An ambulatory gait analysis method using body-attached gyroscopes to estimate spatio-temporal parameters of gait has been proposed and validated against a reference system for normal and pathologic gait. Later, ten Parkinson's disease (PD) patients with subthalamic nucleus deep brain stimulation (STN-DBS) implantation participated in gait measurements using our device. They walked one to three times on a 20-m walkway. Patients did the test twice: once STN-DBS was ON and once 180 min after turning it OFF. A group of ten age-matched normal subjects were also measured as controls. For each gait cycle, spatio-temporal parameters such as stride length (SL), stride velocity (SV), stance (ST), double support (DS), and gait cycle time (GC) were calculated. We found that PD patients had significantly different gait parameters comparing to controls. They had 52% less SV, 60% less SL, and 40% longer GC. Also they had significantly longer ST and DS (11% and 59% more, respectively) than controls. STN-DBS significantly improved gait parameters. During the stim ON period, PD patients had 31% faster SV, 26% longer SL, 6% shorter ST, and 26% shorter DS. GC, however, was not significantly different. Some of the gait parameters had high correlation with Unified Parkinson's Disease Rating Scale (UPDRS) subscores including SL with a significant correlation (r = -0.90) with UPDRS gait subscore. We concluded that our method provides a simple yet effective way of ambulatory gait analysis in PD patients with results confirming those obtained from much more complex and expensive methods used in gait labs.

Grafts of fetal mesencephalic tissue can survive for a long period in the human brain and restore dopaminergic innervation to the striatum in patients with Parkinson's disease. In the patient we studied, clinical improvement and enhanced fluorodopa with uptake on PET scanning were associated the survival of the grafts and dopaminergic reinnervation of the striatum.

The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.

An ambulatory system for quantification of tremor and bradykinesia in patients with Parkinson's disease (PD) is presented. To record movements of the upper extremities, a sensing units which included miniature gyroscopes, has been fixed to each of the forearms. An algorithm to detect and quantify tremor and another algorithm to quantify bradykinesia have been proposed and validated. Two clinical studies have been performed. In the first study, 10 PD patients and 10 control subjects participated in a 45-min protocol of 17 typical daily activities. The algorithm for tremor detection showed an overall sensitivity of 99.5% and a specificity of 94.2% in comparison to a video reference. The estimated tremor amplitude showed a high correlation to the Unified Parkinson's Disease Rating Scale (UPDRS) tremor subscore (e.g., r = 0.87, p < 0.001 for the roll axis). There was a high and significant correlation between the estimated bradykinesia related parameters estimated for the whole period of measurement and respective UPDRS subscore (e.g., r = -0.83, p < 0.001 for the roll axis). In the second study, movements of upper extremities of 11 PD patients were recorded for periods of 3-5 hr. The patients were moving freely during the measurements. The effects of selection of window size used to calculate tremor and bradykinesia related parameters on the correlation between UPDRS and these parameters were studied. By selecting a window similar to the period of the first study, similar correlations were obtained. Moreover, one of the bradykinesia related parameters showed significant correlation (r = -0.74, p < 0.01) to UPDRS with window sizes as short as 5 min. Our study provides evidence that objective, accurate and simultaneous assessment of tremor and bradykinesia can be achieved in free moving PD patients during their daily activities.

STN DBS may act by different mechanisms on the four major parkinsonian signs. At least 3 hours off STN DBS is needed to estimate the clinical effect of stimulation.