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Despite recent progress in the field of genetics, sporadic late-onset ( 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations.We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations.We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p 0.01).Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

Emotional disorders in multiple sclerosis (MS) are frequently described as difficulties in recognizing facial expressions, rarely in the experience dimension. Moreover, interaction between emotional disorders and cognitive or psychological disorders remains little documented. The aim of this study is to explore emotions in MS in emotion recognition and emotional experience and compare these data with cognitive, psychological, and disease aspects. Twenty-five women with MS (MS group) and 27 healthy controls (control group) matched for age, sex, and education were assessed for emotion recognition (Florida Affect Battery) and emotional experience (International Affective Picture System Photographs). Participants were also assessed for cognitive and psychological aspects. Compared to the control group, the MS group had more difficulty in recognizing emotions, and their subjective evaluations when presented IAPS pictures were more scattered, globally increased. Emotional dimensions were each correlated with executive functions but neither correlated with alexithymia, depression, anxiety, or MS characteristics. In conclusion, MS patients present difficulties in identifying emotion and their emotional experience appears to be increased. These disorders are correlated with cognition but remain independent of psychological or disease aspects. Considering the implications that emotional disorders may have, it seems essential to take these aspects into account in clinical practice.

Resume Objectif La syphilis est en pleine recrudescence depuis les annees 2000 et la neurosyphilis constitue une manifestation rare de cette infection sexuellement transmissible dont nous avons voulu evaluer les caracteristiques. Materiels et methodes Etude retrospective de 2004 a 2014 de tous les cas de neurosyphilis codes dans le PMSI des hopitaux universitaires de Strasbourg. Nous avons inclus et analyse le cas de 13 patients hospitalises pendant cette periode et repondant aux criteres diagnostiques de la neurosyphilis. Resultats Neuf patients sur 13 presentaient une atteinte ophtalmologique isolee, 3 (23,1 %) avaient une uveite posterieure, 2 (15,4 %) une panuveite et 4, une papillite (30,8 %). Cinq sur 13 (38,5 %) etaient seropositifs pour le VIH et 3/5 (60 %) avaient plus de 400 lymphocytes T CD4 + /mm 3 au moment du diagnostic de neurosyphilis. Enfin, tous les patients ont beneficie d’un traitement par penicilline ou cephalosporine par voie parenterale et 5/13 (38,5 %) d’une corticotherapie systemique. Conclusion Cette etude revele l’importance des manifestations ophtalmologiques dans la neurosyphilis dont elle constitue la principale manifestation au sein de cette cohorte de patients.

Background Emotional disturbances in multiple sclerosis (MS) are often explored in terms of affect recognition, with controversial results that likely reflect the high lesional heterogeneity. Patients' emotional experience, however, has seldom been studied and has never been explored using fMRI. Objectives To explore the emotional experience in MS and compare these data with fMRI measurements using for the first time real-life emotional scenes differing in valence and arousal. Methods Twenty-five right-handed women with relapsing-remitting MS and 27 right-handed age-, sex-, and education-matched healthy controls visualized during an fMRI session, emotional scenes taken from the international affect picture system (IAPS) and differing in valence (positive, negative, neutral) and arousal (ranging from calm to excited). During a post-scanning debriefing, participants were asked to look again at each image and score it in terms of valence and arousal sensation on a scale of 1–9. Results Cognitively well-preserved MS subjects presented a significantly more scattered emotional experience compared to controls in response to positive and negative pictures. In fMRI, MS patients also presented a higher variability of response when compared to controls in left inferior orbitofrontal cortex for positive stimulations. For negative condition, no significant results were observed between the two groups. However, a trend was detected in left amygdala, right fusiform gyrus, right caudate nucleus and right pallidum for negative stimulations. Conclusion In response to emotional stimuli, MS subjects presented a scattered emotional experience subtended by a greater variability of brain response, highlighting an emotional pattern not previously reported in MS patients.

