Impact of autonomic symptoms on the clinical course of Parkinson's disease.

PURPOSE: Patients with Parkinson's disease (PD) exhibit various degrees of autonomic symptoms, which may be associated with Lewy body pathology distributed extensively in the autonomic nervous system. We hypothesized that the severity of autonomic symptoms reflects the severity of PD-related pathology, resulting in poor outcomes. The purpose of this study was to evaluate the impact of autonomic symptoms on PD progression. METHODS: We conducted a follow-up study among consecutive patients with PD at Dokkyo Medical University Hospital. Patients underwent comprehensive baseline evaluations and were classified into high and low autonomic symptom groups using the Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT). The Kaplan‒Meier survival curves were used to analyze the time to discontinuation of their visits because of PD-related endpoints and to evaluate the association with high SCOPA-AUT scores. RESULTS: Of the 101 patients, 74 (73%) met the inclusion criteria. During the follow-up period (mean 1654 days), 22/74 patients reached PD-related endpoints (death, 4; hospitalization, 9; nursing home institutionalization, 9). PD patients with high SCOPA-AUT scores reached the endpoints faster than those with low SCOPA-AUT scores. A high SCOPA-AUT score, including gastrointestinal, urinary, and thermoregulation domains; high motor symptom scores; and low specific binding ratios (SBRs) on 123I FP-CIT-SPECT (DAT-SPECT) were associated with reaching PD-related endpoints. A high SCOPA-AUT score was associated with reaching the endpoints even after adjustment for covariates. CONCLUSIONS: Patients with high autonomic symptom scores had a greater risk of reaching PD-related endpoints than patients with low autonomic symptom scores.

Impact of diabetes and glycated hemoglobin level on the clinical manifestations of Parkinson's disease.

BACKGROUND: The coexistence of diabetes mellitus (DM) has been suggested to accelerate the progression of Parkinson's disease (PD) and make the phenotype more severe. In this study, we investigated whether DM or glycated hemoglobin (HbA1c) levels affect the differences in motor and nonmotor symptoms. METHODS: We conducted a cross-sectional study including 140 consecutive Japanese patients with PD for whom medical history and serum HbA1c records were available. The PD patients with a DM diagnosis were classified into the diabetes-complicated group (PD-DM) and the nondiabetes-complicated group (PD-no DM). Next, patients were classified based on a median HbA1c value of 5.7, and clinical parameters were compared. The correlations between HbA1c levels and other clinical variables were analyzed. RESULTS: Of 140 patients, 23 patients (16%) had DM. Compared to PD-no DM patients, PD-DM patients showed lower MMSE scores. Compared to the lower HbA1c group, the higher HbA1c group showed a higher MDS-UPDRS part III score and a lower metaiodobenzylguanidine (MIBG) scintigraphy heart-to-mediastinum (H/M) ratio. HbA1c levels were positively correlated with age and the MDS-UPDRS part III score and negatively correlated with the MMSE score and H/M ratio on cardiac MIBG scintigraphy. Binary logistic regression analysis, which included age, sex, disease duration, and MMSE and MDS-UPDRS part III scores as independent variables, revealed that a lower MMSE score was an independent contributor to PD-DM and PD with high HbA1c levels. CONCLUSIONS: DM complications and high HbA1c levels may affect cognitive function in patients with PD.

Factors contributing to sleep disturbances and excessive daytime sleepiness in patients with Parkinson's disease.

Background: Sleep disturbances and excessive daytime sleepiness (EDS) are common non-motor symptoms in patients with Parkinson's disease (PD). The purpose of this study was to identify the contributors to sleep disturbances, including insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder (RBD), sleep-disordered breathing, nocturnal akinesia and EDS, in patients with PD. Methods: We conducted a cross-sectional study including 128 consecutive Japanese patients with PD. Sleep disturbances and EDS were defined as a PD Sleep Scale-2 (PDSS-2) total score ≥15 and an Epworth Sleepiness Scale (ESS) score >10, respectively. The patients were divided into four groups according to the presence or absence of sleep disturbances and EDS. We evaluated the disease severity, motor symptoms, cognition, olfactory test, the Scales for Outcomes in PD-Autonomic dysfunction (SCOPA-AUT), the Beck Depression Inventory-II (BDI-II), and the RBD Screening Questionnaire Japanese version (RBDSQ-J). Results: Of 128 patients, 64 had neither EDS nor sleep disturbances, 29 had sleep disturbances without EDS, 14 had EDS without sleep disturbances, and 21 had both EDS and sleep disturbances. Patients with sleep disturbances had higher BDI-II scores than those without sleep disturbances. Probable RBD was more frequent in patients with both sleep disturbances and EDS than in those with neither EDS nor sleep disturbances. The SCOPA-AUT score was lower in patients with neither EDS nor sleep disturbances than in patients in the other three groups. Using multivariable logistic regression analysis with neither sleep disturbances nor EDS as a reference group, that the SCOPA-AUT score was an independent contributor to sleep disturbances (adjusted OR, 1.192; 95% CI, 1.065-1.333; P = 0.002) or EDS (OR, 1.245; 95% CI, 1.087-1.424; P = 0.001) and that the BDI-II (OR, 1.121; 95% CI, 1.021-1.230; P = 0.016) and RBDSQ-J scores (OR, 1.235; 95% CI, 1.007-1.516; P = 0.043) as well as the SCOPA-AUT score (OR, 1.137; 95% CI, 1.006-1.285; P = 0.040) were independent contributors to both sleep disturbances and EDS. Conclusions: Autonomic symptoms were associated with patients with sleep disturbances or EDS, and depressive and RBD symptoms in addition to autonomic symptoms were associated with patients with both sleep disturbances and EDS.

