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Background: Blood–brain barrier dysfunction in active multiple sclerosis (MS) lesions leads to pathological changes of cerebrospinal fluid (CSF). Theoretically, CSF analyses could help to predict relapse recovery and the course of disability. In this monocentric study, we investigated the impact of CSF findings assessed during the first relapse of MS on the short-term course of disability. Methods: We performed a retrospective observational study including MS patients with available CSF data after onset of first MS relapse. Clinical symptoms had to be accompanied by gadolinium-enhanced lesion on magnetic resonance imaging. Expanded Disability Status Scale (EDSS) assessments at timepoint of relapse and after relapse recovery were studied to analyze disability. A two-step multivariate linear regression analysis adjusted for EDSS at spinal tab, duration of symptoms, sex, time until post relapse EDSS assessment, immunotherapy post relapse, and relapse treatment with glucocorticoids/plasma exchange to predict relapse associated disability was run. Results: In the first step of the regression model, pathological albumin quotient (QAlb) [regression coefficient 0.50, 95% confidence interval (CI) (0.07–0.92), p = 0.02, n = 99] and CSF protein concentration [regression coefficient 0.84, 95% CI (0.33–1.35), p = 0.001, n = 99] predicted EDSS after relapse recovery. In the second step, the sum score of both predictors [range 0–2; n per value: 0 ( n = 73), 1 ( n = 10), 2 ( n = 15)] confirmed the negative impact on course of disability after relapse [regression coefficient 0.38, 95% CI (0.13–0.62), p = 0.003, n = 98]. In this final multivariate linear regression model ( p 2 0.34), also EDSS at lumbar puncture [regression coefficient 0.58, 95% CI (0.35–0.81), p Discussion: Our study conducted in MS patients during first relapse confirmed that both increased CSF protein concentration and pathological QAlb have a negative impact on EDSS after relapse. As secondary finding, we identified time from symptom onset to lumbar puncture as predictor of disability recovery after relapse.

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of highly active relapsing-remitting multiple sclerosis (MS). The principal adverse effect is the development of secondary autoimmune disorders during the immune reconstitution period after alemtuzumab, with autoimmune thyroid disease (AITD) being the most common. To define the type, timing and course of AITD after alemtuzumab treatment for MS we analyzed clinical and serologic data from 31 patients (follow-up range 8 to 58 months). Hashimoto thyroiditis (HT) with positive anti-TPO and/or anti-Tg antibodies was present at baseline in four patients. Of note, one of them 13 months after the first dose developed mild hyperthyroidism [stimulating TRAbs: 1,8U/L, normal range:40 U/L) as well as anti-Tg antibodies. Seven cases of HT with positive anti-TPO/anti-Tg antibodies were documented, of which one developed hypothyroidism. During follow-up, two successful pregnancies were recorded. The first, a 32-year-old woman, developed HT with hypothyroidism 12 months after the first cycle of alemtuzumab and gave birth to a healthy boy 22 months following last dose. The second, a 31-year-old woman, developed GD hyperthyroidism during the first trimester of pregnancy and was started on PTU that was stopped in the beginning of the second trimester. TRAbs titer declined and a healthy girl was delivered. Contrary to published literature, we recorded frequent occurrence of GD with fluctuating and unpredictable course requiring block and replace ATD regimen. This is suggestive of alternating stimulating and inhibitory TRAbs, while further studies are needed to understand the underlying mechanisms responsible for Th1-Th2 balance and cytokine pathways towards AITD. Pretreatment screening and careful follow-up allow for early diagnosis and treatment. Finally, concerning future pregnancies post-alemtuzumab it is important to address the risk for secondary AITD in women of childbearing age in conjunction with their treating obstetrician.

Neurotrophins are well known for their physiological role as key modulators of neuronal survival, neurite out-growth, and synaptic connectivity during development and into adulthood. Moreover, neurotrophins are potent agents, ameliorating neuronal degeneration in many model systems for neurological diseases. However, a causal role for mutations in neurotrophins or neurotrophin receptors in human neurodegenerative diseases has been largely lacking. As neurotrophin receptors are located at synapses and as their signaling involves the neuronal nucleus, they need to bridge tantalizing distances in order to retrogradely communicate their survival signals. On the other hand, anterogradely transported neurotrophins are released at the synapse and act on postsynaptic cells. Antero- and retrograde signaling and trafficking is an emerging focus of interest in neurotrophin research. Some neurodegenerative diseases are known to affect transport of organelles. Thus, it appears likely that neurodegeneration could be caused by "indirect" effects on neurotrophin trafficking and, hence, signaling. In this review we summarize recent work on neurotrophins in neurodegenerative diseases with special focus on possible implications of disturbed trafficking of organelles and retrograde axonal signaling.

Neuronal survival is dependent on continuous trophic stimulation by neurotrophic factors. Anterograde and retrograde transport of neurotrophic factors and their receptors within neurites is essential for the communication of these survival signals. Lack of neurotrophic input has been proposed as a pathomechanism leading to neurodegenerative disease. The present short review provides a summary of some of the recent data on neurotrophic factors in neurodegenerative disorders and describes how disturbances of axonal trafficking might deprive neurons from trophic input.

Introduction Differential diagnosis of a cerebral lesion can prove to be a very challenging task for the treating physician. Many non-neoplastic neurological diseases can mimic brain neoplasms on neuroimaging. Case presentation A previously healthy 23-year-old male, presented with blurred vision to the Emergency Department of our Hospital. After initial clinical and serological examination, he was admitted to our clinic for further investigation. Neurological examination showed left homonymous hemianopsia. Brain MRI revealed edema of the right parietal lobe, compressing the posterior region of the right ventricle. Serum viral, immunological and paraneoplasmatic testing were negative. Spectroscopic MRI described the lesions as tumefactive demyelinated plaques. After treating the patient with intravenous corticosteroids, his symptoms rapidly improved and the extensive lesion of the parietal lobe decreased. Conclusion In case of young patients with tumor-like lesions, demyelination should always be considered in the differential diagnosis.