INTRODUCTION: Wild-type transthyretin amyloidosis (ATTRwt) is not clearly known to be associated with peripheral neurological complications. The aim of our study was to characterize neurological involvement in ATTRwt, as...INTRODUCTION: Wild-type transthyretin amyloidosis (ATTRwt) is not clearly known to be associated with peripheral neurological complications. The aim of our study was to characterize neurological involvement in ATTRwt, as well as its evolution over time, using clinical and electrodiagnostic (EDX) data. METHODS: We prospectively included patients diagnosed with ATTRwt who were addressed by cardiologists. All patients underwent neurological evaluation, including examination (neuropathy impairment score) and an EDX study including electrochemical skin conductance and/or sympathetic skin response testing. Motor, sensory, and small fiber composite sum scores were calculated based on the EDX data. Clinical and EDX scores were then reassessed during the follow-up period. RESULTS: Fifty-two patients were included, 94% of whom were treated with tafamidis. At inclusion 98% of patients presented peripheral nerve involvement at EDX, the most common being carpal tunnel syndrome (88%), polyneuropathy (67%), and ulnar tunnel syndrome (21%). Twenty-nine patients were reevaluated and mean follow-up was 16.7months with no significant change of clinical or neurophysiological data. DISCUSSION: In our cohort, a large majority of ATTRwt patients showed peripheral nerve involvement, generally expressed as the combination of different neurological syndromes (entrapment syndromes, large and/or small fiber polyneuropathy, radicular impairment). Polyneuropathy in ATTRwt seemed stable over our follow-up period. Clinical and EDX screening should be conducted in ATTRwt patients with symptoms suggestive of neurological involvement in order not to oversee these frequent complications which could affect therapeutic decision making.
INTRODUCTION: Some patients remain severely disabled after an episode of optic neuritis. Several studies have shown that plasmapheresis (PE) can improve visual prognosis in the absence of satisfactory recovery after cort...INTRODUCTION: Some patients remain severely disabled after an episode of optic neuritis. Several studies have shown that plasmapheresis (PE) can improve visual prognosis in the absence of satisfactory recovery after corticosteroids. However, there is no clear ophthalmological criterion for doing PE, and practices vary widely. The objective of the present study was to better define the rationales for use of PE. MATERIAL AND METHODS: We investigated the real-life indications for PE in French expert centers. Based on the responses to a questionnaire and the current literature, we further provided guidelines aiming to standardize the use of PE for the management of optic neuritis. RESULTS: Twenty expert centers completed the questionnaire. Together, they accounted for 90% of patients treated by PE in France during the study period. The main criteria for using PE were as follows: severely impaired visual acuity despite corticosteroids (mean visual acuity<0.6 logMAR or 20/80), high suspicion for neuromyelitis optica spectrum disorder, bilateral optic neuritis, or a profound visual field alteration. CONCLUSION: This study provides insightful information about the real-life indications for PE in French centers for the treatment of optic neuritis. Based on our findings and the available data in the literature, we provide a decision-making algorithm for the management of optic neuritis.
BACKGROUND: Previous studies reporting prevalence of psychosis were predominantly cross-sectional, with a limited focus on the full spectrum of features seen in psychosis associated with Parkinson's disease (PDPsy). OBJE...BACKGROUND: Previous studies reporting prevalence of psychosis were predominantly cross-sectional, with a limited focus on the full spectrum of features seen in psychosis associated with Parkinson's disease (PDPsy). OBJECTIVES: To assess the prevalence of PDPsy, explore the association of PDPsy with demographic, drug-related, and disease-related characteristics and describe the management of PDPsy in an outpatient population with PD. METHODS: We analysed the psychosis prevalence and clinical correlates in PD patients seen for an outpatient visit at the Parkinson Expert Centre of Rouen. PD patients were evaluated with detailed clinical history taken by an investigator trained in PD (DM). Psychosis was diagnosed according to NINDS diagnostic criteria. PDPsy characteristics were collected using a standardized questionnaire composed of ten qualitative items on hallucinations, minor phenomena, and delusions. All PD patients considered to have a previous or ongoing PDPsy underwent an interview to assess the age at onset, exacerbating and relieving factors, the management and outcomes. RESULTS: From June to December 2021, 315 outpatients with PD were included in the study, 42% had previous or ongoing psychosis, mostly visual hallucinations. PD patients with PDPsy were older, with a more advanced form of the disease and were treated with a higher dose of anti-Parkinson drugs. Psychotic symptoms can be adequately managed with nonpharmacoligical approaches, while in other patients, reduction or withdrawal of drugs, or introduction of clozapine was necessary. CONCLUSIONS: Untreated PDPsy is associated with impaired quality of life, and significant distress to caregivers and patients. Early detection of psychotic symptoms may yield prognostic and therapeutic benefits.
