Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion.

Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified a biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and a major cause of late onset ataxia. Here we describe the full spectrum of the disease phenotype in our first 100 genetically confirmed carriers of biallelic repeat expansions in RFC1 and identify the sensory neuropathy as a common feature in all cases to date. All patients were Caucasian and half were sporadic. Patients typically reported progressive unsteadiness starting in the sixth decade. A dry spasmodic cough was also frequently associated and often preceded by decades the onset of walking difficulty. Sensory symptoms, oscillopsia, dysautonomia and dysarthria were also variably associated. The disease seems to follow a pattern of spatial progression from the early involvement of sensory neurons, to the later appearance of vestibular and cerebellar dysfunction. Half of the patients needed walking aids after 10 years of disease duration and a quarter were wheelchair dependent after 15 years. Overall, two-thirds of cases had full CANVAS. Sensory neuropathy was the only manifestation in 15 patients. Sixteen patients additionally showed cerebellar involvement, and six showed vestibular involvement. The disease is very likely to be underdiagnosed. Repeat expansion in RFC1 should be considered in all cases of sensory ataxic neuropathy, particularly, but not only, if cerebellar dysfunction, vestibular involvement and cough coexist

Muscle activation during gait in children with Duchenne muscular dystrophy

The aim of this prospective study was to investigate changes in muscle activity during gait in children with Duchenne muscular Dystrophy (DMD). Dynamic surface electromyography recordings (EMGs) of 16 children with DMD and pathological gait were compared with those of 15 control children. The activity of the rectus femoris (RF), vastus lateralis (VL), medial hamstrings (HS), tibialis anterior (TA) and gastrocnemius soleus (GAS) muscles was recorded and analysed quantitatively and qualitatively. The overall muscle activity in the children with DMD was significantly different from that of the control group. Percentage activation amplitudes of RF, HS and TA were greater throughout the gait cycle in the children with DMD and the timing of GAS activity differed from the control children. Significantly greater muscle coactivation was found in the children with DMD. There were no significant differences between sides. Since the motor command is normal in DMD, the hyper-activity and co-contractions likely compensate for gait instability and muscle weakness, however may have negative consequences on the muscles and may increase the energy cost of gait. Simple rehabilitative strategies such as targeted physical therapies may improve stability and thus the pattern of muscle activity

Clinical autonomic nervous system laboratories in Europe: a joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies

© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background and purpose: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. Methods: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. Results: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). Conclusions: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.info:eu-repo/semantics/publishedVersio

Immune Response and Mitochondrial Metabolism Are Commonly Deregulated in DMD and Aging Skeletal Muscle

Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors

EFAS/EAN survey on the influence of the COVID-19 pandemic on European clinical autonomic education and research

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Purpose: To understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe. Methods: We invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders. Results: Forty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN-EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020-2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year. Conclusions: The COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design.info:eu-repo/semantics/publishedVersio

Mutation du gène codant la protéine 0 responsable d'un phénotype clinique et électrophysiologique de neuropathie par hypersensibilité à la pression

La neuropathie par hypersensibilité à la pression est classiquement décrite associée à une délétion ou à des mutations du gène de la PMP22. Les mutations du gène de la P0 sont responsables de phénotypes variés allant de l'hypomyélinisation congénitale à la maladie de Charcot Marie Tooth. Nous décrivons pour la première fois, dans trois familles de l'Ouest, un phénotype clinique d'HNPP associé à une mutation non-sens du codon 116 du gène de la protéine 0 responsable d'une protéine tronquée dans son domaine extra-cellulaire. Ce phénotype est caractérisé par son évolution secondaire vers une neuropathie longueur dépendante, son tableau démyélinisant et axonal précoce à l'électromyographie. Nous discutons les rôles de la P0 au sein de la myéline, les corrélations génotypes-phénoypes dans les neuropathies héréditaires, l'intégration de ce nouveau phénotype parmi les neuropathies héréditaires. Ce nouveau phénotype étudié représente une nouvelle entité dans le spectre clinique des mutations P0.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les potentiels évoqués vestibulaires myogènes (étude à propos de quarante patients atteints de troubles de l'équilibre)

