General Neurology
Brain death/death by neurologic criteria
Nov. 09, 2024
Worddefinition
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
Susac syndrome …
- Updated 05.15.2024
- Released 08.25.1998
- Expires For CME 05.15.2027
Susac syndrome
Introduction
Overview
Susac syndrome presents with a triad of retinal arterial occlusion, deafness, and encephalopathy, although often not all of the components are evident at the onset. Since its recognition in 1973, over 400 cases have been reported in the literature. In this article, the author describes the clinical features, pathology, and diagnosis of this syndrome as well as atypical presentations. The pathological findings include microinfarcts in the territories of end arterioles of the brain, retina, and inner ear. MRI plays an important role in demonstrating the CNS lesions. Management of Susac syndrome is also discussed.
Key points
|
• Susac syndrome is typically a triad of encephalopathy, retinopathy, and hearing loss, but may have an atypical presentation. | |
|
• Over 400 cases have been reported in the literature, mostly in women. | |
|
• Special diagnostic procedures are audiometry, retinal angiography, and MRI of the brain. | |
|
• Important treatments include corticosteroids and immunotherapy. | |
|
• The syndrome is self-limiting but may persist for years, with a fluctuating course. |
Historical note and terminology
Since 1973, there have been reports of patients (mostly young women) presenting with a combination of retinal arterial occlusion, deafness, and encephalopathy (92). American neurologist and neuro-ophthalmologist John Susac (1940-2012) defined the syndrome in 1979 as a noninflammatory vasculopathy causing small infarcts in the cochlea, the retina, and the brain (116; 31; 98).
It has been called “RED-M syndrome” for “Retinopathy,” “Encephalopathy,” and “Deafness-associated Microangiopathy” (75). Another proposal was to call it “SICRET syndrome” for “Small Infarctions of Cochlear, Retinal, and Encephalic Tissue” (110). The triad of microangiopathy of the brain and retina with hearing loss was ultimately dubbed “Susac syndrome” (114; 82; 86), although it is still referred to as SICRET syndrome in the French literature (72), and other authors prefer the term “retinocochleocerebral vasculopathy” (89).
Further cases of this syndrome were reported in subsequent years (11; 19; 109).
In partial or variant forms of this syndrome, only one or two of the three components are clinically manifest. Examples of this are reports of subacute bilateral sensorineural hearing loss with bilateral retinal artery occlusion, but without obvious central nervous system signs (128; 28). MRI findings may be abnormal in these patients in the absence of symptoms specifically referable to the brain (130). Cerebral and retinal involvement may occur without hearing loss (43). A branch retinal artery occlusion subset of this syndrome has been recognized (99).
Clinical manifestations
Presentation and course
|
• Susac syndrome is characterized by a triad of encephalopathy, retinopathy, and hearing loss. | |
|
• There are atypical or partial presentations without the full triad. | |
|
• A careful dermatological examination is indicated as some patients may have prodromal livedo reticularis, livedo racemosa, or a diffuse faint micropapular eruption. | |
|
• The disease is usually self-limited after initial fluctuations that may last from months to years. |
The triad of clinical features in Susac syndrome is encephalopathy, retinopathy, and hearing loss. Most affected individuals do not have the clinical triad at the onset of symptoms but, rather, recurrences of one or more of the triad components. In a series of 10 cases reported from Israel, only two patients presented with the full triad of Susac syndrome, and seven patients developed the full triad during a mean follow-up period of 35 months (126); the authors suggested classifying the disease course into suspected, incomplete, and complete Susac syndrome to facilitate early diagnosis. In a series of 19 cases of Susac syndrome reported from Turkey, only three presented with the complete clinical triad (136). In a retrospective review of 32 adult patients with Susac syndrome from an Australasian cohort, 19% presented with brain-eye-ear involvement, 44% with brain-ear involvement, 19% with brain-eye involvement, and 19% with just brain involvement (121).
Few cases with the complete triad have been reported in children, adolescents, or young adults (51; 35; 101; 56).
The number of attacks in reported cases has varied between one and eight, with an interval of 1 to 34 months between episodes. The mean duration of the illness is about 4 years.
Encephalopathy. Headache is a prodromal symptom that may precede the development of encephalopathy. Headache is often migraine-like and may be accompanied by a visual aura (81). Cognitive disturbance, characterized by short-term memory loss and disorientation, is present in about 75% of the cases. Psychiatric disturbances are frequent and include bizarre behavior. In 25% of patients, the first attack is preceded by slowly progressive personality and mental changes (114). Neurologic signs are diffuse or multifocal and progress over the course of the disease. Corticospinal tract symptoms and signs, including weakness and hyperreflexia, usually occur bilaterally. Rarely, sphincter disturbances and seizures have been described.
Retinopathy. Retinopathy manifests by impaired vision due to multiple bilateral branch retinal artery occlusions without intraocular inflammation. These can be detected by fundoscopic examination (59), which may show occlusion of the branches of the central retinal artery with a cherry-red appearance of the macula (25). Yellow to yellow-white, nonrefractile, or refractile retinal arterial wall plaques (Gass plaques) found at midarteriolar segments are common findings in Susac syndrome (107).
Usually, segmental loss of vision occurs. Hemianopsia has not been reported in any of the cases. If the occlusions are confined to the peripheral branches of the retinal artery, there may be no visual symptoms, and the fundoscopic examination may be negative.
In exceptional cases, unilateral occlusion or staged bilateral occlusions of the central retinal artery may develop rather than branch retinal artery occlusions (06). Recurrent branch retinal artery occlusion without the classic triad may be the only presenting symptom of Susac syndrome (05).
Audiovestibular dysfunction. Neuro-otological symptoms in Susac syndrome are almost universal, and an increasing low- to high-frequency sensorineural hearing loss should prompt consideration of Susac syndrome (55). Hearing loss is often the presenting feature and may be acute, unilateral, or bilateral and may be accompanied by vertigo, tinnitus, nausea, and vomiting. It may also be asymptomatic and evident only on audiometry. Vestibular dysfunction, sensorineural hearing loss, and severe tinnitus in the early phase of Susac syndrome may lead to misdiagnosis as Meniere disease. Additional symptoms include ataxic gait and nystagmus, which may be due to infarction within the membranous labyrinth.
Low- and middle-frequency sensorineural hearing loss is due to microinfarctions of the apical cochlea in the setting of the endotheliopathy rather than due to localized damage to the vestibulocochlear nerve, whereas vestibular dysfunction may indicate lesions in the vestibular apparatus itself or may be the result of central microinfarctions within the cerebellum or brainstem (88).
Dermatological manifestations. A dermatological examination may reveal skin lesions compatible with livedo reticularis or livedo racemosa on the extremities and a diffuse faint pink micropapular (ie, tiny or pinpoint papules) eruption with a “sandpaper” quality on the chest and abdomen (122; 29; 44).
There have been at least 14 reported cases in whom dermatological manifestations were associated with Susac syndrome, most of which were livedo reticularis, and many of which occurred as a prodrome to the onset of classical symptoms and signs (122; 29; 44).
Livedo reticularis results from an impaired blood flow in the dermal arteries, which variously is due to spasm, inflammation, or vascular obstruction (44). The appearance of livedo reticularis at Susac syndrome onset and resolution with immunosuppressant treatment suggests that the underlying etiological processes responsible for Susac syndrome also contributed to the development of livedo reticularis (44).
Livedo reticularis and the micropapular rash may resolve within 2 weeks after initiation of treatment for Susac syndrome (44).
Livedo racemosa (ie, a reddish-blue mottling of the skin in an irregular, reticular pattern) has also been reported as a prodrome of the onset of Susac syndrome (122). A 24-year-old man had the onset of Susac syndrome with the full clinical triad 2 weeks after the onset of a livedo racemosa of the flanks and feet (122); skin biopsies revealed a thrombus in several dermal arterioles, endothelial cell swelling, and a mild perivascular lymphocytic infiltrate. Livedo racemosa differs from the more common livedo reticularis by its shape and response to warming (120). Livedo racemosa consists of broken circular segments in a larger pattern than the fine, regular, complete network of livedo reticularis (120). Livedo racemosa results from impaired peripheral blood flow and, unlike livedo reticularis, persists on warming (120).
Unusual presentations. The triad of encephalopathy, branch retinal artery occlusions, and hearing deficits is seen at some point during the evolution of Susac syndrome in 85% of cases, but only 13% of patients manifest all these symptoms on presentation (29).
Some cases of Susac syndrome present with unusual features (119; 65; 111; 08; 20; 35; 77; 105; 129; 71; 125; 137; 44; 50; 13; 03; 18).
An atypical presentation may lead to a mistaken diagnosis of multiple sclerosis (137; 03) or cerebral infarction (83).
Prognosis and complications
The disease is usually self-limiting after initial fluctuations that may last from months to years. Some reported cases improved during periods when they were not receiving any treatment. About half of the cases recover enough to lead a normal life. One patient, who was treated with cyclophosphamide and methylprednisolone, recovered from encephalopathy, and the retinal arteries became free of obstruction, but deafness remained unchanged at follow-up over 14 months (23). Neurologic deficits remained unchanged in a case that was followed for 13 years (110). Occasionally, a patient may continue to deteriorate with dementia, blindness, and deafness as late sequelae.
In the French CARESS study, about half (53%) of the 36 subjects in the study experienced severe hearing loss that occurred a median of 13 months after diagnosis (91).
Neuropsychological dysfunction generally improves with treatment (123). Significant improvements over time were found for information processing speed, verbal recognition, and semantic and phonological fluency (123). There is, nevertheless, a high psychological and emotional burden associated with the disease (123).
After improvement is stabilized, the syndrome usually does not recur. An exceptional case of recurrence after 18 years of remission was reported in a 51-year-old woman with symptoms, signs, and brain MRI findings consistent with Susac syndrome (90).
A French study of nine cases followed for a mean duration of 6.4 years found that most patients had returned to work, and none had severe impairment, but some cases experienced episodic clinical flares (07). The long-term risk of future relapses of Susac syndrome is not yet clear, but it may be prudent to continue maintenance treatment for at least 2 additional years after achieving clinical remission (127).
Susac syndrome is usually not fatal, but exceptional cases, even with appropriate treatment, may develop severe neurologic complications leading to death (108).
