Acute therapeutic effects and pathophysiology of eosinophilic granulomatosis with polyangiitis neuropathy.

Objective: This study investigated the effects of early treatment and pathophysiology on eosinophilic granulomatosis with polyangiitis neuropathy (EGPA-N).

Methods: Twenty-six consecutive patients with EGPA-N were diagnosed and treated within a day of admission and underwent clinical analysis. Peripheral nerve recovery rates were evaluated after early treatment by identifying the damaged peripheral nerve through detailed neurological findings.

A single-center, single-arm, prospective, open-label, and comparative trial to evaluate the safety and tolerability profile of a 90-day oral L-arginine hydrochloride intervention for patients with amyotrophic lateral sclerosis.

Weight loss, a key indicator of malnutrition in amyotrophic lateral sclerosis (ALS) patients, negatively impacts patient prognosis. However, effective nutritional interventions have not been adequately established. Research in ALS model mice has shown that L-arginine can prolong survival; however, no human intervention studies have been conducted.

Acalabrutinib and Obinutuzumab for Chronic Lymphocytic Leukemia Complicated With Peripheral Neuropathy.

A 40-year-old man presented to our hospital with subacute progressive muscle weakness in the limbs and leukocytosis. Subsequently, the patient was diagnosed with chronic lymphocytic leukemia (CLL) complicated by peripheral motor neuron neuropathy (axonopathy). Serology test for anti-ganglioside GM2 IgG antibody was positive, whereas paraneoplastic syndrome-related and anti-myelin-associated glycoprotein antibodies were not detected.

Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus.

To explore the potential efficacy of early initiation of intravenous cyclophosphamide (IVCPA), we reviewed consecutive four cases of super-refractory cryptogenic-new onset refractory status epilepticus (C-NORSE) between 2015 and 2023. We compared functional outcomes at 3 months and 1 year after the onset between patients who received IVCPA within 20 days (early-treated) and those who received it later (late-treated). All patients (median age: 43 years) had a prodromal fever.

Identification of ZNF850 as a novel CTG repeat expansion-related gene in myotonic dystrophy type 1 patient-derived iPSCs.

Myotonic dystrophy type 1 (DM1) is a dominantly inherited multi-system disease caused by expanded CTG repeats in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Similar to other repeat disorders, the expanded trinucleotide repeat is unstable and demonstrates a tendency to increase repeat size with age in affected tissues. DNA mismatch repair system is implicated in somatic instability.

Time-course assessment of oral intake function and its impact on end-of-life in older individuals over 90 years with frailty.

Aim: The study investigates end-of-life trajectories, focusing on the degree of oral intake function in older individuals with frailty aged over 90 years.

Methods: This retrospective observational study examined individuals aged 90 years and older who passed away at a long-term chronic care hospital and related facilities in Japan. We assessed their Clinical Frailty Scale (CFS) and Function Oral Intake Scale (FOIS), categorizing them into two groups-"preserved CFS" (CFS score ≤7) and "poor CFS" (CFS score ≥8)-considering evaluations conducted 6 months before death.

Myelin measurement in amyotrophic lateral sclerosis with synthetic MRI: A potential diagnostic and predictive method.

Background: Myelin damage has recently been highlighted as a major causative factor of amyotrophic lateral sclerosis (ALS). Although myelin damage has been pathologically identified in ALS, it has not been clinically evaluated. This study aimed to quantify myelin volume using synthetic MRI to evaluate myelin damage in patients with ALS, and determine its association with clinical parameters.

Machine Learning-Based Prediction of the Inhibitory Activity of Chemical Substances Against Rat and Human Cytochrome P450s.

The prediction of cytochrome P450 inhibition by a computational (quantitative) structure-activity relationship approach using chemical structure information and machine learning would be useful for toxicity research as a simple and rapid tool. However, there are few models focusing on the species differences between rat and human in the P450s inhibition. This study aimed to establish models to classify chemical substances as inhibitors or non-inhibitors of various rat and human P450s, using only molecular descriptors.

Alternative splicing dysregulation across tissue and therapeutic approaches in a mouse model of myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1), the leading cause of adult-onset muscular dystrophy, is caused by a CTG repeat expansion. Expression of the repeat causes widespread alternative splicing (AS) defects and downstream pathogenesis, including significant skeletal muscle impacts. The mouse model plays a significant role in therapeutic development.

