CASE REPORT Susac's Syndrome: Beneficial Effects of Corticosteroid Therapy in a Japanese Case Kazuhiro Tashima, Eiichiro Uyama, Yoichiro Hashimoto*, Toshiro Yonehara** and Makoto Uchino Abstract Wedescribe the first Japanese patient with Susac's syndrome. The patient showed beneficial responses to high-dose intraveSusac's syndromeis a rare disorder characterized by the nous methylprednisolone and oral prednisone therapy. triad of microangiopathy of the brain and retina with hearing loss. More than 50 affected individuals have been reCase Report ported worldwide, all Caucasians. Weherein identify the first Japanese patient with Susac's syndrome. A 36-year- A 36-year-old Japanese man with a history of bronchial old mandeveloped recurrent subacute encephalopathy, bi- asthma, noted a partial defect in his visual field, followed by a lateral sensorineural hearing loss, and retinal arteriolar non-throbbing headache, nausea, and slight fever. Two weeks occlusions, caused by microangiopathy from a year previ- later, he developed personality changes, his intellectual faculously. T2-weighted MRIshowed multiple high-signal lesions ties declined, and he experienced episodic confusion. He was predominantly in the periventricular white matter. During admitted to Hospital A, where the results of serologic studies, the exacerbated phase both high-dose intravenous methyl- ECG,brain CT, and EEGwere all normal. Soon thereafter, prednisolone and oral prednisone therapy produced ben- symptomssuch as a numbnessin the left hand, and difficulties eficial effects. He showed definite remission within 2 years from the disease onset. (Internal Medicine 40: 135-139, 2001) in speaking and walking developed. Immediately thereafter, he was transferred to Hospital B. A cerebrospinal fluid sample showed 3 lymphocytes/jol under normal pressure, a protein level of 288 mg/dl, Key words: microangiopathy, subacute encephalopathy, reti- nal arterior occlusion, sensorineural hearing loss Introduction and IgG level of 16.4 mg/dl (5.7%). Neither myelin basic protein nor the oligoclonal IgG band were positive. On T2-weighted MRI (1.5 tesla, TR: 2,300, TE: 90), there were multiple high-intensity lesions in the internal capsules, bilateral basal ganglia (Fig. 1A), and periventricular white matter (Fig. IB). These lesions showed nearly iso-intensity on Tl-weighted MRI (TR: 600, TE: 15). Several lesions were slightly enhanced with Gd-DTPAand a tentative diagnosis of Susac's syndromeis a rare sporadic disorder characterized multiple sclerosis was made. Treatment with intravenous (1 g/day for 3 days) was instituted, folby the triad of microangiopathy of the brain and retina with methylprednisolone hearing loss (1, 2). The syndrome predominantly occurs in lowed by oral prednisone (60 mg/day) with standard tapering. young women, with the neurologic features frequently leading Over the subsequent 3 weeks, his consciousness level and motor to a misdiagnosis, such as multiple sclerosis or collagen vas- functions gradually recovered. However, 3 weeks later, he comcular diseases, or it is initially managed as a psychiatric disor- plained of hearing disturbances in both ears, and visual disturder (1, 2). Neither a neuropathologic hallmark such as a dis- bances in the left eye. He was then admitted to Hospital C, ease-specific inclusion, nor a serologic marker has been iden- where ophthalmoscopic examination disclosed bilateral nartified. The pathogenesis of the syndrome and the reason for the rowing of retinal arteries and multiple segmented branch arfemale predominancy are unknown. Patients tend to improve tery occlusions with retinal microinfarcts (Fig. 2). Six months spontaneously with definite remission within 2 years, thus the later, he had a relapse consisting of headache, nausea, time and efficacy of treatment also remains obscure. So far, at least 50 place disorientation, and behavioral changes. High-dose (1 g) cases have been reported from communities around the world intravenous methylprednisolone was administered for 1 day, (1-19), all were Caucasians. followed by oral prednisone (60 mg/day). Soon thereafter, he From the Department of Neurology, KumamotoUniversity School of Medicine, *the Department of Neurology, KumamotoCity Hospital and **the Department of Neurology, Cerebrovascular Center, Saiseikai KumamotoHospital, Kumamoto Received for