Prospective Cohort Study

Parkinson's disease: Mechanisms and models

We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha = 0.79-0.93 across parts) and correlated with the original UPDRS (rho = 0.96). MDS-UPDRS across-part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.

/pdf/movement-disorder-society-sponsored-revision-of-the-unified-3shjr1g3wc.pdf

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results.

Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

https://jnnp.bmj.com/content/jnnp/79/4/368.full.pdf

Parkinson’s disease: clinical features and diagnosis

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

/pdf/meta-analysis-of-74-046-individuals-identifies-11-new-406eax0kye.pdf

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

We systematically evaluated the efficacy of both unilateral and bilateral stereotactic pallidotomy in eight patients with generalized dystonia. Six patients had a marked improvement in dystonic movements and motor function; the other two patients also benefited from the procedure but to a lesser extent. The severity of dystonia was assessed before and after surgery by the Burke-Marsden-Fahn Dystonia Scale (BMFDS), the Unified Dystonia Rating Scale (UDRS), and the Activity of Daily Living Scale (ADL). The BMFDS scores decreased by 59.0%, UDRS by 62.5%, and ADL by 47.8% postoperatively. Adverse events were limited to a transient weakness in one patient. We conclude that pallidotomy is a safe and effective treatment in medically refractory cases of generalized dystonia.

Pallidotomy for generalized dystonia

Restless legs syndrome (RLS) is a common neurological disorder that affects 5%–12% of all whites. To genetically dissect this complex disease, we characterized 15 large and extended multiplex pedigrees, consisting of 453 subjects (134 affected with RLS). A familial aggregation analysis was performed, and SAGE FCOR was used to quantify the total genetic contribution in these families. A weighted average correlation of 0.17 between first-degree relatives was obtained, and heritability was estimated to be 0.60 for all types of relative pairs, indicating that RLS is a highly heritable trait in this ascertained cohort. A genomewide linkage scan, which involved >400 10-cM–spaced markers and spanned the entire human genome, was then performed for 144 individuals in the cohort. Model-free linkage analysis identified one novel significant RLS-susceptibility locus on chromosome 9p24-22 with a multipoint nonparametric linkage (NPL) score of 3.22. Suggestive evidence of linkage was found on chromosome 3q26.31 (NPL score 2.03), chromosome 4q31.21 (NPL score 2.28), chromosome 5p13.3 (NPL score 2.68), and chromosome 6p22.3 (NPL score 2.06). Model-based linkage analysis, with the assumption of an autosomal-dominant mode of inheritance, validated the 9p24-22 linkage to RLS in two families (two-point LOD score of 3.77; multipoint LOD score of 3.91). Further fine mapping confirmed the linkage result and defined this novel RLS disease locus to a critical interval. This study establishes RLS as a highly heritable trait, identifies a novel genetic locus for RLS, and will facilitate further cloning and identification of the genes for RLS.

Genomewide Linkage Scan Identifies a Novel Susceptibility Locus for Restless Legs Syndrome on Chromosome 9p

Object The object of this study was to assess the long-term safety of deep brain stimulation (DBS) in a large population of patients with a variety of movement disorders. Methods All patients treated with DBS at the authors' center between 1995 and 2005 were assessed for intraoperative, perioperative, and long-term adverse events (AEs). A total of 319 patients underwent DBS device implantation. Of these 319, 182 suffered from medically refractory Parkinson disease; the other patients had essential tremor (112 patients), dystonia (19 patients), and other hyperkinetic movement disorders (six patients). Intraoperative AEs were rare and included vasovagal response in eight patients (2.5%), syncope in four (1.2%), severe cough in three (0.9%), transient ischemic attack in one (0.3%), arrhythmia in one (0.3%), and confusion in one (0.3%). Perioperative AEs included headache in 48 patients (15.0%), confusion in 16 (5.0%), and hallucinations in nine (2.8%). Serious intraoperative/perioperative AEs included isolat...

Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders

To better understand genetic characteristics of restless legs syndrome (RLS) and identify nongenetic factors that may influence phenotype, the authors studied 12 identical twins in which at least one member expressed RLS. Ten of the 12 twin pairs were concordant for RLS symptoms. Despite the high concordance rate, the disease severity, age at onset, and symptom descriptions often varied between twins. Birth order, birth weight, and serum ferritin levels did not predict RLS severity or age at onset.

Restless legs syndrome in monozygotic twins: Clinical correlates

http://analisedemarcha.com/papers/pkd/Long-term%20monitoring%20of%20gait.pdf

William G. Ondo

Papers

Pallidotomy for generalized dystonia

Genomewide Linkage Scan Identifies a Novel Susceptibility Locus for Restless Legs Syndrome on Chromosome 9p

Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders

Restless legs syndrome in monozygotic twins: Clinical correlates

Long-term monitoring of gait in Parkinson's disease