Persistence of Kii amyotrophic lateral sclerosis after the 2000s and its characteristic aging-related tau astrogliopathy.

Kii amyotrophic lateral sclerosis (ALS) is a unique disease that occurs in the southern portion of the Kii Peninsula and exhibits a dual pathology of TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy and tauopathy. The incidence of ALS in this region was very high in the 1960s, briefly decreased through the 1980s, but began increasing again after 2000 with a change of high-concentration geographic foci. It is unclear, however, whether the unique pathological features have changed along with the incidence changes. This study analyzed postmortem specimens from neuropathologically confirmed Kii ALS cases from the 1970s (n = 4) and those after 1999 (n = 12) from the southern Kii Peninsula or outside of the area. Our results confirm the continued occurrence of Kii ALS after 2000 in the southern Kii Peninsula and the preservation of disease-specific neuronal tau pathology, including the widespread occurrence throughout the brain and spinal cord, sparse neuropil threads, and predominance in superficial layers. Furthermore, we assessed the glial tau pathology of Kii and non-Kii ALS in accordance with the aging-related tau astrogliopathy classification method for the first time and detected a unique brainstem predominant appearance of gray matter aging-related tau astrogliopathy in Kii ALS cases, which may provide clues to pathogenetic mechanisms.

Japanese Mucuna pruriens (Hasshou beans) Showed Fast-acting and Long-lasting Effects in Parkinson's Disease.

Objective Mucuna pruriens (MP) is a legume whose seeds contain levodopa (LD), which has potential therapeutic effects against Parkinson's disease (PD). However, further research is needed to thoroughly evaluate its efficacy and safety for treating this condition. In this study, we analyzed the pharmacokinetics of MP grown in Japan and investigated its mechanism of action in PD. Methods MP seeds ground after roasting (containing 4.02% LD per MP powder) were used as the reagent and compared with an equivalent LD/carbidopa (CD) preparation. This clinical trial was conducted using a crossover design among PD patients attending our institution. Each patient received a single dose of 100/10 mg LD/CD tablets and 11 g of MP reagent. Results Among the seven patients with PD, MP prolonged the ON time 2-fold compared to LD/CD. The LD concentrations after MP intake were higher than those after LD/CD intake, whereas dyskinesia did not increase. An analysis of the LD metabolites showed that the 3-O-methyl-dopa/LD metabolic ratio was significantly lower after MP ingestion than after LD/CD ingestion, indicating that MP has a catechol-O-methyl transferase inhibitory effect. Conclusions This is the first report of a pharmacokinetic analysis conducted on actual patients with PD showing that MP significantly prolongs the ON time. The advantages of MP as a treatment for PD have been confirmed: it is inexpensive, as effective as LD, works faster and longer than LD, and does not increase dyskinesia.

Three-year follow-up of rheumatoid meningitis with matrix metalloprotease-9 levels in the serum and cerebrospinal fluid as indicators of disease activity: A case report.

Rheumatoid meningitis (RM) is an extra-articular complication of rheumatoid arthritis (RA). Although reports of RM sine arthritis exist, most patients with this presentation were diagnosed with RA within one year of RM onset. There are no established biomarkers reflecting the disease activity of RM. This case report highlights the elevation of matrix metalloprotease (MMP)-9 levels during the acute phase of RM and decline during remission. Additionally, this is the first case report of RA diagnosed three years after the onset of RM. It is important to further validate the utility of MMP-9 and conduct long-term follow-up of RM sine arthritis.

Effect of istradefylline on postural abnormalities in patients with Parkinson's disease: An association study of baseline postural angle measurements with changes in Unified Dystonia Rating Scale total score.

In our previous study, istradefylline treatment in patients with Parkinson's disease (PD) improved postural abnormalities (PAs), as seen from a decrease in the mean Unified Dystonia Rating Scale (UDRS) total score from week 0 to week 24. A subgroup analysis based on baseline clinical characteristics investigated the association between improvement in the UDRS total score and istradefylline treatment. However, the association between an objective assessment of PAs and improvement in the UDRS total score is unclear. This ad hoc analysis investigated the association between improvement in the UDRS total score after istradefylline treatment and baseline trunk and neck angles, objective assessments of PAs, measured from patients' photographs taken in the previous study. The patients (n = 31) were stratified into groups based on the trunk forward flexion angle (TFFA), trunk lateral flexion angle (TLFA), and neck flexion angle (NFA) values at baseline. From week 0 to week 24, significant improvements in the UDRS total score were found in median percent change (-8.33% [interquartile range: -43.97, 0.00], P = 0.039) in patients with equal to or above the median TFFA values, and in median change (-|1.50 [-9.25, 0.00], P = 0.015) and median percent change (-13.33% [-50.47, 0.00], P = 0.009) in patients with equal to or above the median TLFA values. Patients with more advanced PAs showed more consistent improvements in the UDRS total score with istradefylline. Baseline TFFA and TLFA values, which are objective values, may be useful to assess the istradefylline effectiveness in patients with PD and PAs.