publication May 1 1, 2000; Accepted for publication August 2, 2000 Reprint 860-0811 requests should be addressed to Dr. Eiichiro Uyama, the Department of Neurology, KumamotoUniversity School of Medicine, 1- 1- 1 Honjo, Kumamoto Internal Medicine Vol. 40, No. 2 (February 2001) 135 c D A B Tashima et al Figure 1. Cranial MRI (1.5 tesla) before corticosteroid treatment. T2-weighted images (TR: 2,300, TE: 90) show multiple highintensity lesions in the internal capsules, the basal ganglia (A) and periventricular white matter (B). These lesions were shown as iso-intensity on enhanced Tl-weighted images (TR: 600, TE: 15) (C, D) and several lesions were enhanced. showed daily improvement, but the condition was exacerbated again 2 weeks later when oral prednisone was tapered to 20 mg/day. He was then transfered to our hospital. On admission, physical examination was normal except for scattered livedo reticularis of the skin. Neurologically, he was 136 alert but disoriented. Recent and remote memorieswere impaired. Visual acuity was 12/200 (corrected to 30/20) on the right side and 2/200 (uncorrected) on the left. There was bilateral sensorineural deafness, increased tendon reflexes and an ataxic gait. Laboratory studies including C-reactive protein, Internal Medicine Vol. 40, No. 2 (February 2001) Susac's Syndrome dB -30| à" Rtair X Ltair C Rtbone 1 1 1 H Ltbone 1 1 1 1 -20 -10 0 10 20 30 40 60 !J 1 \--^ 70 80 ~~^Q-^^sr ^ia e :-JL*-"^ -< l-^== ^^ k-^t 500 2,000 -- -- 90 100 110 Figure 2. Fundus photograph of the left eye shows multiple branch retinal arterial occlusions and ischemic retinal edema in the temporal side. Ratio of diameter; artery : vein=l : 2-3, normal,2: 3. 120 130 125 250 1,000 4,000 8,000Hz Figure 3. Pure-tone audiometry showsbilateral asymmetric senantinuclear antibody, lupus anticardiolipin antibody, rheuma- sorineural hearing loss predominantly in low to moderate fretoid factor, tests for coagulopathy, syphilis, AIDS, and endo- quency tones. crine diseases were all negative. On T2-weighted MRI(TR: 2,200, TE: 90), there were multiple high-intensity lesions similar to that obtained in Hospital B (Fig. 1), but the size and numDiscussion ber of lesions had decreased. An MRangiography and ultrasonographic evaluation for intra- and extra-cerebral vessels showed no abnormal findings. Wedid not perform four- In the present case, the diagnosis of Susac's syndrome was vessel angiography due to an allergy to iodine solutions. Pure- made on the basis of its characteristic triad, MRIfindings, negatone audiometry showedbilateral asymmetric sensorineural tive reference data for other disorders, and a definite remission hearing loss ranging from 30 dB to 80 dB, predominantly in within 2 years. From an epidemiological aspect, this syndrome low to moderate frequency tones (Fig. 3). A recruitment test of is a very rare disorder (1), with all previously reported cases short increment sensitivity index was positive. Bekesy audi- being Caucasians (1-19). A recent review (16), however, indiometry revealed type II pattern on Jerger's classification, indi- cates that this syndromeis more commonthan previously cating cochlear dysfunction. These results and the clinical char- thought. To our knowledge, the present patient is the first conacteristics led us to a diagnosis of Susac's syndrome. In a thera- firmed Japanese case of Susac's syndrome. Internationally, dipeutic trial, we increased the dose of oral prednisone to 60 mg/ agnostic criteria have not been established, howevercharacterday for 2 weeks. Apparent improvement was observed in his istic signs consisting of subacute encephalopathy, sensorineuhigher brain functions such as acalcuria, dressing apraxia for ral hearing loss, and retinal arteriolar occlusions caused by neck tie, and anterograde amnesia, from the second day of this microangiopathy can lead to the diagnosis. As shown in the trial. Oral prednisone therapy was maintained in a range be- present case, the disease is often initially confused with multween 40 mg and 30 mg per day together with diltiazem (200 tiple sclerosis due to the similarity of MRIpatterns and the mg/day) and ticlopidine (300 mg/day). Over several months, presence of exacerbations (2, 14, 16). Hearing loss is usually he apparently recovered. A summaryof the clinical course and bilateral and rather prominent in the low to