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The immune system has garnered attention due to its association with disease progression in amyotrophic lateral sclerosis (ALS). However, the role of peripheral immune cells in this context remains controversial. Here, we conducted single-cell RNA-sequencing of peripheral blood mononuclear cells to comprehensively profile immune cells concerning the rate of disease progression in patients with ALS. Our analysis revealed increased frequencies of T helper 17 cells (Th17) relative to regulatory T cells, effector CD8 T cells relative to naïve CD8 T cells, and CD16 high CD56 low mature natural killer cells relative to CD16 low CD56 high naïve natural killer cells in patients with rapidly progressive ALS. Additionally, we employed serum proteomics through a proximity extension assay combined with next-generation sequencing to identify inflammation-related proteins associated with rapid disease progression. Among these proteins, interleukin-17 A correlated with the frequency of Th17, while killer cell lectin-like receptor D1 (CD94) correlated with the frequency of effector CD8 T cells. These findings further support the active roles played by these specific immune cell types in the progression of ALS., Competing Interests: Declarations. Ethics approval and consent to participate: All study protocols were approved by the Ethics Committee of Tokushima University Hospital under protocol #3682. All clinical information was collected after patients provided written informed consent. The investigations were conducted following the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: TI, YO, DW, SM, and YK are employees of Takeda Pharmaceutical Company Limited., (© 2024. The Author(s).)

Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1 year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.

Background: Multifocal motor neuropathy (MMN) is characterized by clinical improvement with intravenous immunoglobulin and the frequent detection of anti-ganglioside antibodies. However, the immunological background of the neuronal damage in MMN is still unclear., Objective: The aim of this study is to investigate abnormalities in the cytokine and chemokine profiles of MMN patients., Methods: Sera from 16 patients with MMN, 16 patients with sporadic amyotrophic lateral sclerosis (ALS), and 15 patients with other non-inflammatory neurological diseases (ONDs) were analyzed for 27 cytokines and chemokines using a multiplex bead array. We also checked whether the altered cytokine/chemokine profile in the MMN group differed significantly in the presence or absence of abnormal electrophysiological findings., Results: Serum IL-1Ra, IL-2, G-CSF, TNF-α, and TNFR1 levels were significantly higher in the MMN group than in the ONDs group. Of these, G-CSF and TNF-α also showed significant increases compared to the ALS group. Serum G-CSF and TNF-α levels were significantly higher in MMN patients presenting with focal demyelination including conduction block than in patients without any focal demyelination., Conclusions: Proinflammatory cytokines may contribute to peripheral nerve demyelination in MMN., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Our objective was to do an epidemiologic survey of patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan., Methods: In this retrospective study, we examined 46 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. Diagnosis was based on the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) and the revised El Escorial criteria. The efficacy of intravenous immunoglobulin (IVIg) was also taken into consideration in the diagnosis of MMN., Results: The ratio of MMN to ALS patients (0–0.10) varied among the centers, but mostly converged to 0.05. The prevalence was estimated to be 0.29 MMN patients and 6.63 ALS patients per 100,000 population., Conclusions: The frequency of MMN patients was around 1 out of 20 ALS patients, and MMN was possibly underdiagnosed in some centers.

We surveyed patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan. This retrospective study consisted of 47 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. The ratio of MMN to ALS patients (0-0.10) varied among the centers, but mostly converged to 0.05. The prevalence was estimated to be 0.3 cases for MMN and 6.63 cases for ALS per 100,000 persons. Twenty-seven of 47 patients (56.5%) showed conduction block (CB). Of the 45 patients who received intravenous immunoglobulin (MVg), 34(75.6 %) demonstrated clear clinical improvement.

We report a case of an 82‐year‐old woman with inclusion body myositis (IBM), who presented with severe dysphagia, finger flexor weakness, and respiratory dysfunction. In addition, the patient showed prominent forearm weakness with quadriceps sparing and was seropositive for the anti‐cytosolic 5′‐nucleotidase 1A (NT5c1A) antibody. The presence of the anti‐NT5c1A antibody is presumably associated with dysphagia. We speculate that the anti‐NT5c1A antibody is associated with the large discrepancy between distal upper limb weakness and proximal lower limb weakness in IBM. [ABSTRACT FROM AUTHOR]