Les vertiges sont habituellement explorés par les tests caloriques, mais ceux-ci s'avèrent insuffisants pour étudier l'ensemble de l'organe de l'équilibre puisqu'ils ne testent que la fonction du canal semi-circulaire latéral.Une technique de développement récent, les potentiels évoqués vestibulaires myogènes, mettant en jeu le réflexe sacculo-collique permet d'objectiver un dysfonctionnement otolithique, en particulier sacculaire. Elle repose sur la propriété du saccule à être stimulé par des sons graves de forte intensité ou par des stimulations électriques. Elle met enjeu le nerf vestibulaire inférieur, les noyaux vestibulaires et les voies vestibulo-spinales...L'intérêt de ce test est diagnostique, en particulier dans les syndromes otolithiques, les suspicions de fistule -lymphatique et les sensations vertigineuses mal définies. Il présente aussi un intérêt pronostique dans les névrites vestibulaires et la maladie de Menière et contribue à orienter la rééducation vestibulaire....NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude de la discontinuité de l électroencéphalogramme du nouveau-né prématuré

L EEG fait partie des examens complémentaires utilisés pour le dépistage des lésions cérébrales des nouveau-nés prématurés. La naissance avant terme expose à un risque de séquelles neurosensorielles. Les lésions cérébrales sont souvent asymptomatiques en période néonatale. L EEG du nouveau-né prématuré est physiologiquement discontinu, constitué de bouffées d activité séparées par des intervalles interbouffées. Une augmentation de la durée des intervalles interbouffées est un marqueur d atteinte cérébrale sévère indiquant un risque élevé de séquelles neurologiques. Nous avons étudié le nombre et la durée des bouffées et des intervalles interbouffées chez des nouveau-nés prématurés nés avant 33 semaines d aménorrhée et recherché des facteurs de variation. Nous avons montré que l administration d un morphinomométique de synthèse comme le sufentanil faisait varier de façon significative la discontinuité et pouvait interférer avec l interprétation des tracés. Nous avons ensuite développé un logiciel spécifiquement dédié à l analyse automatique de ces paramètres et démontré la validité de cette analyse par rapport à l analyse visuelle. L application de cette technique à des tracés considérés comme normaux après analyse visuelle a montré que la durée des intervalles interbouffées diminue avec l âge post menstruel, quelque soit l'âge gestationnel, et de façon indépendante de l'augmentation des bouffées d activité. Les bouffées et les intervalles interbouffées semblent générés par des mécanismes physiologiques différents. Les périodes de discontinuité devraient donc être considérées comme une forme immature d activité cérébrale dont l origine électrophysiologique reste à explorer.The EEG is currently used in neonatal care units to assess brain maturation. Premature birth exposes to an increased risk of neurological impairments. However, cerebral injuries remain clinically silent in the neonatal period. The use of EEG and ultrasound scan is mandatory to early diagnosis of brain lesion. The preterm EEG has the unique characteristic to be discontinuous, constituted of bursts alternating with interburst intervals. Increased discontinuity is a strong marker of cerebral injury and is well-correlated with further impairments. We studied factors that can influence the degree of discontinuity and the effect of a sedative drug (sufentanil) on number and duration of bursts and interburst intervals in preterm EEG. We showed that administration of Sufentanil significantly increased the discontinuity and could interfere with clinical analysis. Considering that these quantitative values were valuable parameters to assess brain maturation, we designed a specific tool for automatic analysis of discontinuity, meant to be a user-friendly help for neurophysiologist. Comparison of automatic and visual results showed a strong correlation. Automatic analysis of normal EEGs of preterm infants born before 33 weeks of gestation showed that the degree of discontinuity decreased as post menstrual age increased, without influence of gestational age at birth. Burst and interburst intervals varied following different pattern suggesting that they reflect independent mechanisms. Interburst intervals could be considered as an immature form of cerebral activity and not as periods of inactivity. Further studies are needed to elucidate electrophysiological basis of this activity.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Cas clinique no 3

International audiencer e v u e n e u r o l o g i q u e 1 7 8 (2 0 2 2) S141-S182 S179 pathie type CMT2, sans épisode de paralysie périodique. La patiente n'a pas de mutation des gènes codant le canal calcique (CACLN1A) ou le canal sodique (SCN4A), ni des gènes classiquement mutés dans les CMT. La suite en live.. . Mots clés CMT2 ; Neuropathie ; Paralysie périodique Déclaration de liens d'intérêts L'auteur n'a pas précisé ses éventuels liens d'intérêts