Benign versus malignant Parkinson disease: the unexpected silver lining of motor complications.

OBJECTIVE: We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson's disease (PD). METHODS: Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressive, malignant, PD (mPD). bPD was defined as Hoehn and Yahr (H&Y) stage ≤ 3, normal cognitive function, and Schwab and England (S&E) score ≥ 70 after ≥ 20 years of PD (≥ 10 years if older than 60 at PD onset); mPD as H&Y > 3, S&E score < 70, and cognitive impairment within 10 years from PD onset. We performed between-group analysis of demographic, habits/occupational, and clinical features at baseline and follow-up and unsupervised data-driven analysis of the clinical homogeneity of bPD and mPD. RESULTS: At onset, bPD subjects (n = 210) were younger, had a single limb affected, lower severity and greater asymmetry of symptoms, and lower prevalence of depression than mPD (n = 155). bPD was associated with active smoking and physical activity, mPD with agricultural occupation. At follow-up, mPD showed higher prevalence of depression, hallucinations, dysautonomia, and REM behaviour disorder. Interestingly, the odds of mPD were significantly reduced by the presence of dyskinesia and wearing-off. Data-driven analysis confirmed the independent clustering of bPD and mPD, with age at onset emerging as a critical discriminant between the two groups (< 46-year-old vs. > 68-year-old). CONCLUSIONS: Phenotypic PD extremes showed distinct demographic, clinical, and habits/occupational factors. Motor complications may be conceived as markers of therapeutic success given their attenuating effects on the odds of mPD.

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.