José Berciano

PurposeWe describe three families with Charcot-Marie-Tooth neuropathy (CMT), harboring a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant previously linked to fatal Leigh syndrome. We aimed to characterize clinically and molecularly the newly identified patients and understand the mechanism underlying their milder phenotype.MethodsThe patients underwent extensive clinical examinations. Exome sequencing was done in four affected individuals. The functional effect of the c.309+5G>A variant was investigated in patient-derived EBV-transformed lymphoblasts at the cDNA, protein and mitochondrial level. Alternative splicing was evaluated using cDNA long-read sequencing.ResultsAll patients presented with early-onset, slowly progressive axonal CMT and nystagmus; some exhibited additional central nervous system symptoms. The c.309+5G>A substitution caused the expression of aberrantly …

The objective of this review was to analyze the pathophysiological role of endoneurial inflammatory edema in initial stages of classic Guillain-Barré syndrome (GBS), arbitrarily divided into very early GBS (≤ 4 days after symptom onset) and early GBS (≤ 10 days). Classic GBS, with variable degree of flaccid and areflexic tetraparesis, encompasses demyelinating and axonal forms. Initial autopsy studies in early GBS have demonstrated that endoneurial inflammatory edema of proximal nerve trunks, particularly spinal nerves, is the outstanding lesion. Variable permeability of the blood-nerve barrier dictates such lesion topography. In proximal nerve trunks possessing epi-perineurium, edema may increase the endoneurial fluid pressure causing ischemic changes. Critical analysis the first pathological description of the axonal form GBS shows a combination of axonal degeneration and demyelination in spinal roots …

I read with great interest the paper by Keddie and colleagues, 1 who report that serum peripherin is a promising, new and specific biomarker of acute axonal damage in several disorders of the peripheral nervous system. I wish to comment on just their findings in Guillain-Barré syndrome (GBS). The series comprises 45 GBS patients, with clinical data available for 25 of them. 1 Based on nerve conduction studies, performed in 21 cases, the syndrome was categorized as demyelinating in 14 (67%), primarily axonal in five (23%) and mixed in two (10%). Serial peripherin levels conformed to distinct longitudinal patterns, the majority of them displaying a rise-and-fall, with the highest value either at the first assessment or within the first week after onset, namely in the period arbitrarily assigned for early GBS. 2 Just five (20%) patients exhibited peripherin levels below the lower limit of detection. The paper states that ‘We …

Potassium channels (KCN) are transmembrane complexes that regulate the resting membrane potential and the duration of action potentials in cells. The opening of KCN brings about an efflux of K+ ions that induces cell repolarization after depolarization, returns the transmembrane potential to its resting state, and enables for continuous spiking ability. The aim of this work was to assess the role of KCN dysfunction in the pathogenesis of hereditary ataxias and the mechanisms of action of KCN opening agents (KCO). In consequence, a review of the ad hoc medical literature was performed. Among hereditary KCN diseases causing ataxia, mutated Kv3.3, Kv4.3, and Kv1.1 channels provoke spinocerebellar ataxia (SCA) type 13, SCA19/22, and episodic ataxia type 1 (EA1), respectively. The K+ efflux was found to be reduced in experimental models of these diseases, resulting in abnormally prolonged depolarization …

Introduction. The term hereditary ataxia was introduced by Nikolaus Friedreich to designate a clinicalpathological description of a new form of early-onset familial ataxia, described in papers published between 1863 and 1877. This designation was soon replaced by the eponym Friedreich ataxia, leaving vacant the term hereditary ataxia. In 1893, Pierre Marie proposed that the term hereditary ataxia be reintroduced, adding the epithet cerebellar; many authors, particularly French-speaking researchers, replaced this designation with the eponym Marie ataxia.Objective. To clarify the nosology of Marie ataxia, addressing the question as to whether or not continued use of the term is warranted.Development. The original descriptions of Friedreich ataxia and Marie ataxia are reviewed in depth. Friedreich gave a magnificent description of a disease, which quite rightly carries his name. Marie based his proposal not on his own clinical-pathological studies, but on four previous reports by other authors. Essential features differentiating it from Friedreich ataxia were older age of onset and preservation of tendon reflexes. By 1893, two autopsy studies had revealed predominant cerebellar changes; because of this, Pierre Marie introduced the term hereditary cerebellar ataxia. Over the following four decades, eight additional studies showed that main lesions affected the spinal cord, involving the columns of Clarke, the anterior spinocerebellar tracts, and to a lesser degree the posterior spinocerebellar tracts and posterior columns. With no appropriate justification, Marie and his pupils proposed that ventral spinocerebellar tract degeneration was a distinctive …

