Headache & Pain

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.)

(From: Yeung AW, Wong NS. The historical roots of visual analog scale in psychology as revealed by reference publication year spectroscopy. Front Hum Neurosci. 2019;13: 86.)

Schema of diagnostic approach in a patient with indomethacin-sensitive headache, separated into characteristics of primary stabbing headache, trigeminal autonomic cephalalgias, and exertional headaches.

From:
Wei DY, Yuan Ong JJ, Goadsby PJ. Overview of trigeminal autonomic cephalalgias: nosologic evolution, diagnosis, and management. Ann Indian Acad Neurol 2018;21(Suppl 1):S39-44.
Gonzalez-Quintanilla V, Madera J, Pascual J. Update on headaches associated with physical exertion. Cephalalgia 2023;43(3):3331024221146989.
Kwon S, Lee MJ, Kim M. Epicranial headache part 1: primary stabbing headache. Cephalalgia 2023;43(2):3331024221146985.)

The red box indicates epidural fluid collection in a heavily T2-weighted fat-suppressed spinal MRI. (Contributed by Dr. Simy Parikh.)

The red box indicates venous engorgement of the superior sagittal sinus in a patient with a spontaneous spinal CSF leak. (Contributed by Dr. Simy Parikh.)

Pachymeningeal enhancement in patients with spontaneous spinal CSF leak, as demonstrated in this coronal MRI brain with gadolinium enhancement, is diffuse, uninterrupted, and non-nodular, and it involves the supratentorial and intratentorial pachymeninges. (Contributed by Dr. Simy Parikh.)

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.)

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.)

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.)

(Contributed by Dr. J W G Jacobs.)

(Contributed by Dr. J W G Jacobs.)

This figure shows the nine areas for self-assessment by patients. Patients are asked to check the areas in which they experience pain on the 2-view manikins. Alternatively, patients may use the checklist of body sites. The number of separate sites is summed (range 0–9). (Contributed by Dr. J W G Jacobs.)

Approach to patient with medication overuse headache. Treatment on medication overuse headache is based on three pillars: education and counselling, withdrawal of medication in a different clinical setting according to the patient characteristics, and preventive treatment. (Contributed by Patricia Pozo-Rosich MD PhD)

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.)

Image demonstrates reduced intraepidermal nerve fiber density with rare remaining nerve fibers. (Courtesy of Dr. Kurenai Tanji.)

Skin biopsy cryosection, stained with PGP 9.5 stain for epidermal nerve fibers. Image demonstrates normal intraepidermal nerve fiber staining. (Courtesy of Dr. Kurenai Tanji.)

A 22-year-old female spent 20 hours in an immobile recumbent state and was found to have bilateral leg weakness. Electromyography localized the lesions to the sciatic nerves bilaterally, and subsequent computerized tomography of the pelvis demonstrated marked hypodensity with interspersed hyperdense regions indicating hemorrhage within the gluteal muscles bilaterally, with the areas of necrosis surrounded by solid arrows bilaterally. (Contributed by Dr. Cory Toth.)

(A) Sagittal T1 image showing descent of the cerebellar tonsils into the foramen magnum and associated cervical syrinx. (B) Axial T2 image showing cross-section of the cervical syrinx. (C) Sagittal T1 image showing extent of the cervical syrinx. (Contributed by Dr. Christopher Boes.)