A case report of an individual with Creutzfeldt-Jakob disease characterized by prolonged isolated thalamic lesions and rare MM2-cortical-type pathology.

Background: Diffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing Creutzfeldt-Jakob disease (CJD). Thalamic lesions are rarely detected by DWI in sporadic CJD (sCJD) cases with methionine homozygosity at polymorphic codon 129 (129MM) of the prion protein (PrP) gene. Here, we describe an unusual sCJD case, characterized by prolonged isolated thalamic diffusion hyperintensities and atypical brain pathology, in combination with the 129MM genotype.

RNA Foci in Two bi-Allelic RFC1 Expansion Carriers.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp.

The advances in the early and accurate diagnosis of Creutzfeldt-Jakob disease and other prion diseases: where are we today?

Introduction: Before the introduction of MRI diffusion-weighted images (DWI), the diagnosis of Creutzfeldt-Jakob disease (CJD) relied upon nonspecific findings including clinical symptoms, EEG abnormalities, and elevated levels of cerebrospinal fluid 14-3-3 protein. Subsequently, the use of DWI has improved diagnostic accuracy, but it sometimes remains difficult to differentiate CJD from encephalitis, epilepsy, and other dementing disorders. The revised diagnostic criteria include real-time quaking-induced conversion (RT-QuIC), detecting small amounts of CJD-specific prion protein, and clinically sensitive DWI.

Reduced likelihood of the Poggendorff illusion in cerebellar strokes: a clinical and neuroimaging study.

This study aimed to test our hypothesis that the cerebellum plays an important role in the generation of the optical-geometric illusion known as the Poggendorff illusion, the mechanism of which has been explained by accumulated experience with natural scene geometry. A total of 79 participants, comprising 28 patients with isolated cerebellar stroke, 27 patients with isolated cerebral stroke and 24 healthy controls, performed Poggendorff illusion tasks and 2 different control tasks. We also investigated core brain regions underpinning changes in the experience of the illusion effect using multivariate lesion-symptom mapping.

Rapid and comprehensive diagnostic method for repeat expansion diseases using nanopore sequencing.

We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed.

Relationship between motor learning and gambling propensity in Parkinson's disease.

Introduction: The basal ganglia and related dopaminergic cortical areas are important neural systems underlying motor learning and are also implicated in impulse control disorders (ICDs). Motor learning impairments and ICDs are frequently observed in Parkinson's disease (PD). Nevertheless, the relationship between motor learning ability and ICDs has not been elucidated.

Repeat conformation heterogeneity in cerebellar ataxia, neuropathy, vestibular areflexia syndrome.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied. To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION.

Case Report: Extremely Early Detection of Preclinical Magnetic Resonance Imaging Abnormality in Creutzfeldt-Jakob Disease With the V180I Mutation.

The diagnosis of presymptomatic Creutzfeldt-Jakob disease (CJD) is challenging. The levels of total tau protein, 14-3-3 protein, and protease-resistant isoform of prion protein (PrP) in the cerebrospinal fluid; periodic sharp wave complexes on electroencephalography; and diffusion-weighted imaging (DWI) of brain magnetic resonance imaging (MRI) have all been used to diagnose symptomatic CJD, but none of these markers have been established in the diagnosis of presymptomatic CJD. Here, we report a case of genetic CJD with the V180I mutation in which a small punctate cortical hyperintensity was detected on DWI 6 months before symptom onset and 9 months before diagnosis.

Therapeutic efficacy of heparin and direct factor Xa inhibitors in cancer-associated cryptogenic ischemic stroke with venous thromboembolism.

Background: Anticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE.

Qualitative Deficits in Verbal Fluency in Parkinson's Disease with Mild Cognitive Impairment: A Clinical and Neuroimaging Study.

Background: Mild cognitive impairment (MCI) in Parkinson's disease (PD) is considered a risk factor for PD with dementia (PDD). Verbal fluency tasks are widely used to assess executive function in PDD. However, in cases of PD with MCI (PD-MCI), the relative diagnostic accuracy of different qualitative verbal fluency measures and their related neural mechanisms remain unknown.

PLA2G6 variants associated with the number of affected alleles in Parkinson's disease in Japan.