MOG antibody-associated disease (MOGAD) is a new entity within the spectrum of autoimmune inflammatory diseases of the central nervous system. It is distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum...MOG antibody-associated disease (MOGAD) is a new entity within the spectrum of autoimmune inflammatory diseases of the central nervous system. It is distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Although they share certain clinical characteristics, these 3 diseases differ in terms of their pathophysiology, disease course and response to treatment. MOGAD is a rare disease affecting both adults and children, with a higher frequency in the latter. The clinical presentation of MOGAD varies depending on age: in children under the age of 10, presentations of acute disseminated encephalomyelitis (ADEM) are frequently described, whereas in children over the age of 10 and in adults, unilateral or bilateral optic neuritis or acute myelitis is more often observed. Other, rarer presentations have also been reported, including encephalitic presentations with seizures. Radiologic findings can sometimes help guide the diagnosis: extensive anterior optic nerve involvement, perineuritis, extensive lesions of the spinal cord with involvement of the conus medullaris, and involvement of the pons, for example. Diagnosis is confirmed by measuring anti-MOG antibodies in the serum. In case of diagnostic doubt, the result must be confirmed in a reference laboratory (currently available in Lyon and Le Kremlin Bicêtre in France). The disease course is usually monophasic in children, but relapses are possible. In adults, the frequency of relapses seems higher than in children, estimated at more than 40% after 5 years. Visual, bladder/sphincter, cognitive and, to a lesser extent, motor sequelae may occur, but much less frequently than in NMOSD. In children and adults, attacks are treated with high-dose IV corticosteroids, which are often very effective, followed by an oral taper. In certain situations, long-term immunoactive therapy may be proposed, particularly when a relapse occurs, after discussion with a reference or expert center for Inflammatory diseases of the central nervous system. Long-term follow-up is proposed at the reference/expert center at least once a year. In between these appointments, follow-up with the referring pediatric neurologist, pediatrician, treating physician or referring neurologist is carried out every 6 months. It is important to check for the occurrence of a new attack and the onset of complications but also, in the case of long-term therapy, adherence to and tolerance of the treatment. Multidisciplinary management is essential and involves a variety of healthcare professionals (neurologist or pediatric neurologist, ophthalmologist, physiatrist, physiotherapist, speech therapist, occupational therapist, psychologist and social worker).
BACKGROUND: Linking disease registries to nationwide healthcare administrative databases increases the research opportunities. Recent guidelines emphasize the need of transparency in this process. OBJECTIVE: Our aims wer...BACKGROUND: Linking disease registries to nationwide healthcare administrative databases increases the research opportunities. Recent guidelines emphasize the need of transparency in this process. OBJECTIVE: Our aims were to describe the process of record linkage between the French multiple sclerosis (MS) cohort (OFSEP) and the national health insurance database (SNDS) and to evaluate the linkage quality. METHODS: As no unique identifier was available in the two databases, the OFSEP-SNDS data linkage was performed by indirect matching using the following sixteen patient variables to create a unique key: sex, dates of birth and death, of visits to a neurologist, of MS-related hospitalizations, of MRI, and use of disease-modifying therapies. Three indicators were computed to assess the linkage quality. RESULTS: Among the 52,034 eligible patients in the OFSEP registry, 42,603 (81.9%) were matched with patients in the SNDS database, with good overall quality (robustness=3.19; this is the number of linkage variables that can be removed without losing the uniqueness of the linked pair; 87.8% of common information). Comparison of the linked and unlinked populations revealed no major selection bias regarding age and sex distributions. CONCLUSION: The successful linkage of more than 40,000 patients with MS broadens the research perspectives by allowing access to a wide range of clinical and administrative data (e.g., comorbidities, care pathways) over a long mean disease duration (> 15 years).