Introducción Nikolaus Friedreich introdujo el término ataxia hereditaria para designar una nueva forma de ataxia hereditaria de inicio temprano, una entidad clinicopatológica que describió en una serie de estudios publicados entre 1863 y 1877. Este término fue pronto remplazado por el epónimo ataxia de Friedreich, dejando vacante el término ataxia hereditaria. En 1893, Pierre Marie propuso reintroducir el término ataxia hereditaria, añadiendo el calificativo ?cerebelosa?. Muchos autores, especialmente en el ámbito francófono, cambiaron este término por el epónimo ataxia de Marie. Objetivos Aclaramos la nosología de la ataxia de Marie, y abordamos la cuestión de si está justificado el uso de este término. Desarrollo Analizamos en detalle las descripciones originales de la ataxia de Friedreich y la ataxia de Marie. Friedreich realizó una descripción magistral de una enfermedad que posteriormente, y de pleno derecho, pasaría a conocerse por su apellido. Marie propuso otra entidad, basándose no en casos clínico-patológicos propios sino en cuatro estudios previamente descritos por otros autores. Las principales diferencias de la ataxia de Marie con respecto de la ataxia de Friedreich eran la mayor edad de inicio y la conservación de los reflejos tendinosos. Hacia 1893, dos estudios post mortem habían mostrado cambios predominantemente en el cerebelo, lo que llevó a Pierre Marie a acuñar el término ataxia cerebelosa hereditaria. Durante las cuatro décadas siguientes, otros ocho estudios mostraron que las lesiones más importantes se hallaban en la médula espinal, afectando a las columnas de Clarke, los tractos …

To the Editor: I read with interest the paper by Qamar et al. describing the case of a 6-y-old girl presenting with classic GBS associated with COVID-19 [1]. Here, on days 7 and 12 after onset nerve conduction studies (NCS) are reported as normal, regrettably, there is no indication to either the number of nerves studied or to possible evaluation of late responses. CSF showed albuminocytological dissociation, and MRI revealed patchy meningeal enhancement at the level of conus medullaris. In children with any GBS subtype, either demyelinating or axonal, comparable enhancement of cauda equina has been reported in 95% of cases, so MRI can be used as a supplementary diagnostic modality to clinical and laboratory findings of GBS [2]. Mungmunpuntipantip and Wiwanitkit literally indicate that the normal NCS observed here is a false negative [3]. This merits a brief comment. In the early stages (particularly on≤ 4 …

Letter to the Editor regarding "Immune-inflammation mapping in Guillain-Barré syndrome". - Abstract - Europe PMC Sign in | Create an account https://orcid.org Europe PMC Menu About Tools Developers Help Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus Search life-sciences literature (43,645,967 articles, preprints and more) Search Advanced search Feedback This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text Letter to the Editor regarding "Immune-inflammation mapping in Guillain-Barré syndrome". Berciano J 1 Author information Affiliations 1. University of Cantabria, University Hospital "Marqués de Valdecilla (IDIVAL)" and "Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (…