Biological basis
Etiology and pathogenesis
|
• The pathological findings are microinfarcts in the territories of end arterioles of the brain, retina, and inner ear. | |
|
• The exact mechanism of arteriolar occlusion in Susac syndrome is not known but is presumed to be mediated by an autoimmune response to an unknown antigen. |
The cause of Susac syndrome is unknown.
The pathological findings are microinfarcts in the territories of end arterioles of the brain, retina, and inner ear (48; 54; 15).
Brain biopsies show wedge-shaped microinfarcts surrounded by microglia (54). Microscopic examination shows areas of necrosis measuring up to 500 µ in diameter in the cerebral cortex and white matter with loss of neurons, axons, and myelin. The microinfarcts are caused by a microangiopathic process with arteriolar wall proliferation, lymphocytic infiltration, and basal lamina thickening (48; 15).
Selective distribution of the infarcts in the brain, eyes, and ears may be due to the common embryologic origin of these tissues. Both the retina and the inner ear have barriers analogous to the blood-brain barrier.
One case with a patent foramen ovale improved after anticoagulation, leading the authors to postulate that the syndrome was due to microembolism (47). However, typical ophthalmologic findings point to thrombosis, rather than embolism, as the mechanism of arterial occlusion. In a series of four cases, retinal arterial wall plaques were seen, and the authors cautioned that these should not be misinterpreted as emboli (33); these plaques resolved over time. Retinal arterio-arterial collaterals have also been reported (93).
In six reported patients, virologic studies suggested recent viral infection, suggesting an immune-mediated mechanism triggered by an infectious antigenic agent (89). No infectious agent, however, has been identified in the CSF. Biopsies of various tissues, including the brain, have provided few etiologic clues. Brain biopsy specimens usually demonstrate small infarcts and minimal perivascular inflammatory changes. There is no evidence of a vasculitis. In a few cases, subclinical microangiopathy in muscles suggested that the vasculopathy in Susac syndrome is a systemic disease with a preponderance of retinal, cochlear, and cerebral manifestations (89).
The exact mechanism of arteriolar occlusion in Susac syndrome is unknown but is presumed to be mediated by an autoimmune response to an unknown antigen. Susac himself proposed that the syndrome is an autoimmune endotheliopathy, and pathological studies have shown endothelial changes typical for an antiendothelial cell injury syndrome (115). Cases rarely have demonstrable thrombophilia or overt coagulopathy, such as factor V Leiden mutation (11).
Some cases have other concurrent pathological processes. One patient suffered from both Susac syndrome and a lupus-like systemic disease and had abnormal CSF as well as disseminated white matter hyperintensities on brain MRI (79). One patient was on fenfluramine for weight reduction before the onset of the disease (110); because fenfluramine is neurotoxic and may also cause vasculitis, its potential etiologic role remains suspect but unproven.
Various hypotheses attribute aspects of the etiopathogenesis of Susac syndrome to an autoimmune process (115), an inflammatory process (01; 133), in situ clot formation with microembolization (11), and vasospasm (40). None of these have been proven. An inflammatory process is suggested by the common clinical fluctuations in the course, but histologically no evidence of vasculitis has been demonstrated, and cases have developed severe adverse outcomes while on aggressive immunosuppressive treatment (01; 133). A vasospastic disorder in one case report was suggested by a history of cold hands, a prolonged flow arrest time after cooling in nailfold capillary microscopy, and an increased plasma level of endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells (40).
Skin involvement in Susac syndrome is pathologically plausible because serum antibodies have been identified that bind directly to the CNS and generic endothelium cells (122). High titers of circulating antibodies directly binding to generic endothelium cells have been observed in the serum of 30 patients with Susac syndrome (115; 122). In addition, antibodies belonging to the complement activating IgG1 subclass and binding to endothelial cells of the CNS and the inner ear have been demonstrated in the serum of a patient with Susac syndrome (57).
Epidemiology
|
• Susac syndrome is rare with over 400 cases reported in the literature. |
Susac syndrome is rare. However, the frequency is underestimated because some cases are not correctly diagnosed and reported. With better awareness of Susac syndrome, cases are being reported worldwide. Compared to the annual incidence of Susac syndrome in Austria of 0.024/100,000, a single-center retrospective study in Israel found a 7-fold greater annual incidence and, based on serological findings, suggested a postinfectious mechanism to explain the significantly higher incidence (131).
There have been over 400 cases reported, including case reports and case series. Among reported cases, 86% had arterial occlusions, which were bilateral in 47%; 75% reported hearing loss; and 68% had some form of encephalopathy. Women are more commonly affected than men by a ratio of 3:1; the age of onset ranges from 9 to 72 years, but young women between the ages of 20 and 40 are most vulnerable (115).
Susac syndrome is rarely diagnosed in Asia, but two cases were reported from China (135), and two cases were reported from Korea (58; 22).
Prevention
No means of primary prevention is available for Susac syndrome.
Differential diagnosis
Confusing conditions
The differential diagnosis of Susac syndrome includes any condition that can cause multifocal neurologic symptoms, visual loss, hearing loss, or any combination of these. Exclusion of neurologic manifestations of systemic disease is an important criterion for diagnosing Susac syndrome.
Susac syndrome is frequently misdiagnosed at initial presentation despite many symptoms or radiological features that are red flags for the diagnosis (121). The varied presentations of Susac syndrome and clinician failure to consider or recognize Susac syndrome are the main factors leading to misdiagnosis (121). Unfortunately, misdiagnosis or delayed diagnosis can lead to unnecessary patient morbidity.
In a retrospective review of the medical records of 32 adult patients from an Australasian cohort of patients with Susac syndrome, 30 (94%) were initially misdiagnosed, with seven (22%) receiving two or more incorrect diagnoses (121). The median time to diagnosis of Susac syndrome was 3 months (range 0.5 to 100 months). The commonest misdiagnoses were migraine (31%), cerebral vasculitis (19%), multiple sclerosis (16%), and stroke (16%). Approximately two thirds (69%) were treated for alternative diagnoses, and about one third (31%) had further clinical manifestations before diagnosis of Susac syndrome. At presentation, 22% met criteria for definite Susac syndrome, 59% for probable Susac syndrome, and 19% for possible Susac syndrome. Diagnostic delay varied with presentation; for example, among patients with the complete triad of symptoms, the median delay to diagnosis was 3 months (range 1 to 9 months) compared to 5.25 months (range 0.5 to 100 months) for patients presenting with encephalopathy and ocular symptoms.
Migraine. Cerebral as well as retinal ischemia may occur in migraine. Because headache is an early symptom of Susac syndrome, it may be confused with migraine, particularly when there are visual scotomata. Infarctions from migraine usually involve larger cerebral vessels and can be distinguished from those in Susac syndrome clinically and by MRI.
Vasculopathies.
Primary angiitis of the CNS. Primary angiitis of the CNS may cause multifocal neurologic deficits with an MRI appearance like that seen in Susac syndrome, but it rarely involves the retinal vessels. Brain biopsy shows a necrotizing vasculitis, something not seen in patients with Susac syndrome.
Temporal arteritis. Temporal arteritis is a disease of the elderly and may cause cerebral and retinal infarctions. Ocular manifestations are due to occlusion of the posterior ciliary arteries rather than the small arteriolar occlusions seen in Susac syndrome. Erythrocyte sedimentation rate is elevated in temporal arteritis, and the diagnosis can be confirmed by biopsy of the temporal artery.
Drug-induced cerebral vasculitis. Drug-induced cerebral vasculitis may occur as an adverse reaction to several therapeutic drugs (or drug abuse) and can result in strokes with multifocal neurologic signs. History of drug intake is often helpful in the evaluation of cases, but a history of drug abuse may also be misleading. For example, a young male drug user who presented with psychosis was initially suspected of having drug-induced CNS vasculitis but was finally diagnosed with Susac syndrome (12). On angiography, cerebral vasculitis characteristically shows intracranial arterial beading (ie, alternating areas of constriction in the intracranial arteries give the appearance of beads strung together).
Takayasu arteritis. Takayasu arteritis tends to afflict younger women; stroke with retinal ischemia may occur but involves medium-sized and larger arteries.
Granulomatosis with polyangiitis (formerly called Wegener granulomatosis). Granulomatosis with polyangiitis is a rare, necrotizing, small-vessel vasculitis that affects various organs. Hallmark features include necrotizing granulomas and pauci-immune vasculitis (ie, associated with minimal evidence of hypersensitivity on immunofluorescent staining for IgG) that most commonly affects the upper respiratory tract, lungs, and kidneys. It may cause stroke, visual loss, and hearing loss due to involvement of the eighth cranial nerve.
Sneddon syndrome. Sneddon syndrome is a rare progressive disorder affecting small- and medium-sized blood vessels, especially of the skin and nervous system. Characteristic findings include episodes of cerebral ischemia and livedo reticularis (ie, a bluish net-like pattern of discoloration surrounding normal-appearing skin). Clinical features may include headache, dizziness, cognitive impairment, memory loss, personality changes, hypertension, and heart disease. The exact cause of Sneddon syndrome is not fully understood.
Systemic lupus erythematosus. Systemic lupus erythematosus can cause cerebral infarction and retinal ischemia. Ophthalmologic findings differ from those in Susac syndrome and consist of ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Two common findings in lupus retinopathy are cotton wool exudates and retinal hemorrhages, neither of which is found in Susac syndrome. Antiphospholipid antibodies are a more common cause of CNS disorder in systemic lupus erythematosus.
CADASIL. CADASIL may have retinal involvement. The pathological feature of the disease is a noninflammatory vasculopathy of the penetrating arteries of the brain with thickening of the arterial wall and deposition of eosinophilic material in the media. CADASIL can be distinguished by its hereditary nature and demonstration of juxtafoveal telangiectasis on fundus examination.
Mitochondrial disorders. MELAS can occur in young women but can be distinguished from Susac syndrome by clinical, radiological, and pathological features. Retinal arteriolar occlusions are absent in MELAS. Patients with Susac syndrome do not show ragged red fibers on muscle biopsy.
Cerebral infarction. Compared to Susac syndrome, cerebral infarction usually involves discrete thromboembolic infarcts in larger arterial territories in the brain. These do not resemble the MRI abnormalities seen in Susac syndrome; however, the MRI appearance of lacunar stroke can resemble that in Susac syndrome, but this tends to occur in older patients with vascular risk factors, such as atherosclerosis and hypertension.