Clinical trials are essential to the development of innovative treatments. Many patients and families have limited knowledge of biomedical research. This study aimed to determine whether families of children with epileps...Clinical trials are essential to the development of innovative treatments. Many patients and families have limited knowledge of biomedical research. This study aimed to determine whether families of children with epilepsy were interested in learning more about biomedical research, what specific trial-related topics they wanted to know more about, and how they preferred to receive this information. An online survey was emailed to 29 partner associations and shared on the social networks of our Rare Epilepsy Reference Center. Of the 152 respondents, 63% knew about biomedical research, and 99% expressed interest in learning more. Topics of interest included how new anti-seizure medications are developed, the stages involved in drug approval, using placebos, randomization, and assessing treatment efficacy and side effects. Side effects and treatment efficacy attracted the most interest. While awareness of clinical trials is improving, there is still a need for a better understanding of critical concepts such as placebos, safety, and randomization. Social media, educational videos, and written resources could be practical tools for increasing knowledge and participation in clinical trials among patients with epilepsy and their families.
INTRODUCTION: Pleomorphic xanthoastrocytomas (PXA) are primary brain tumors challenging to diagnose due to their morphological and molecular overlap with other tumors. While DNA methylation profiling (MP) aids pathologic...INTRODUCTION: Pleomorphic xanthoastrocytomas (PXA) are primary brain tumors challenging to diagnose due to their morphological and molecular overlap with other tumors. While DNA methylation profiling (MP) aids pathological classification, it alone may be inconclusive. Magnetic resonance imaging (MRI), routinely performed for lesion assessment, provides valuable information. Combining histo-molecular features, MP, and MRI is thus beneficial, particularly in cases of diagnostic uncertainty. In this study, we retrospectively analyzed MRI features of methylation-confirmed PXAs (mcPXAs) versus tumors with PXA-like histology using WHO 2021 criteria. METHODS: We included 29 adult patients with tumors displaying PXA-suggestive histology, completed MP, and preoperative MRI. Tumors were classified into three groups: mcPXA, histological PXA with methylation-confirmed glioblastoma (mcGBM), and other MP-confirmed diagnoses (mcMimic). Clinical and molecular data were recorded. RESULTS: All tumors were supratentorial with heterogeneous enhancement. The mcGBM group showed significantly more peritumoral edema and hypercellularity than mcPXA (P=0.002 and P=0.023). No significant differences were found in tumor location, cystic components, or hemorrhagic content. The BRAF mutation appeared in 89% of mcPXA, 8% of mcGBM, and 29% of mcMimic cases (P<0.05). Our composite MRI and molecular score for PXA diagnosis achieved an area under the curve of 0.95, with 95% specificity and 77% sensitivity. CONCLUSION: In cases of histological uncertainty, lack of peritumoral edema and hypercellularity supports a PXA epigenetic profile. Our specific score could aid in challenging cases, though further validation in larger cohorts is warranted.
