Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey.

Background And Objectives: To elucidate current epidemiologic, clinical, and immunologic profiles and treatments of stiff-person syndrome (SPS) in Japan.

Methods: A nationwide mail survey was conducted using an established method. Data processing sheets were sent to randomly selected departments of internal medicine, neurology, pediatrics, psychiatry, and neurosurgery in hospitals and clinics throughout Japan to identify patients with SPS who were seen between January 2015 and December 2017.

A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA.

All the currently used type A botulinum neurotoxins for clinical uses are of subtype A1. We compared the efficacy and safety for the first time head-to-head between a novel botulinum toxin A2NTX prepared from subtype A2 and onabotulinumtoxinA (BOTOX) derived from A1 for post-stroke spasticity. We assessed the modified Ashworth scale (MAS) of the ankle joint, the mobility scores of Functional Independence Measure (FIM), and the grip power of the unaffected hand before and after injecting 300 units of BOTOX or A2NTX into calf muscles.

Direct cerebello-striatal loop in dystonia as a possible new target for deep brain stimulation: A revised view of subcortical pathways involved.

Dystonia is the second most common movement disorder next to tremor, but its pathophysiology remains unsettled. Its therapeutic measures include anti-cholingerics and other medications, in addition to botulinum neurotoxin injections, and stereotaxic surgery including deep brain stimulation (DBS), but there still remain a number of patients resistant to the therapy. Evidence has been accumulating suggesting that basal ganglia in association with the cerebellum are playing a pivotal role in pathogenesis.

IncobotulinumtoxinA for Post-stroke Upper Limb Spasticity in Neutralizing Antibody-positive Patients after Botulinum Toxin Therapy: A Report of Two Cases.

Background: Botulinum toxin type A is an effective treatment widely used to address post-stroke spasticity. Long-term repeated treatment with botulinum toxin type A may result in reduced efficacy due to the induction of neutralizing antibodies. Based on data from a phase 3 study of incobotulinumtoxinA for post-stroke upper limb spasticity, we describe the therapeutic response to botulinum toxin type A treatment in two neutralizing antibody-positive patients previously treated with other preparations of botulinum toxin type A.

Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease.

Background And Objectives: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact.

Methods: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19B220 thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed.

Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia.

Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD.

The value of serum uric acid as a prognostic biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis.

Objective: To determine the value of uric acid (UA) as a prognostic biomarker for amyotrophic lateral sclerosis (ALS) using a meta-analysis of hazard ratio-based studies.

Methods: We included data from Tokushima University (47 patients with ALS) and three previous studies (1835 patients with ALS) with a hazard ratio (HR) identified by a systematic computational search. A total of four studies and 1882 patients were enrolled in the pooled analysis.

Efficacy of Istradefylline for the Treatment of -Related Disease.

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Association of anti-NR2 and U1RNP antibodies with neurotoxic inflammatory mediators in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus.

Background: Autoantibodies (auto Abs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). It is suggested that anti--methyl D-aspartate receptor NR2 subunit (NR2) Ab can develop NP manifestation after blood-brain barrier (BBB) abruption. We also reported the association between NPSLE and CSF anti-U1RNP Ab.

Significance of left atrial overload by electrocardiogram in the assessment of left ventricular diastolic dysfunction.

Background: Although assessment of left ventricular (LV) diastolic function (DF) using echocardiography is important, it is not always feasible in the clinical practice. On the other hand, left atrial (LA) overload shown by electrocardiogram (ECG) indicates LA pressure rise and LA dilatation. The purpose of this study is to examine whether LA overload by ECG can be used as an aid for evaluation of LVDF.

De novo hotspot variants in CYFIP2 cause early-onset epileptic encephalopathy.

Objective: The cytoplasmic fragile X mental retardation 1 interacting proteins 2 (CYFIP2) is a component of the WASP-family verprolin-homologous protein (WAVE) regulatory complex, which is involved in actin dynamics. An obvious association of CYFIP2 variants with human neurological disorders has never been reported. Here, we identified de novo hotspot CYFIP2 variants in neurodevelopmental disorders and explore the possible involvement of the CYFIP2 mutants in the WAVE signaling pathway.

Safety and efficacy of levodopa-carbidopa intestinal gel: results from an open-label extension study in Japanese, Korean and Taiwanese patients with advanced Parkinson's disease.

Objectives: Levodopa-carbidopa intestinal gel (LCIG) was developed to reduce motor complications in Parkinson's disease (PD) caused by pulsatile levodopa plasma concentrations following oral levodopa administration. Dyskinesia and 'wearing off' symptoms can vary between Asian and Caucasian patients with PD, thus highlighting the importance of assessing the effectiveness of LCIG in an Asian population. Efficacy and safety of LCIG were previously assessed in a 12-week open-label study; we report the efficacy and safety of at least 52 weeks of LCIG treatment in Japanese, Taiwanese, and Korean patients with advanced PD in the ongoing extension study.

Impact of UGT1A1 gene polymorphisms on plasma dolutegravir trough concentrations and neuropsychiatric adverse events in Japanese individuals infected with HIV-1.

Background: Dolutegravir (DTG) is metabolized mainly by uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1), and partly by cytochrome P450 3A (CYP3A). Therefore, we focused on UGT1A1 gene polymorphisms (*6 and *28) in Japanese individuals infected with human immunodeficiency virus (HIV)-1 to examine the relationship between their plasma trough concentration of DTG and gene polymorphisms. Recently, neuropsychiatric adverse events (NP-AEs) after the use of DTG have become a concern, so the association between UGT1A1 gene polymorphisms and selected NP-AEs was also investigated.

Efficacy and safety of levodopa-carbidopa intestinal gel from a study in Japanese, Taiwanese, and Korean advanced Parkinson's disease patients.

In a previous multinational, randomized, double-blind, double-dummy study, levodopa-carbidopa intestinal gel (LCIG) was tolerable and significantly improved 'off' time in advanced Parkinson's disease (PD) patients. However, efficacy and safety in the Asian population has not yet been demonstrated. In this open-label study, efficacy and safety of LCIG were assessed in Japanese, Korean, and Taiwanese advanced PD patients with motor complications not adequately controlled by available PD medication.

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.

Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months.

Feasibility of a Respiratory Movement Evaluation Tool to Quantify Thoracoabdominal Movement for Neuromuscular Diseases.

Background: An objective method to evaluate thoracoabdominal movement is needed in daily clinical practice to detect patients at risk of hypoventilation and to allow for timely interventions in neuromuscular diseases. The clinical feasibility, reliability, and validity of a newly developed method for quantifying respiratory movement using fiber grating sensors, called the Respiratory Movement Evaluation Tool (RMET), was evaluated.

Methods: The time needed to measure respiratory movement and the usability of the measurement were determined by 5 clinicians using the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) 2.

Clinicopathological features of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID.

GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.

Objective: Recently, de novo mutations in GRIN1 have been identified in patients with nonsyndromic intellectual disability and epileptic encephalopathy. Whole exome sequencing (WES) analysis of patients with genetically unsolved epileptic encephalopathies identified four patients with GRIN1 mutations, allowing us to investigate the phenotypic spectrum of GRIN1 mutations.

Methods: Eighty-eight patients with unclassified early onset epileptic encephalopathies (EOEEs) with an age of onset <1 year were analyzed by WES.

Pontine malformation, undecussated pyramidal tracts, and regional polymicrogyria: a new syndrome.

Background: Horizontal gaze palsy and progressive scoliosis is caused by mutations in the ROBO3 gene, which plays a role in axonal guidance during brain development. Horizontal gaze palsy and progressive scoliosis is characterized by the congenital absence of conjugate lateral eye movements with preserved vertical gaze and progressive scoliosis as well as dysgenesis of brainstem structures and ipsilateral projection of the pyramidal tract.

Patient: A 4-year, 11-month, girl presented with psychomotor retardation and autistic traits.

Utility of real-time three-dimensional echocardiography for Duchenne muscular dystrophy with echocardiographic limitations.

Duchenne muscular dystrophy (DMD) is strongly associated with a unique form of dilated cardiomyopathy. Cardiac complications are the leading cause of death in DMD; thus, longitudinal assessments and early intervention for cardiac dysfunction are necessary to improve prognosis. Two-dimensional echocardiography, which is routinely used for cardiac assessment, has some limitations for quantitative analyses in DMD patients with thoracic deformities and regional wall motion abnormalities in the left ventricle.

Anti-U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease.

Objective: To determine the significance of anti-U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE).

Methods: The frequency of antinuclear antibodies including anti-U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme-linked immunosorbent assay. The frequency of anti-U1 RNP antibodies in the CSF of patients with central NPSLE was examined, and the anti-U1 RNP index ([CSF anti-U1 RNP antibodies/serum anti-U1 RNP antibodies]/[CSF IgG/serum IgG]) was compared with CSF interleukin-6 (IL-6) levels and the albumin quotient (Qalb, an indicator of blood-brain barrier damage).