Leukoencephalopathies.
Multiple sclerosis. Some cases of Susac syndrome had the initial diagnosis of multiple sclerosis (137; 03; 103), but hearing loss and retinal arteriolar occlusive disease are not features of multiple sclerosis (103; 41; 121). Susac syndrome is characterized by a neuroimaging triad of white matter lesions, grey matter lesions, and leptomeningeal enhancement on MRI, whereas multiple sclerosis shows only white matter lesions (104). Moreover, MRI lesions in Susac syndrome are usually more numerous and smaller than in multiple sclerosis and occur in deep gray matter, an unlikely location for lesions in multiple sclerosis. Unlike multiple sclerosis, Susac syndrome progresses over a 1- to 2-year period and then goes into remission. Besides the clinical symptoms, Susac syndrome is differentiated from multiple sclerosis by typical radiological features on MRI and branch retinal artery occlusions, which are best evaluated using fluorescein angiography (118).
An atypical presentation may lead to cerebral infarction (83).
Acute disseminated encephalomyelitis. Acute disseminated encephalomyelitis was the initial diagnosis of the first Japanese case of Susac syndrome reported in a 34-year-old man (78). There was no evidence of systemic disease during the first episode. Remission occurred 1 year after symptom onset, and the patient demonstrated all the clinical features associated with Susac syndrome.
Leukoencephalopathy with sensorineural hearing loss. There is a report of a patient with fluctuating sensorineural hearing loss, episodic headache, and white matter stroke due to platelet hypercoagulability (80). No visual symptoms or abnormalities on funduscopic examination were reported in this case. Such cases should be followed up with detailed retinal examination to rule out the possibility of developing Susac syndrome.
Other.
CNS infections. Cogan syndrome is an autoimmune disease characterized by inflammation of the inner ears and the eyes, cochleovestibular symptoms, and loss of vision due to interstitial keratitis. There is rarely retinal vasculitis or CNS involvement, helping to distinguish this syndrome from Susac syndrome.
Primary CNS lymphoma. Primary CNS lymphoma may manifest with multifocal neurologic manifestations and visual loss with multiple MRI lesions. These patients usually have uveitis, a condition that does not occur in Susac syndrome.
Diagnostic workup
Key tests and procedures
|
• Susac syndrome is underdiagnosed. | |
|
• Audiometry, fluorescein angiography, and brain MRI should be performed regardless of the mode of presentation to avoid missing triad components and to provide a baseline to assess progression and response to treatment. | |
|
• The European Susac Consortium has integrated clinical presentation and paraclinical findings into formal criteria to facilitate the diagnosis of Susac syndrome. |
Because many patients do not have the complete triad of encephalopathy, retinal arterial occlusion, and hearing loss at symptom onset and diagnostic delays depend heavily on the presenting manifestations, Susac syndrome is likely underdiagnosed (97). Audiometry, fluorescein angiography, and brain MRI should be performed regardless of the mode of presentation to avoid missing components of the triad and to provide a baseline to assess progression and response to treatment (87); these three tests should be repeated during the first year and periodically for long-term follow-up.
The European Susac Consortium has integrated clinical presentation and paraclinical findings into formal criteria to facilitate the diagnosis of Susac syndrome (62; 132); for a definite diagnosis of Susac syndrome, all subcriteria under the main criteria of involvement of the brain, retina, and vestibulocochlear system must be fulfilled, whereas probable and possible cases fulfill these criteria partially (Table 1).
Table 1. Summary of European Susac Consortium Diagnostic Criteria
|
I. Definite Susac syndrome requires all the following criteria and subcriteria: | ||
|
1. Brain | ||
|
i. New symptoms or clinical findings (ie, cognitive impairment, behavioral changes, focal neurologic symptoms, or headache). | ||
|
ii. Typical findings on cranial MRI--hyperintense, multifocal, round small lesions, at least one of them in the corpus callosum (“snowball”) on T2-weighted (or FLAIR) sequences. | ||
|
2. Retina | ||
|
i. Documented branch retinal artery occlusions or arterial wall hyperfluorescence in fluorescein angiography or characteristic signs of retinal branch ischemia in funduscopy or spectral domain optical coherence tomography (SD-OCT). | ||
|
3. Vestibulocochlear | ||
|
i. New vestibulocochlear symptoms and clinical findings (ie, tinnitus, hearing loss, or peripheral vertigo). | ||
|
ii. Hearing loss or vestibular vertigo is supported by specific investigations of inner ear function (eg, audiogram, electronystagmography or videonystagmography, video head impulse test, auditory brainstem response, vestibular evoked myogenic potentials (VEMPs; both cervical and ocular), or rotary chair testing). | ||
|
II. Probable Susac syndrome meets only two of the three major criteria for definite Susac syndrome. | ||
|
III. Possible Susac syndrome cases show some clinical or paraclinical findings of the Susac triad but do not fulfill the criteria for definite or probable Susac syndrome. Susac syndrome must be included in the differential diagnosis in these cases but should not be considered the most probable diagnosis. | ||
|
| ||
The most important diagnostic procedures for suspected Susac syndrome are neuroimaging with brain MRI, fluorescein angiography, and audiometry.
Neuroimaging. Clinical diagnosis of Susac syndrome is supported by the neuroimaging triad of (1) white matter lesions, (2) gray matter lesions, and (3) leptomeningeal enhancement (32).
-
Focal lesions involving the corpus callosum, periventricular and subcortical white matter, and deep grey matter in man with Susac syndrome (MRI)
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 gan...
-
Focal lesions involving the cerebellum in man with Susac syndrome (transverse MRI)
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 s...
-
Focal lesion involving the corpus callosum in man with Susac syndrome (sagittal MRI)
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 ca...
-
Multiple small white matter lesions in woman with Susac syndrome (FLAIR)
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 i...
-
Hyperintense lesions in periventricular and subcortical areas in Susac syndrome (axial T2 FLAIR)
(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...
-
Hyperintense lesions in subcortical areas in Susac syndrome (sagittal T2 FLAIR)
(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...
On T2-weighted brain MRI, small, multifocal white matter hyperintensities are characteristic (04).
-
Hyperintense white matter lesions with "snowball"-like lesions in the corpus callosum in Susac syndrome (transverse FLAIR)
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 un...
-
Follow-up transverse FLAIR sequence showing improvement of radiological findings in Susac syndrome
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 cau...
The distribution of lesions in the corpus callosum is disease-specific in Susac syndrome and only a few other entities, such as Marchiafava-Bignami disease (38). MRI shows a distinctive pattern of supratentorial white matter lesions that always involve the corpus callosum, often having the appearance of "snowballs" on mid-sagittal T2/FLAIR sequences, and "black holes" on T1-weighted images (117; 131).
-
Hyperintense lesions (“snowballs”) in the corpus callosum in Susac syndrome (sagittal T2 FLAIR)
(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...
Early in the disease, callosal lesions are usually best seen on thin-section sagittal FLAIR and sagittal T1 images with contrast (101).
-
Hyperintense white matter lesions with "snowball"-like lesions in the corpus callosum in Susac syndrome (sagittal FLAIR)
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 unco...
-
Follow-up sagittal FLAIR sequence showing improvement of radiological findings in Susac syndrome
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...
Acutely, lesions may enhance with gadolinium (36).
Multiple small contrast-enhancing lesions in woman with Susac syndrome (MRI)
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...
Central callosal lesions on MRI are specific for Susac syndrome and are considered "diagnostic" of the syndrome (32; 15).
-
Corpus callosum lesions and one lesion with spoke-like morphology in woman with Susac syndrome (MRI)
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. ...
Rapid cystic transformation of callosal lesions can be considered pathognomonic of this condition. Callosal atrophy is a common late manifestation of the callosal lesions.
Serial diffusion-weighted MRI and apparent diffusion coefficient maps may be useful in differentiating Susac syndrome from demyelinating diseases (44; 04).
-
Multiple small lesions exhibiting diffusion restriction in woman with Susac syndrome (DWI)
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, ...
-
Multifocal subacute punctate supratentorial white matter lesions in man with Susac syndrome (MRI)
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 ...
"Iron dot" lesions have been identified in Susac syndrome cases on highly resolving 7T T2*w (T2 star) and quantitative susceptibility mapping (QSM) images in vivo and have been proposed as a promising neuroimaging marker of Susac syndrome (112); the "iron dot" sign was present in 71% (5/7) of the Susac syndrome patients, compared to 0% in controls.
-
Comparison of lesion morphology of “iron dot” lesions in Susac syndrome and multiple sclerosis
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...
The type and severity of encephalopathy in Susac syndrome are much better demonstrated by the impairment of fiber integrity in prefrontal white matter detected by diffusion tensor imaging than by the mostly sparse white matter abnormalities seen on conventional MRI (61).
Cerebral angiography should be considered if vasculitis is suspected.
Ophthalmological examinations. On funduscopy, branch retinal artery occlusions may be evident (36).
Small punctate yellow Gass plaques are almost unique to this disorder, and their characteristic location and color should assist in confirming the diagnosis (34). Funduscopy may also show fluffy white patches corresponding to areas of dye leakage on fluorescein angiography (44).
Fluffy white patches along the inferotemporal arcade in man with Susac syndrome
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 hyperfluo...
Ultra-widefield fundus imaging has been used for both diagnosis and follow-up (106; 15). Widefield and ultra-widefield fundus imaging provides high-resolution details of the central and peripheral damage in Susac syndrome (45; 09; 15).
Abnormalities in fluorescein angiography serve as a valuable biomarker of Susac syndrome, and serial examinations may be useful for monitoring the effect of the treatment and for detection of complications, such as capillary nonperfusion and new vessel formation (59; 94; 131; 09; 15). New leakage on fluorescein angiography is the most sensitive marker of active disease (24); persistent leakage represents unresolved prior damage, whereas new areas of leakage indicate ongoing disease activity that warrants consideration of modifying immunosuppressive therapy (24).
-
Branch retinal artery occlusion in the left eye in Susac syndrome (fluorescein angiography examination) (1)
(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, crea...
-
Branch retinal artery occlusion in the left eye in Susac syndrome (fluorescein angiography examination) (2)
(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, crea...
