Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

Cognitive complaints in Parkinson's disease patients: from subjective cognitive complaints to dementia and affective disorders.

Subjective cognitive complaints (SCC) are frequent in elderly populations. PD patients report SCC more often than healthy controls. The association between SCC, objective cognitive impairment and affective symptoms remains controversial. We assessed consecutive PD patients between March 2014 and March 2015. Presence of SCC was defined as a score ≥ 1 in the Non-Motor Symptom Assessment Scale for Parkinson's Disease (NMSS) Domain 5. MoCA was used for cognitive impairment assessment. Pill Questionnaire measured the impact in daily activities. PD with Dementia (PDD) and PD with Mild Cognitive Impairment (PDMCI) were defined as the presence of cognitive impairment with or without impact on daily activities. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scales. Significance was set at p < 0.05. From 134 patients, 128 were included. PDD was diagnosed in 21 (16.4%), PDMCI in 31 (24.2%), and 76 (59.4%) had normal cognition (PDCN). SCC were present in 85% of whole cohort and evenly distributed (p = 0.361), PDD (95.2%), PDMCI (83.9%) and PDCN (82.9%). Severity was significantly different between PDD (20.00 ± 10.81), PDMCI (6.54 ± 5.5) and PDCN (6.97 ± 6.98), p < 0.001. A score ≥ 19 had a specificity of 77.3% and a sensitivity of 78.8% for identifying PDD. In PDCN, SCC severity was found to be related to depression (OR 1.23, CI 95% 1.02-1.47, p = 0.026) more than with MoCA scores (OR: 0.86, CI 95% 0.69-1.05, p = 0.141). SCC are common in PD. Their severity can help distinguish PDD from non-demented PD patients. In PDCN, SCC should alert the clinician for an affective disorder.

Heart rate variability in Parkinson disease and idiopathic REM sleep behavior disorder.

PURPOSE: Heart rate variability, a marker of autonomic function modulation, is known to be blunted in Parkinson disease, although data remains conflicting and a putative modifying role of REM sleep behavior disorder persists unclarified. METHODS: We assessed ten patients with idiopathic REM sleep behavior disorder patients, 18 patients with Parkinson disease and REM behavior disorder and eight patients with Parkinson disease without REM sleep behavior disorder. Heart rate variability analysis was performed in 5-min epochs selected from wake, Non-REM and REM polysomnography records. We compared heart rate variability measures by stage between two sets of groups: Parkinson disease vs. idiopathic RBD and patients with vs. without RBD, by using repeated measures ANOVA. RESULTS: There were no heart rate variability differences between Parkinson disease and idiopathic REM sleep behavior disorder groups. There were significant stage vs. group interactions (p = 0.045) regarding the high frequencies components when comparing patients with and without REM sleep behavior disorder, with the former presenting lower values and attenuation of sleep stage variations. CONCLUSION: Our study suggests that RBD is related with reduction in parasympathetic modulation of heart rate variability and blunting of sleep stage related variations.

Characterization of motor events in REM sleep behavior disorder.

We used video-polysomnography to characterize motor events (ME) in 14 Parkinson's disease (PD-RBD) and 18 idiopathic (iRBD) REM sleep behavior disorder cases. ME occurred predominantly in the upper limbs and were mostly simple, non-emotional, distal and focal. There were no significant differences in ME features between PD-RBD and iRBD groups. Our data suggests that RBD ME are mostly non violent. Similarity between PD-RBD and iRBD groups suggests that motor dysfunction does not affect ME features.

Tetrabenazine in treatment of hyperkinetic movement disorders: an observational study.

BACKGROUND: Tetrabenazine (TBZ) is commonly used in hyperkinetic movement disorders. In this retrospective study, we aimed to assess the TBZ effectiveness and adverse events (AEs) in Huntington disease (HD), vascular chorea, tics, dystonia, tardive oromandibular (OM) dyskinesia and other tardive syndromes (TS). METHODS: Qualitative analysis of clinical response was used to estimate TBZ effectiveness. TBZ-associated AE frequency and subsequent discontinuation rate were used to estimate tolerability; the tolerability profile was measured through the TBZ minimal dose and exposure time required to elicit AEs. RESULTS: Of 108 included patients, 87% had a clinically meaningful improvement sustained over a period of 40 months. TBZ-responder rate ranged from 100% in HD to 62.5% and 77.1% in tic disorders and OM dyskinesia, respectively (p < 0.001). TBZ-associated AE frequency ranged from 40.9% in other TS and 41.7% in vascular chorea and HD, to 60% in OM dyskinesia (p < 0.001). The most common AEs were Parkinsonism (51.8%) and psychiatric disorders (25%). The 'other AEs' category (mainly somnolence) presented the shortest minimal exposure time (3 months). AE-eliciting dose differed from 18.8 mg and 25 mg in tics and tardive disorders, to 75 mg in HD (p = 0.003). Patients with AEs were tendentiously older at TBZ initiation (p = 0.022). CONCLUSIONS: TBZ proved an effective and relatively well tolerated treatment in hyperkinetic disorders, with excellent results in HD. AEs were more common in OM dyskinesia, which may be related to higher age at TBZ initiation. TBZ-associated somnolence and Parkinsonism were more frequent during the titration and maintenance periods, respectively.

Motor and non-motor symptoms in old-age onset Parkinson's disease patients.

Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

Non-Motor symptoms in Portuguese Parkinson's Disease patients: correlation and impact on Quality of Life and Activities of Daily Living.

The prevalence of non-motor symptoms (NMS) in Parkinson's Disease (PD) has varied between studies. Their interrelation isn't totally understood. Also, the relative importance of each symptom, regarding its impact on activities of daily living (ADL) and health related quality of life (HRQL), remains debatable. We assessed all PD patients attending a Portuguese tertiary movement disorders center during one year (n = 134), with ADL, HRQL and other clinical scales approved for identifying the most relevant NMS in PD. All patients had at least one NMS. Sleep/fatigue, affect/cognition, attention/memory were the most frequent complaints, and their prevalence, above 80%, was higher than in most studies. There were significantly correlations between: sleepiness, psychosis and cognition; gastrointestinal, cardiovascular symptoms and pain; depression and apathy; anxiety and insomnia; olfaction, weight and hyperhidrosis. Depression/apathy exerted the strongest influence on HRQL and non-tremor motor dysfunction on ADL. Compared to studies in other countries, we found a higher prevalence of NMS, which could be specific of this population. The interrelation between NMS could be related to degeneration of different brain structures. NMS exert a stronger influence than MS in HRQL, which should be taken in account regarding treatment options.

The syndrome of deafness-dystonia: clinical and genetic heterogeneity.

The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 (C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions.