Upper motor neuron assessment in amyotrophic lateral sclerosis using the patellar tendon reflex and motor-evoked potentials to the lower limbs.

Amyotrophic lateral sclerosis (ALS) diagnosis relies on signs of progressive damage to both lower motoneuron (LMN), given by clinical examination and electromyography (EMG), and upper motoneuron (UMN), given by clinical examination only. Recognition of UMN involvement, however, is still difficult, so that diagnostic delay often remains too long. Shortening the time to clinical and genetic diagnosis is essential in order to provide accurate information to patients and families, avoid time-consuming investigations and for appropriate care management. This study investigates whether combined patellar tendon reflex recording with motor-evoked potentials to the lower limbs (T-MEP-LL) is relevant to assess corticospinal function in ALS, so that it might serve as a tool improving diagnosis. T-MEP-LL were recorded in 135 patients with suspected motor neuron disease (MND) from February 2010 to March 2021. The sensitivity, specificity, and ability to improve diagnosis when added to Awaji and Gold Coast criteria were determined. The main finding of the study is that T-MEP-LL can detect UMN dysfunction with a 70% sensitivity and 63% specificity when UMN clinical signs are lacking. The sensitivity reaches 82% when considering all MND patients. Moreover, at first evaluation, using T-MEP-LL to quantify reflex briskness and to measure central conduction time, can improve the diagnostic accuracy. T-MEP-LL is easy to perform and does not need any electrical stimulation, making the test rapid, and painless. By the simultaneous quantification of both UMN and LMN system, it could also help to identify different phenotype with more accuracy than clinical examination in this broad-spectrum pathology. The question whether T-MEP-LL could further be a real biomarker need further prospective studies.

Current clinical management of CIDP with immunoglobulins in France: An expert opinion.

Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Neuropathy and pregnancy: An overview.

Peripheral nerve injuries are rare in pregnant women. Nevertheless, physiological changes linked to pregnancy may induce nerve lesion. In this review we propose to focus on peripheral nerve disorders the most frequently encountered in pregnant patients. Focal neuropathy or polyneuropathy may appear during pregnancy or at delivery. In other cases, pre-existing neuropathies may deteriorate during pregnancy. In addition to clinical description, we summarised management proposed in the literature.

Pregnancy and myopathies: Reciprocal impacts between pregnancy, delivery, and myopathies and their treatments. A clinical review.

During pregnancy, women undergo physical and physiological changes, which can impact the neuromuscular disease course, but also delivery and fetus health. Generally, there is little impact on the disease course, but sometimes an impairment is noticed, which could be attributed to pregnancy and not to disease progression. Cardiac and respiratory functions have to be assessed at the beginning of pregnancy and a close follow-up is mandatory in case of disorder. Labour and delivery are often impacted. Labour is prolonged because of muscle weakness that is an increased risk of instrumental delivery or Cesarean sections. Patients with myotonic dystrophy are at risk of postpartum hemorrhage. Fetal loss can be associated with fetal disease in myotonic dystrophy, and is at high risk for patients with active inflammatory myopathy only.

Intravenous immunoglobulin for treatment of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy in France: are daily practices in accordance with guidelines?

BACKGROUND AND PURPOSE: Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are rare autoimmune diseases. Guidelines were published in 2010 for their diagnosis and treatment. In France, intravenous immunoglobulins (IVIGs) are mainly used for the first-line treatment. The burden of healthcare costs is often underlined but rarely studied. The aim of this survey was to compare to guidelines, the daily practice of French neurologists with IVIGs for CIDP and MMN treatment. METHODS: This was a retrospective observational study consisting of an online questionnaire performed between March and May 2014. A total of 49 questionnaires were included, a quarter of which were from neurologists working in neuromuscular reference centers (NRCs). RESULTS: A total of 182 patient case reports were studied. Patients were referred to an NRC for initial diagnosis in approximately 30% of cases in CIDP and 50% of cases in MMN. The initial management of IVIG (frequency, dose and duration) was not different between NRCs and non-NRCs. Guidelines were followed and neurologists were relatively at ease in diagnosing and treating patients. CONCLUSIONS: This was the first national study to describe the implementation of the European Federation of Neurological Sciences/Peripheral Nerve Society guidelines in the daily management of IVIGs in patients with MMN and CIDP in France. Efforts are needed to improve long-term tailored treatment and home treatment to reduce economic costs.