-
Branch retinal artery occlusion in the left eye in Susac syndrome (fluorescein angiography examination) (3)
(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, crea...
-
Branch retinal artery occlusion in the left eye in Susac syndrome (fluorescein angiography examination) (4)
(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, crea...
Wide field fluorescein angiography may demonstrate peripheral branch retinal artery occlusions and focal arterial leakage.
Right eye peripheral branch artery occlusions and focal arterial leakage in an inferior branch artery in Susac syndrome
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, Aizens...
In the absence of the full clinical triad, arteriolar wall hyperfluorescence on fluorescein angiography in retinal arterioles remote from areas of retinal ischemia is highly specific for and, therefore, strongly supportive of a diagnosis of Susac syndrome (32; 15).
Important ophthalmologic features on retinal angiography include (1) absence of intraocular inflammation, (2) focal, labile, nonperfused retinal arterioles, and (3) integrity of the choroidal circulation (74).
Paracentral acute middle maculopathy on optical coherence tomography is reported in Susac syndrome (52); patients who present with multifocal retinal ischemia and are found to have paracentral acute middle maculopathy should be checked for characteristic MRI lesions and hearing loss.
High-definition optical coherence tomography angiography may show decreased vascular perfusion corresponding to ischemic areas observed on fluorescein angiography as well as an increased foveal avascular zone area in both superficial and deep vascular plexuses (09).
-
Foveal avascular zone enlargement in Susac syndrome (OCT, superficial layer, right eye)
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 ...
-
Foveal avascular zone enlargement in Susac syndrome (OCT, deep layer, right eye)
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 lit...
-
Foveal avascular zone enlargement in Susac syndrome (OCT, superficial layer, left eye)
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 a...
-
Foveal avascular zone enlargement in Susac syndrome (OCT, deep layer, left eye)
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 lite...
Multifocal electroretinography may be useful for assessing subclinical retinal dysfunction after recovery of subjective symptoms of branch retinal artery occlusion in Susac syndrome (124).
Audiovestibular function testing. In a case series of 30 patients with Susac syndrome, a rising configuration of low-frequency worse than high-frequency sensorineural hearing loss was the most characteristic finding on audiological testing (present in 37% of reviewed audiograms), although this pattern can also be seen, for example, in Meniere syndrome (55; 131). Disproportionately poor speech discrimination was identified in 20% of cases, and one case demonstrated a retrocochlear pattern on electrophysiological testing. Hearing loss in Susac syndrome may not recover (113).
Bilateral low- and middle-frequency sensorineural hearing loss in Susac syndrome (audiogram)
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. Creati...
Cervical vestibular evoked myogenic potentials may be absent acutely, with gradual recovery later over a period of months (84; 113).
Video head impulse test results may be abnormal in a minority of patients with Susac syndrome and vertigo (84).
Other studies. Other studies may selectively include the following as well as others appropriate to particular presenting complications:
|
• Complete blood count with coagulation studies. | |
|
• Anti-endothelial cell antibodies, which can be detected in serum samples by indirect immunofluorescence and Western blot studies, may prove to be a biomarker of Susac syndrome, although it is not yet certain if these antibodies are of diagnostic value or a nonspecific epiphenomenon (57; 70). Measurement of anti-endothelial cell antibody titers in the serum, however, may be used to gauge the severity of illness as well as response to therapy (115). | |
|
• Skin biopsies of livedo reticularis and livedo racemosa lesions may reveal the congestion of dermal vessels without inflammation of the vessel walls, thrombi in dermal arterioles with deposition of complement components, endothelial cell swelling, ot perivascular lymphocytic infiltration (122; 44), whereas skin biopsy of a micropapular rash may show nonspecific findings of superficial perivascular lymphocytic infiltration (44). There is no evidence for a procoagulant state or vasculitis (122). | |
|
• Muscle biopsies have also shown swollen endothelial cells, sparse periarteriolar inflammatory cells, and occlusion of endomysial capillaries with deposition of complement components (10; 82; 89; 122). | |
|
• Brain biopsy should be considered if the diagnosis remains in doubt and the patient does not improve with immunosuppressant therapy. |
Management
|
• There are no controlled clinical trials, and anecdotal reports of diverse treatment regimens abound. | |
|
• Corticosteroids are the most frequently used drugs in Susac syndrome and, given orally or intravenously, are recommended as the first-line therapy. | |
|
• Immunosuppressants such as IVIG, mycophenolate mofetil, cyclophosphamide, azathioprine, methotrexate, and rituximab have been given, either alone or in combination, or have been added to corticosteroids to achieve adequate control of disease activity. | |
|
• About 90% of reported cases improve with immunosuppressive therapies, although tapering the corticosteroid dose may result in the development of new signs and symptoms. | |
|
• Therapy is considered inadequate if there are new or enhancing lesions on MRI or new visual field defects and fluorescein angiography shows arterial wall hyperfluorescence remote from branch retinal artery occlusions. | |
|
• Therapy is considered adequate and should be maintained if there are no new or enhancing lesions on MRI or new visual field defects, even if fluorescein angiography shows arterial wall hyperfluorescence remote from branch retinal artery occlusions. | |
|
• Therapy can be stopped or reduced if there are no new or enhancing lesions on MRI and no new visual field defects and if fluorescein angiography shows no arterial wall hyperfluorescence. |
Because of the limited number of patients treated with a wide variety of agents and regimens, it is difficult to recommend a definitive plan of action. There are no controlled clinical trials, and anecdotal reports of diverse treatment regimens abound. Nevertheless, a treatment and monitoring algorithm has been proposed in conjunction with a simplified diagnostic algorithm (15).
Therapy is considered inadequate if there are new or enhancing lesions on MRI or new visual field defects and fluorescein angiography shows arterial wall hyperfluorescence remote from branch retinal artery occlusions (32). Therapy is considered adequate and should be maintained if there are no new or enhancing lesions on MRI and no new visual field defects, even if fluorescein angiography shows arterial wall hyperfluorescence remote from branch retinal artery occlusion (32). Therapy can be stopped or reduced if there are no new or enhancing lesions on MRI and no new visual field defects and if fluorescein angiography shows no arterial wall hyperfluorescence (32).
Corticosteroids and other immunosuppressants. From available case reports and case series, Susac syndrome generally responds well to immunosuppressive therapy when treatment is prompt, aggressive, and sustained. Corticosteroids are the most frequently used drugs in Susac syndrome and, given orally or intravenously, are recommended as the first-line therapy. However, oral prednisolone was considered ineffective in several patients who deteriorated while on this therapy (69; 114). Thus, corticosteroids are often combined with intravenous immunoglobulin (IVIg) or other immunosuppressants, even at the initiation of treatment.
Immunosuppressants, such as mycophenolate mofetil, cyclophosphamide, azathioprine, methotrexate, and rituximab, have been given alone or in combination or have been added to corticosteroids to achieve adequate control of disease activity (85; 42; 100; 101; 30; 63; 73; 44; 68; 91). For example, a 16-year-old girl who presented with Susac syndrome was successfully treated with a complicated multi-immunosuppressant regimen (pulsed prednisone, IVIG, cyclophosphamide, mycophenolate mofetil, and methotrexate) modeled after the treatment of juvenile dermatomyositis, an autoimmune endotheliopathy that causes ischemic injury in a different triad of tissues (ie, muscle, skin, and gastrointestinal tract) (101). In the French CARESS study, about half (53%) of the 36 subjects in the study experienced severe hearing loss that occurred a median of 13 months after diagnosis; the odds of severe hearing loss were significantly lower in patients who received immunosuppressant drugs at diagnosis (91).
One recommended treatment approach for initial treatment of Susac syndrome includes corticosteroids plus IVIg monthly for 6 months (32). For breakthrough disease, add mycophenolate mofetil and/or rituximab (32). For breakthrough disease after adding mycophenolate mofetil and rituximab, add cyclophosphamide (32).
About 90% of reported cases improve with immunosuppressive therapies, although tapering the corticosteroid dose may result in the development of new signs and symptoms.
Some examples will give an idea of the management of this disorder:
Case 1 (17). A 21-year-old female college student developed paresthesias in her fingers, mouth, and lips, followed by fatigue and forgetfulness and was subsequently "giddy and giggly" before developing headache, vomiting, and incoherence. On day 12 of illness, she was admitted with headaches, vomiting, decreased mental alertness, slow thought processing, confusion and disorientation, short-term memory impairment, odd behaviors, impaired insight, decreased executive function (disorganized, not able to take care of her affairs or make good decisions), personality change, emotional lability, apraxia, paresthesias, imbalance, bladder dysfunction, and vertigo but no hearing loss, tinnitus, or convincing visual symptoms. Brain MRI on admission revealed several “snowball” lesions in her corpus callosum, as well as several scattered smaller lesions elsewhere in her white matter.
-
Serial neurologic subscores from self-reported information on the Susac Symptoms (SuSx) Form (1)
(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 At...
-
Serial disease activity scores derived from self-reported information on the Susac Symptoms (SuSx) Form (1)
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 cas...
Case 2 (17). A 14-year-old girl developed headache followed by “slowed thinking,” difficulty verbalizing her thoughts, urinary incontinence, ataxia, fatigue, somnolence, emotional lability, occasional vomiting, right-hand numbness, and left jaw or lateral neck region pain. Admission MRI on day 12 revealed multifocal T1 hypointensity and T2 hyperintensity lesions in the periventricular and supraventricular cerebral white matter and of the corpus callosum. CSF protein was elevated, with a CSF white blood cell count of 5/mm3. Erythrocyte sedimentation rate was normal. On day 13, ophthalmological evaluation revealed a branch retinal artery occlusion in the left eye. On day 15, she was started on aggressive immunosuppression.
-
Susac sydrome admission MRI showing lesions in periventricular and supraventricular cerebral and cerebellar white matter
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:...
-
Serial neurologic subscores from self-reported information on the Susac Symptoms (SuSx) Form (2)
(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 At...
-
Serial disease activity scores derived from self-reported information on the Susac Symptoms (SuSx) Form (2)
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 cas...
