Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain (p=.008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms

Pregnancy in multiple system atrophy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Multiple system atrophy is a late, adult-onset α-synucleinopathy with no data on the effect of pregnancy on the disease course. Early stage multiple system atrophy can be difficult to distinguish from Parkinson's disease.</p> <p>Case presentation</p> <p>We describe the case of an Irish woman with parkinsonism starting at age 31, initially diagnosed as having dopa-responsive, idiopathic Parkinson's disease, who successfully delivered a full-term child at age 35. Her pregnancy was complicated by severe orthostatic hypotension and motor fluctuations. Two years post-partum, she underwent bilateral subthalamic nuclei deep brain stimulation for intractable motor fluctuations and disabling dyskinesia. After this treatment course she experienced deterioration of motor symptoms and death eight years after disease onset. Post-mortem neuropathological examination revealed striatonigral degeneration and α-synuclein-positive glial cytoplasmic inclusions in brain stem nuclei, basal ganglia and white matter tracts, consistent with a neuropathological diagnosis of multiple system atrophy.</p> <p>Conclusions</p> <p>Multiple system atrophy can affect women of child-bearing age and pregnancy may be associated with marked disease progression.</p

High-throughput mutational analysis of TOR1A in primary dystonia

<p>Abstract</p> <p>Background</p> <p>Although the c.904_906delGAG mutation in Exon 5 of <it>TOR1A </it>typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify <it>TOR1A </it>Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia.</p> <p>Methods</p> <p>High resolution melting (HRM) was used to examine the entire <it>TOR1A </it>Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia.</p> <p>Results</p> <p>HRM of <it>TOR1A </it>Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the <it>TOR1A </it>ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia.</p> <p>Conclusion</p> <p>First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in <it>TOR1A </it>are rarely associated with non-generalized primary dystonia.</p

A rapid method for mass screening for parkinsonism

Epidemiology studies of parkinsonism employ a variety of techniques for unbiased sampling of populations. No current method permits mass screening of all subjects in a population for parkinsonism by movement disorders specialists. We developed and piloted a new approach to facilitate accurate and efficient screening of large populations for diagnosis of parkinsonism and provide data on sensitivity and specificity. We evaluated 2081 welders referred for medical-legal screening. Subjects were video taped using a standardized protocol, and videos were rated on the Unified Parkinson\u27s Disease Rating Scale motor subsection 3 (UPDRS3). A video rater viewed video tapes and entered ratings through a web-based database. An in-person examiner performed a UPDRS3 examination in a randomly selected subgroup of 48 workers drawn from the 2081. We developed quantitative diagnostic criteria for parkinsonism that established minimum diagnostic thresholds based upon UPDRS3 scores and compared these criteria with diagnosis by an in-person examiner. Specificity of these criteria compared to in-person examination was 91-100% but sensitivity was 56%. A threshold UPDRS3 score greater than nine provided 100% sensitivity and 81% specificity. Liberal criteria identified 266 (13.1%) subjects with probable parkinsonism and 220 (10.8%) subjects with definite parkinsonism. Conservative criteria identified 260 (12.8%) with probable parkinsonism and 122 (6%) with definite parkinsonism. Our screening method permits rapid assessment of parkinsonian signs. An absolute UPDRS3 score greater than nine provided the best combination of sensitivity and specificity for the diagnosis of parkinsonism, while quantitative exam-based criteria for cardinal parkinsonian signs maximized specificity. Parkinsonism as diagnosed by our criteria was common in this group of welders

The c.-237-236GA\u3eTT THAP1 sequence variant does not increase risk for primary dystonia

Background: Sequence variants in coding and noncoding regions of THAP1 have been associated with primary dystonia. Methods: In this study, 1,446 Caucasian subjects with mainly adult-onset primary dystonia and 1,520 controls were genotyped for a variant located in the 5\u27-untranslated region of THAP1 (c.-237-236GA\u3eTT). Results: Minor allele frequencies were 62/2892 (2.14%) and 55/3040 (1.81%) in subjects with dystonia and controls, respectively (P=0.202). Subgroup analyses by gender and anatomical distribution also failed to attain statistical significance. In addition, there was no effect of the TT variant on expression levels of THAP1 transcript or protein. Discussion: Our findings indicate that the c.-237-236GA\u3eTT THAP1 sequence variant does not increase risk for adult-onset primary dystonia in Caucasians. © 2011 Movement Disorder Society