This study aimed to evaluate genotype-phenotype correlations of Parkinson's disease (PD) patients with phospholipase A2 group V (PLA2G6) variants. We analyzed the DNA of 798 patients with PD, including 78 PD patients reported previously, and 336 in-house controls. We screened the exons and exon-intron boundaries of PLA2G6 using the Ion Torrent system and Sanger method.

Clinical characterization of patients with leucine-rich repeat kinase 2 genetic variants in Japan.

Variants of leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD). We aimed to investigate the genetic and clinical features of patients with PD and LRRK2 variants in Japan by screening for LRRK2 variants in three exons (31, 41, and 48), which include the following pathogenic mutations: p.R1441C, p.

Adjustment of Subthalamic Deep Brain Stimulation Parameters Improves Wheeze and Dyspnea in Parkinson's Disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for motor features in Parkinson's disease (PD). We present the case of a 56-year-old man with a 17-year history of PD. He underwent bilateral STN-DBS at the age of 51 years because of troublesome dyskinesia and wearing off.

GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy.

Leukoencephalopathies comprise a broad spectrum of disorders, but the genetic background of adult leukoencephalopathies has rarely been assessed. In this study, we analyzed 101 Japanese patients with genetically unresolved adult leukoencephalopathy using whole-exome sequencing and repeat-primed polymerase chain reaction for detecting GGC expansion in NOTCH2NLC. NOTCH2NLC was recently identified as the cause of neuronal intranuclear inclusion disease.

White matter hyperintensities on MRI in dementia with Lewy bodies, Parkinson's disease with dementia, and Alzheimer's disease.

Background: In dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), it is still debated whether white matter hyperintensities (WMH) on MRI reflect atherosclerotic cerebrovascular changes or Alzheimer's disease (AD)-related pathology such as cerebral amyloid angiopathy. To examine AD-related pathology in DLB and PDD, we compared the severity of WMH and medial temporal lobe atrophy among patients with DLB, PDD, non-demented PD (PDND), and AD.

Methods: We retrospectively studied sex- and age-matched outpatients with AD, DLB, PDD, and PDND, as well as subjects without central nervous system disorders as normal controls (n=50 each).

A Novel Mutation in ELOVL4 Leading to Spinocerebellar Ataxia (SCA) With the Hot Cross Bun Sign but Lacking Erythrokeratodermia: A Broadened Spectrum of SCA34.

Importance: Although mutations in 26 causative genes have been identified in the spinocerebellar ataxias (SCAs), the causative genes in a substantial number of families with SCA remain unidentified.

Objective: To identify the causative gene of SCA in 2 Japanese families with distinct neurological symptoms and radiological presentations.

Design, Setting, And Participants: Clinical genetic study at a referral center of 11 members from 2 Japanese families, which started in 1997.

A Japanese case of cerebellar ataxia, spastic paraparesis and deep sensory impairment associated with a novel homozygous TTC19 mutation.

Mitochondrial complex III (CIII) deficiency comprises a group of complex and heterogeneous genetic disorders. TTC19 mutations constitute a rare cause of CIII deficiency and are associated with neurological disorders in childhood and adulthood. Herein, we describe a 27-year-old Japanese man with cerebellar ataxia, spastic paraparesis, loss of deep sensation, mild frontal lobe dysfunction and transient psychiatric symptoms.

Quantitative analysis of upper-limb ataxia in patients with spinocerebellar degeneration.

Spinocerebellar degeneration (SCD) is a progressive neurodegenerative disorder in which cerebellar ataxia causes motor disability. There are no widely applicable methods for objective evaluation of ataxia in SCD. An objective system to evaluate ataxia is necessary for use in clinical trials of newly developed medication and rehabilitation.

Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses.

Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because >30 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing.

Multiple cerebral infarction and cardiomyopathy with pheochromocytoma.

A 44-year-old woman was admitted to our hospital with altered mental status and weakness in the left upper and lower limbs. A brain magnetic resonance imaging indicated multiple cerebral infarctions in the bilateral frontal and parietal lobes and in the left occipital lobe. Magnetic resonance angiography indicated overall arterial wall irregularity and stenosis.

P1 and P2 components of human visual evoked potentials are modulated by depth perception of 3-dimensional images.

Objective: To determine the cerebral activity correlated with depth perception of 3-dimensional (3D) images, by recording of human visual evoked potentials (VEPs).

Methods: Two figures consisting of smaller and larger squares were presented alternately. VEPs were recorded in two conditions.