Mania-Pâris L, Ewenczyk C, Nicolas G
… +14 more, Anheim M, Durr A, Pichon B, Isner-Horobeti ME, Angelini C, Goizet C, Roubertie A, Soudrie B, Davion JB, Marolleau I, Maumy I, Pichon V, Thauvin C, Thomas Q
INTRODUCTION: Hereditary spastic paraplegia (HSP) describes a group of rare genetic neurological diseases characterized by a common clinical presentation made of progressive motor weakness and spasticity of the lower lim...INTRODUCTION: Hereditary spastic paraplegia (HSP) describes a group of rare genetic neurological diseases characterized by a common clinical presentation made of progressive motor weakness and spasticity of the lower limbs. The global prevalence is estimated at 3.6 individuals per 100,000 inhabitants. CLINICAL: The age of onset of first symptoms, the severity and the rate of progression are highly variable between different HSP subtypes, ranging from juvenile forms that present in the first years of life, to the later-onset forms, sometimes presenting after the age of 60. The medical history most often reveals an insidious onset of gait disturbances due to lower limb stiffness. The clinical examination reveals the key symptoms of HSP: pyramidal signs of the lower limbs with motor weakness predominantly involving the proximal muscles. As the condition progresses, moderate upper limb involvement as well as bladder and sphincter disorders may be present. When associated with other neurological or extra-neurological signs such as cerebellar ataxia, optic neuropathy, cardiomyopathy, or intellectual disability, HSP is referred to as "complex". This is in contrast to the pure forms of HSP, where the pyramidal syndrome of the lower limbs occurs in isolation, which will be treated here. PHYSIOPATHOLOGY: HSPs are a genetically heterogeneous group of disorders involving numerous distinct molecular pathways. However, regardless of the initial mechanism, they share a common pathophysiology characterized by primary first motor-neuron involvement. Lesions tend to predominate in the spinal cord, following a phenomenon of retrograde degeneration ("dying-back") of the corticospinal tract. DIAGNOSIS AND GENETIC COUNSELING: The diagnostic approach will first aim to eliminate all non-genetic acquired forms of spastic paraplegia as well as other various differential diagnoses. More than 100 genes and disorders are grouped under the term HSP, with age of onset, disease progression and clinical presentation being highly variable. Pure forms of HSP are primarily inherited in an autosomal dominant or recessive manner. Genetic counseling for the patient and their family is ideally provided by a clinical geneticist once the precise molecular diagnosis has been obtained. MANAGEMENT AND CARE: The management of pure HSP is multidisciplinary. Its goal is to prevent complications and to propose symptomatic treatment at all stages of the disease. It is primarily based on motor rehabilitation through physiotherapy and physical activity. Psychological support should be offered from the moment the diagnosis is announced and throughout the follow-up. Multidisciplinary follow-up is coordinated by the primary care physician, in consultation with the expert pediatric neurologist/neurologist or neurogeneticist, and equally involves a physical medicine and rehabilitation physician and paramedical professionals (such as physiotherapists, social workers, occupational therapists, and psychologists).
INTRODUCTION: Matrin-3 autosomal dominant myopathy, most commonly caused by a Ser85Cys (S85C) missense mutation, is a rare distal myopathy, presenting a heterogeneous phenotype. METHODS: We report the clinical, physiolog...INTRODUCTION: Matrin-3 autosomal dominant myopathy, most commonly caused by a Ser85Cys (S85C) missense mutation, is a rare distal myopathy, presenting a heterogeneous phenotype. METHODS: We report the clinical, physiological, radiological, and histological features of the first Portuguese patients diagnosed with p.Ser85Cys MATR3-related myopathy using a specific gene panel dedicated to "distal myopathies". Additionally, a narrative review of the literature was performed to contextualize our findings within the broader landscape of MATR3-related pathologies. RESULTS: Our case series describes the clinical findings of three patients diagnosed and followed in our center. The first patient was a 57-year-old male presenting with lower limb weakness, followed by loss of muscle force for fine motor gestures in the distal upper limb. Neurological examination revealed important muscle atrophy of the distal limbs and symmetrical motor deficit. The second patient, the brother of the aforementioned subject, was a 54-year-old male with similar symptoms associated with dysphagia and dysphonia. The third patient was a 58-year-old female, unrelated to the previous patients, presenting with distal weakness in the upper limbs and severe Achillean contractures. All three patients were investigated using needle electromyography and whole-body magnetic resonance imaging that disclosed a fatty infiltration pattern in the gastrocnemius, soleus, and tibialis anterior muscles. A muscle biopsy was performed solely for one patient and revealed rimmed vacuoles, consistent with previous reports. Genetic analysis found the same mutation in all three cases: c.254C>G, p.Ser85Cys in the MATR3 gene. The literature review included nine articles reporting families diagnosed with the p.Ser85Cys mutation in the MATR3 gene, and the main phenotypes associated with this genetic variant. CONCLUSION: Despite being a rare myopathy, with only a few cases reported, MATR3 gene mutations should be considered in patients with distal myopathy and rimmed vacuoles on muscle biopsy.