moderate frequency the effects of treatment are shownin Fig. 4. Although some tones, as was shownin the present case. The impairment might visual deficit, hearing loss, and a slight dullness of mentality be due to microinfarction of the apical turn of the cochlea. remained, he was able to return to an almost normal lifestyle 2 Branch retinal artery occlusions are also invariably bilateral. years after the onset of the disease, and had no relapses in the These mayimpair the vision whenthey involve the posterior following 2 years under a regime of 10 mgper every other day pole but may be asymptomatic if the occlusions occur in the of oral prednisone together with diltiazem (200 mg/day) and more peripheral portion of the retina. In the present case, viticlopidine (300 mg/day). sual loss worsened18 weeks after onset and was persistently Internal Medicine Vol. 40, No. 2 (February 2001) 137 Tashima et al Nicardipine Methylprednisolone 1,000 mg Ticlopidine ^^^^=^ mnná"n«WmXW& _ V i su a l Hearing loss o ___ ss WSS///////////////////////////////////////////Xffl^^ W^^9Z^^^ZWZW^ l j % ^^^^^^. 5 1995 CSFprotein ~~~~~" Cognitive dysfunction 7 593 9 ^^L ll 1 1996 100 140 Figure 4. Clinical course. High-dose intravenous methylprednisolone was effective, present. Varying degrees of headache and of the fnigraine type, or a non-throbbing nature, are recognized as prodromal symptoms. Ten previous brain biopsies (2, 5, 15) showed findings of microinfarctions, or perivascular inflammatory infiltrates of small vessels mimicking active small vessel angitis without fibrinoid necrosis. In addition to histopathologic characteristics, the presence of steroid responsive multiple lesions with enhancement on MRIshare a similar pattern to that of isolated central nervous system angiopathy (20). However, none of the biopsied tissues revealed granulomatous or necrotising inflammation. Further studies are necessary to clarify the pathogenesis of retinocochleocerebral vasculopathy in this syndrome. The syndromehas the nature of a self-limiting course, although therapeutic trials are usually required to prevent exacerbation, and for the purpose of avoiding complicating permanent deficits. To dater hyperbaric oxygen (12, 19), dextran (9), plasmapheresis (10, 1 1), high-doses of intravenous immunoglobulin (10), or various kinds of drugs such as corticosteroid (1, 3, 6, 7, ll, 15, 19), cyclophosphamide (3, 7, 10, ll), warfarin (8), aspirin (8, 9, 13), and nimodipine (13) have been used in treatment. Our review of the literature indicates that early treatment with corticosteroids seems to be the most useful to prevent the progression of the disease. If the patient fails to respond, cyclophosphamide should be tried as an adjunctive """"*" Jk 3 200 76 5 137 70 Month Year mg/dl especially for cognitive dysfunction. Recently, O'Halloran et al, including Susac, recomended intravenous methylprednisone 1 g/day for 3 days followed by prednisone at 80 mg/day with gradual tapering, as the first choice (15). The mechanismof the effect remains obscure, however, we believe that high-dose corticosteroid may immunologically suppress small vessel angitis. Corroboratory results in the present case also indicate the beneficial effects of corti- costeroid therapy in patients with exacerbated phases of Susac's syndrome, which can now be seen as a geographically wide- spread disorder. Clinical features of the present case were reported at the 135th Regional Meeting In Kyushu of the Japanese Society of Neurology, September 28, 1 996, Kagoshima. References 1) Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology 29: 313-316, 1979. 2) Susac JO. Susac's syndrome: the triad of microangiopathy of the brain and 1994. retina with hearing loss in young women. Neurology 44: 591-593, 3) Monteiro MLR, Swanson RA, Coppeto JR, Cuneo RA, DeArmond SJ, Prusiner SB. A microangiopathic syndrome of encephalopathy, hearing loss, and retinal arteriolar occlusions. Neurology 35: 1 1 13-1 121, 1985. 4) MacFadyen DJ, Schneider RJ, Chisholm IA. A syndrome of brain, inner ear and retinal microangiopathy. Can J Neurol Sci 14: 315-318, 1987. 5) Heiskala H, Somer H, Kovanen J, Poutiainen E, Karli H, Haltia M. Microangiopathy with encephalopathy, hearing loss and retinal arteriolar agent. Other treatments seem to be less effective. 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