Background and purpose Anti-β2-glycoprotein I (anti-β2-GPI) antibodies are part of the heterogeneous family of antiphospholipid antibodies and seem to be present in various neurological manifestations in addition to antiphospholipid syndrome (APS). Our objective was to analyse the clinical, radiological and therapeutic characteristics of neurological patients with positive anti-β2-GPI antibodies and without the Sapporo criteria for APS. Methods The medical records were retrospectively reviewed of 28 consecutive patients hospitalized in the Neurology Department of Strasbourg University Hospital, France, in whom anti-β2-GPI antibodies (immunoglobulin G and/or immunoglobulin M) were positive and other antiphospholipid antibodies negative, from November 2005 to July 2011. Clinical, radiological, biological and therapeutic data and clinical course were studied. Results Positive anti-β2-GPI antibodies were present in 28 patients. The predominant physiopathological process was mainly inflammatory (25% with myelitis, 14.3% with optic neuritis) or vascular (14.3% with cerebral ischaemia, 7.1% with cerebral vasculitis). Brain magnetic resonance imaging was performed in 89.3% of patients: atypical lesions were observed in 44% and typical inflammatory and vascular lesions in 16% and 12%, respectively. Conclusion The anti-β2-GPI antibody seems to be involved in two types of neurological disease: vascular or inflammatory ‘multiple sclerosis-like’ disease. These two types of patients frequently develop an autoimmune disease (multiple sclerosis, systemic lupus erythematosus, APS). However, a large proportion of the patients had an undefined profile with aspecific cerebral lesions and required monitoring. This study raises questions about a separate entity at the border between APS and multiple sclerosis which remains to be better defined in a larger cohort.

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS), two inflammatory demyelinating diseases, are characterized by different therapeutic strategies. Currently, the only biological diagnostic tool available to distinguish NMO from MS is the specific serum autoantibody that targets aquaporin 4, but its sensitivity is low.Objective:To assess the diagnostic accuracy of metabolomic biomarker profiles in these two neurological conditions, compared to control patients.Methods:We acquired serum spectra (47 MS, 44 NMO and 42 controls) using proton nuclear magnetic resonance (1H-NMR) spectroscopy. We used multivariate pattern recognition analysis to identify disease-specific metabolic profiles.Results:The1H-NMR spectroscopic analysis evidenced two metabolites, originating probably from astrocytes, scyllo-inositol and acetate, as promising serum biomarkers of MS and NMO, respectively. In 87.8% of MS patients, scyllo-inositol increased 0.15 to 3-fold, compared to controls and in 74.3% of NMO patients, acetate increased 0.4 to 7-fold, compared to controls. Using these two metabolites simultaneously, we can discriminate MS versus NMO patients (sensitivity, 94.3%; specificity, 90.2%).Conclusion:This study demonstrates the potential of1H-NMR spectroscopy of serum as a novel, promising analytical tool to discriminate populations of patients affected by NMO or MS.

After a decade of constant decline, the number of syphilis cases has been steadily increasing since the 2000s, particularly in HIV infected patients. Neurosyphilis is a rare manifestation of this sexually transmitted disease for which we performed a retrospective study and analyzed clinical manifestations.We reviewed retrospectively all the neurosyphilis cases admitted to Strasbourg University Hospital between 2004 and 2014. We included and analyzed 13 patients admitted during this period who met the diagnostic criteria for neurosyphilis.Nine of 13 patients had isolated visual manifestations; three (23.1%) experienced posterior uveitis, two (15.4%), panuveitis, and 4 (30.8%) had papillitis. Out of five patients (38.5%) who were HIV positive, three (60%) had a CD4 cell count above 400/mmOphthalmologists appear as key players in the identification, management and follow-up of neurosyphilis, since ocular findings are key diagnostic features in these patients.

Background: The burden of multiple sclerosis (MS) includes fatigue, depression and worsening of health-related quality of life (HRQOL). These changes have not been yet measured in neuromyelitis optica (NMO). Our aim was to assess the HRQOL, fatigue and depression in NMO. Methods: We administered French validated self-questionnaires on HRQOL (SEP-59), fatigue (EMIF-SEP) and depression (EHD) to 40 patients followed up in two centres. We assessed the relationship of these parameters with gender, age, disability, disease duration, visual acuity and NMO-antibody status and also compared our results with equivalent data in MS and normal subjects derived from previous studies. Results: Health-related quality of life scores were lower (P

Le neurologue pratiquant l’electroneuromyogramme (ENMG) est frequemment confronte dans sa pratique a des patients souffrant d’une atrophie des muscles de la main. Cette anomalie peut etre le premier signe de nombreuses pathologies, notamment une lesion focale (du nerf ulnaire ou median, du plexus brachial, de la racine C8–T1 voire d’une atteinte de la moelle) ou du debut d’une pathologie plus generale (sclerose laterale amyotrophique, neuropathie motrice multifocale voire pathologie genetique). Au cours de cet atelier, nous allons etudier quels elements cliniques et ENMG seront pertinents pour orienter la recherche etiologique. Au niveau clinique, nous nous interesserons notamment a la repartition de l’atrophie dans le territoire ulnaire ou median (ou les deux), la presence de douleurs et d’hypoesthesie dans le meme territoire et d’un deficit moteur a distance de la main. Au niveau ENMG, il sera important de rechercher une demyelinisation focale du nerf ulnaire au coude ou au canal de Guyon et du nerf median au canal carpien ou dans sa partie plus proximale. Les anomalies des potentiels sensitifs des memes nerfs orienteront vers une atteinte tronculaire ou plexuelle et celle du nerf cutane medial de l’avant-bras sera un argument pour une atteinte plexuelle. La denervation des muscles paravertebraux C8–T1 orientera au contraire vers une lesion radiculaire ou de la corne anterieure. Les anomalies dans les autres membres plaideront pour une maladie plus diffuse. Nous discuterons au cours de l’atelier les differents pieges qui peuvent perturber l’interpretation de l’ENMG ou indices qui peuvent l’aider.