Respiratory involvement has been identified as a cardinal feature of amyotrophic lateral sclerosis (ALS) since its earliest descriptions in the 19th century. Since these initial reports, considerable research has been un...Respiratory involvement has been identified as a cardinal feature of amyotrophic lateral sclerosis (ALS) since its earliest descriptions in the 19th century. Since these initial reports, considerable research has been undertaken to clarify the pathophysiology and progression rates associated with respiratory compromise and effective management strategies have been developed. Clinical trials routinely incorporate respiratory measures as study end points, non-invasive ventilation is now widely used in the home setting, cough-assist techniques are commonly used, advanced neurophysiology techniques and wearable technologies have been integrated into respiratory monitoring protocols, and palliative guidelines have been developed to effectively manage respiratory distress. Despite the widespread implementation of these interventions, epidemiology studies are inconsistent and some studies suggest that survival in ALS has not improved significantly with the introduction of these measures. The outcomes of diaphragmatic pacing trials have been disappointing, advanced neurophysiology techniques are not routinely utilised, spinal and brainstem imaging are not commonly undertaken and significant geographical differences exist in proceeding to tracheostomy. The worldwide COVID pandemic has given impetus for remote monitoring, connected devices, video-consultations, and timely vaccinations in ALS; lessons that are invaluable long after the pandemic. Respiratory monitoring and management in ALS is a swiftly evolving facet of ALS care with considerable quality of life benefits.
BACKGROUND: While the benefits of urgent management of transient ischemic attacks (TIA) are now well established, there is still no consensus on the best care pathway for TIA, particularly regarding hospitalization in an...BACKGROUND: While the benefits of urgent management of transient ischemic attacks (TIA) are now well established, there is still no consensus on the best care pathway for TIA, particularly regarding hospitalization in an intensive care stroke unit compared to outpatient management in a TIA clinic. The objective of this study was to report the different steps required for the development of a TIA clinic addressing both the healthcare needs as well as architectural and economic constraints of a hospital, then to describe the results of the first year of activity of our TIA clinic. METHOD: First, we described the various steps of the development of our TIA clinic and its operational modalities. Then we performed a cohort study of all patients with suspected TIA admitted in the outpatient clinic at Bordeaux University Hospital between November 7, 2022, until November 7, 2023. We analyzed data including characteristics of the population, diagnoses, treatments, hospitalization rate and length of stay. To assess the risk reduction of stroke occurrence three months after TIA, we compared the stroke rate predicted by the ABCD score to the observed stroke rate of our population at three months. RSULTS: A total of 507 patients were admitted to the TIA clinic during the first year with a median length of stay of 5hours. Compared to the period when TIA were hospitalized in our intensive care stroke unit, this represents a tenfold increase in the rate of TIA patients admitted in our stroke unit with a tenfold reduction in the length of hospital stay. Among patients, 13.4% had a minor stroke, 34.5% had a probable TIA, 25.4% had a possible TIA, 26.6% had a differential diagnosis and 11% were subsequently hospitalized in the intensive care stroke unit. Most patients were referred by general practitioners. Our TIA clinic demonstrated a 68% reduction in the risk of stroke after TIA with an observed stroke rate of 0.98% after 3 months compared to the 3.1% predicted by the ABCD2 score. CONCLUSION: The opening of a TIA clinic in Bordeaux metropole has significantly improved the management of TIA patients, which was previously inadequate in our territory. This study demonstrated that a hybrid model operating as an outpatient day hospital is effective as it successfully reduced the stroke rate after TIA, while increasing the capacity of TIAs admission to a stroke unit and shortening hospital stays.
INTRODUCTION: The efficacy of endovascular therapy (EVT) in reducing disability is strongly time-dependent. Door to groin puncture (DTP) time has been reported to be a reliable parameter to assess the delay between admis...INTRODUCTION: The efficacy of endovascular therapy (EVT) in reducing disability is strongly time-dependent. Door to groin puncture (DTP) time has been reported to be a reliable parameter to assess the delay between admission and treatment initiation and can be shortened via faster, more optimized workflow. We aimed to assess the DTP time in France and have analyzed potentially associated factors at both patient and hospital levels. METHODS: From January 2020 to December 2022, data were collected in the prospective, multi-centered, ongoing Endovascular Treatment in Ischemic Stroke (ETIS) registry. All patients directly admitted to comprehensive stroke centers with large vessel occlusion treated by EVT were included in the analysis and their DTP times were analyzed. We investigated hospital-related factors (prenotification, patient's hospital arrival location, type of imaging, number of available angiosuites, type of anesthesia) and patient-related factors, which could affect DTP time. RESULTS: Among 3847 patients from 28 centers [mean age: 71.2; median NIHSS: 16 (10-20)], the median DTP time was 105minutes (IQR: 84 to 137). Pre-stroke mRS>1, admission during off-hours and admission to centers equipped with only one dedicated angiosuite were associated with a longer DTP time. Centers not equipped with an emergency department had a significantly shorter DTP time. CONCLUSION: The median DTP time in France is 105min. Further efforts, such as increasing the number of available angiosuites in CSCs, and implementing direct imaging paradigms should be applied to optimize workflows and to reduce DTP time, a major marker of the efficacy of comprehensive stroke centers.
