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 report on a 26-year-old woman with subacute sclerosing panencephalitis (SSPE) who presented with frequent paroxysmal dystonic posturing. Electroencephalogram demonstrated generalized 5 to 10-second episodes of high-amplitude (150-300 microV) delta activity alternating with 10 to 20-second periods of theta activity (40-50 microV). The patient experienced episodes of dystonic posturing coinciding with the periods of delta activity. Ictal Tc-99m Ceretec SPECT demonstrated marked increased activity in the bilateral caudate (R>L). The frequency and amplitude of the episodes initially markedly improved after the addition of carbamazepine. We suggest that the movements seen in this case of SSPE may represent basal ganglia ictal activity.

Physiological assessment of paroxysmal dystonia secondary to subacute sclerosing panencephalitis.

Background: Orthostatic tremor is an uncommon disorder manifest by high frequency, low amplitude leg tremor upon weight bearing. Treatment with oral tremor agents is inconsistent and usually not satisfactory. Methods: We implanted bilateral ventralis intermedius nuclei deep brain stimulators into an 82-year-old male with refractory orthostatic tremor. Results: The patient had a marked subjective and objective improvement in leg and arm tremor, mainly manifested by an improved ability to stand. Discussion: Bilateral thalamic deep brain stimulation may be considered in refractory cases of orthostatic tremor.

/pdf/thalamic-deep-brain-stimulation-for-orthostatic-tremor-26xfb6r9xt.pdf

Thalamic Deep Brain Stimulation for Orthostatic Tremor

Task-specific focal hand dystonia in a professional pistol-shooter.

Objective

This systematic review was performed to elucidate dosing practices, dosing conversions, and related outcomes from randomized, controlled trials that directly compared onabotulinumtoxinA (ONA) and abobotulinumtoxinA (ABO) at various dose conversion ratios for therapeutic use in movement disorders.



Methods

A systematic review of three medical literature databases (PubMed, the Cochrane Library, and EMBASE) was performed to identify relevant comparative clinical studies, systematic reviews, and meta-analyses published in the English language between January 1991 and January 2015. Studies that met predefined inclusion criteria were selected for formal data extraction and quality assessment.



Results

A total of 182 manuscripts were identified, of which four were included for analysis. Targeted clinical applications included neurological disorders. The studies compared ONA to ABO dose conversion ratios of 1:2.5 (n = 1), 1:3 (n = 2), and 1:4 (n = 2). One study compared both 1:3 and 1:4 ratios. An ONA:ABO conversion factor of 1:2.5 was associated with similar efficacy and side effects. An ONA:ABO ratio of 1:3 provided similar or higher efficacy, but an increased rate of adverse effects, and an ONA:ABO ratio of 1:4 was associated with higher efficacy, but with an excessive rate of intolerable side effects.



Conclusion

A dose conversion ratio of ONA to ABO between 1:2.5 and 1:3.0 provides comparable safety and efficacy for therapeutic movement disorders chemodenervation procedures.

OnabotulinumtoxinA and AbobotulinumtoxinA Dose Conversion: a Systematic Literature Review.

Objective: Iron deficiency anemia (IDA) is a well-known cause of secondary restless legs syndrome (RLS). Iron deficiency without anemia (IDNA) is insidious, and its association with RLS is less evaluated. We investigate prevalence and features of IDNA in a consecutive cohort of patients with RLS. Methods: We included sequential primary RLS patients and RLS patients with IDA. We also recruited age- and gender-matched healthy controls. RLS mimics and other comorbidities were carefully excluded. Results: One-hundred and ninety-six RLS patients without anemia, 26 RLS patients with IDA, and 63 controls were included. 42.3% of RLS patients without anemia had iron deficiency. Women were much more susceptible for IDNA with a relative risk of 5.51 (p < 0.0001). Women with IDNA and RLS had younger age both at interview and at RLS onset compared to women with RLS without iron deficiency (NID) (P < 0.01). IDNA RLS patients showed a tendency to higher risk of severe/very severe tiredness or sleepiness during the day as compared to NID RLS patients. Furthermore, IDNA RLS patients had longer duration of RLS (P < 0.01 in men, P < 0.05 in women) and younger age at onset (only in men, P < 0.05) compared to IDA RLS patients. Conclusion: IDNA is frequent in RLS and iron deficiency may be severe despite a normal hemoglobin level. Women are at much higher risk for IDNA, and IDNA in women presents some specific clinical features. Features of IDNA RLS are different from IDA RLS. Regular screening of peripheral iron parameters even in patients with normal blood counts is recommended for timely optimal management.

/pdf/correlates-of-nonanemic-iron-deficiency-in-restless-legs-1je4vwicdi.pdf

William G. Ondo

Papers

Physiological assessment of paroxysmal dystonia secondary to subacute sclerosing panencephalitis.

Thalamic Deep Brain Stimulation for Orthostatic Tremor

Task-specific focal hand dystonia in a professional pistol-shooter.

OnabotulinumtoxinA and AbobotulinumtoxinA Dose Conversion: a Systematic Literature Review.

Correlates of Nonanemic Iron Deficiency in Restless Legs Syndrome.