Broad white matter impairment in multiple system atrophy.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p < .001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought

Leucine-Rich Glioma-Inactivated 1 Encephalitis: Broadening the Sphere

Background: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare entity. Its typical features are seizures, faciobrachial dystonic seizures (FBDS), cognitive impairment, and personality changes. Case report: We report the case of a 66-year-old man with an unusual presentation, consisting of two types of FBDS, one starting in the foot and the other consisting of asynchronous myoclonic and dystonic jerks of the face triggered by noise and chin stimulation. The patient displayed no personality changes or cognitive impairment. Discussion: LGI1 encephalitis is a heterogeneous disease. Many different forms of FBDS may be observed, and these seizures can be the only symptom. This type of encephalitis should be suspected in presenting very frequent episodic events with dystonic features, regardless of the part of the body affected

Alterations in electrochemical skin conductance as a marker of autonomic dysfunction in multiple system atrophy

BACKGROUND: Multiple System Atrophy (MSA) is a rare neurodegenerative disease with pronounced autonomic failure (AF). Severe cardiovascular AF is associated with poor prognosis. Since sweating dysfunction is less well known, we investigated the interest of a quick and non-invasive assessment of sweating using electrochemical skin conductance (ESC) as a marker for AF in MSA. METHODS: 138 MSA patients of the French Reference center for MSA with an annual follow-up including the Unified MSA Rating Scale (UMSARS), COMPASS (autonomic symptoms) and measurements of foot and hand ESC (Sudoscan®) participated to this study (age 65 ± 8 years, 66% probable MSA, 72% AMS-P). Statistical analysis included: (i) correlations between ESC and MSA type, age, disease duration, severity, blood pressure (BP), COMPASS, (ii) comparisons between groups with normal or abnormal ESC, and (iii) multivariate analysis by logistic regression. Relationships between severity progression during follow-up with ESC and other variables were modeled by Generalized Estimating Equation. RESULTS: Hands and feet ESCs were abnormal in 81/138 (59%) and 93/138 (67%) cases, respectively. Abnormal ESCs were significantly correlated to disease severity and several features of AF. ESCs worsening over time was more pronounced than other autonomic features such as orthostatic hypotension. Abnormal ESCs at baseline were significantly associated with a higher progression of UMSARS's score during follow-up. CONCLUSION: Sweating dysfunction assessed by ESC is frequent in MSA and is significantly related to disease severity and AF. The gradual decrease in ESC with disease duration could be useful as a quantitative marker of autonomic dysfunction

Devenir à 5 ans d'une cohorte de 95 patients âgés de moins de 45 ans, victimes d'un accident vasculaire cérébral ischémique

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Case Report: Presence of Anti-MAG in the CSF Can Be Associated With a Neurodegenerative Process With Frontal Involvement

International audienceBackground: Autoimmune encephalitis (AIE) is an increasingly broad nosological framework that may clinically mimic neurodegenerative diseases (NDDs). Cases Reported: We describe here the clinical, radiological, electrophysiological, and biological evolution of three patients. Two women aged 73 and 72 years and a 69year-old man presented with complex cognitive and focal neurological symptoms and each had a predominant frontal dysexecutive involvement and an unexpectedly high titer of anti-MAG antibodies in the serum and cerebrospinal fluid (CSF). The question of an autoimmune cause was raised. After 2 years of follow-up and, for two of them, without improvement despite immunosuppressive treatments, diagnoses of NDD were eventually retained: post-radiation encephalopathy, progressive supranuclear palsy (PSP), and Alzheimer's disease. Conclusion: The presence of a high titer of anti-MAG antibodies may be found in NDD. It could reflect cerebral tissue damages, particularly in the case of significant frontal involvement. Atypical presentations may lead to a search for a paraneoplastic neurologic syndrome or AIE. However, the indirect immunofluorescence staining positivity on a monkey cerebellum section linked with anti-MAG antibodies should not lead to those diagnoses being retained

Case Report: Presence of Anti-MAG in the CSF Can Be Associated With a Neurodegenerative Process With Frontal Involvement

International audienceBackground: Autoimmune encephalitis (AIE) is an increasingly broad nosological framework that may clinically mimic neurodegenerative diseases (NDDs). Cases Reported: We describe here the clinical, radiological, electrophysiological, and biological evolution of three patients. Two women aged 73 and 72 years and a 69year-old man presented with complex cognitive and focal neurological symptoms and each had a predominant frontal dysexecutive involvement and an unexpectedly high titer of anti-MAG antibodies in the serum and cerebrospinal fluid (CSF). The question of an autoimmune cause was raised. After 2 years of follow-up and, for two of them, without improvement despite immunosuppressive treatments, diagnoses of NDD were eventually retained: post-radiation encephalopathy, progressive supranuclear palsy (PSP), and Alzheimer's disease. Conclusion: The presence of a high titer of anti-MAG antibodies may be found in NDD. It could reflect cerebral tissue damages, particularly in the case of significant frontal involvement. Atypical presentations may lead to a search for a paraneoplastic neurologic syndrome or AIE. However, the indirect immunofluorescence staining positivity on a monkey cerebellum section linked with anti-MAG antibodies should not lead to those diagnoses being retained

Reconciling west nile virus with the autophagic pathway

© 2015, Taylor & Francis Group, LLC. West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus responsible for recurrent outbreaks of meningitis and encephalitis. Several studies analyzing the interactions of this pathogen with the autophagic pathway have reported opposite results with evidence for and against the upregulation of autophagy in infected cells. In this regard, we have recently reported that minimal genetic changes (single amino acid substitutions) in nonstructural proteins of WNV can modify the ability of the virus to induce autophagic features such as LC3 modification and aggregation in infected cells. We think that these results could help explain some of the previously reported discrepancies. These findings could also aid in deciphering the interactions of this pathogen with the autophagic pathway at the molecular level aimed to develop feasible antiviral strategies to combat this pathogen, and other related flaviviruses.INIA (RTA2011-0036 and E-RTA2013-00013-C01) and the Comunidad Autónoma de Madrid PLATESA (P2013/ABI-2906)Peer Reviewe