After initiation of immunosuppression, she initially improved but then developed an acute and intense relapse at 5 weeks: ataxia and urinary incontinence returned and were accompanied by inability to stand, extremity weakness, muteness, emotional lability, and moderate-severe binaural hearing loss (from which she never recovered). Repeat MRI revealed multiple new diffusely scattered lesions, with restricted diffusion and enhancement, and new diffuse leptomeningeal enhancement. Additional lesions were noted throughout the basal ganglia, thalami, putamen, and anterior limb of the internal capsule. This acute relapse prompted an escalation of immunosuppressive treatment. Her neurologic status slowly but steadily improved during weeks 6 to 21 but then did not significantly improve thereafter. After week 21, she continued to have neurologic deficits, apparently due to damage sustained during the first 5 to 6 weeks of illness. She experienced no further flare-ups of disease activity in the brain, retina, or inner ear but suffered considerable neurologic and cochlear residua.
In summary, she experienced a severe encephalopathy during the first 2 to 3 months of her disease, which was difficult to control despite prompt and aggressive immunosuppression. After 3 months of sustained, aggressive immunosuppression, her active disease subsided, but by this point, she had sustained significant damage despite aggressive treatment during her initial severe and unrelenting encephalopathy.
Case 3 (101). Over a 2-week period, a 16-year-old girl developed incapacitating headaches, recurrent vomiting, visual disturbance ("round, dark black spots"), hearing loss, "roaring" tinnitus, dysarthria, unsteady gait, mild neck stiffness, confusion, emotional lability, personality change, and somnolence. When seen 2 weeks into the course of her illness, her visual acuity was 20/20 in both eyes, but dilated ophthalmologic examination revealed a subtle "cotton wool" spot in her right eye. She had difficulty performing rapid alternating movements, her gait was unsteady, and she had bilateral long tract signs. In addition, formal neuropsychological evaluation revealed a Full Scale IQ of 104 with an estimated pre-morbid IQ of 121. She had poor verbal fluency, mild aphasia, short-term memory impairment, slow processing speed, and executive dysfunction.
Brain MRI showed widespread small hyperintense white matter lesions on T2 and FLAIR in the supratentorial and infratentorial compartments. Several lesions enhanced, and there was marked leptomeningeal enhancement surrounding the cerebral and cerebellar hemispheres. The central corpus callosum was extensively involved.
Similar lesions were present in the basal ganglia. Diffusion-weighted images showed restriction in many of these lesions. The MRI findings were initially misinterpreted as atypical acute disseminated encephalomyelitis or atypical multiple sclerosis.
CSF examination revealed an elevated protein (166 mg/dl), mild lymphocytic pleocytosis (11 WBC/mm3, all lymphocytes), and an elevated myelin basic protein (28.5 ng/ml, with the upper limit of the reference range 4.1 ng/ml). The CSF IgG index was normal, and there were no oligoclonal bands.
Fluorescein retinal angiography showed a resolved branch retinal artery occlusion in the right eye and multifocal arteriolar disease in the retinal periphery. Audiograms showed bilateral, low-frequency sensorineural hearing loss sloping to normal above 2 KHz. Speech discrimination was impaired.
The ophthalmological and audiological findings led to a reinterpretation of the MRI findings, and when coupled with the central location of the corpus callosal lesions, the involvement of the basal ganglia, and the presence of leptomeningeal enhancement, a correct diagnosis of Susac syndrome was made.
She was aggressively treated with a complicated immunosuppressant regimen initially involving high-dose oral prednisone, frequent pulses of methylprednisolone, monthly IVIg, and monthly pulses of intravenous cyclophosphamide.
Within 2 days after treatment initiation, her headache and vomiting resolved, and her encephalopathy began to improve. After receiving six monthly pulses of cyclophosphamide, she was placed on mycophenolate mofetil maintenance therapy; however, she was unable to tolerate mycophenolate mofetil due to malaise and nausea, so pulse cyclophosphamide therapy was resumed.
A repeat neuropsychological evaluation at week 41 revealed a Full Scale IQ of 122, consistent with her expected baseline. Her branch retinal artery occlusion quickly resolved without further visual complaints and without recurrence. Her vision at 41 weeks was 20/20 in both eyes, with only a tiny asymptomatic field defect in the right eye. Her audiogram improved modestly during the first 2 weeks of treatment but did not change afterward. Her tinnitus was initially very distressing during the first 2 months but has since been tolerable. One year after treatment onset, she scored in the 98th percentile on her college entrance examination. A repeat MRI at 60 weeks revealed marked resolution of the previously noted white matter lesions, but her corpus callosum was thinned and showed the typical residual callosal "holes" of Susac syndrome.
Pathognomonic central callosal "holes" (microinfarcts) of Susac syndrome
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 ...
Her immunosuppressant medications were tapered and ultimately discontinued after 2 years of therapy. At her last follow-up at 36 months, she had stable residual hearing loss and mild tinnitus, subtle short-term memory impairment, and mild executive dysfunction. Although much improved from a neurologic perspective, she was struggling emotionally to cope with her impairments.
Intraocular injection of triamcinolone, a long-acting synthetic corticosteroid. A 23-year-old woman presented with sudden visual loss in the left eye along with multiple bilateral occlusions of retinal artery branches shown on fluorescein angiography and other features of Susac syndrome; she received a single intravitreal injection of triamcinolone in the left eye with resolution of visual loss before the start of systemic corticosteroids (134).
Anticoagulants. Anecdotal experience with anticoagulants in Susac syndrome has not been encouraging (with clinical improvement less common than either clinical stabilization or improvement), so anticoagulants are not recommended unless there is evidence of a procoagulant state.
Aspirin. Low doses of aspirin carry little risk of hemorrhagic complications and may be beneficial.
Nimodipine. Nimodipine has been recommended as adjuvant therapy on the presumption that it will have an antivasospastic and neuroprotective effect. However, no significant efficacy has been shown in reported cases in which it was tried.
Tumor necrosis factor inhibitor therapy. A patient with Susac syndrome was reported to improve immediately after treatment with the monoclonal antibody infliximab, which inhibits tumor necrosis factor (53); histological examination of brain lesions in this case as well as two other cases suggested a T cell-mediated inflammatory contribution to lesion pathogenesis and provided a rationale for using infliximab (54). A patient with Susac syndrome who was refractory to a conventionally prescribed combination of immunosuppressive agents (including high-dose corticosteroids, intravenous cyclophosphamide, methotrexate, plasma exchange, rituximab, and mycophenolate) was stabilized with infliximab in combination with a tapering course of low-dose prednisone (37).
A small multicenter retrospective cohort study of five patients diagnosed with Susac syndrome evaluated patient disease activity before and after the introduction of anti-TNF therapy and its value as a steroid-sparing agent (16). All were initially treated with a combination of corticosteroids and classical immunosuppressive drugs. Infliximab was started in three patients and adalimumab in two patients. Anti-TNF treatment reduced relapses of ocular symptoms and enabled the reduction of corticosteroid dosage with complete discontinuation in four patients. Both drugs were well tolerated, and no serious adverse events were reported. Anti-TNF therapy may be a valuable option for treating ocular Susac syndrome and may be considered in those patients unresponsive to conventional immunosuppressive treatment.
Hyperbaric oxygen therapy. In the first report of hyperbaric oxygen therapy for Susac syndrome, there was dramatic posttreatment improvement in visual fields and visual acuity (67). HBOT reduced the visual sequelae in a patient in whom single photon emission computed tomography showed a microangiopathic disorder of the brain (76). In another reported case, HBOT minimized ischemic lesions (26).
Cochlear implantation for hearing loss. Patients with Susac syndrome and significant hearing impairment may benefit from cochlear implantation, either unilaterally or bilaterally (102; 14; 49; 66). Bilateral simultaneous cochlear implantation successfully restored significant hearing in a patient with Susac syndrome (102). A patient with unilateral hearing loss due to Susac syndrome achieved 100% open-set sentence recognition in noise conditions and 92% monosyllable and 68% medial consonant recognition in quiet conditions after 6 months of cochlear implant use (14). In a Susac syndrome patient with unilateral hearing loss, a left cochlear implant was placed, although there was possible involvement of retrocochlear pathways (49). Unilateral cochlear implantation gave good results in a patient with Susac syndrome who presented with the classical triad, including bilateral sensory neural nearing loss, and failed to respond to initial treatment using immunoglobulin and plasmapheresis (66). Within 6 months, he could talk on the telephone and showed satisfying speech recognition without lip reading; within a year, audiometry revealed a pure-tone average threshold of 33 dB and a speech recognition threshold of 100% in open field.
Management of sequelae of Susac syndrome and rehabilitation. Patients with persisting neurologic deficits and psychiatric disturbances require appropriate rehabilitation services (95). Vestibular rehabilitation and hearing aids may be required for patients with persisting cochleovestibular disturbances.
Ocular neovascularization with vitreous hemorrhage can be a late manifestation of occlusive arteriopathy in Susac syndrome and may require panretinal photocoagulation (64).
Special considerations
Pregnancy
Susac syndrome has been reported during pregnancy in several patients, although it is still rare. The course of the disease and outcome of pregnancy depend on coexisting pathology and treatment and vary from normal course to complications. No definitive score or clinical feature can predict the outcome of the disease. Guidelines for treating Susac syndrome in pregnant women are not well established (96).
Examples of good response to therapy during pregnancy. A 35-year-old pregnant patient who presented at 31 weeks with acute bilateral visual loss due to retinal arteritis, as well as acute unilateral hearing loss in combination with cerebral changes detectable by MRI, was diagnosed with Susac syndrome and treated with steroids, resulting in improvement and normal course of the pregnancy (39). A pregnant woman with a 1-month history of behavioral changes and MRI changes diagnostic of Susac syndrome showed a marked and prompt clinical and radiological improvement after treatment with intravenous immunoglobulins (46). Another case of Susac syndrome was successfully managed using intravenous methylprednisolone followed by oral prednisone and intravenous immunoglobulin up to 36 weeks of gestation with minimal disease burden to both the mother and newborn (02).
Induction of premature delivery due to potential toxicity of therapy on the fetus. A 25-year-old woman who presented in the 20th week of pregnancy with Susac syndrome initially received corticosteroids and intravenous immunoglobulin with improvement, but recurrent disease was treated with cyclophosphamide and rituximab after induction of premature delivery at 35 weeks' gestation "to spare the fetus possible toxicity" (27).
