Susac's syndrome: 1975–2005 microangiopathy/autoimmune endotheliopathy
Introduction
Since first reported in 1979 [1], there have been over a hundred cases of SS reported [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]. This syndrome has protean manifestations and is often misdiagnosed [5]. Misinterpretation of the MRI leads to diagnoses of multiple sclerosis or acute disseminated encephalomyelitis (ADEM). Herpes simplex encephalitis is frequently considered when the patients present with a rather profound encephalopathy that has evolved over a short period of time. The rapid onset of dementia, sometimes associated with myoclonus and seizures, suggests Creutzfeldt–Jakob disease. Headaches are almost always associated with the encephalopathy and may be quite severe and migrainous in nature; when associated with sensory symptoms, a diagnosis of complicated migraine may be made. Occasionally a diagnosis of metastatic cancer is considered because of the headache with the MRI showing enhancement of the leptomeninges and enhancing lesions in the brain. Although the onset is usually subacute, the presentation may be so acute, as to suggest stroke.
Section snippets
MRI findings
Careful interpretation of the MRI with particular attention to the corpus callosum will yield the answer in almost all patients. The corpus callosum is always involved. Although any part of the corpus callosum may be affected, the central portion is preferentially involved [3], [5], [7] with microinfarcts that are typically small but may be large and assume a “snowball” appearance [3]. Occasionally, linear defects (spokes) may extend from the callosal septal surface to the superior margin of
Branch retinal artery occlusions
These corpus callosum lesions should alert the clinician to examine the retina for BRAO. This requires dilation of the pupil, and perhaps sedation; neuro-ophthalmological and retinal consultation is desirable. Fluorescein angiography is useful in evaluating these BRAO, which may be subtle, and may show the distinctive multifocal fluorescence that may be pathognomonic. Gass plaques, which are yellow–white deposits seen at the mid segments of the arteriole, are a helpful finding in making the
Hearing loss
Like the BRAO, the hearing loss may be difficult to evaluate in the encephalopathic patient. Brainstem auditory evoked response may show loss of wave I (cochlear response). A prominent jerk nystagmus with vertigo should alert the clinician to infarction of the membranous labyrinth. Should the patient be cooperative, audiometry shows that the lower tones are first affected; this reflects the vulnerability of the cochlear apex to microinfarction. Occasionally, the hearing loss is acute and may
Laboratory investigations
Despite extensive laboratory investigation, no consistent abnormalities have been found. The erythrocyte sedimentation rate and C-reactive protein may be elevated. Minor elevations of the antinuclear antibody and antiphospholipid antibody are infrequent. A procoagulant state has never been demonstrated. Cerebrospinal fluid examination may show a lymphocytic pleocytosis (less than 20), and the protein is invariably elevated during the encephalopathy. The presence of oligoclonal bands and
Pathology
Cynthia Magro [27] eloquently showed endothelial damages in the precapillary arterioles in a patient at the Susac's Syndrome Symposium held at Ohio State University, April 2005. These changes ranged from mummification to frank necrosis of the endothelial cells. C4d deposition, the hallmark of autoimmune antiendothelial cell antibody syndromes, was present in the endothelium. The pathological findings included pauci inflammatory, perivascular cuffing of the microvasculature with
Treatment
The treatment of SS requires immunosuppression. Steroid therapy is the mainstay of treatment, and is most effective in severe cases, when used in conjunction with IVIG and cyclophosphamide. While there is a natural tendency for the disease to spontaneously improve, there are devastating cases that progress dramatically to severe dementia in a relatively short period of time. In the accompanying paper, we propose a protocol for treating both the encephalopathic presentation, and the BRAO/hearing
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