B) Multifocal visual evoked potential responses from the right eye (blue) and the left eye (red) of a normal subject are very similar. (C) The multifocal visual evoked potential responses from the right eye with a history of optic neuritis are delayed in some sectors compared to those from the left eye (red). (D) An interocular latency probability plot marks the locations with significantly delayed latencies in the right eye with an optic neuritis history (dark blue for p < 0.01, light blue for p < 0.05) compared to the left eye. Black symbols denote no significant differences compared to a normative database; small gray symbols denote responses too small for comparisons. (Contributed by Dr. Han Cheng.)

Pattern-reversal visual evoked potential stimulus (A) and waveform (B). (Contributed by Dr. Han Cheng.)

(Contributed by Dr. Rosa Ana Tang.)

(Contributed by Dr. Rosa Ana Tang.)

OCT of optic nerve shows resolution of papilledema 4 months after diagnosis of pseudotumor cerebri and treatment with acetazolamide. (Contributed by Dr. Rosa Ana Tang.)

OCT of right eye shows edema of the optic disc after nonarteritic anterior ischemic optic neuropathy. To be noticed is a small cup-to-disc ratio of the contralateral eye, which translates into an increased risk of nonarteritic anterior ischemic optic neuropathy in that eye. (Contributed by Dr. Rosa Ana Tang.)

(Contributed by Dr. Rosa Ana Tang.)

(Contributed by Dr. Rosa Ana Tang.)

A) Retinal OCT centered on the fovea shows the foveal depression and multiple retinal layers seen. (B) Optic nerve OCT shows a cross-section. (Contributed by Dr. Rosa Ana Tang.)

This 20-year-old man had developmental delay but did well until recently, with some memory decline, dysarthria, and imbalance since his late teens. The video begins with intact horizontal saccades, then vertical saccades that are slow and limited in range, followed by intact horizontal pursuit and then limited vertical pursuit. (Courtesy of www.neuroophthalmology.ca. Contributed by Dr. Jason Barton.)

Cross section of the temporal bone through the external auditory meatus, the tympanic cavity surrounding the bones of the middle ear, the superior and horizontal semicircular canals, and the cochlea. Illustration from Tabula 45 of Bartolomeo Eustachi’s Tabulae Anatomicae (Eustachii 1714).

Woodcut frontispiece portrait of Flemish anatomist, physician, and surgeon Andreas Vesalius (1514-1564) from the Fabrica (1543). (Courtesy of the U.S. National Library of Medicine.)

This photo was taken approximately 2 weeks after several weeks of orbital radiation in daily fractions. The lid is less boggy, and ocular motility and alignment have improved. The patient now has no diplopia in the central 20 degrees of visual field. (Contributed by Dr. Mark Duffy.)

In this axial CT, orbital mass has the appearance of an intraconal tumor. Note the homogeneous appearance of the intraconal tumor and its characteristic molding to the space it occupies. It molds at the globe instead of indenting it, and it molds along the posterior lateral orbital wall without expanding the orbital space, resulting in bony erosion. It extends to the inferior orbital fissure posteriorly. (Contributed by Dr. Mark Duffy.)

Coronal CT shows an inferior orbital mass that displaces the optic nerve. It is in the exact location of the inferior rectus muscle and seems to completely replace it. The other rectus extraocular muscles appear normal bilaterally. Biopsy is indicated to rule out lymphoma versus a primary myositis or vasculitis. (Contributed by Dr. Mark Duffy.)

This 76-year-old man presented with diplopia in all directions of gaze. The right periorbital tissues showed diffuse boggy edema concentrated in the inferior lid. There was significant clear chemosis of the right bulbar conjunctiva. The globe was relatively immobile and displaced superiorly by several millimeters. The differential diagnosis included unilateral thyroid-related orbitopathy, lymphoma, and vasculitis. (Contributed by Dr. Mark Duffy.)

This 8-year-old girl presented with slow progressive ptosis of the left upper lid and fullness to the left periorbital tissues. There was a dense, nonmobile palpable mass over the lacrimal gland area. By imaging, the mass was separate from the lacrimal gland. The dense presumed fibrosis of the orbit had severely limited the movement of the levator palpebrae superioris without affecting the superior or lateral rectus. The patient underwent an orbital biopsy through a lid crease incision. (Contributed by Dr. Mark Duffy.)