Deterioration may occur after delivery. Clinical exacerbation of Susac syndrome occurred immediately following the delivery of a stillborn anencephalic child (25). Another patient deteriorated after delivery of a normal baby and improved after treatment with corticosteroids (69). In a series examining Susac syndrome, three patients had four pregnancies; two needed induced abortions, one was uneventful, and one was complicated with disease flare in the early postpartum period (07).
Anesthesia
A patient with Susac syndrome developed papilledema due to raised intracranial pressure and required anesthesia for brain biopsy (60). The authors administered propofol and instituted mild hyperventilation to reduce intracranial pressure but cautioned that this technique may not be advisable as it can worsen cerebral-retinal-cochlear perfusion in an already existing microangiopathic state. Volatile anesthetics with normocapnia would be desirable in the absence of raised intracranial pressure.
Media
References
- 01
- Agamanolis DP, Klonk C, Bigley K, Rennebohm RM. Neuropathological findings in susac syndrome: an autopsy report. J Neuropathol Exp Neurol 2019;78(6):515-9. PMID 31100145
- 02
- Al-Hasan Y, Hoskin JL, Wolf JC, Kamala S. Susac syndrome and pregnancy. Case Rep Neurol Med 2020;2020:6049126. PMID 33425410
- 03
- Algahtani H, Shirah B, Amin M, Altarazi E, Almarzouki H. Susac syndrome misdiagnosed as multiple sclerosis with exacerbation by interferon beta therapy. Neuroradiol J 2018;31(2):207-12. PMID 28644112
- 04
- 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. PMID 35468771
- 05
- Ammar MJ, Kolomeyer AM, Bhatt N, Tamhankar MA, Mullen MT, Brucker AJ. Recurrent branch retinal artery occlusion from Susac syndrome: case report and review of literature. Retin Cases Brief Rep 2020;14(4):315-20. PMID 29870024
- 06
- Apostolos-Pereira SL, Kara-Jose LB, Marchiori PE, Monteiro ML. Unilateral central retinal artery occlusion as the sole presenting sign of Susac syndrome in a young man: case report. Arq Bras Oftalmol 2013;76(3):192-4. PMID 23929083
- 07
- Aubart-Cohen F, Klein I, Alexandra JF, et al. Long-term outcome in Susac syndrome. Medicine (Baltimore) 2007;86(2):93-102. PMID 17435589
- 08
- Avino JA, Espana E, Peris-Martinez C, Menezo JL. Atypical ophthalmic findings in Susac syndrome. Arch Soc Esp Oftalmol 2007;82(3):179-81. PMID 17357897
- 09
- 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. PMID 33810247
- 10
- Ballard E, Butzer JF, Donders J. Susac's syndrome: neuropsychological characteristics in a young man. Neurology 1996;47(1):266-8. PMID 8710093
- 11
- Barker RA, Anderson JR, Meyer P, Dick DJ, Scolding NJ. Microangiopathy of the brain and retina with hearing loss in a 50-year-old woman: extending the spectrum of Susac's syndrome. J Neurol Neurosurg Psychiatry 1999;66:641-3. PMID 10209178
- 12
- Barrio P, Balcells M, La Puma D, Gaig C. Autoimmune-mediated psychosis: a case of Susac syndrome in a drug user. J Dual Diagn 2017;13(2):133-5. PMID 28368694
- 13
- Betend R, Humm AM, Medlin F. Delirium as presentation of late-onset and relapsing Susac syndrome. BMJ Case Rep 2017;2017. PMID 28784886
- 14
- Bittencourt AG, Santos AF, Goffi-Gomez MV, et al. Microangiopathy of the inner ear, deafness, and cochlear implantation in a patient with Susac syndrome. Acta Otolaryngol 2011;131(10):1123-8. PMID 21736516
- 15
- 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. PMID 37608221
- 16
- Buelens T, Ossewaarde-van Norel J, de Boer JH, et al. Evaluation of tumor necrosis factor inhibitor therapy in Susac syndrome. Retina 2020;40(3):581-90. PMID 30707148
- 17
- 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. PMID 37046335
- 18
- Campbell P, Kaski D, Saifee TA. Susac syndrome presenting with acute hemibody paraesthesia. JRSM Cardiovasc Dis 2019;8:2048004019844687. PMID 31041097
- 19
- Castellanos MM, Teruel C, Davalos A. Susac syndrome: presentation of a new case. Neurologia 1999;14:43-5. PMID 10079693
- 20
- Chawla A, Sathasivam S, Nayar R, Doran M. Susac syndrome in a patient with hepatitis C. J Neuroophthalmol 2007;27(1):55-6. PMID 17414876
- 21
- 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. PMID 19755604
- 22
- Cho HJ, Kim CG, Cho SW, Kim JW. A case of Susac syndrome. Korean J Ophthalmol 2013;27(5):381-3. PMID 24082778
- 23
- Clement P, Conessa C, Dot C, Kossowski M, Flocard F, Poncet JL. Susac syndrome or microangiopathy of the cochlea, brain and retina. Ann Otolaryngol Chir Cervicofac 2003;120:49-53. PMID 24424186
- 24
- Cohen DA, Tajfirouz D, Vodopivec I, et al. Fluorescein angiography findings in Susac syndrome: a multicenter retrospective case series. J Neuroophthalmol 2023;43(4):481-90. PMID 37075250
- 25
- Coppeto JR, Currie JN, Monteiro MLR, Lessell S. A syndrome of arterial-occlusive retinopathy and encephalopathy. Am J Ophthalmol 1984;98:189-202. PMID 6476046
- 26
- Cubillana Herrero JD, Soler Valcarcel A, Albaladejo Devis I, et al. Susac syndrome as a cause of sensorineural hearing loss. [Spanish] Acta Otorrinolaringol Esp 2002;53:379-83. PMID 12185873
- 27
- Deane KD, Tyler KN, Johnson DW, et al. Susac syndrome and pregnancy: disease management. J Clin Rheumatol 2011;17(2):83-8. PMID 21325959
- 28
- Delaney WV, Torrisi PF. Occlusive retinal vascular disease and deafness. Am J Ophthalmol 1976;82:232-6. PMID 949074
- 29
- Dorr J, Krautwald S, Wildemann B, et al. Characteristics of Susac Syndrome: a review of all reported cases. Nat Rev Neurol 2013;9(6):307-16. PMID 23628737
- 30
- Dorr J, Radbruch H, Bock M, et al. Encephalopathy, visual disturbance and hearing loss-recognizing the symptoms of Susac syndrome. Nat Rev Neurol 2009;5(12):683-8. PMID 19953118
- 31
- Egan R. John O. Susac, MD (1940-2012). J Neuroophthalmol 2012;32(3):292. PMID 22878606
- 32
- Egan RA. Diagnostic criteria and treatment algorithm for Susac syndrome. J Neuroophthalmol 2019;39(1):60-7.** PMID 29933288
- 33
- Egan RA, Ha Nguyen T, Gass JD, Rizzo JF 3rd, Tivnan J, Susac JO. Retinal arterial wall plaques in Susac syndrome. Am J Ophthalmol 2003;135:483-6. PMID 12654364
- 34
- Egan RA, Hills WL, Susac JO. Gass plaques and fluorescein leakage in Susac Syndrome. J Neurol Sci 2010;299(1-2):97-100. PMID 20880549
- 35
- Eluvathingal Muttikkal TJ, Vattoth S, Keluth Chavan VN. Susac syndrome in a young child. Pediatr Radiol 2007;37(7):710-3. PMID 17476496
- 36
- 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. PMID 24274741
- 37
- Fernando SL, Boyle T, Smith A, Parratt JDE. The successful use of infliximab in a relapsing case of Susac's syndrome. Case Rep Neurol Med 2020;2020:9317232. PMID 32566335
- 38
- Filippi CG, Cauley KA. Lesions of the corpus callosum and other commissural fibers: diffusion tensor studies. Semin Ultrasound CT MR 2014;35(5):445-58. PMID 25217298
- 39
- Finis D, Stammen J, Gonnermann J. Retinal arteritis in pregnancy. [Article in German] Ophthalmologe 2011;108(7):676-82. PMID 21487713
- 40
- Flammer J, Kaiser H, Haufschild T. Susac syndrome: a vasospastic disorder. Eur J Ophthalmol 2001;11:175-9. PMID 11456021
- 41
- Fonderska P, Tomalka-Kochanowska J, Kochanowski J, Domitrz I. Susac's syndrome diagnostic difficulties: the neurological point of view. Neurol Neurochir Pol 2022;56(2):141-7. PMID 34985117
- 42
- Fox RJ, Costello F, Judkins AR, et al. Treatment of Susac syndrome with gamma globulin and corticosteroids. J Neurol Sci 2006;251(1-2):17-22. PMID 17052732
- 43
- Gass JD, Tiedeman J, Thomas MA. Idiopathic recurrent branch retinal arterial occlusion. Ophthalmology 1986;93:1148-57. PMID 3808626
- 44
- 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. PMID 27234436
- 45
- Giuffre C, Miserocchi E, Marchese A, et al. Widefield OCT angiography and ultra-widefield multimodal imaging of Susac syndrome. Eur J Ophthalmol 2020;30(5):NP41-5. PMID 30968728
- 46
- Gomez-Figueroa E, Garcia-Trejo S, Garcia-Santos RA, Quiñones-Pesqueira G, Calleja-Castillo JM. Exquisite response to intravenous immunoglobulin in Susac syndrome during pregnancy. eNeurologicalSci 2017;10:1-4. PMID 29736421
- 47
- Gordon DL, Hayreh SS, Adams HP. Microangiopathy of the brain, retina, and ear: improvement without immunosuppressive therapy. Stroke 1991;22:933-7. PMID 1853414
- 48
- Greco A, De Virgilio A, Gallo A, et al. Susac's syndrome--pathogenesis, clinical variants and treatment approaches. Autoimmun Rev 2014;13(8):814-21. PMID 24727151
- 49
- Grover N, Whiteside OJ, Ramsden JD. Susac syndrome: outcome of unilateral cochlear implantation. J Laryngol Otol 2011;125(8):856-8. PMID 21481296
