Validation study of the Japanese version of the King's Parkinson's Disease Pain Scale and the King's Parkinson's Disease Pain Questionnaire.

INTRODUCTION: The King's Parkinson's Disease Pain Scale (KPPS)/King's Parkinson's Disease Pain Questionnaire (KPPQ) was developed as a tool to quantitatively assess pain in patients with Parkinson's disease (PwPD). Here, we conducted a Japanese multicenter validation study to verify the reliability of KPPS/KPPQ in Japanese PwPD. METHODS: PwPD, ≥20 years, with unexplained pain were included; those with a definitive primary cause of pain other than PD were excluded. A total of 151 patients who fulfilled the criteria were analyzed, and test-retest reliability was investigated in 25 individuals. RESULTS: The 151 patients included 101 women (66.9 %); mean age 68.3 ± 9.9 years, mean disease duration 9.2 ± 5.2 years. The most frequent pain type in the KPPS classification was musculoskeletal pain (82.8 %). There was a positive correlation between KPPS total score and the Non-Motor Symptoms Scale (NMSS) total score, NMSS item 27, the Parkinson's disease sleep scale-version 2 (PDSS-2) total score, PDSS-2 item 10, the Parkinson's Disease Questionnaire-8 (PDQ-8) summary index and PDQ-8 item 7. Cronbach's alpha of KPPS was 0.626 (0.562-0.658) and the intraclass correlation coefficient of test-retest reliability was 0.740. Cronbach's alpha of KPPQ was 0.660 (0.617-0.705) and a test-retest reliability of kappa coefficient was 0.593 (0.0-1.0). CONCLUSIONS: KPPS correlated well with other scales for assessing pain. KPPS correlated well with patients' quality of life, non-motor symptoms, and sleep disturbances. The reproducibility of KPPS/KPPQ makes it suitable for continuous evaluation of the same patient. On the other hand, the internal consistency of KPPS/KPPQ is rather low.

Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes.

Background: Distinguishing multiple system atrophy from other parkinsonian syndromes is challenging. Objectives: To evaluate vagus nerve ultrasonography for differentiating parkinsonian syndromes. Methods: A single-center, cross-sectional, observational study assessed 85 consecutive adult patients with de novo parkinsonism between June 2020 and December 2022, using 12 MHz ultrasonography of the vagus nerve cross-sectional area. Results: Bilateral vagus nerves were smaller in multiple system atrophy than in other parkinsonian syndromes. The area under the receiver operating characteristic curve for differentiating multiple system atrophy was 0.79 on the right side and 0.74 on the left. The cut-off values to diagnose multiple system atrophy were 0.71 and 0.86 mm2 on the right and left sides, respectively, with sensitivities of 82.6% and 87.0%, specificities of 74.2% and 64.5%, positive predictive values of 54% and 47.6%, and negative predictive values of 92.0% and 93.0%. Conclusions: Vagus nerve ultrasonography may differentiate multiple system atrophy from other parkinsonian syndromes.

A cross-sectional study of Parkinson's disease and the prodromal phase in community-dwelling older adults in eastern Japan.

Introduction: Parkinson's disease (PD) is more prevalent in the aging population, and epidemiological evidence must be constantly updated to provide an accurate understanding of PD prevalence. Various nonmotor symptoms of PD precede the onset of motor symptoms and prodromal PD. The detection of such symptoms is crucial yet remains challenging. In this study, we aimed to clarify the current prevalence of PD and prodromal PD. Methods: We enrolled 714 community-dwelling older adults (330 men and 384 women) aged ≥ 65 years (mean age 76.3 years). We used a self-administered questionnaire based on the International Parkinson and Movement Disorder Society prodromal PD criteria to obtain information on prodromes and calculate PD probability. Patients with a probability of ≥ 0.3 were considered as having prodromal PD. We analyzed the crude prevalence rates of PD and prodromal PD. Results: The crude prevalence rate of PD in our sample was 279.7 per 100,000 persons. The crude prevalence rate of prodromal PD and PD probability were 5034.5 per 100,000 persons and 0.057 ± 0.121, respectively. Never smoker (61.4%), physical inactivity (47.0%), regular pesticide exposure (30.7%), and urinary dysfunction (26.5%) were frequent positive prodromes. Subjects with higher PD probability possessed more variable prodromal markers than those with lower probability. Conclusion: We examined current prevalence rates of PD and prodromal PD in community-dwelling older adults aged ≥ 65 years in Japan. Our questionnaire-based approach to examine prodromal PD provided valuable evidence for the prevalence of prodromal PD in the aging population.

Altered gut microbiota in Parkinson's disease patients with motor complications.

INTRODUCTION: Parkinson's disease (PD) is associated with gut dysbiosis. However, whether gut dysbiosis can cause motor complications is unclear. METHODS: Subjects were enrolled from four independent movement disorder centers in Japan. We performed 16S ribosomal RNA gene sequence analysis of gut microbiota. Relative abundance of gut microbiota and relationships between them and clinical characteristics were statistically analyzed. Analysis of co-variance (ANCOVA) was used to assess altered gut microbiota associated with wearing-off or dyskinesia. RESULTS: We enrolled 223 patients with PD. Wearing-off was noted in 47.5% of patients and dyskinesia in 21.9%. We detected 98 genera of bacteria. Some changes in the gut microbiota were observed in patients with PD and motor complications. After Bonferroni correction, patients with wearing-off showed decreased relative abundance of Lachnospiraceae Blautia (p < 0.0001) and increased relative abundance of Lactobacillaceae Lactobacillus (p < 0.0001), but patients with dyskinesia no longer showed significant changes in the gut microbiota. Adjustment with two models of confounding factors followed by ANCOVA revealed that age (p < 0.0001), disease duration (p = 0.01), and wearing-off (p = 0.0004) were independent risks for the decreased relative abundance of Lachnospiraceae Blautia, and wearing-off (p = 0.009) was the only independent risk factor for the increased relative abundance of Lachnospiraceae Lactobacillus. CONCLUSION: Relative abundance of Lachnospiraceae Blautia and Lactobacillaceae Lactobacillus was significantly decreased and increased, respectively, in the gut microbiota of PD patients with motor complications. This indicates that an altered gut microbiota is associated with the development of motor complications in patients with advanced PD.

Cerebrospinal fluid levels of oxidative stress measured using diacron-reactive oxygen metabolites and biological antioxidant potential in patients with Parkinson's disease and progressive supranuclear palsy.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Because no curative therapy is available for PD, elucidation of its pathophysiology is important to establish more effective treatments. Oxidative stress (OS) has gained attention and been investigated as one of the candidates involved in the pathogenesis of PD. This study aimed to evaluate OS in the cerebrospinal fluid (CSF) of patients with PD and progressive supranuclear palsy (PSP) using diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests, which can easily assess OS in liquid samples. Results were compared to the clinical background of patients and with those of the normal control (NC) group. CSF samples were obtained from 69 patients with PD, 14 patients with PSP, and 22 individuals in the NC group. OS levels and antioxidant capacity were measured using d-ROMs and BAP tests, respectively. CSF d-ROM levels were extremely low (<10 U.CARR) in all 3 groups than the plasma d-ROM levels. Antioxidant capacity was significantly higher in patients with PSP (1074 ± 79 µM) than in patients with PD (918 ± 350 µM) (p = 0.019). In the PD group, antioxidant capacity was significantly lower in patients with tremor (858 ± 269 µM) than in those without tremor (1132 ± 505 µM) (p = 0.004). Our study suggests that the CSF level of OS is under homeostatic control of antioxidative mechanisms in healthy individuals as well as those with neurodegenerative diseases, and increased antioxidant capacity can indicate the CSF level of OS. The lower CSF level of OS in the tremor dominant subtype of PD may be the reason for the benign clinical course.

Impaired metabolism of kynurenine and its metabolites in CSF of parkinson's disease.

AIM: The kynurenine (KYN) pathway plays an important role in degrading molecules responsible for oxidative stress in the central nervous system (CNS), but can also have neurotoxic effects. Both 3-hydroxykynurenine (3-HK) and quinolinic acid are neurotoxic metabolites produced from this pathway. In Parkinson's disease (PD), oxidative stress is suspected to represent a key pathogenic mechanism. This study aimed to investigate the function of the KYN pathway and interactions between oxidative stress and neuroinflammation in PD. METHODS: Participants comprised 20 patients with PD and 13 controls. Cerebrospinal fluid (CSF) levels of KYN and 3-HK were measured using high-performance liquid chromatography coupled with an electrochemical detector. CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and interferon (IFN)-γ were measured with an enzyme-linked immunosorbent assay, and results were statistically compared between PD patients and controls. RESULTS: Median CSF levels of KYN and 3-HK were 49.0 nM and 4.25 nM in PD and 30.5 nM and 1.55 nM in controls, respectively, showing significantly higher levels in PD (p < 0.05). CSF levels of measured cytokines showed that TNF-α and IL-1ß were significantly higher in PD patients than in controls. No positive correlation between 3-HK and TNF-α was seen in PD. CONCLUSION: Dysfunction of the KYN pathway may induce oxidative stress in the CNS in PD, and may also induce cytokine-mediated neuroinflammation. Functional amelioration of the KYN pathway may facilitate modification of neurodegenerative processes in PD.

[A case of adult-onset mitochondrial encephalopathy due to m.4296G>A gene abnormality].

The case is a 30-year-old woman. From the age of 25 years, she had several episodes of cortical blindness and visited a local doctor. Mitochondrial disease was suspected based on findings of cerebral infarction-like imaging and a history of diabetes. However, serum and cerebrospinal fluid lactate levels were normal and no abnormal muscle pathology was found. At the age of 30 years, she visited our hospital with impaired consciousness, cortical blindness, and tremor-like involuntary movements in the neck and right fingers. Brain MRI showed abnormal signals in bilateral basal ganglia, with an increased lactate peak by magnetic resonance spectroscopy and high cerebrospinal fluid lactate levels. Mitochondrial gene analysis identified a m.4296G>A gene mutation. Consequently, we reached a diagnosis of mitochondrial encephalopathy. Adult-onset mitochondrial encephalopathy with m.4296G>A gene mutation is extremely rare. This case showed clinical features caused by damage of both the cerebral cortex and subcortical basal ganglia.

Conceptual definition in the metamorphosing Parkinson's disease.

Two hundred years ago, James Parkinson wrote 'An Essay on the Shaking Palsy'. The discovery of Lewy bodies in the substantia nigra and dopamine deficiency in the nigro- striatal dopaminergic system have confirmed the disease concept of Parkinson's disease. Dopamine replacement therapy dramatically improves the clinical prognosis. However, variable nonmotor symptoms have been noticed by many clinical researches, which can deteriorate the quality of life. Visual hallucination, fall and dementia can prescribe the late stage prognosis. In addition, part of nonmotor symptoms can develop before motor symptoms appear. Nowadays, the prodromal stage of Parkinson's disease may be detected using with the research criteria. The disease concept of Parkinson's disease is still metamorphosing under the storage of the novel evidences.