Pathogenic Potential of Eomesodermin-Expressing T-Helper Cells in Neurodegenerative Diseases.

Eomesodermin-expressing (Eomes) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls.

Parkinsonism in spinocerebellar ataxia with axonal neuropathy caused by adult-onset COA7 variants: a case report.

Background: Individuals with variants of cytochrome c oxidase assembly factor 7 (COA7), a mitochondrial functional-related gene, exhibit symptoms of spinocerebellar ataxia with axonal neuropathy before the age of 20. However, COA7 variants with parkinsonism or adult-onset type cases have not been described.

Case Presentation: We report the case of a patient who developed cerebellar symptoms and slowly progressive sensory and motor neuropathy in the extremities, similar to Charcot-Marie-Tooth disease, at age 30, followed by parkinsonism at age 58.

Cynomolgus macaque model of neuronal ceroid lipofuscinosis type 2 disease.

Neuronal ceroid lipofuscinoses (NCLs) are autosomal-recessive fatal neurodegenerative diseases that occur in children and young adults, with symptoms including ataxia, seizures and visual impairment. We report the discovery of cynomolgus macaques carrying the CLN2/TPP1 variant and our analysis of whether the macaques could be a new non-human primate model for NCL type 2 (CLN2) disease. Three cynomolgus macaques presented progressive neuronal clinical symptoms such as limb tremors and gait disturbance after about 2 years of age.

Tracheoarterial fistula in a patient with amyotrophic lateral sclerosis successfully managed by overinflation of the tracheostomy tube cuff alone: a case report.

Background: Tracheoarterial fistula is the most devastating complication after tracheostomy, and its mortality, without definitive treatment, approaches 100%. In general, the combination of bedside emergency management, that is, overinflation of the tracheostomy tube cuff, and definitive treatment such as surgical or endovascular intervention is necessary to prevent the poor outcome. Patients with neuromuscular diseases such as amyotrophic lateral sclerosis are susceptible to tracheoarterial fistula because of long-term mechanical ventilation and muscle weakness.

[Waldenström macroglobulinemia complicated by peripheral neuropathy due to neural infiltration].

A 51-year-old man with the chief complaint of glove- and stocking-type dysesthesia for >3 years was diagnosed with Waldenström's macroglobulinemia (WM) based on IgM-type M-proteinemia, bone marrow infiltration of plasmacytoid B cells, multiple lymphadenopathies, and splenomegaly. A nerve conduction examination suggested demyelinating neuropathy. Serum anti-myelin-associated glycoprotein antibody was negative.

Dentatorubropallidoluysian Atrophy with Prominent Autonomic Dysfunction.

We herein report a 45-year-old man with dentatorubropallidoluysian atrophy (DRPLA) who presented with mild dementia, ataxia, and involuntary movement and developed constipation, dysuria, and orthostatic hypotension. Thermography revealed an abnormal thermal response of the skin to cold stimulation. Skin temperature reflects the skin blood flow and is regulated by the sympathetic nervous system.

Reduced CSF orexin levels in rats and patients with systemic inflammation: a preliminary study.

Objective: Sepsis is a lethal condition characterized by systemic inflammation and multiple organ failure; this condition was initially defined as systemic inflammatory response syndrome (SIRS) due to infection. We previously reported that the hypothalamic neuropeptide orexin improved survival in a murine model of sepsis by mainly acting in the medullary raphe nucleus through orexin type-2 receptors. We hypothesized that orexin treatment enhances recovery from sepsis by reversing the reduction in orexin levels in the cerebrospinal fluid (CSF).

Amyloid-β oligomers interact with NMDA receptors containing GluN2B subunits and metabotropic glutamate receptor 1 in primary cortical neurons: Relevance to the synapse pathology of Alzheimer's disease.

Recent evidence suggests that soluble amyloid-β oligomers (AβOs) act as a key factor in the pathogenetic mechanism of Alzheimer's disease (AD). AβOs induce neurotoxic and synaptotoxic effects probably through binding to certain receptors, however it remains unclarified which receptors are most critically involved. In addition, dysregulation in glutamatergic signaling is implicated in AD.

Reliability of antinuclear matrix protein 2 antibody assays in idiopathic inflammatory myopathies is dependent on target protein properties.

A line blotting assay (LB) is currently used to detect myositis-specific autoantibodies (MSAs) in patients with idiopathic inflammatory myopathies (IIMs), because of its simplicity; however, the sensitivity and specificity of this assay is low. The aim of this study is to evaluate the accuracy of the commercial LB in detection of antinuclear matrix protein 2 (NXP2) antibody. Seventy-seven serum samples from patients with IIMs, in which anti-NXP2 antibodies were detected through immunoprecipitation and western blotting (IP-WB) using K562 cell lysate, were enrolled.

Cybernic treatment with wearable cyborg Hybrid Assistive Limb (HAL) improves ambulatory function in patients with slowly progressive rare neuromuscular diseases: a multicentre, randomised, controlled crossover trial for efficacy and safety (NCY-3001).

Background: Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients.

Anti-nuclear matrix protein 2 antibody-positive inflammatory myopathies represent extensive myositis without dermatomyositis-specific rash.

Objectives: Myositis-specific autoantibodies (MSAs) define distinct clinical subsets of idiopathic inflammatory myopathies (IIMs). The anti-nuclear matrix protein 2 (NXP2) antibody, a MSA detected in juvenile/adult IIMs, has been reported to be associated with a high risk of subcutaneous calcinosis, subcutaneous oedema and internal malignancies. The study aimed to clarify the clinical features of anti-NXP2 antibody-positive IIMs in detail.

Transcriptome analysis of gravitational effects on mouse skeletal muscles under microgravity and artificial 1 g onboard environment.

Spaceflight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artificial earth-gravity (artificial 1 g; AG) and microgravity (μg; MG), to investigate whether artificial 1 g exposure prevents muscle atrophy at the molecular level. Our main findings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fiber type composition but also in the alteration of gene expression profiles.

Clinical Application of the Vestibular Stimulation Effect on Balance Disorders with Dementia.

Background: In a previous study on Alzheimer's disease (AD), we showed that vestibular dysfunction derived from cerebral disorders contributes to balance disorders. No previous clinical study has attempted to prevent the progression of balance disorders in dementia patients through vestibular stimulation using an air caloric device.

Objective: The purpose of this pilot study was to delay the progression of balance disorders by inducing vestibular compensation, specifically by utilizing the effect of vestibular stimulation to activate the cerebrum.

Amyopathic dermatomyositis combined with peripheral neuropathy.

We provide the first report of amyopathic dermatomyositis combined with peripheral neuropathy. Our patient, a 49-year-old woman, initially experienced muscle weakness and tingling sensations in her legs, and nerve conduction study findings and the detection of antiganglioside antibodies indicated that she had autoimmune peripheral neuropathy. The unexpected presence of skin lesions, interstitial pneumonia and antibodies to melanoma differentiation-associated protein 5 prompted an additional diagnosis of amyopathic dermatomyositis.

Normocalcemic Primary Hyperparathyroidism Presenting with Muscle Weakness and Body Pain.

We herein report a 39-year-old woman who had aggravated body pain, waddling gait, and fatigability for the past 2 years. A neurological examination showed hyperreflexia and proximal muscle weakness. The serum calcium level was normal (10.

Two distinct prions in fatal familial insomnia and its sporadic form.

Fatal familial insomnia is a genetic prion disease, which is associated with the aspartic acid to asparagine substitution at codon 178 of the prion protein gene. Although the hallmark pathological feature is thalamic and olivary degeneration, there is a patient with an atypical fatal familial insomnia without the hallmark feature. The cause of the pathological variability is unclear.

Splice-site mutations in KIF5A in the Japanese case series of amyotrophic lateral sclerosis.

Our objective was to investigate the frequency of KIF5A variants in amyotrophic lateral sclerosis (ALS) and the clinical characteristics of familial ALS (FALS) associated with variants in KIF5A. Whole-exome sequence analysis was performed for a Japanese series of 43 families with FALS and 444 patients with sporadic ALS (SALS), in whom causative variants had not been identified. We compared the frequencies of rare variants (MAF < 0.