First Japanese autopsy case showing LRRK2 mutation G2019S and TDP-43 proteinopathy.

This is the first Japanese autopsy case of Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation with atypical TDP43 proteinopathy. Our case is important that presented clinically dysphagia and pathologically TDP-43 proteinopathy. TDP43 may play an important role of clinical presentation with LRRK2 G2019S mutation carriers.

A web-based questionnaire survey on the influence of coronavirus disease-19 on the care of patients with muscular dystrophy.

To clarify the influence of coronavirus disease-19 (COVID-19) on the care of muscular dystrophy patients, we performed a questionnaire survey that was posted on the internet on May 11, 2020. By the end of July 2020, 542 responses had been collected. Approximately 30% of patients postponed regular consultations, and one-quarter of patients who received consultation more than once a month used telephone consultations.

An autopsy case of PARK2 due to a homozygous exon 2 deletion of parkin and associated with α-synucleinopathy.

Lewy bodies (LBs) are usually detected in patients with idiopathic Parkinson's disease (PD), but there have been few reports of LBs in a familial form of early-onset PD associated with several mutations in parkin, a gene that encodes a ubiquitin E3 ligase involved in mitochondrial homeostasis, being also known as PARK2. Here, we report a case of PD with a PARK2 mutation characterized by a homozygous deletion of exon 2 and incidental LB pathology. A 60-year-old man developed tremor in the upper limbs.

Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene.

We investigated the immunohistochemical localization of several proteins related to excitation-contraction coupling and ultrastructural alterations of the sarcotubular system in biopsied muscles from a father and a daughter in a family with permanent myopathy with hypokalemic periodic paralysis (PMPP) due to a mutation in calcium channel CACNA1S; p. R1239H hetero. Immunostaining for L-type calcium channels (LCaC) showed linear hyper-stained regions indicating proliferation of longitudinal t-tubules.

Cognitive and behavioral status in Japanese ALS patients: a multicenter study.

Objectives: Amyotrophic lateral sclerosis (ALS) patients may present with cognitive and behavioral abnormalities similar to frontotemporal dementia (FTD). In this multicenter study we examined Japanese ALS patients with and without FTD in order to characterize the full extent of cognitive and behavioral abnormalities, including associations with functional motor status, anxiety and depression.

Methods: Patients were evaluated using the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Hospital Anxiety and Depression Scale, ALS Functional Rating Scale-Revised, spirometry, and verbal fluency tests.

The First Case of Spinocerebellar Ataxia Type 8 in Monozygotic Twins.

Spinocerebellar ataxia type 8 (SCA8) is a rare hereditary cerebellar ataxia showing mainly pure cerebellar ataxia. We herein report cases of SCA8 in Japanese monozygotic twins that presented with nystagmus, dysarthria, and limb and truncal ataxia. Their ATXN8OS CTA/CTG repeats were 25/97.

Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J).

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common clinical, genetic and neuropathological features. Some ALS patients have behavioral/personality changes, which could result in significant obstacles in the care provided by family members and caregivers. An easy screening tool would contribute greatly to the evaluation of these symptoms.

Autopsy case of spinocerebellar ataxia type 31 with severe dementia at the terminal stage.

Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant cerebellar ataxia commonly observed in Japan. However, few neuropathological examinations have been conducted. Here we report the case of a 76-year-old Japanese male SCA31 patient.

Repeated encephalopathy and hemicerebral atrophy in a patient with familial hemiplegic migraine type 1.

We herein describe a case of a 38-year-old man with familial hemiplegic migraine with a T666M mutation in the electrical potential-dependent calcium ion channel (CACNA1A) gene. His migraine was accompanied by hemiparesis and impaired consciousness. Brain magnetic resonance imaging revealed abnormalities in the right cortical hemisphere.

[Birt-Hogg-Dubé syndrome with repeated pneumothorax; report of a case].

A 36-year-old man had been treated by thoracoscopic bullectomy because of left pneumothorax at another hospital. 2 weeks post-surgery, he was transferred to our hospital because of recurrent left pneumothorax. Chest computed tomography (CT) revealed multiple, irregular-shaped pulmonary cysts of various sizes predominating in the apex of both lungs.

A 3-year cohort study of the natural history of spinocerebellar ataxia type 6 in Japan.

Background: Only a few prospective studies have determined which clinical symptoms and factors are associated with the disease severity of spinocerebellar ataxia type 6 (SCA6). A multicenter longitudinal cohort study was conducted to clarify both the natural history of SCA6 in Japan and the factors influencing disease progression.

Methods: Patients were consecutively recruited between 2007 and 2008.

Leber's Hereditary Optic Neuropathy with Olivocerebellar Degeneration due to G11778A and T3394C Mutations in the Mitochondrial DNA.

