Movement disorders : official journal of the Movement Disorder Society
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Review
The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism.
A body of work has emerged over the past decade demonstrating a relationship between mutations in glucocerebrosidase gene (GBA), the gene implicated in Gaucher disease (GD), and the development of parkinsonism. Several different lines of research support this relationship. First, patients with GD who are homozygous for mutations in GBA have a higher than expected propensity to develop Parkinson's disease (PD). ⋯ In addition, neuropathologic studies of subjects with parkinsonism carrying GBA mutations demonstrate Lewy bodies, depletion of neurons of the substantia nigra, and involvement of hippocampal layers CA2-4. Although the basis for this association has yet to be elucidated, evidence continues to support the role of GBA as a PD risk factor across different centers, synucleinopathies, and ethnicities. Further studies of the association between GD and parkinsonism will stimulate new insights into the pathophysiology of the two disorders and will prove crucial for both genetic counseling of patients and family members and the design of relevant therapeutic strategies for specific patients with parkinsonism.
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Comparative Study Controlled Clinical Trial
Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study.
There is debate over the cognitive and behavioral effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD). To evaluate these effects, we performed a prospective, naturalistic controlled, 3-year follow-up study. A total of 65 PD patients were enrolled, of whom 32 underwent STN-DBS (PD-DBS) and 33, even though eligible for this treatment, declined surgery and chose other therapeutic procedures (PD-control). ⋯ FAS scores at T36 were significantly worse in the PD-DBS compared with the PD-control patients. This is the first long-term naturalistic controlled study of cognitive functions in PD patients submitted to STN-DBS. Our results confirm previous reports of a worsening of verbal fluency after DBS, but show that STN-DBS seems to be relatively safe from a cognitive standpoint, as the short-term worsening of frontal-executive functions was found to be transient.
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Comparative Study Controlled Clinical Trial
MIBG scintigraphy for differentiating Parkinson's disease with autonomic dysfunction from Parkinsonism-predominant multiple system atrophy.
Parkinson's disease (PD) with autonomic dysfunction is difficult to differentiate from Parkinsonism-predominant multiple system atrophy (MSA-p). This study aimed to analyze the validity of MIBG scintigraphy for PD with autonomic dysfunction and MSA-p. Thirty-nine patients (PD: 27 patients, MSA-p type: 12) and 12 age-matched controls were prospectively enrolled and underwent MIBG scintigraphy and autonomic function test (AFT). ⋯ Only the WR could differentiate PD with abnormal AFT from MSA-p (47.07 +/- 57.48 vs. 31.39 +/- 31.52, respectively) (P = 0.026). According to the results, WR may be more useful than the early and delayed H/M ratio to distinguish MSA-p from PD with abnormal AFT. Furthermore, the MIBG uptake did not reflect the disease duration or severity.
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The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on fall risk in patients with Parkinson's disease (PD) currently remain unclear. Although several gait parameters, such as gait speed, have shown improvement with DBS, some studies have reported an increased fall risk following DBS. The purpose of this study was to examine the effect of bilateral DBS on gait variability, a marker of fall risk. ⋯ Following treatment with both levodopa and STN DBS, subjects displayed improved gait speed, reduced gait variability (enhanced stability), and lower Unified Parkinson's Disease Rating Scale (UPDRS) scores. Although UPDRS scores improved with STN DBS alone, parallel improvements were not seen for gait variability. These findings suggest that different mechanisms may contribute to performance on UPDRS motor testing and gait stability in response to DBS.