Amyotrophic lateral sclerosis or not: Keys for the diagnosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease (MND) which prognosis is poor. Early diagnosis permit to set up immediately adapted treatment and cares. Available diagnostic criteria are based on the detection of both central and peripheral motor neuron injury in bulbar, cervical, thoracic and lumbar regions. Electrodiagnostic (EDX) tests are the key tools to identify peripheral motor neuron involvement. Needle examination records abnormal activities at rest, and looks for neurogenic pattern during muscle contraction. Motor unit potentials morphology is modified primary to recruitment. Motor evoked potentials remain the test of choice to identify impairment of central motor neurons. In the absence of diagnostic biomarker of ALS and among essential investigations of suspected MND, a careful clinical and neurophysiological work-up is essential to rule out the differential diagnosis.

Evaluation of the application of the European guidelines for the diagnosis and clinical care of amyotrophic lateral sclerosis (ALS) patients in six French ALS centres.

BACKGROUND AND PURPOSE: Our objective was to evaluate the extent to which the 2005 recommendations of the European Federation of Neurological Sciences (EFNS) on the multidisciplinary management of amyotrophic lateral sclerosis (ALS) are followed in clinical practice. METHODS: This was a multicentre observational study involving six French ALS referral centres receiving prevalent and incident cases. Recommendations were translated into ad hoc questions referring to key aspects of management, and their application was evaluated by a clinical research assistant who independently examined the medical charts (MCs). When necessary, an independent board-certified neurologist answered the questions based on examination of the MC and interview of the caring neurologist. Questions regarding diagnosis and communication were put to patients in a self-administered questionnaire. RESULTS: In all, 376 patients [176 incident, 200 prevalent cases; median age at diagnosis 62.8 years (interquartile range 55.7-72.3); sex ratio 1.37; 27.3% bulbar onset] were included. All the topics covered in the recommendations were evaluated: diagnostic delay (e.g. mean 13.6 months, associated with age and onset); breaking the news (e.g. criteria for communication quality were satisfactory in more than 90%); multidisciplinary and sustained support (e.g. clinic visits were scheduled every 2-3 months in 90%). Also considered were whether riluzole had been offered, symptom management, genetic testing, ventilation, communication defects, enteral nutrition, palliative and end-of-life care. Characteristics associated with poor compliance with some guidelines (schedule of visits, delayed riluzole initiation) were also identified. CONCLUSION: This is the first evaluation of the application of the EFNS recommendations for the management of ALS in a nationwide sample. The results allow us to highlight areas for improvement.

Pathophysiology and biomarkers in chronic inflammatory demyelinating polyradiculoneuropathies.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired dysimmune disorder characterized by strong heterogeneity in terms of clinical manifestations, prognostic and response to treatment. To date, its pathophysiology and potential target antigens are not totally identified despite substantial progress in the understanding of the involved molecular mechanisms. Recent researches in the field have underlined the importance of cell-mediated immunity (lymphocytesT CD4+, CD8+ and macrophages), the breakdown of blood-nerve barrier, a failure of T-cell regulation, and the disruption of nodal and paranodal organization at the node of Ranvier. This last point is possibly mediated by autoantibodies towards axoglial adhesion molecules which may disrupt sodium and potassium voltage-gated channels clustering leading to a failure of saltatory conduction and the apparition of conduction blocks. The purpose of this article is to overview the main pathophysiologic mechanisms and biomarkers identified in CIDP.

Brain immunohistopathological study in a patient with anti-NMDAR encephalitis.

BACKGROUND AND PURPOSE: Anti-N-methyl-D-asparate (NMDA) receptor encephalitis is thought to be antibody-mediated. To perform an immunohistopathological study of the inflammatory reaction in a brain biopsy performed before immunomodulatory treatments in a patient with anti-NMDA receptor encephalitis. METHODS: An immunohistochemical study was performed using CD3, CD68, CD20, CD138 and CD1a antibodies. RESULTS: Prominent B-cell cuffing was present around brain vessels accompanied by some plasma cells, while macrophages and T cells were scattered throughout the brain parenchyma. CONCLUSION: These findings suggest that the B cells interact with the T cells and are involved in antibody secretion by the plasma cells.

[Small fiber sensory neuropathies: contribution of laser evoked potentials]. / Neuropathies sensitives des petites fibres : intérêt des potentiels évoqués laser.

