Our objective was to develop parameters for objective ambulatory measurements of levodopa‐induced dyskinesias (LID) in patients with Parkinson's disease (PD). Twenty‐three PD patients with mild to severe LID were submitted to a standardized protocol of 1‐minute recordings during rest, talking, stress, and four activities of daily life (ADL). Patients were simultaneously monitored with portable multi‐channel accelerometry (four pairs of bi‐axial sensors mounted onto the most affected arm, leg, and at the trunk) and recorded by video. LID severity was assessed with a modified Abnormal Involuntary Movement Scale (m‐AIMS). The signals were analyzed, and every 1/8‐second interval the amplitude was obtained of the dominant frequency within 1–4 Hz and 4–8 Hz frequency bands (Amp1–4 and Amp4–8). For both measures, convergent validity, reproducibility, and responsiveness were determined. In absence of voluntary movements, a significant relation was found between Amp1–4 and Amp4–8 and m‐AIMS. Repeated measurements during rest showed a high reproducibility (intraclass correlation coefficient = 0.90 [Amp1–4] and 0.86[Amp4–8]). The extent to which LID increased with talking and stress correlated significantly (p = 0.02) between the objective and clinical measures (intraclass correlation for differences = 0.67). During ADL, LID occurred in a similar frequency band as voluntary movements and only Amp1–4 and Amp4–8 of the trunk and leg sensor remained highly correlated with m‐AIMS. Although objective measures of LID are reliable and responsive, they fail to distinguish LID from voluntary movements. These measures are of value only when obtained during rest (all sensor sites) or during ADL when derived from those body segments that are normally not involved in these ADL tasks (trunk and leg). Mov. Disord. 16:58–61, 2001. © 2001 Movement Disorder Society.

Shortcomings of existing assessment methods in Parkinson disease (PD) have led to the development of continuous ambulatory multichannel accelerometry for the assessment of the core features of PD. Although measures for hypokinesia, bradykinesia, and tremor have been validated in groups of patients with PD, it is unclear whether this method is able to detect "on" with or without dyskinesias, and "off" in individual PD patients. This study therefore addressed the accuracy of objective ambulatory accelerometry in detecting motor complications in 15 PD patients, using a self-assessment scale as gold standard. Measures for hypokinesia, bradykinesia, and tremor showed limited sensitivity (0.60-0.71) and specificity (0.66-0.76) for motor complications in individual PD patients. In the group of PD patients, comparing the "on" with the "off" state yielded statistically significant differences for tremor only. Objective dyskinesia measures correlated with time spent with dyskinesias (r = 0.89). Although validated for the measurement of hypokinesia, bradykinesia, and tremor, continuous ambulatory multichannel accelerometry currently cannot detect "on" and "off" in individual PD patients.

Spinocerebellar ataxias are phenotypically, neuropathologically, and genetically heterogeneous. The locus of autosomal recessive spinocerebellar ataxia type 7 (SCAR7) was previously linked to chromosome band 11p15. We have identified TPP1 as the causative gene for SCAR7 by exome sequencing. A missense and a splice site variant in TPP1, cosegregating with the disease, were found in a previously described SCAR7 family and also in another patient with a SCAR7 phenotype. TPP1, encoding the tripeptidyl-peptidase 1 enzyme, is known as the causative gene for late infantile neuronal ceroid lipofuscinosis disease 2 (CLN2 disease). CLN2 disease is characterized by epilepsy, loss of vision, ataxia, and a rapidly progressive course, leading to early death. SCAR7 patients showed ataxia and low activity of tripeptidyl-peptidase 1, but no ophthalmologic abnormalities or epilepsy. Also, the slowly progressive evolution of the disease until old age and absence of ultra structural curvilinear profiles is different from the known CLN2 phenotypes. Our findings now expand the phenotypes related to TPP1-variants to SCAR7. In spite of the limited sample size and measurements, a putative genotype-phenotype correlation may be drawn: we hypothesize that loss of function variants abolishing TPP1 enzyme activity lead to CLN2 disease, whereas variants that diminish TPP1 enzyme activity lead to SCAR7.

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We used ambulatory monitoring to quantify body position, bradykinesia, and hypokinesia simultaneously in 50 patients with Parkinson's disease (PD) and 43 healthy elderly during the diurnal period. Reliable automatic detection of three defined body positions proved possible. As compared with controls, PD patients spent less time upright and more time during the day lying down, which correlated well with the self-reported time spent lying down. PD patients had significantly lower mean values of extremity acceleration and higher mean values of immobility than controls. The objective measures of bradykinesia and hypokinesia showed only a modest or no relation to the semiquantitative subjective Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, which most likely was due to differences between the methods. In contrast to bradykinesia measures, hypokinesia measures showed clear sex differences in both patients and controls. Over time, trunk and arm movements occurred more frequently in women than in men. Our ambulatory monitoring assessment disclosed clinically relevant information about the mobility profile and offers a way to quantify cardinal movement features simultaneously in PD patients throughout the day.