After the diagnosis of limited granulomatosis polyangiitis was made, the patient was treated by a pediatric rheumatologist. This photograph was taken 6 weeks after initiation of oral prednisone treatment (note the facial fullness). The ptosis is spontaneously resolving, and the levator excursion has returned to near normal. The orbital mass is no longer palpable. (Contributed by Dr. Mark Duffy.)

This patient underwent urgent apical and orbital decompression. In this axial CT, note the increased space at the orbital apices bilaterally. This relief of optic nerve compression was associated with return of significant visual acuity and color vision. (Contributed by Dr. Mark Duffy.)

Coronal sections identify the classic enlargement of extraocular muscle bellies. The most common muscles involved (in order and degree) are the inferior rectus, medial rectus, superior rectus, and lateral rectus, in that order. In this case, it appears the superior oblique muscles may even be slightly enlarged. The lateral rectus is rarely enlarged to a significant degree. This is a classic presentation of extreme diffuse muscle enlargement resulting in compressive optic neuropathy. (Contributed by Dr. Mark Duffy.)

(A) Visual field testing of the left eye at presentation. In the visual field of the left eye, defects include an inferior nasal step and an inferior altitudinal defect to less visible stimuli. The right eye shows similar defects. (B) Following 1 week of treatment with prednisone 100 mg/day, repeat examination shows progression of visual field loss in the left eye. There is now a dense paracentral scotoma (likely an evolving cecocentral scotoma) and increased definition of the inferior nasal step. Also of note is the increasing constriction of isopters to the larger or brighter stimuli. (Contributed by Dr. Mark Duffy.)

This 72-year-old man with a history of hypothyroidism presented with complaints of blurred vision and chronic swelling of the eyes. He had been treated for 2 months with vasoconstrictors and antibiotic ointment for a presumed chronic conjunctivitis before referral to an eye center. (Contributed by Dr. Mark Duffy.)

On this axial CT, the apex is seen to be completely crowded out by the rectus muscle bellies. Proptosis, increased orbital fat, and extraocular muscular enlargement are present. (Contributed by Dr. Mark Duffy.)

A 54-year-old female presented with a history of progressive proptosis, ptosis, diplopia, and periocular pain over a 6-week interval, despite prednisone treatment. CT scan revealed a mass that indented the globe. Orbital biopsy revealed a dense fibrotic mass consistent with sclerosing orbital pseudotumor. A debulking procedure and release of the superior and medial rectus muscles resulted in return of full motility. High-dose corticosteroid treatment prevented further progression. The ptosis was complete and permanent, requiring a silicone frontalis sling procedure. (Contributed by Dr. Mark Duffy.)

Bone marrow biopsy showing a “foam cell,” cholesterol-laden macrophage, from the patient with Niemann Pick type C from mutation in the NPC1 gene. (Courtesy of www.neuroophthalmology.ca. Contributed by Dr. Jason Barton.)

The optic disc is swollen, and there is subretinal fluid extending to the macula. Extensive patches of retinal edema (white) extend along the upper and lower vascular arcades. (Contributed by Dr. James Goodwin.)

Persons with retinal manifestations of toxoplasmosis may have from three to seven reactivations of the retinochoroiditis during a lifetime. This picture shows an active lesion with the typical cellular deposits in the vitreous. This appearance gives rise to the label of “a headlight in the fog.” (Contributed by Dr. Rosa Tang.)

Central retinal artery occlusion usually presents as a sudden onset of painless and profound visual loss. The condition may be preceded by episodes of transient visual loss. The cause of central retinal artery occlusion is most commonly emboli from the carotid artery or the heart. This patient is showing an unusual sparing of the papillomacular nerve fiber bundle due to a patent cilioretinal artery. Approximately one in four patients with central retinal artery occlusion have significant carotid artery disease, cardiac valvular disease, or diabetes. (Contributed by Dr. Rosa Tang.)

Purtscher retinopathy in a patient with shaken baby syndrome. (Contributed by Dr. Rosa Tang.)