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.

Plasma prostaglandin D2 synthase levels in sleep and neurological diseases.

BACKGROUND: Prostaglandin D2 (PGD2) induces sleep and may play a role in sleep and neurological disorders. We investigated PGD synthase (PGDS) levels in various sleep and neurological disorders. METHODS: Sixty-three patients with neurological or sleep disorders (Parkinson's disease with excessive daytime sleepiness (PDS), n = 19; PD without sleepiness (PDWS), n = 14; Alzheimer's disease (AD), n = 10; narcolepsy (NA), n = 10; sleep apnea syndrome (SAS), n = 10) and 21 healthy controls were included in this study. Plasma lipocalin-type PGDS (L-PGDS) and glutathione-dependent hematopoietic PGDS (H-PGDS) levels were assessed using an enzyme-linked immunosorbent assay. RESULTS: H-PGDS levels were not significantly different among the groups. Compared with healthy controls, the PDWS, PDS and AD groups had higher levels of L-PGDS. Neither H-PGDS nor L-PGDS levels correlated with scores on the Epworth Sleepiness Scale or Pittsburgh Sleep Quality Index in any group. CONCLUSION: We found higher levels of L-PGDS in patients with neurodegenerative diseases such as PD and AD. Whether increased L-PGDS levels reflect underlying sleepiness or the pathophysiology of neurodegenerative diseases needs further study.

Involvement of legs and other body parts in patients with restless legs syndrome and its variants.

BACKGROUND: Restless legs syndrome (RLS) is characterized by the urge to move the legs accompanied by movement-responsive, abnormal sensations, which worsen at rest and night. We investigated the distribution of sensory symptoms and clinical correlations in patients with RLS and its variants. METHODS: Eighty-nine patients diagnosed with RLS or RLS variants (age 61.4 ±â€¯18.5 years 40 M/49 F) according to established criteria, with the exclusion of those with augmentation, were included in this study. The international RLS rating scale (IRLS) was used to assess the severity of RLS/RLS variant symptoms. RESULTS: Eighty-three patients (93.3%) had RLS, and 6 patients (6.7%) had RLS variants. Among the patients with RLS and RLS variants, 33 patients (36.0%) reported restlessness involving other body parts: arms (16.9%) were the most frequent region, followed by the back (10.1%), abdomen (6.7%), and buttocks (4.5%). There were no between-group differences in clinical characteristics, except for the level of sleep disturbances being higher in patients with RLS variants (n=6) than in patients with RLS (n=83). No significant difference was observed in clinical characteristics including RLS severity and treatment between patients with RLS only (n=57) and patients with RLS with other body part involvement (n=26). No relationship was observed between the onset of symptoms in the legs and other body parts, but the IRLS scores for legs and other body parts were significantly correlated. CONCLUSION: We should recognize that RLS can involve not only legs but also other body parts to varying degrees in each patient.

Leg restlessness preceding the onset of motor symptoms of Parkinson disease: A case series of 5 patients.

Patients with Parkinson disease (PD) often show restless legs syndrome (RLS), leg motor restlessness (LMR) and other leg restlessness (OLR) related to sensorimotor symptoms.Here, we describe 5 patients who presented with leg restlessness as an early manifestation of PD.In case 1, the patient had leg restlessness that was not LMR or RLS and preceded the onset of motor symptoms by 1 year. In case 2, LMR preceded motor symptoms by 2 years. Case 3 had unilateral RLS symptoms on the left side of the body for 33 years. Two and a half years after the spread of RLS symptoms to the right leg with increased frequency of left-sided RLS symptoms, the patient developed PD at the age of 58 years. In cases 4 and 5, RLS symptoms preceded motor symptoms by 3 months and 1 month, respectively. All patients developed Parkinsonism within 3 years (median, 1.0 year; range 0.083-2.5 years) after initial onset or exacerbation of leg restlessness. All patients had frequent leg restlessness symptoms (6-7 days per week). In our series, the preceding leg restlessness was unilateral and confined to the dominant side of the subsequent Parkinsonism, or preceding leg restlessness was bilateral but dominant on the dominant side of the subsequent Parkinsonism.Clinicians should be aware that late-onset leg restlessness (>50 years of age) including RLS, LMR, and OLR, particularly if frequent and asymmetrical, can be an early nonmotor manifestation of PD.