Recovery of cardiac metabolic function after high-dose prednisolone in a patient with inflammatory myopathy associated with anti-mitochondrial antibody.

Myocardial complications in the setting of inflammatory myopathy associated with anti-mitochondrial antibody (AMA) cause various cardiovascular complications. A 64-year-old Japanese man was diagnosed with inflammatory myopathy associated with AMA, and three years after diagnosis, the patient was referred to our hospital with leg edema and dyspnea on exertion. Right ventricular endomyocardial biopsy showed no disease-specific findings, with neither inflammatory cell infiltration nor non-caseating epithelioid cell granuloma, and only mild fibrosis; therefore, we finally diagnosed this patient with cardiac involvement in inflammatory myopathy associated with AMA. 123I-ß-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) cardiac scintigraphy showed decreased uptake in wider areas discordant with late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR). One month after starting prednisolone (PSL), the symptoms of congestive heart failure and left ventricular (LV) systolic function had improved. Additionally, BMIPP uptake in the LV myocardium significantly improved compared to that before PSL administration, although decreased BMIPP uptake remained in areas concordant with LGE on CMR. Moreover, it is suggested that recovery of cardiac metabolic function after high-dose PSL administration, which was confirmed through improvement in BMIPP uptake in the LV myocardium, may have led to the improvement in both LV systolic function and heart failure. Learning objective: Although the definitive diagnosis of cardiac involvement in inflammatory myopathy associated with anti-mitochondrial antibody is difficult because of the rarity of this condition and no disease-specific findings in imaging and histology, physicians should consider this in patients with cardiac dysfunction and muscle weakness. 123I-ß-methyl-p-iodophenyl-pentadecanoic acid scintigraphy should be used to assess cardiac metabolic function and treatment efficacy and should be considered for patient management.

Noise Pareidolia Test in Parkinson's Disease and Atypical Parkinsonian Syndromes: A Retrospective Study.

INTRODUCTION: Pareidolias, or visual misperceptions, are a non-motor symptom of Parkinson's disease (PD) with unclear pathophysiology. The noise pareidolia test (NPT) is a tool for screening pareidolias. The usefulness of the NPT in differentiating PD from atypical parkinsonian syndromes (APS) is also unknown. METHODS: We retrospectively investigated 74 patients with PD and 18 patients with APS who took the NPT. Correlations between the number of pareidolic responses, gray matter volume, and cerebral blood flow were also examined in the patients with PD. RESULTS: The median number of pareidolic responses in patients with PD and patients with APS was 0 (interquartile range (IQR): 0-3) and 0 (IQR: 0-1), respectively, and tended to be higher in patients with PD than in those with APS (p = 0.077). It was significantly higher in patients with PD who had hallucinations (2; IQR: 0-9) (p = 0.016). The area under the receiver operating characteristic curve for the number of pareidolic responses in the NPT was 0.62 when used to differentiate PD and APS, and the optimal cutoff number of pareidolic responses was 2/3. Sensitivity and specificity were 25.7% and 100%, respectively. In the PD group, the number of pareidolic responses was correlated with age (r = 0.27; p = 0.021) and the Frontal Assessment Battery (FAB) score (r = -0.34; p = 0.0099). Magnetic resonance imaging showed no significant correlation between the number of pareidolic responses and the volume of focal gray matter. On cerebral hypoperfusion mapping, the left parietal lobe had a significant correlation with the number of pareidolic responses (r = 0.35; p = 0.027). CONCLUSION: The number of pareidolic responses in NPT was suggested to be useful as a red flag to rule out APS in differentiating PD from APS. In PD without dementia, the number of pareidolic responses was associated with reduced blood flow in the left parietal lobe.

Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.

BACKGROUND: MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia. OBJECTIVES: To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease. METHODS: Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin-induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti-tau antibody and PM-PBB3. RESULTS: We identified a variant, c.896_897insACA, p.K298_H299insQ, in the MAPT gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four-repeat tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM-PBB3. CONCLUSIONS: This study confirmed that the insACA mutation caused FTDP-17. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of MAPT mutations or specific pathogeneses of each mutation.