Vanishing White Matter Disease With c.254 >A Variant: Mild Clinical and MRI Findings.

Objectives: Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges.

Methods: We describe 2 of 3 individuals carrying the homozygous c.

p.Arg191Gln mutation in a patient with semantic dementia: a case report.

Variants in (encoding valosin-containing protein) lead to inclusion body myopathy, which is typically associated with Paget's disease of the bones and frontotemporal dementia (FTD). When symptoms of frontotemporal lobar degeneration (FTLD) develop in patients with pathogenic variants, the symptoms mainly present as behavioral-variant (bv) FTD and rarely as semantic dementia (SD). Various pathogenic variants have been reported to cause bvFTD, whereas the only variant previously linked to SD is p.

Spatiotemporal dynamics of reading Kana (syllabograms) and Kanji (morphograms).

Reading engages complex neural networks integrating visual, phonological, and semantic information. The dual-stream model posits ventral and dorsal pathways for lexical and sublexical processing in the left hemisphere and is well-supported in alphabetic languages. However, its applicability to non-alphabetic scripts remains unclear.

Therapeutic time window of disease-modifying therapy for early Alzheimer's disease.

Introduction: Recently approved disease-modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited "therapeutic time window," after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities.

Argatroban plus dual antiplatelet therapy versus dual antiplatelet alone for acute atherothrombotic cerebral infarction.

Background: Dual antiplatelet therapy (DAPT) is more effective than aspirin alone in preventing early recurrences of non-cardioembolic strokes. In Japan, DAPT is often combined with argatroban, a direct thrombin inhibitor, for treating acute atherosclerotic stroke. However, the safety and effectiveness of this combination compared with those of DAPT alone remains unclear.

Frequency of Guillain-Barré Syndrome During the COVID-19 Pandemic: A Multicenter Study.

Introduction/aims: The incidence of Guillain-Barré syndrome (GBS) during the COVID-19 pandemic varies according to country. We investigated the changes in the number of patients with GBS and their characteristics who were reported in Tokyo in 2020 at the beginning of the COVID-19 pandemic, compared to those two years prior.

Methods: Patients with GBS who were admitted between January 2018 and December 2020 to hospitals in Tokyo were retrospectively included.

Widespread distribution of α-synuclein oligomers in LRRK2-related Parkinson's disease.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson's disease (PD). While the clinical features of patients with LRRK2-PD resemble those of typical PD, there are significant differences in the pathological findings. The pathological hallmark of definite PD is the presence of α-synuclein (αSYN)-positive Lewy-related pathology; however, approximately half of patients with LRRK2-PD do not have Lewy-related pathology.

Elevated serum autotaxin levels and multiple system atrophy-like presentation in a patient with PLA2G6-associated neurodegeneration.

PLA2G6-associated neurodegeneration (PLAN) encompasses a spectrum of phenotypes caused by biallelic pathogenic variants in PLA2G6. Initially linked to infantile and atypical neuroaxonal dystrophy, PLAN now includes adult-onset conditions such as dystonia-parkinsonism, ataxia, and spastic paraplegia. We report a female patient presenting young-onset parkinsonism with pyramidal tract signs, cerebellar atrophy, and autonomic dysfunction, mimicking multiple system atrophy (MSA).

Regulation of MCCC1 expression by a Parkinson's disease-associated intronic variant: implications for pathogenesis.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein aggregation. While some familial cases result from single-gene mutations, most are sporadic, involving complex genetic and environmental interactions. Among PD risk loci identified through genome-wide association studies, MCCC1 encodes a mitochondrial enzyme essential for leucine catabolism; however, the causal variant remains unclear.

Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy.

Biallelic loss-of-function variants in CLCN2 lead to CLCN2-related leukoencephalopathy (CC2L), also called leukoencephalopathy with ataxia (LKPAT). CC2L is characterized clinically by a spectrum of clinical presentations including childhood- to adult-onset mild ataxia, spasticity, cognitive decline, and vision loss as well as typical MRI findings of symmetrical high signal intensities on the DWIs/T2WIs of the middle cerebellar peduncles (MCPs). We searched for pathogenic variants of CLCN2 in a case series of undiagnosed leukoencephalopathy accompanied by MCP signs, which led to the identification of four Japanese patients with CC2L.

Clinicopathological features of anti-HMGCR and anti-SRP myopathies that do not satisfy the EULAR/ACR criteria of inflammatory myopathies.

Objectives: The clinicopathological features of immune-mediated necrotizing myopathy (IMNM) sometimes mimic muscular dystrophy, complicating accurate diagnosis. The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria of idiopathic inflammatory myopathies (IIMs) are superior in terms of sensitivity and specificity; however, the sensitivity is reported to be relatively low in IMNM. We examined the clinicopathological characteristics and the prognoses of anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody-positive and anti-signal recognition particle (SRP) antibody-positive cases that do not satisfy the EULAR/ACR classification criteria.