- 50
- Grygiel-Gorniak B, Puszczewicz M, Czaplicka E. Neurological, otolaryngological and ophthalmological implications of Susac syndrome - a case report. Eur Rev Med Pharmacol Sci 2016;20(14):3073-7. PMID 27460737
- 51
- Hahn JS, Lannin WC, Sarwal MM. Microangiopathy of brain, retina, and inner ear (Susac's syndrome) in an adolescent female presenting as acute disseminated encephalomyelitis. Pediatrics 2004;114(1):276-81. PMID 15231946
- 52
- Haider AS, Viswanathan D, Williams D, Davies P. Paracentral acute middle maculopathy in Susac syndrome. Retin Cases Brief Rep 2020;14(2):150-6. PMID 29016525
- 53
- Hardy TA, Garsia RJ, Halmagyi GM, et al. Tumour necrosis factor (TNF) inhibitor therapy in Susac's syndrome. J Neurol Sci 2011;302(1-2):126-8. PMID 21167503
- 54
- Hardy TA, O'Brien B, Gerbis N, et al. Brain histopathology in three cases of Susac's syndrome: implications for lesion pathogenesis and treatment. J Neurol Neurosurg Psychiatry 2015;86(5):582-4. PMID 25168394
- 55
- Hardy TA, Taylor RL, Qiu J, et al. The neuro-otology of Susac syndrome. J Neurol 2020;267(12):3711-22. PMID 32696340
- 56
- Jaramillo Velasquez D, Escobar Gómez HD, Cárdenas Angelone PL, Moreno Polit JJ, Vélez Álvarez C. Complete Susac syndrome in a 22-year old male in Colombia: case report and a review of the literature. Arch Soc Esp Oftalmol 2020;95(8):396-9. PMID 32595006
- 57
- Jarius S, Neumayer B, Wandinger KP, Hartmann M, Wildemann B. Anti-endothelial serum antibodies in a patient with Susac's syndrome. J Neurol Sci 2009;285(1–2): 259-61. PMID 19643446
- 58
- Joe SG, Kim JG, Kwon SU, Lee CW, Lim HW, Yoon YH. Recurrent bilateral branch retinal artery occlusion with hearing loss and encephalopathy: the first case report of Susac syndrome in Korea. J Korean Med Sci 2011;26(11):1518-21. PMID 22065912
- 59
- Khan IJ, Allroggen H, Pagliarini S. Susac's syndrome: the value of fundus fluorescein angiography. BMJ Case Rep 2014;2014. PMID 25281252
- 60
- Khandelwal A, Prasad C, Sokhal N, Chaturvedi A. Anesthetic management of a patient with Susac syndrome: a rare neurological disorder. Saudi J Anaesth 2020;14(4):551-2. PMID 33447210
- 61
- Kleffner I, Deppe M, Mohammadi S, et al. Neuroimaging in Susac's syndrome: focus on DTI. J Neurol Sci 2010;299(1-2):92-6. PMID 20850137
- 62
- Kleffner I, Dörr J, Ringelstein M, et al; European Susac Consortium (EuSaC). Diagnostic criteria for Susac syndrome. J Neurol Neurosurg Psychiatry 2016;87(12):1287-95.** PMID 28103199
- 63
- Klein M, Illies T, Georgi S, Rosenkranz T, Terborg C. Aggressive immunotherapy in Susac's syndrome. Nervenarzt 2009;80(12):1502-5. PMID 19888559
- 64
- Kumar K, Jariwala B, Raj P, Agarwal A. Retinal neovascularisation in Susac syndrome: a rare complication. Semin Ophthalmol 2017;32(4):492-5. PMID 27127902
- 65
- Landa G, Marcovich A, Leiba H, Springer A, Bukelman A, Pollack A. Multiple branch retinal arteriolar occlusions associated with smallpox vaccination. J Infect 2006;52(1):e7-9. PMID 15936086
- 66
- Lavinsky L, Scarton F, Lavinsky-Wolff M, Lavinsky J, Motta LH. Successful cochlear implantation in a Susac syndrome patient. Braz J Otorhinolaryngol 2012;78(6):123. PMID 23306580
- 67
- Li HK, Dejean BJ, Tang RA. Reversal of visual loss with hyperbaric oxygen treatment in a patient with Susac syndrome. Ophthalmology 1996;103:2091-8. PMID 9003343
- 68
- London F, Pothalil D, Duprez TP, Sindic CJ. Potential benefits of early aggressive immunotherapy in Susac syndrome. Acta Neurol Belg 2016;116(4):451-60. PMID 26786477
- 69
- MacFadyen DJ, Schneider RJ, Chisholm IA. A syndrome of brain, inner ear and retinal microangiopathy. Can J Neurol Sci 1987;14:315-8. PMID 3311327
- 70
- Magro CM, Poe JC, Lubow M, Susac JO. Susac syndrome: an organ-specific autoimmune endotheliopathy syndrome associated with anti-endothelial cell antibodies. Am J Clin Pathol 2011;136(6):903-12. PMID 22095376
- 71
- Maillart E, Deschamps R, Moulignier A, et al. Susac syndrome: study of five cases. Rev Neurol (Paris) 2009;165(6-7):575-82. PMID 19124141
- 72
- Mala L, Bazard MC, Berrod JP, Wahl D, Raspiller A. Small retinal, cochlear, and cerebral infarctions in the young patient, "SICRET" syndrome of Susac syndrome. J Fr Ophthalmol 1998;21:375-80. PMID 9759431
- 73
- Mallam B, Damato EM, Scolding NJ, Bailey C. Serial retinal fluorescein angiography and immune therapy in Susac's syndrome. J Neurol Sci 2009;285(1-2):230-4. PMID 19577774
- 74
- Martinet N, Fardeau C, Adam R, et al. Fluorescein and indocyanine green angiographies in Susac syndrome. Retina 2007;27(9):1238-42. PMID 18046231
- 75
- Mass M, Bourdette D, Bernstein W, et al. Retinopathy, encephalopathy, deafness associated microangiopathy (the RED M syndrome): three new cases [abstract]. Neurology 1988;38(Suppl):215.
- 76
- Meca-Lallana JE, Martin JJ, Lucas C, et al. Susac syndrome: clinical and diagnostic approach. A new case report. Rev Neurol 1999;29(11):1027-32. PMID 10637864
- 77
- Mike A, Gaal V, Nemeth A, Kover F, Komoly S, Illes Z. Susac syndrome: neurologic, psychiatric, ophthalmologic otorhinolaryngologic and neuroradiologic features of a rare autoimmune disease. Orv Hetil 2007;148(19):897-905. PMID 17478405
- 78
- Murata Y, Inada K, Negi A. Susac syndrome. Am J Ophthalmol 2000;129(5):682-4. PMID 10844072
- 79
- Nicolle MW, McLachlan RS. Microangiopathy with retinopathy, encephalopathy and deafness (RED-M) and systemic features. Semin Arthritis Rheum 1991;21:123-8. PMID 1788549
- 80
- Nobutoki T, Sasaki M, Fukumizu M, et al. Fluctuating hearing loss, episodic headache, and stroke with platelet hyperaggregability: coexistence of auditory neuropathy and cochlear hearing loss. Brain Dev 2006;28(1):55-9. PMID 16168600
- 81
- Obelieniene D, Macaitytė R, Balnytė R, Pėstininkaitė R, Gleiznienė R, Balčiūnienė J. Characteristics of headache in relation to the manifestation of Susac syndrome. Medicina (Kaunas) 2017;53(6):420-5. PMID 29449066
- 82
- O'Halloran HS, Pearson PA, Lee WB, Susac JO, Berger JR. Microangiopathy of the brain, retina, and cochlea (Susac syndrome). A report of five cases and a review of the literature. Ophthalmology 1998;105:1038-44. PMID 9627654
- 83
- Onat Demirci N, Hacımustafaoğlu AM, Kenangil G, Cevher AZ, Demir MK. Susac's syndrome as a rare arterial stroke mimic. Neuroradiol J 2019;32(3):200-2. PMID 30839238
- 84
- Oron Y, Handzel O, Habot-Wilner Z, et al. Vestibular function assessment of Susac syndrome patients by the video head impulse test and cervical vestibular-evoked myogenic potentials. J Vestib Res 2020;30(6):393-9. PMID 33337398
- 85
- Papeix C, Laloum L, Richet A, et al. Susac's syndrome: improvement with combined cyclophosphamide and intravenous immunoglobulin therapy. Rev Neurol (Paris) 2000;156:783-5. PMID 10992124
- 86
- Papo T, Biousse V, Lehoang P, et al. Susac syndrome. Medicine 1998;77:3-11. PMID 9465860
- 87
- Papo T, Klein I, Sacré K, et al. Susac syndrome. [French] Rev Med Interne 2012;33(2):94-8. PMID 22192516
- 88
- Patel VA, Dunklebarger M, Zacharia TT, Isildak H. Otologic manifestations of Susac syndrome. Acta Otorhinolaryngol Ital 2018;38(6):544-53. PMID 30623900
- 89
- Petty GW, Engel AG, Younge BR, et al. Retinocochleocerebral vasculopathy. Medicine 1998;77:12-40. PMID 9465861
- 90
- Petty GW, Matteson EL, Younge BR, et al. Recurrence of Susac syndrome (retinocochleocerebral vasculopathy) after remission of 18 years. Mayo Clin Proc 2001;76:958-60. PMID 11560310
- 91
- Peyre M, Mageau A, Henry Feugeas MC, et al. Risk factors for severe hearing loss in Susac syndrome: A national cohort study. Eur J Neurol 2024;31(5):e16211. PMID 38235955
- 92
- Pfaffenbach DD, Hollenhorst RW. Microangiopathy of retinal arterioles. JAMA 1973;225:480-3. PMID 4740335
- 93
- Postelmans L, Willermain F, Guillaume MP, et al. Retinal arterio-arterial collaterals in SUSAC syndrome. Retina 2008;28(8):1171-3. PMID 18685540
- 94
- Prasad S, Young LH, Bouffard M, Gupta R. Case 37-2018: a 23-year-old woman with vision loss. N Engl J Med 2018;379(22):2152-9.** PMID 30485774
- 95
- Ramey LN, Lopez E, Young T. Rehabilitation of Susac syndrome: a case report. Am J Phys Med Rehabil 2016;95(4):e48-52. PMID 26829078
- 96
- Ramos-Ruperto L, Martínez-Sánchez N, Bartha-Rasero JL, Robles-Marhuenda Á. Susac syndrome and pregnancy: a relationship to clarify. About two cases and review of the literature. J Matern Fetal Neonatal Med 2020;1-6. PMID 31937158
- 97