Background Foreign accent syndrome (FAS) consists of a speech rhythm disorder different from dysarthia or aphasia. It is unusually met in multiple sclerosis (MS). Objective We report a case of FAS as an initial symptom of a MS. Methods A right-handed French woman developed an isolated German foreign accent. Brain magnetic resonance imaging (MRI), SPECT and analysis of CSF were performed. Results Brain MRI revealed a large hypersignal on T2-weighted images in the left prerolandic white matter. Single photon emission computed tomography showed a right prerolandic hypoperfusion. Unmatched oligoclonal bands in cerebrospinal fluid and occurrence of new abnormal hypersignals on the following MRI led us to diagnose MS. Conclusion FAS may be the first symptom of MS. It could result from extensive disturbances of brain function involving the right hemisphere.

A serial assessment of biomarkers related to disease activity could be clinically useful in some autoimmune diseases. Neuromyelitis optica (NMO) is a severe inflammatory disease of the optic nerves and spinal cord that can be associated with lupus erythematosus, Sjögren syndrome or myasthenia gravis. In this review, we discuss the existing data on the use of biomarkers of disease activity in NMO. A specific and pathogenic antibody (Ab) directed against aquaporin 4 (AQP4) was recently discovered in this disease. The relapses were frequently accompanied by a rise and immunosuppressive therapy by a decrease in serum anti-AQP4 Ab concentrations. However, this association is not strong enough to justify treatment changes based only on anti-AQP4 Ab level variations. This parameter might be helpful as a longitudinal biomarker but only if a threshold inducing a relapse and justifying a switch in therapy can be established. A link between disease severity and serum cytotoxicity against AQP4-expressing cells was proposed but has not yet been confirmed. Finally, the assessment of T cell immunity against AQP4 and specific cytokines could be future directions for research.

Summary Objectives Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe attacks of optic neuritis and myelitis. Brain was classically, unlike in multiple sclerosis (MS), spared. Nevertheless recent studies showed that brain lesions can be seen with MRI. We studied the diffusion characteristics of normal-appearing white matter (NAWM) and abnormal white matter in NMO patients compared with NAWM in healthy subjects. Patients and methods Diffusion tensor imaging (DTI) scans of the brain and spinal cord were obtained from 25 patients with NMO and 20 age- and gender-matched healthy subjects. Region of interest (ROI) analysis of the apparent diffusivity coefficient (ADC) and fractional anisotropy (FA) was performed in brain NAWM (optic radiations, corpus callosum [CC] and anterior and posterior limbs of the internal capsule [IC]) and in spinal cord NAWM and in lesions. Results ADC was increased and FA decreased in NMO patients in the posterior limb of the IC in the optic radiations and in spinal cord NAWM. FA was lower in spinal cord lesions. In contrast, there was no difference between the two groups in the anterior limb of the IC nor in the CC. Conclusion These results suggest that DTI abnormalities are very severe in NMO spinal cord lesions. In our study, DTI abnormalities in NAWM were restricted to optic radiations and cortico-spinal tracts, suggesting secondary Wallerian degeneration. In contrast, NAWM outside these tracts (CC and anterior IC) remained normal suggesting that, unlike what is observed in MS, there is no infra-lesional abnormality in NMO.

Cerebral calcifications are a cause of secondary dystonia and may be an uncommon complication of radiotherapy. We report a very severe case of generalized dystonia due to postradiotherapy basal ganglia calcifications.An 8-year-old girl received 53 grays radiotherapy after surgery for craniopharyngioma. One year later she developed generalized dystonia. Computed tomography showed bilateral basal ganglia calcifications, especially of the lenticular nuclei. Pharmacological treatment with tetrabenazine, clonazepam and trihexiphenydile allowed a very limited improvement of dystonia; the course was complicated by dystonic storms and decompensations resulting from the iatrogenous panhypopituitarism.This case illustrates a severe complication of cranial irradiation which should be considered in the indications of this treatment, especially for children.