Background: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder with optic nerve atrophy. Although there are no other associated neurological abnormalities in most cases of LHON, cases of "LHON plus" have been reported.

Case Report: The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age.

ALS-parkinsonism-dementia complex of Kii and other related diseases in Japan.

The ALS/parkinsonism-dementia complex (PDC) of Kii is an endemic disease with a diverse phenotypic expression characteristic of classical ALS, parkinsonism and dementia. Its clinical and neuropathological manifestations are similar to a syndrome found in Guam, sharing classical ALS pathology together with many neurofibrillary tangles in the brain. The incidence rates of ALS declined dramatically between the 1950s and 1980s.

Hemiconvulsion-hemiplegia-epilepsy syndrome associated with CACNA1A S218L mutation.

Hemiconvulsion-hemiplegia-epilepsy syndrome involves sudden and prolonged unilateral seizures, followed by transient or permanent hemiplegia and epilepsy during infancy or early childhood. Some patients with familial hemiplegic migraine and demonstrating the S218L mutation in CACNA1A experience severe attacks with unilateral cerebral edema after trivial head trauma. We report on a 5-year-old Japanese girl presenting with hemiconvulsion-hemiplegia-epilepsy syndrome after infection with parvovirus B19.

An unusual case of elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with multiple cerebrovascular risk factors.

Here we report a female patient with elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). At age 71, she developed gait disturbance, followed by memory disturbance 1 year later. She had been treated for hypertension and diabetes mellitus for 19 years.

[Case of sporadic hemiplegic migraine with cerebellar ataxia].

A 34-year-old man was admitted with his unsteady gait, difficulty in speech and a paroxysmal severe headache accompanied with sensori-motor disturbance of the right extremities and aphasic symptom. His family history was unremarkable. His unsteadiness has progressed very slowly from childhood.

Prevalence of dementia in the rural island town of Ama-cho, Japan.

Background: With the striking increase in the number of elderly people in Japan, dementia has not only become a medical but also a social issue.

Methods: We studied the prevalence of dementing disorders in a rural island town of Japan (Ama-cho), using a door-to-door 2-phase design.

Results: Of the 120 persons screened as having cognitive impairment, 104 people were diagnosed as having dementia.

Detection of compound heterozygous deletions in the parkin gene of fibroblasts in patients with autosomal recessive hereditary parkinsonism (PARK2).

Mutations in the parkin gene are a common cause of autosomal recessive, juvenile or early onset parkinsonism (PARK2). In this report, we use RT-PCR to detect compound heterozygous deletions of the parkin gene in fibroblasts from two cases of middle age-onset familial parkinsonism with lower extremities-dominant resting tremor and mild cogwheel rigidity. Although exonic amplification of the parkin gene showed a deletional mutation of exon 3-4, their family histories suggested that the deletional mutations were a compound heterozygous abnormality of discrete origin.

Triple stimulation technique in patients with spinocerebellar ataxia type 6.

Objective: To establish further evidence that SCA6 may not be a pure cerebellar syndrome.

Methods: Seven patients with genetically confirmed SCA6 and 9 age-matched normal controls were studied. Recordings of the CMAP were obtained from the right first dorsal interosseus muscle.

Mouse motor neuron disease caused by truncated SOD1 with or without C-terminal modification.

Mutation of Cu/Zn superoxide dismutase (SOD1) contributes to a portion of the cases of familial amyotrophic lateral sclerosis (FALS). We previously reported on a FALS family whose members had a mutant form of SOD1 characterized by a 2-base pair (bp) deletion at codon 126 of the SOD1 gene. To investigate the cellular consequences of this mutation, we produced transgenic mice that expressed normal and mutated copies of human SOD1: wild-type SOD1 (W), wild-type SOD1 with a FLAG epitope at C-terminal (WF), mutated SOD1 with the 2-bp deletion (D), and SOD1 with the 2-bp deletion with FLAG (DF).

[An update on the familial headache syndromes].

Migraine is a common form of the chronic headache syndromes. Although the pathogenesis of migraine still remains enigmatic, there have been remarkable progress in headache research. Point mutations of P/Q-type Ca2+ channel alpha 1 subunit (CACNA1A) gene have been identified in familial hemiplegic migraine (FHM), which linked to chromosome 19 (FHM-1, OMIM 141500).

Huntington's Disease-like 2 (HDL2) in North America and Japan.

Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3.

Prevalence of progressive supranuclear palsy in Yonago, Japan.

There have been few reports of the prevalence of progressive supranuclear palsy (PSP): the present study examines its prevalence in Japan and compares the findings with those in Europe and the United States. The prevalence per 100,000 was 5.82 (men, 9.