Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease.

LRRK2 G2019S is the most common known cause of Parkinson disease (PD) in patients of European origin, but little is known about its distribution in other populations. The authors identified two of 586 Japanese patients with PD heterozygous for the mutation who shared a haplotype distinct from that observed in Europeans. This suggests that G2019S originated from separate founders in Europe and Japan and is more widely dispersed than previously recognized.

A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations.

Referral-based studies indicate that a mutation (G2019S) in exon 41 of the LRRK2 gene might be a common cause of Parkinson disease (PD). The authors sequenced leucine-rich repeat kinase 2 (LRRK2) exons 31, 35, and 41 in 371 consecutively recruited patients with PD and found mutations in six (1.6%) subjects, including two heterozygous for new putative pathogenic variants (R1441H, IVS31 + 3A-->G). These data confirm the important contribution of LRRK2 to PD susceptibility in a clinic-based population.

Movement precues in planning and execution of aiming movements in Parkinson's disease.

Two experiments tested how changing a planned movement affects movement initiation and execution in idiopathic Parkinson's disease (PD) patients. In Experiment 1, PD patients, elderly controls, and young adults performed discrete aiming movements to one of two targets on a digitizer. A precue (80% valid cue and 20% invalid cue of all trials) reflecting the subsequent movement direction was presented prior to the imperative stimulus. All groups produced slower reaction times (RTs) to the invalid precue condition. Only the subgroup of patients with slowest movement time showed a significant prolongation of movement for the invalid condition. This suggests that, in the most impaired patients, modifying a planned action also affects movement execution. In Experiment 2, two-segment aiming movements were used to increase the demand on movement planning. PD patients and elderly controls underwent the two precue conditions (80% valid, 20% invalid). Patients exhibited longer RTs than the controls. RT was similarly increased for the invalid condition in both groups. The patients, however, exhibited longer movement times, lower peak velocities, and higher normalized jerk scores of the first segment in the invalid condition compared to the valid condition. Conversely, the controls showed no difference between the valid and invalid cue conditions. Thus, PD patients demonstrated substantially pronounced movement slowness and variability when required to change a planned action. The results from both experiments suggest that modifying a planned action may continue beyond the initiation phase into the execution phase in PD patients.

Discrete and dynamic scaling of the size of continuous graphic movements of parkinsonian patients and elderly controls.

OBJECTIVES: To systematically investigate the ability of Parkinson's disease patients to discretely and dynamically scale the size of continuous movements and to assess the impact of movement size on outcome variability. METHODS: Ten patients with Parkinson's disease (mean age 72 years) were compared with 12 healthy elderly controls (mean age 70 years). The subjects wrote with a stylus on a graphics tablet. In experiment 1 they drew circles, matching the size of five target circles ranging in magnitude from a radius of 0.5 cm up to 2.5 cm. In experiment 2 they drew spirals with a radius of at least 2 cm. In both experiments the drawings were initially performed as accurately as possible then as fast and accurately as possible. RESULTS: In both experiments the patients and controls drew at a similar speed. The within trial variability of the pen trajectory was greater for patients than controls, and increased disproportionately with the size of the movement. When the emphasis was on size rather than variability (circles), the patients' drawing movements were the same size as controls. When the emphasis was on accuracy of pen trajectory (that is, minimum variability) rather than size (spirals), the patients' drawing movements were smaller than controls. CONCLUSIONS: The movements made by Parkinson's disease patients are hypometric partly as an adaptive strategy used to reduce movement variability. This strategy is used primarily when the requirement to make accurate movements outweighs the need to make large movements.