- Reiniger IW, Thurau S, Haritoglou C, et al. Susac syndrome: case reports and review of the literature. Klin Monatsbl Augenheilkd 2006;223(2):161-7. PMID 16485231
- 98
- Rennebohm R, Daroff RB. In memoriam. John O Susac, MD (1940-2012). Neurology 2012;79(3):211-2. PMID 22988552
- 99
- Rennebohm R, Susac JO, Egan RA, Daroff RB. Susac's Syndrome--update. J Neurol Sci 2010;299(1-2):86-91. PMID 20855088
- 100
- Rennebohm RM, Egan RA, Susac JO. Treatment of Susac's syndrome. Curr Treat Options Neurol 2008a;10(1):67-74. PMID 18325301
- 101
- 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 2008b;6:3. PMID 18230188
- 102
- Roeser MM, Driscoll CL, Shallop JK, Gifford RH, Kasperbauer JL, Gluth MB. Susac syndrome--a report of cochlear implantation and review of otologic manifestations in twenty-three patients. Otol Neurotol 2009;30(1):34-40. PMID 19108037
- 103
- Roskal-Wałek J, Biskup M, Dolecka-Ślusarczyk M, Rosołowska A, Jaroszyński A, Odrobina D. Manifestation of Susac syndrome during interferon beta-1a and glatiramer acetate treatment for misdiagnosed multiple sclerosis: a case report. BMC Ophthalmol 2021;21(1):352. PMID 34592956
- 104
- Roskal-Wałek J, Mackiewicz J, Wypchło Ł, Biskup M, Odrobina D. Susac's syndrome: the crucial role of imaging tests for proper diagnosis. Ann Agric Environ Med 2022;29(2):190-200. PMID 35767750
- 105
- Saliba M, Pelosse B, Momtchilova M, Laroche L. Susac syndrome and ocular manifestation in a 14-year-old girl. J Fr Ophtalmol 2007;30(10):1017-22. PMID 18268443
- 106
- Salvanos P, Moe MC, Utheim TP, Bragadóttir R, Kerty. Ultra-wide-field fundus imaging in the diagnosis and follow-up of Susac syndrome. Retin Cases Brief Rep 2018;12(3):234-9. PMID 27828899
- 107
- Sauma J, Rivera D, Wu A, et al. Susac's syndrome: an update. Br J Ophthalmol 2020;104(9):1190-5.** PMID 32029433
- 108
- Saux A, Niango G, Charif M, et al. Susac's syndrome, a rare, potentially severe or lethal neurological disease. J Neurol Sci 2010;297(1-2):71-3. PMID 20723912
- 109
- Saw VP, Canty PA, Green CM, et al. Susac syndrome: microangiopathy of the retina, cochlea and brain. Clin Exper Ophthalmol 2000;28:373-81. PMID 11097286
- 110
- Schwitter J, Agosti R, Ott P, Kalman A, Waespe W. Small infarctions of cochlear, retinal, and encephalic tissue in young women. Stroke 1992;23:903-7. PMID 1595113
- 111
- Snyers B, Boschi A, De Potter P, Duprez T, Sindic C. Susac syndrome in four male patients. Retina 2006;26(9):1049-55. PMID 17151493
- 112
- 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. PMID 38166655
- 113
- Suman NS, Poovaiah PP, Rangarajan A, et al. Cervical and ocular vestibular evoked myogenic potential recovery in Susac syndrome: a case report. Am J Audiol 2022;31(4):1059-66. PMID 36356212
- 114
- Susac JO. Susac's syndrome: the triad of microangiopathy of the brain and retina with hearing loss in young women. Neurology 1994;44:591-3. PMID 8164809
- 115
- Susac JO, Egan RA, Rennebohm RM, Lubow M. Susac's syndrome: 1975-2005 microangiopathy/autoimmune endotheliopathy. J Neurol Sci 2007;257(1-2):270-2. PMID 17331544
- 116
- Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology 1979;29:313-6. PMID 571975
- 117
- Susac JO, Murtagh FR, Egan RA, et al. MRI findings in Susac's syndrome. Neurology 2003;61(12):1783-7. PMID 14694047
- 118
- Sveinsson O, Kolloch J, Träisk F, Brundin L. Susac syndrome - an unusual syndrome which can be mistaken for multiple sclerosis]. [Article in Swedish] Lakartidningen 2020;117:FSSS. PMID 32045006
- 119
- Szilasiova J, Klimova E. Susac syndrome: retinocochleocerebral vasculopathy. Croat Med J 2004;45(3):338-43. PMID 15185430
- 120
- Timoney I, Flynn A, Leonard N, Wynne B. Livedo racemosa: a cutaneous manifestation of Sneddon's syndrome. BMJ Case Rep 2019;12(11):e232670. PMID 31753828
- 121
- Triplett JD, Qiu J, O'Brien B, et al. Diagnosis, differential diagnosis and misdiagnosis of Susac syndrome. Eur J Neurol 2022;29(6):1771-81. PMID 35262238
- 122
- Turc G, Monnet D, Dupin N, et al. Skin involvement in Susac's syndrome. J Neurol Sci 2011;305(1-2):152-5. PMID 21440909
- 123
- Van Vrekhem T, Miatton M, Hemelsoet D, et al. Cognitive outcomes in Susac syndrome: A 2-year neuropsychological follow-up study. Eur J Neurol 2024;31(4):e16186. PMID 38308420
- 124
- van Winden M, Salu P. Branch retinal artery occlusion with visual field and multifocal ERG in Susac syndrome: a case report. Doc Ophthalmol 2010;121(3):223-9. PMID 20740301
- 125
- Vattoth S, Compton CJ, Roberson GH, Vaphiades MS. Susac syndrome: a differential diagnosis for demyelination. Neurosciences (Riyadh) 2013;18(1):74-8. PMID 23291802
- 126
- Vishnevskia-Dai V, Chapman J, Sheinfeld R, et al. Susac syndrome: clinical characteristics, clinical classification, and long-term prognosis. Medicine (Baltimore) 2016;95(43):e5223. PMID 27787385
- 127
- Vodopivec I, Prasad S. Treatment of Susac syndrome. Curr Treat Options Neurol 2016;18(1):3. PMID 26715396
- 128
- Weidauer H, Tenner A. Hörsturtz beiderseits in Verbindung mit doppelseitigen transitorischen Astarterienverschlüssen des Auges. Z Laryng Rhinol 1973;52:121-8. PMID 4692079
- 129
- Westreich R, Chandrasekhar S. Is Susac syndrome (microangiopathy of the inner ear, retina, and central nervous system) an underdiagnosed cause of sensorineural hearing loss. Ear Nose Throat J 2008;87(7):E4-7. PMID 18633920
- 130
- Wildemann B, Schulin C, Storch-Hagenlocher B, et al. Susac's syndrome: improvement with combined antiplatelet and calcium antagonist therapy [letter]. Stroke 1996;27:149-51. PMID 8553395
- 131
- Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20(1):332. PMID 32878610
- 132
- Wilf-Yarkoni A, Zmira O, Tolkovsky A, et al. Clinical characterization and ancillary tests in Susac syndrome: a systematic review. Neurol Neuroimmunol Neuroinflamm 2024;11(3):e200209. Erratum in: Neurol Neuroimmunol Neuroinflamm 2024;11(3):e200247. PMID 38364193
- 133
- Yang YS, Zhang L, Asdaghi N, Henry CR, Davis JL. Acute macular neuroretinopathy in Susac syndrome: a new association. Retin Cases Brief Rep 2020;14(4):310-4. PMID 29596114
- 134
- Yepez JB, Murati FA, Pettito M, Arevalo JF. Intravitreal triamcinolone in Susac syndrome. Retin Cases Brief Rep 2017;11(3):236-9. PMID 27276498
- 135
- Yu G, Peng GG, Wang L, Dong WW, Deng QM. Susac syndrome: a report of two cases. Zhonghua Nei Ke Za Zhi 2003;42(12):843-6. PMID 14728874
- 136
- Zengin Karahan S, Boz C, Saip S, et al. Susac syndrome: clinical characteristics, diagnostic findings and treatment in 19 cases. Mult Scler Relat Disord 2019;33:94-9. PMID 31176296
- 137
- Zhovtis Ryerson L, Kister I, Snuderl M, Magro C, Bielekova B. Incomplete Susac syndrome exacerbated after natalizumab. Neurol Neuroimmunol Neuroinflamm 2015;2(5):e151. PMID 26445727
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Author
-
Douglas J Lanska MD MS MSPH
Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile
Editor
-
Douglas J Lanska MD MS MSPH
Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile
Former Authors
- K K Jain MD†
- K K Jain MD (original author)
Patient Profile
- Age range of presentation
-
- 13 to 64 years
- Sex preponderance
-
- female>male, >2:1
- Heredity
-
- none
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-10
-
- Retinal vascular occlusion, unspecified: H34.9
- Sensorineural hearing loss, unspecified: H90.5
- ICD-11
-
- Other specified white matter disorders due to vascular abnormality or ischemia: 8A45.2Y
- Retinal vascular occlusions, unspecified: 9B74.Z
This is an article preview.
Start a Free Account
to access the full version.
-
Nearly 3,000 illustrations, including video clips of neurologic disorders.
-
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
-
Full spectrum of neurology in 1,200 comprehensive articles.
-
Listen to MedLink on the go with Audio versions of each article.
Questions or Comment?
MedLink®, LLC
3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122
Toll Free (U.S. + Canada): 800-452-2400
US Number: +1-619-640-4660
Support: service@medlink.com
Editor: editor@medlink.com
ISSN: 2831-9125
Also in This Category
-
-
General Neurology
Hepatic encephalopathy
Oct. 23, 2024
-
General Neurology
Bowel dysfunction in neurologic disorders
Oct. 10, 2024
-
Neuroimmunology
Anti-IgLON5 disease
Oct. 10, 2024
-
General Neurology
Coma due to primary brainstem and diencephalic lesions
Oct. 05, 2024
-
Neuro-Oncology
Anti-LGI1 encephalitis
Oct. 03, 2024
-
Headache & Pain
Headache associated with intracranial neoplasms
Sep. 30, 2024
-
Neuro-Ophthalmology & Neuro-Otology
Giant cell arteritis
Sep. 25, 2024