Standard neurophysiological techniques evaluate exclusively large myelinated fibers, but are not useful to explore sensory small fibers. Quantitative sensory tests have been developed to explore the thermal nociceptive function but this exploration is only subjective. Laser evoked potentials (LEPs) represent a noninvasive and objective test to explore thermal and nociceptive pathways. The clinical interest of LEPs have been assessed recently in the diagnosis of small fibers sensory neuropathies. In routine, the determination of detection and nociceptive thresholds, the analysis of N2P2 latencies and amplitudes enable demonstration of a dysfunction of A delta nerve fibers, to quantify these lesions and to determine whether the neuropathies are length-dependent or not. The LEP amplitude is negatively correlated to deafferentation. The interest of LEPs remained to be studied compared to skin biopsy.

[Research in amyotrophic lateral sclerosis: what is new in 2009?]. / La recherche sur la SLA en 2009 : compte rendu du groupe bibliographique de la coordination des centres SLA.

This paper, written by French amyotrophic lateral sclerosis (ALS) center experts, presents an update of recent advances in fundamental, epidemiological and clinical research in ALS based on a review of the literature between September 2008 and November 2009. Among other pathophysiological mechanisms, the role of stress of the endoplasmic reticulum and the importance of energetic metabolic disturbances have been underscored. In the field of genetics, research has been advanced through the identification of mutations of the gene FUsed in Sarcoma/Translated in LipoSarcoma (FUS/TLS) in individuals with familial and sporadic ALS. This gene is involved in the regulation of transcription, splicing and RNA transport, and has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration. A report showed that mice expressing a mutant form of human TDP-43 develop a progressive and fatal neurodegenerative disease reminiscent of both ALS and frontotemporal lobar degeneration with ubiquitin aggregates (FTLD-U), providing a new animal model that may help to better understand the pathophysiology and test new therapeutics. Beside genetic studies, several epidemiologic studies have investigated the role of environmental factors. A recent study suggests that smoking is a risk factor for developing ALS and it is hypothesized that this could occur through lipid peroxidation via formaldehyde exposure. From a neuroprotective perspective, trials with IGF-1, sodium valproate, coenzyme Q or glatiramer acetate have failed to demonstrate any beneficial effect. A study published in 2008 argued that lithium may have a neuroprotective effect in ALS mice and also in patients. However, two preclinical studies failed to replicate the neuroprotective effect of lithium in ALS mice. Therapeutic trials have been performed or are currently ongoing in Europe and North America. Their results have not yet been published.

[Polyradiculopathy revealing an enteropathy associated T-cell lymphoma in a patient with celiac disease]. / Polyradiculopathie révélant un lymphome T associé à une entéropathie au cours de la maladie coeliaque.

INTRODUCTION: Celiac disease (CD) may be complicated by an enteropathy associated T-cell lymphoma (EATL), but lymphomatous dissemination outside the gastrointestinal tract is uncommon especially to the peripheral nervous sytem. OBSERVATION: We report a 54-year-old CD patient with EATL revealed by subacute polyradiculopathy. DISCUSSION: Peripheral neuropathies associated with CD are generally not polyradiculopathies, but sensorimotor neuropathies. Peripheral neurological complications of non-Hodgkin lymphoma are more frequent with B-lymphoma and a neurological presentation of EATL is very rare. CONCLUSION: This case illustrates the usefulness of searching for EATL in CD patients with polyradiculopathy.

[Update on fundamental and clinical research in amyotrophic lateral sclerosis]. / Actualités dans la recherche fondamentale et clinique sur la sclérose latérale amyotrophique.

This paper from a group of French experts in amyotrophic lateral sclerosis (ALS) presents an update of recent advances in fundamental, epidemiological and clinical research in ALS. Recent development in the pathogenesis of ALS suggests that motor neuron degeneration is a multifactorial and noncell autonomous process. Research has been advanced through the identification of the TAR-DNA-binding protein (TDP-43) as a common neuropathological marker of ALS and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Recently, mutations in the TDP-43 gene have been described in individuals with familial and sporadic ALS. Fundamental research in ALS is expected to lead to the disclosure of new diagnostic markers and therapeutic targets. A small trial has suggested that lithium carbonate may slow ALS progression but larger trials will be needed to confirm these results.