Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor pathways, invariably leading to death within a few years of onset. Most cases of ALS are sporadic, but familial forms ...of the disease (FALS) constitute 10% of the cases. Since the first identification of a causative gene in the 1990s and with recent advances in genetics, more than twenty genes have now been linked to FALS. This increased number of genes led to a tremendous amount of research, clearly contributed to a better understanding of the pathophysiology of this disorder, and paved the way for the development of new therapeutics and new hope for this fatal disease.
•Familial amyotrophic lateral sclerosis (FALS) represents <10% of the total ALS patients.•FALS are mainly due to the mutations of four genes: C9ORF72, SOD1, FUS and TDP-43.•The increased number of genes has clearly contributed to a better understanding of the pathophysiology of ALS.•This increased number of genes also risk to led to difficulties to their classification.•Gene therapy is probably a therapeutic way to explore in ALS.
The ataxic neuropathies Mathis, Stéphane; Duval, Fanny; Soulages, Antoine ...
Journal of neurology,
10/2021, Volume:
268, Issue:
10
Journal Article
Peer reviewed
Ataxia is a frequent symptom in neurological cases with many causes. Sensory ataxia (due to involvement of the proprioceptive pathways) is observed in conditions affecting the central nervous system ...(spinal cord disorder) and the peripheral nervous system (peripheral neuropathy). The latter correspond to what we refer to as ‘ataxic neuropathies’. Ataxic neuropathies represent a wide and heterogeneous spectrum of disorders that may affect dorsal root nerves, dorsal root ganglia, nerve trunks, distal nerve endings or all of them together. The identification of a predominant sensory ataxia in a case of peripheral neuropathy should raise the possibility of some specific etiologies. We propose here to present the main causes of ataxic neuropathies, which are identified with diagnostic workflows that are dictated by the topography of the likely sites of lesions in the proprioceptive pathway together with the timing of their occurrence (acute, subacute, or chronic).
Peripheral neuropathies have various causes, both infectious and non-infectious. When we think of “epidemics”, we often refer to an infectious or even post-infectious origin. Nevertheless, the ...history of mankind is marked by episodes of epidemics of peripheral neuropathies of non-infectious nature, either of nutritional or toxic origin: we present here the main causes of such epidemics.
The history of mankind is marked by numerous epidemics, some of which involved diseases of the peripheral nervous system, either infectious or otherwise. We describe here the three main infectious ...causes of epidemics that affect the peripheral nervous system: leprosy, poliomyelitis and diphtheria. We then discuss the main epidemics of immune-mediated origin.
Introduction
Myasthenia gravis (MG) Lambert-Eaton (LE) overlap syndrome is a rare condition. Here, we describe the first case of MG-LE overlap syndrome revealed by the anti-programmed cell death 1 ...inhibitor, nivolumab, in a patient treated for metastatic melanoma.
Case
Three months after receiving nivolumab and 1 month after brain metastasis radiotherapy, our patient developed generalized fatigue with intermittent ptosis and swallowing difficulty suggesting a myasthenic syndrome. Electromyogram findings, anti-acetylcholine receptor, and anti-calcium channel antibodies levels were consistent with an immune-related myasthenic syndrome with specific features for both MG and LE syndromes. Immunotherapy with nivolumab was stopped. Patient was treated with systemic immunosuppressive and anti-cholinesterase drugs, with remarkable improvement of his neurological symptoms. Prolonged partial remission was obtained for his metastatic melanoma without need for a third-line treatment. Two years later, a relapse of hismyasthenic symptoms was observed along with new neurological symptoms related to brain radiation necrosis.
Conclusion
We describe the first case of MG-LE overlap syndrome diagnosed after anti-PD1 immunotherapy for metastatic melanoma, which appeared after radiation therapy and then relapsed after brain radiation necrosis. We hypothesized a role for brain inflammation as a trigger for MG-LE onset. Neuro-muscular junctions disease induced or revealed by checkpoint inhibitors can be challenging and requires long-term follow-up.
Background
Anti-MAG polyneuropathy (anti-MAG PN) is an immune-mediated peripheral sensorimotor neuropathy characterized by distal demyelination and ataxia. However, this disorder, unlike other ...immune-mediated neuropathies, is difficult to treat in most cases.
Method
We retrospectively collected all anti-MAG PN patients followed in two hospitals for a period of 12 years to determine prognostic factors, especially those that indicated a good response to the various therapeutic strategies used.
Results
Forty-seven patients were included in the study; of these, 61% had a classical ‘distal demyelinating pattern’, 34.2% had a ‘CIDP-like pattern’, and the others had an ‘axonal pattern’. The most commonly used treatments were intravenous immunoglobulin (IVIg) as the first-line treatment and rituximab as the second- or third-line treatment. No prognostic factor was identified for IVIg, but electrophysiological parameters at onset were better in patients with a good response to rituximab than in non-responder patients, even though mild or high disability was observed in nearly half the patients at last examination.
Conclusion
Even though disability seems to progress in most cases despite the treatments used, our results suggest that an early electrophysiological reduction in sensory nerves could be considered a ‘red flag’ for the prompt initiation of rituximab to try to delay long-term disability.
Introduction. Amyotrophic lateral sclerosis (ALS), usually fatal in a few years, is a neurodegenerative disorder where the diagnostic delay, although variable according to the studies, remains too ...long. The main objective of this study was to determine the average time to diagnose ALS and the role of each physician, general practitioner (GP), or specialist (neurologist or not) involved in the management of these patients. The secondary objective was to propose some simple schemes to quickly identify an ALS suspicion with the aim to reduce this delay. Patients and Methods. This retrospective study evaluated the diagnostic delay (and other intermediate delays) of 90 ALS patients registered in the ALS Center of Bordeaux (France) in 2013. The main clinical signs encountered (and their order of appearance) were studied. Results. The average diagnostic delay was 17 months, with a median diagnostic delay of 12 months. The average diagnostic delay was 2.7 months between the first symptoms and the first complaint to GP, followed by an additional 6.5 month delay before the patient’s first visit to a neurologist. This period could be shortened, especially if GP performed additional tests quickly (p=0.01), as the time spent consulting various specialists often extends this crucial step. Overall, diagnostic delay accounted for 40% of the total duration of the disease progression. Conclusion. In relation to total survival time, the diagnostic delay of ALS appears to be proportionately very long, sometimes longer than that observed in previous studies (because it also included the total delay to diagnostic or treatment initiation). The rapid execution of useful additional tests by the first medical doctor, often GP (with the help of a neurologist), considerably reduces the diagnostic delay. The central role of GP seems to be crucial in the management of patients with ALS. The main objective is, of course, to initiate appropriate treatment and care as soon as possible. Finally, based on our results, we also provide a short practical diagram to help nonneurologist practitioners to quickly discuss the diagnosis of ALS in case of some specific symptoms (“red flags”).
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