[Susac Syndrome: A Diagnostic Chameleon]. / Susac-Syndrom: ein diagnostisches Chamäleon.

Susac's syndrome (SuS) is a rare, probably autoimmune endotheliopathy of the central nervous system, retina and inner ear. It is characterized by a clinical triad of encephalopathy, branch retinal artery occlusions (BRAOs) and sensorineural hearing loss. To date, more than 300 cases of SuS have been reported in the literature. However, SuS remains an under- and misdiagnosed entity in the clinical setting. This report presents an exemplary case of a patient, who was initially misdiagnosed with relapsing-remitting multiple sclerosis. At initial presentation, the patient did not demonstrate the complete clinical triad, and the interval between symptom onset and diagnosis was 4 months. Typical diagnostic features, which enabled the diagnosis of SuS were: a) MRI findings with T2-hyperintense snowball-like lesions of the corpus callosum and subcortical white matter and hyperintense lesions in diffusionweighted imaging with reduced apparent diffusion coefficient; b) BRAOs and vessel wall hyperfluorescence in fluorescein angiography and a significant thickness reduction of the inner retinal layers in optical coherence tomography; c) bilateral sensorineural hearing loss. The patient was aggressively treated with cyclophosphamide, rituximab, glucocorticoids and acetylsalicylic acid with a good response to therapy. This report draws attention to the need to take SuS into consideration in the differential diagnosis at the interface of neurological, psychiatric, ophthalmological and otorhinolaryngological disorders. As SuS may result in severe and persistent neurological deficits, an interdisciplinary collaboration is fundamental for the prompt diagnosis and initiation of adequate immunosuppressive treatment.

Recurrent ischaemic cerebrovascular events as presenting manifestations of myeloproliferative neoplasms.

BACKGROUND AND PURPOSE: Myeloproliferative neoplasms (MPNs) - polycythemia vera, essential thrombocythemia and primary myelofibrosis - are associated with increased risk for ischaemic cerebrovascular events (ICVEs). Due to their low prevalence, MPNs often remain undiagnosed as the cause of ICVEs. METHODS: Case records at the University of Tübingen between 2014 and 2017 were screened to identify patients with MPN-related ICVEs. Clinical features, brain imaging, laboratory findings, applied treatments and neurological outcomes were assessed. RESULTS: In all, 3318 patients with ICVEs were identified, and amongst them 17 patients with MPN-related ICVEs were included in a retrospective study. In 58% of these patients, ICVEs were the first manifestation of the underlying MPN; 24% presented with transient ischaemic attack and 76% with ischaemic stroke. Potentially concurrent ICVE etiologies were noted in 70% of the patients. The majority (94%) of patients were positive for the JAK2 V617F mutation, whilst in 29% recurrent ICVEs (range two to three) were noted prior to MPN diagnosis. Early MPN diagnosis and management was the only significant prognostic factor for ICVE recurrence (P < 0.001). DISCUSSION: Evidence is provided that, although rare, MPNs represent an underdiagnosed cause of recurrent ICVEs. High clinical awareness is warranted to identify an underlying MPN in patients presenting with sustained, abnormal blood count findings. Clinical algorithms for prompt MPN diagnosis and initiation of MPN treatment (e.g. cytoreductive therapy, phlebotomy) are required. As MPN management comprises a significant protective factor against ICVE recurrence, induction of MPN treatment should be regarded as an integral component of secondary stroke prevention in MPN-associated ICVEs.

Central and peripheral nervous system immune-mediated demyelinating disease after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: We aimed to evaluate clinical and diagnostic features of central and peripheral immune-mediated demyelinating disease (CPID) in allogeneic hematopoietic stem cell transplantation (aHSCT) recipients. BACKGROUND: CPID refers to the late-onset, immune-mediated neurological complications following aHSCT, when other frequent differential diagnoses have been ruled out, and when symptoms and signs of systemic GvHD manifestations are absent. METHODS: Case records at the University of Tuebingen, between 2001 and 2015, were screened to identify patients with CPID after aHSCT. RESULTS: Seven patients who developed CPID after aHSCT were identified. The average time interval from aHSCT until onset of CPID was 2.6 (±2.8) years (mean±SD). The most prevalent manifestations of CPID were optic neuritis and/or myelitis and polyneuropathy. Cerebrospinal fluid analyses involved elevated protein concentration and lymphocytic pleocytosis, while oligoclonal bands in CSF, but not in serum, were detected in 28% of cases. Aquaporin-4-antibodies were consistently absent. MRI studies showed features suggestive of demyelination processes, with cerebral and/or spinal cord white-matter involvement, and features compatible with cerebral vasculitis. Corticosteroids, Immunoglobulins, Cyclophosphamide, Rituximab and Interferon beta-1a showed marginal treatment responses, whereas plasma exchange resulted in marked clinical improvement in two treated patients. A chronic disease-course with persisting neurological deficits was prevalent. CONCLUSIONS: CPID may comprise a rare complication of aHSCT, which manifests as optic neuritis and/or myelitis and is accompanied by sensorimotor polyneuropathy. A concomitant systemic manifestation of GvHD is not mandatory for CPID diagnosis. Usually, CPID exhibits a chronic, persisting disease course. Thus, clinical awareness is required, as early diagnosis and aggressive treatment may be prognostically advantageous.

A case of late-onset, thymoma-associated myasthenia gravis with ryanodine receptor and titin antibodies and concomitant granulomatous myositis.

BACKGROUND: Myasthenia gravis is an autoimmune neuromuscular disorder, which has only rarely been reported to co-manifest with myositis. The diagnosis of concomitant myositis in patients with myasthenia gravis is clinically challenging, and requires targeted investigations for the differential diagnosis, including EMG, autoantibody assays, muscle biopsy and, importantly, imaging of the mediastinum for thymoma screening. CASE PRESENTATION: This report presents a case-vignette of a 72-year-old woman with progressive proximal muscle weakness and myalgias, diagnosed with thymoma-associated myasthenia and bioptically verified granulomatous myositis, with positive autoantibody status for ryanodine receptor and titin antibodies. CONCLUSIONS: The diagnosis of concurrent myositis and myasthenia gravis, especially in the presence of ryanodine receptor and titin antibodies, should lead neurologists to adopt different treatment strategies compared to those applied in myasthenia or myositis alone. Moreover, further evidence is warranted that titin and, particularly, ryanodine receptor antibodies may co-occur or be pathophysiologically involved in myasthenia-myositis cases.