Pembrolizumab-associated Neuronopathy with Improved Lower Limb Somatosensory Evoked Potential After Intravenous Methylprednisolone Treatment: A Case Report.

Cases of neuronopathy associated with immune checkpoint inhibitors (ICIs) have rarely been reported. We herein report a case of ICI-associated neuronopathy. A 54-year-old man underwent chemotherapy for right maxillary sinus cancer.

Establishment of a novel amyotrophic lateral sclerosis patient ( )-derived brain microvascular endothelial cell model reveals defective Wnt/β-catenin signaling: investigating diffusion barrier dysfunction and immune cell interaction.

Amyotrophic lateral sclerosis (ALS) is a major neurodegenerative disease for which there is currently no curative treatment. The blood-brain barrier (BBB), multiple physiological functions formed by mainly specialized brain microvascular endothelial cells (BMECs), serves as a gatekeeper to protect the central nervous system (CNS) from harmful molecules in the blood and aberrant immune cell infiltration. The accumulation of evidence indicating that alterations in the peripheral milieu can contribute to neurodegeneration within the CNS suggests that the BBB may be a previously overlooked factor in the pathogenesis of ALS.

Combination Biologic Therapy with Mepolizumab and Dupilumab for Severe Eosinophilic Granulomatosis with Polyangiitis and Chronic Rhinosinusitis with Nasal Polyp.

We report the case of a 55-year-old female with eosinophilic granulomatosis with polyangiitis and chronic rhinosinusitis with nasal polyp. Rhinosinusitis recurred 6 months after full-house endoscopic sinus surgery. Although conventional treatment with azathioprine and mepolizumab with steroids was given, it was difficult to simultaneously control both rhinosinusitis and eosinophilic granulomatosis with polyangiitis.

Cervical percutaneous interferential current stimulation improves citric acid cough tests in patients with Parkinson's disease on medication.

Aspiration pneumonia is the leading cause of death in patients with Parkinson's disease. The incidence of silent aspiration is high in such patients owing to decreased pharyngeal and laryngeal sensation; thus, interventions for this condition may help prevent pneumonia. In this single-arm, open-label study, we used a cervical percutaneous interferential current stimulation device to activate pharyngeal and laryngeal sensory nerves.

Analysis of the suprahyoid muscles during tongue elevation: High-density surface electromyography as a novel tool for swallowing-related muscle assessment.

Background: High-density surface electromyography (HD-sEMG) has enabled non-invasive analysis of motor unit (MU) activity and recruitment, but its application to swallowing-related muscles is limited.

Objective: We aimed to investigate the utility of HD-sEMG for quantitatively evaluating the MU recruitment characteristics of the suprahyoid muscles during tongue elevation.

Methods: We measured the sEMG activity of the suprahyoid muscles of healthy participants during tongue elevation using HD-sEMG.

Large-Scale Whole-Genome Analysis of HTLV-1-Associated Myelopathy Identified Hereditary Spastic Paraplegias.

Objectives: Distinguishing human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy from hereditary spastic paraplegia in patients infected with HTLV-1 is challenging due to overlapping clinical symptoms. The aim of this study was to explore the possibility that hereditary spastic paraplegia is inherently present in patients diagnosed with HTLV-1-associated myelopathy.

Methods: We performed whole-genome sequencing on 315 unrelated patients registered in the HTLV-1-Associated Myelopathy patient registry "HAM-net," from 2013 to 2022 in Japan.

Erythromycin for myotonic dystrophy type 1: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Myotonic dystrophy type 1 (DM1) is a devastating multisystemic disorder caused by a CTG repeat expansion in the gene, which subsequently triggers toxic RNA expression and dysregulated splicing. In a preclinical study, we demonstrated that erythromycin reduces the toxicity of abnormal RNA and ameliorates the aberrant splicing and motor phenotype in DM1 model mice.

Methods: This multicentre, randomised, double-blind, placebo-controlled, phase 2 trial was conducted at three centres in Japan to translate preclinical findings into practical applications in patients with DM1 by evaluating the safety and efficacy of erythromycin.