Sleep and Autonomic Manifestations in Parkinson's Disease Complicated With Probable Rapid Eye Movement Sleep Behavior Disorder.

Patients with Parkinson's disease (PD) complicated with rapid eye movement sleep behavior disorder (RBD) present with distinct clinical features. The purpose of this study was to determine the clinical features of sleep and autonomic symptoms in PD patients with probable RBD (pRBD). The study included 126 patients with PD. pRBD was defined as having a history of dream-enacting behavior with a total score of 5 or greater on the Japanese version of the RBD Screening Questionnaire (RBDSQ-J). The Parkinson's Disease Sleep Scale-2 (PDSS-2) was used to evaluate sleep disturbances. Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction (SCOPA-AUT) were used to evaluate autonomic symptoms. Clinical assessments included disease severity, motor symptoms, olfaction, depression, cognitive function, levodopa equivalent dose (LED), and cardiac metaiodobenzylguanidine (MIBG) scintigraphy. Correlations between RBDSQ-J total scores and clinical variables were analyzed. Compared to PD patients without pRBD, PD patients with pRBD showed severe hyposmia, severe sleep-related symptoms, severe dysautonomia, and more reduced cardiac MIBG scintigraphy. Within the PDSS-2, the "PD symptoms at night" domain was significantly more severe in PD patients with pRBD. Within the SCOPA-AUT, the "urinary" and "cardiovascular" domains were significantly higher in PD patients with pRBD. In correlation analyses, RBDSQ-J total scores were positively correlated with PDSS-2 total scores, "PD symptoms at night" and "disturbed sleep" domains, Epworth Sleepiness Scale scores, SCOPA-AUT total scores, "urinary," "cardiovascular," and "thermo" domain scores, and LED. RBDSQ-J total scores were negatively correlated with cardiac MIBG scintigraphy uptake. Binary logistic regression analysis showed that PDSS-2 subitem 7 (distressing hallucinations) and SCOPA-AUT subitem 11 (weak stream of urine) were significant determinants for pRBD. Our study showed that PD patients with pRBD had characteristic sleep and autonomic symptoms.

[Anti-mitochondrial M2 antibody-positive myositis preceded by heart failure and cardiac conduction disturbance. A case report].

A 69-year-old man visited our hospital complaining of fatigue in the lower extremities while walking. The patient had a two-year history of congestive heart failure and received a permanent artificial pacemaker implantation for sick sinus syndrome. Physical examination revealed proximal muscle weakness and exaggerated lumbar lordosis. Serum creatine kinase level was 1,455 U/l. The atrophies of the paraspinal muscles at thoracic to lumbar spine levels, rectus abdominis and soleus muscles were detected on computed tomography. Muscle biopsy showed mild to moderate variability in muscle fiber size with regenerating and necrotic muscle fibers. Mononuclear cell infiltration was not found. HLA-ABC expression was minimum. After anti-mitochondrial M2 antibody was detected, administration of oral prednisolone resulted in improvements in muscle strength and serum creatine kinase level. Based on the clinical course, examination and clinical findings, the patient was diagnosed as anti-mitochondrial M2 antibody positive myositis. Anti-mitochondrial M2 positive myositis is not only difficult to diagnose by muscle biopsy, but can also be preceded or complicated by fatal cardiac complications.

V180I genetic Creutzfeldt-Jakob disease with cardiac sympathetic nerve denervation masquerading as Parkinson's disease: A case report.

RATIONALE: Creutzfeldt-Jakob disease (CJD) with a point mutation of valine to isoleucine at codon 180 of the prion protein gene (V180I) is the most frequent form of genetic CJD in Japan. However, peripheral nerve involvement, especially cardiac sympathetic denervation, has not been investigated in cases with V180I genetic CJD.We herein report a genetically confirmed case of V180I genetic CJD presenting with parkinsonism and cardiac sympathetic nerve denervation. PATIENT CONCERNS: The patient was a 79-year-old Japanese woman who presented with subacute progressive gait disturbance and cognitive impairment. Clinical diagnosis of Parkinson's disease (PD) with mild cognitive impairment was initially suspected based on parkinsonism, such as bradykinesia, rigidity and tremor, and reduced accumulation of cardiac meta-iodobenzylguanidine (MIBG) scintigraphy. INTERVENTIONS: Based on parkinsonism and impaired cardiac MIBG findings, levodopa/decarboxylase inhibitor was administered up to 300 mg/day; however, her symptoms were not improved. OUTCOMES: Her motor and cognitive function progressively deteriorated. DIAGNOSIS: Although the patient had no family history of CJD, genetic CJD was diagnosed according to extensive hyperintensities in the bilateral cortices on diffusion-weighted magnetic resonance images, positive tau protein and 14-3-3 protein in the cerebrospinal fluid and a V180I mutation with methionine homozygosity at codon 129 by prion protein gene analysis. LESSONS: We should be aware that reduced uptake of cardiac MIBG scintigraphy in patients presenting with parkinsonism cannot confirm a diagnosis of PD. CJD should be considered when patients show a rapid progressive clinical course with atypical manifestations of PD.