Distinct cerebral perfusion patterns and linguistic profiles in Alzheimer's disease-related primary progressive aphasia.

Alzheimer's disease (AD)-related primary progressive aphasia (PPA) exhibits considerable heterogeneity in clinical presentation and neuroimaging patterns. No studies have quantitatively assessed cerebral perfusion patterns or systematically evaluated the internal heterogeneity of linguistic and neuroimaging features in this population. This study aimed to investigate cerebral hypoperfusion patterns and elucidate their correlation with diverse linguistic features in patients with AD-related PPA using a data-driven approach.

Factors affecting participation in web-based Alzheimer's questionnaire surveys: Lessons from the Japanese trial-ready cohort.

Background: Web-based approach is considered helpful for the research focused on screening and early detection of individuals with preclinical Alzheimer's disease (AD); obtaining sufficient responses is critical to the success of such online study.

Objectives: This study examined factors influencing response rates to an online survey about disease-modifying drugs for AD among participants in the Japanese Trial-Ready Cohort (J-TRC) webstudy.

Design: This was a retrospective observational study.

Case of Pure Agraphia in Kana and Romaji Without Sensorimotor Deficits After a Small Infarct of the Posterior Limb of the Internal Capsule.

Objectives: Infarctions of the posterior limb of the internal capsule (plIC) typically cause contralateral motor deficits. Cases with pure agraphia, writing impairments alone, are rare. We present a case of agraphia as the sole symptom after a small infarction in the anterior portion of the left plIC, which facilitates understanding of the interplay between the subcortical and cortical networks controlling writing.

In-frame deletion variant of ABCD1 in a sporadic case of adrenoleukodystrophy.

Adrenoleukodystrophy (ALD), an X-linked leukodystrophy caused by pathogenic variants in ABCD1, exhibits a broad range of phenotypes from childhood-onset cerebral forms to adult-onset adrenomyeloneuropathy (AMN). We report a rare in-frame ABCD1 deletion c.1469_71delTGG (p.

Clinical and Genetic Analyses of SPG7 in Japanese Patients with Undiagnosed Ataxia.

Objective Spastic paraplegia 7 (SPG7) is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in SPG7. It is predominantly characterized by adult-onset slowly progressive spastic paraparesis. While SPG7 presenting with ataxia with or without spasticity is relatively common in Europe and North America, it is considered rare in Japan.

[SELENON-related myopathy with scoliosis and respiratory failure since early childhood diagnosed through reassessment during pediatric-to-adult healthcare transition: a case report].

The patient was a 33-year-old woman with no family history of a similar disorder. At one year of age, she exhibited scoliosis and respiratory failure, necessitating a tracheostomy performed at 5 years of age (1990s). During that time, the patient was provisionally diagnosed with "non-Fukuyama congenital muscular dystrophy" via muscle biopsy.

[Guidelines for presymptomatic genetic testing for adult-onset hereditary neuromuscular diseases in Japan].

In Japan, there are no nationwide guidelines for presymptomatic testing for hereditary neuromuscular diseases. Although each institution has been dealing with this situation by using their own procedures to date, it is necessary to develop a standardized guidelines based on the Japanese medical system, because the development of disease-modifying therapies has progressed, and we are entering an era in which early diagnosis and early treatment are necessary. The guidelines presented here were devised by the Committee on Medical Genetics of the Japan Neurological Society.

Safety and outcomes of intravenous thrombolysis in acute ischemic stroke with intracranial artery dissection.

Background: Intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) related to underlying intracranial artery dissection (IAD) poses potential risks, including the exacerbation of intramural hematoma and the rupture of the dissected arterial wall. However, the safety of IVT in this specific population remains uncertain.

Aims: This study aimed to assess whether IAD is associated with an increased risk of intracranial hemorrhage (ICH) following IVT and to evaluate its impact on functional outcomes.

A subgroup of multiple system atrophy with rapid decline in vital capacity.

Introduction: Patients with neurodegenerative disorders resulting in progressive dysphagia often require gastrostomy. Pulmonary function tests (PFTs) are crucial in presurgical evaluation; however, reports on pulmonary function in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are limited.

Materials And Methods: This single-center, retrospective study analyzed the PFT records from patients with MSA and PSP admitted between January 2012 and October 2023.

Widespread Distribution of α-Synuclein Oligomers in -related Parkinson's Disease.

Mutations in leucine-rich repeat kinase 2 () are the most common cause of familial and sporadic Parkinson's disease (PD). While the clinical features of -PD patients resemble those of typical PD, there are significant differences in the pathological findings. The pathological hallmark of definite PD is the presence of α-synuclein (αSYN)-positive Lewy-related pathology; however, approximately half of -PD cases do not have Lewy-related pathology.