OnabotulinumtoxinA and cognitive behavioral therapy in functional dystonia: A pilot randomized clinical trial.

INTRODUCTION: Functional dystonia (FD) is a disabling movement disorder with limited therapeutic options. We aimed to examine the efficacy and safety of chemodenervation with OnabotulinumtoxinA (BoNT) versus placebo prior to cognitive behavioral therapy (CBT) in FD patients. METHODS: FD patients with a Psychogenic Movement Disorders Rating Scale (PMDRS) score ≥ 10 and persistent dystonic posturing for ≥ 1 year were randomized to BoNT or placebo injections prior to 12 weekly individualized 1-h CBT sessions. Clinical assessments included PMDRS, Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Katz index of independence in activities of daily living (ADL), and Lawton instrumental ADL (iADL). The efficacy endpoints were the change in clinical assessments at 12 weeks from baseline between and within groups. RESULTS: Of 18 screened patients, 14 were randomized, and 10 completed the study. All patients showed reductions in PMDRS irrespective of treatment group at the end of the follow-up period. There was no difference in clinical assessments between groups at 12 weeks. Change from baseline in PMDRS score was significantly improved only in the CBT group with prior administration of placebo (mean change -9.0, 95% CI -16.5, -1.5; p = 0.02). CONCLUSIONS: CBT yielded robust improvement in FD patients but was unaffected by prior administration of BoNT. These pilot data do not eliminate the potential for examining future BoNT benefit in FD patients with selected topographical involvement, such as face or neck.

Orthostatic hypotension in Parkinson disease: Impact on health care utilization.

INTRODUCTION: Orthostatic hypotension (OH) represents a frequent yet overlooked source of disability in Parkinson disease (PD). In particular, its impact on health care utilization has been insufficiently examined. We sought to determine the differential health care utilization in PD patients with (PDOH+) and without OH (PDOH-). METHODS: We quantified the emergency room (ER) visits, hospitalizations, outpatient clinic evaluations, phone calls, and e-mails from PD patients on whom supine and orthostatic blood pressure (BP) measurements were obtained during routine clinical practice between June 2013 and July 2016. Comparative costs between PDOH+ and PDOH- were adjusted for age, disease duration, motor severity, levodopa equivalent daily dose, and Montreal Cognitive Assessment. RESULTS: From a total of 317 PD patients, 29.3% were classified as PDOH+ (n = 93) and 70.6% as PDOH- (n = 224) over 30.2 ± 11.0 months, in which there were 247 hospitalizations, 170 ER visits, 2386 outpatient evaluations, and 4747 telephone calls/e-mails. After-adjusting for relevant covariates, PDOH+ was associated with more hospitalization days (+285%; p = 0.041), ER visits (+152%; p = 0.045), and telephone calls/e-mails than PDOH- (+142%; p = 0.009). The overall health care-related cost in PDOH+ was 2.5-fold higher than for PDOH- ($25,205 ± $6546 vs. $9831 ± $4167/person/year; p = 0.037). CONCLUSION: OH increases health care utilization in PD independently from age, disease duration, motor severity, dopaminergic treatment, and cognitive function.

Tablet-Based Application for Objective Measurement of Motor Fluctuations in Parkinson Disease.

BACKGROUND: The motor subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) has limited applicability for the assessment of motor fluctuations in the home setting. METHODS: To assess whether a self-administered, tablet-based application can reliably quantify differences in motor performance using two-target finger tapping and forearm pronation-supination tasks in the ON (maximal dopaminergic medication efficacy) and OFF (reemergence of parkinsonian deficits) medication states, we recruited 11 Parkinson disease (PD) patients (age, 60.6 ± 9.0 years; disease duration, 12.8 ± 4.1 years) and 11 healthy age-matched controls (age, 62.5 ± 10.5 years). The total number of taps, tap interval, tap duration, and tap accuracy were algorithmically calculated by the application, using the more affected side in patients and the dominant hand in healthy controls. RESULTS: Compared to the OFF state, PD patients showed a higher number of taps (84.2 ± 20.3 vs. 54.9 ± 26.9 taps; p = 0.0036) and a shorter tap interval (375.3 ± 97.2 vs. 708.2 ± 412.8 ms; p = 0.0146) but poorer tap accuracy (2,008.4 ± 995.7 vs. 1,111.8 ± 901.3 pixels; p = 0.0055) for the two-target task in the ON state, unaffected by the magnitude of coexistent dyskinesia. Overall, test-retest reliability was high (r >0.75) and the discriminatory ability between OFF and ON states was good (0.60 ≤ AUC ≤ 0.82). The correlations between tapping data and MDS-UPDRS-III scores were only moderate (-0.55 to 0.55). CONCLUSIONS: A self-administered, tablet-based application can reliably distinguish between OFF and ON states in fluctuating PD patients and may be sensitive to additional motor phenomena, such as accuracy, not captured by the MDS-UPDRS-III.

Orthostatic hypotension in Parkinson's disease: Does it matter if asymptomatic?

INTRODUCTION: Orthostatic hypotension (OH) may frequently be asymptomatic in patients with Parkinson's disease (PD). However, the relationship between symptomatic/asymptomatic status and functional disability remains unclear. METHODS: Using orthostatic blood pressure (BP) measurements and the Orthostatic Hypotension Symptom Assessment (OHSA) questionnaire, 121 consecutive PD patients without history of chronic hypertension and not taking alpha-adrenergic antagonists for bladder disorders were classified according to (1) OH symptomatic status, based on presence/absence of orthostatic symptoms (symptomatic OH: OHSA item 1 ≥ 1), and (2) OH severity, based on the magnitude of BP fall on the lying-to-standing test: OH- (<20/10 mmHg); moderate OH+ (≥20/10 mmHg but < 30/15 mmHg); and severe OH+ (≥30/15 mmHg). The primary endpoints were the activities of daily living/instrumental activities of daily living (ADL/iADL) and the Ambulatory Capacity Measure (ACM). Secondary endpoints included PD quality of life (PDQ-8) and prevalence of falls. RESULTS: The overall prevalence of OH+ was 30.6% (37/121 patients), with 62.2% symptomatic (23/37) and 37.8% asymptomatic (14/37). Symptomatic and asymptomatic OH + patients had similar impairments in ADL/iADL and ACM, significantly worse than OH- (p ≤ 0.035). There was a trend for worse ADL/iADL and ACM scores in severe OH + compared to moderate OH+, but both were worse than OH- (p ≤ 0.048). Symptomatic and asymptomatic OH + showed similar impairment in PDQ-8 and higher prevalence of falls compared to OH-. CONCLUSIONS: Asymptomatic OH+ was associated with similar impairments in ADL/iADL and ACM than symptomatic OH+. These findings support screening for OH in PD patients regardless of postural lightheadedness.