Background and purpose Spinocerebellar ataxia type 15 (SCA15) is a degenerative, adult onset autosomal dominant cerebellar ataxia, caused almost exclusively by deletions in the inositol 1,4,5 triphosphate receptor type 1 (ITPR1) gene (ITPR1). ITPR1 mediates calcium release from the endoplasmic reticulum, and particularly abounds in Purkinje cells. It plays a pivotal role in excitatory and inhibitory actions on Purkinje cells, and alterations in their balance cause cerebellar dysfunction in ITPR1 knockout mice. To date, only two single missense mutations have been reported to cause SCA15. They were considered pathogenic because cosegregation occurred with disease, and haploinsufficiency was hypothesized as their pathogenic mechanism. Methods In this study, three Caucasian kindreds with different heterozygous missense variants in ITPR1 are reported. The main clinical manifestation was a slowly …

The aim of this paper is to carry out a historical overview of the evolution of the knowledge on degenerative cerebellar disorders and hereditary spastic paraplegias, over the last century and a half. Original descriptions of the main pathological subtypes, including Friedreich’s ataxia, hereditary spastic paraplegia, olivopontocerebellar atrophy and cortical cerebellar atrophy, are revised. Special attention is given to the first accurate description of striatonigral degeneration by Hans Joachim Scherer, his personal and scientific trajectory being clarified. Pathological classifications of ataxia are critically analysed. The current clinical-genetic classification of ataxia is updated by taking into account recent molecular discoveries. We conclude that there has been an enormous progress in the knowledge of the nosology of hereditary ataxias and paraplegias, currently encompassing around 200 genetic subtypes.

IntroductionGuillain-Barré syndrome (GBS) is an acute-onset, immune-mediated disease of the peripheral nervous system. It may be classified into 2 main subtypes: demyelinating (AIDP) and axonal (AMAN). This study aims to analyse the mechanisms of axonal damage in the early stages of GBS (within 10 days of onset).DevelopmentWe analysed histological, electrophysiological, and imaging findings from patients with AIDP and AMAN, and compared them to those of an animal model of myelin P2 protein-induced experimental allergic neuritis. Inflammatory oedema of the spinal nerve roots and spinal nerves is the initial lesion in GBS. The spinal nerves of patients with fatal AIDP may show ischaemic lesions in the endoneurium, which suggests that endoneurial inflammation may increase endoneurial fluid pressure, reducing transperineurial blood flow, potentially leading to conduction failure and eventually to …

IntroductionGuillain-Barré syndrome (GBS) is an acute-onset, immune-mediated disease of the peripheral nervous system. It may be classified into 2 main subtypes: demyelinating (AIDP) and axonal (AMAN). This study aims to analyse the mechanisms of axonal damage in the early stages of GBS (within 10 days of onset).DevelopmentWe analysed histological, electrophysiological, and imaging findings from patients with AIDP and AMAN, and compared them to those of an animal model of myelin P2 protein–induced experimental allergic neuritis. Inflammatory oedema of the spinal nerve roots and spinal nerves is the initial lesion in GBS. The spinal nerves of patients with fatal AIDP may show ischaemic lesions in the endoneurium, which suggests that endoneurial inflammation may increase endoneurial fluid pressure, reducing transperineurial blood flow, potentially leading to conduction failure and eventually to …

Genetic paroxysmal neurological disorders featuring episodic ataxia and epilepsy (Amadori E et al., 2022). - Abstract - Europe PMC Sign in | Create an account https://orcid.org Europe PMC Menu About Tools Developers Help Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus Search life-sciences literature (41,201,311 articles, preprints and more) Search Advanced search Feedback This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text Genetic paroxysmal neurological disorders featuring episodic ataxia and epilepsy (Amadori E et al., 2022). Gazulla J 1 , Izquierdo-Alvarez S 2 , Berciano J 3 Author information Affiliations 1 author 1. Department of Neurology, Hospital Universitario Miguel Servet, Spain. 1 author 2. Section of …

