Long-term outcome in Susac syndrome.

Susac syndrome is characterized by the clinical triad of encephalopathy, hearing loss, and retinal artery branch occlusions, mostly in young women. To our knowledge, long-term outcome and impact of pregnancy have not been specifically addressed. We report a series of 9 patients (7 female, 2 male) followed at the same institution, with special emphasis on clinical outcome including pregnancy and long-term sequelae. Clinical, brain magnetic resonance imaging (MRI), funduscopy, retinal angiography, and audiogram data were recorded every 3-12 months. We also analyzed the 92 previously reported cases of Susac syndrome. Mean follow-up was 6.4 years. Age at onset was 30.4 years. The first symptom occurred between April and September in 7 of 9 patients in the current study, and in 68% of all patients. The complete triad at onset was clinically obvious in only 1 of 9 patients. Brain involvement was heralded by headache and symptoms of encephalopathy. Cerebrospinal fluid was abnormal in 5 patients showing pleocytosis (mean, 24.6; range, 6-85 cells/mL) and elevated protein level (mean, 210; range, 113-365 mg/dL). Over time, quantitative brain MRI analysis showed that the number of lesions diminished and did not parallel clinical flares, and MRI never normalized. At the end of follow-up, no patient had severe impairment, and all but 1 returned to work. Inner ear involvement was present at onset in 2 patients and occurred in others with a mean delay of 11 months. Initially unilateral in 3, it became bilateral in all. Mean hearing loss was 34 dB (range, 15-70 dB). Hearing loss never improved, either spontaneously or under treatment. The eye was involved at onset in 8 patients, and after 3 years in 1. All had multiple bilateral retinal artery branch occlusions and/or dye leakage with hyperfluorescence of the arterial wall on fluorescein angiography. Over time, angiography normalized in 3 patients. In others, it was still abnormal at the end of follow-up (range, 1.5-10 yr). On late findings, fluorescein leakage was more frequent than true arterial occlusion. Eye involvement was mostly asymptomatic, unilateral, peripheral, and resumed spontaneously to remit in other sites over time. Corticosteroids were efficient to treat encephalopathy, with relapses occurring when the dosage was tapered. Steroid treatment did not improve hearing loss or prevent new retinal arteriolar occlusions. Anticoagulation had a role in treating encephalopathy and retinal arteriolar occlusions. Three patients had 4 pregnancies. Two pregnancies needed induced abortion. One pregnancy was uneventful. One pregnancy was complicated with Susac disease flare in the early postpartum period. In conclusion, at the end of follow-up, most patients had returned to work and none had severe impairment. Pregnancy may affect the course of Susac syndrome, with relapse of encephalopathy postpartum. Our main finding was that the course of Susac syndrome is not self-limited as previously thought, since isolated retinal arteriolar involvement may occur as a very late manifestation.

Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

BACKGROUND: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. RESULTS: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients. INTERPRETATION: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.