The cascade of events that occur in the human brain, from neurons to local circuits and global network dynamics during epileptic seizures, is barely understood. Ictogenesis in humans has been described in relation to ele...The cascade of events that occur in the human brain, from neurons to local circuits and global network dynamics during epileptic seizures, is barely understood. Ictogenesis in humans has been described in relation to electrophysiological concepts based on local field potentials (LFP) recorded by standard macroelectrodes (macro-LFP). Microelectrodes, however, record at the cellular scale. Despite over four decades of such recordings in patients with epilepsy, there remains a significant gap between these scales. This narrative review explores the contribution of microelectrode recordings of seizures in humans. By focusing closely on neuronal activity, researchers often overlook that microelectrodes also allow recording LFP at the micro-electrode level (micro-LFP). Above all, there is a gap between local circuits recorded at the micro-LFP level and large-scale network dynamics at the macro-LFP level, with little theoretical work to reconcile these two scales. Consequently, to date, analyses of seizures have been coarse, incomplete, and based on small numbers of patients. In particular, most multiscale seizure analyses have not included all three levels of scales (single units, micro-LFP, and macro-LFP) simultaneously, but doing so is key to providing a synthesis of ictal genesis. This review highlights the various challenges that face researchers using microelectrodes: (1) carrying out a systematic descriptive and quantitative analysis of the micro-LFP seizure signal, (2) improving the spatial correspondence between micro- and macroelectrodes in order to achieve better comparability between the two scales, (3) improving brain sampling thanks to specific devices, in particular deep electrodes with microwires, (4) reporting the reference electrode used in each study and how it may impact the results, (5) long duration of recordings over hours and days, and (6) shared simultaneous micro-LFP/macro-LFP databases.
This prospective observational study assessed how well patients with neuromuscular disorders (NMDs) tolerated coronavirus disease 2019 (COVID-19) vaccination, and the safety thereof. Patients treated in 55 expert centres...This prospective observational study assessed how well patients with neuromuscular disorders (NMDs) tolerated coronavirus disease 2019 (COVID-19) vaccination, and the safety thereof. Patients treated in 55 expert centres of the French NMD (FILNEMUS) network were asked to complete online questionnaires that explored COVID-19 vaccine injection status, adverse effects (AEs), and the impacts thereof on the activities of daily living (ADLs). All patients were followed-up for 12 months. We enrolled 1,020 patients with various NMDs; 38% with myopathy, 33% peripheral neuropathy, 20% myasthenia and 5% spinal muscular atrophy (SMA). Of all patients, 18% were on immune system-modifying therapies. A total of 1,865 vaccine injections were given. Of all patients, 70.4% lacked AEs impacting ADLs (they experienced no AEs or minor AEs), 20.4% reported AEs compromising ADLs, 9% AEs preventing ADLs and 0.2% AEs that required hospitalisation. We found no association between AEs impacting ADLs and the NMD type, physiopathology, or treatment. However, correlations were found between the development of AEs that impacted ADLs and both the modified Rankin score at baseline and vaccination with mRNA-1273 (Moderna). The AE types and frequencies were similar to those of the general population. Our study is reassuring; COVID-19 vaccination is safe for patients with NMDs including those with immune system-mediated diseases and those who are receiving immune system-modifying therapies. Patients with severe disabilities were at an increased risk of AEs that impacted ADLs but this must be weighed against the fact that they are also at increased risk of severe COVID-19 infection. Our mRNA-1273 (Moderna) vaccine findings require confirmation; few patients received this vaccine compared to those injected with BNT162b2 (Pfizer-BioNTech).