Guillain–Barré syndrome (GBS) is an acute-onset, immunemediated disorder of the peripheral nervous system, which includes at least three disease patterns: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal and motor-sensory axonal neuropathy (AMAN and AMSAN), and Miller Fisher syndrome [1, 2]. Furthermore, GBS is sub-classified into classical (weakness involving all four limbs) and localized subtypes [3]. Experimental autoimmune neuritis (EAN) is a widely accepted model of GBS [4]. Anti-ganglioside antibodies in AMAN/AMSAN are complement-fixing that mainly bind to GM1 and GD1a gangliosides; in animal models, they induce axonal damage by fixing complement, recruiting macrophages, and depositing membrane attack complex in the axolemma membrane [2]. By contrast with AMAN, the immunological cascade involved in AIDP is less understood, given that specific …

Spinocerebellar ataxia type 38 is an infrequent autosomal dominant disease caused by mutations in ELOVL5, which encodes for the ELOVL5 enzyme. This is an elongase that participates in the synthesis of long-chain fatty acids; ELOVL5-knock-out mice show decreased synthesis of docosahexaenoic acid (DHA), and lower than normal serum DHA levels have been found in affected humans [1–3]. Manes et al. first reported that oral dispensation of DHA induced amelioration of ataxic signs in SCA38 [4]. In a previous article, we described a kindred with SCA38, in which the 5 study members exhibited progressive cerebellar ataxia, together with transient diplopia, sensorineural hypoacusis, vestibular hypofunction and downbeat nystagmus; a sensory neuronopathy was found in the 3 patients from the first generation, and low serum DHA levels, in 4. A missense variant in ELOVL5, c. 779A> G (p. Tyr260Cys …

Hereditary adult onset PLS coexists with ALS in some kindreds and may form part of a PLS-ALS phenotypic continuum, as proposed by Corcia et al. Hence, Corcia et al.'s results do not allow generalization of their PLS-ALS continuum hypothesis to comprise every kindred with familial PLS, due to the finding that not each one of them displays cases with ALS.[Extracted from the article]Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. Copyright applies to all Abstracts.

Das Guillain-Barré-Syndrom (GBS) ist eine entzündliche Erkrankung des Nervensystems mit fortschreitenden Lähmungen und Sensibilitätsstörungen. Es ist umstritten, ob GBS-Subtypen bereits durch einzelne elektrophysiologische Untersuchungen sicher klassifizierbar sind. In dieser Studie verglichen die Autoren elektrophysiologische Tests in frühen und späten Stadien des GBS und bewerteten im Ultraschall sichtbare Nervenveränderungen.

Using recent optimized electrodiagnostic criteria sets, we aimed at verifying the accuracy of initial nerve conduction studies (NCS) in classic very early Guillain-Barré syndrome (VEGBS), ≤ 4 days after onset, compared with the results of serial NCS. This is a retrospective study based on unreported and consecutive VEGBS patients admitted to two university hospitals between 2015 and 2019. Each patient had serial NCS in at least four nerves. Initial NCS studies were done within 4 days after onset, and serial ones from days 20 to 94. Electrophysiological recordings were blinded evaluated by four of the authors, GBS subtype being established accordingly. Seven adult classic VEGBS patients were identified with a median age of 58 years. At first NCS, GBS subtyping was only possible in 1 case that exhibited an axonal pattern, the remaining patterns being equivocal in 3, and mixed (combining axonal and …

Background Guillain–Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain–Barré syndrome. Methods Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We …

The aim of this review was to analyse the pathophysiology of axonal degeneration in Guillain–Barré syndrome (GBS) with emphasis on early stages (≤ 10 days after onset). An overview of experimental autoimmune neuritis (EAN) models is provided. Originally GBS and acute inflammatory demyelinating polyneuropathy were equated, presence of axonal degeneration being attributed to a “bystander” effect. Afterwards, primary axonal GBS forms were reported, designated as acute motor axonal neuropathy/acute motor–sensory axonal neuropathy. Revision of the first pathological description of axonal GBS indicates the coexistence of active axonal degeneration and demyelination in spinal roots, and pure Wallerian-like degeneration in peripheral nerve trunks. Nerve conduction studies are essential for syndrome subtyping, though their sensitivity is scanty in early GBS. Serum markers of axonal …