Parkinson Disease: Stevens J

Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, Hallett M, Miyasaki J, Stevens J, Weiner WJ, Anonymous00045. · University of Kansas Medical Center, Kansas City, USA. · Neurology. · Pubmed #16606909 No free full text.

Abstract: OBJECTIVE: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? METHODS: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. RESULTS, CONCLUSIONS, AND RECOMMENDATIONS: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

Sutherland G, Mellick G, Newman J, Double KL, Stevens J, Lee L, Rowe D, Silburn P, Halliday GM. · School of Biomolecular and Biomedical Sciences, Eskitis Institute, Griffith University, Brisbane, Australia. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #18085551 No free full text.

Abstract: Idiopathic Parkinson's disease is a common movement disorder characterized by a loss of dopaminergic neurons in the substantia nigra. Its pathogenesis is postulated to involve complex interactions between genetic susceptibility and environmental exposures. The IGF2-INS-TH gene cluster on the telomeric end of human chromosome 11 is a gene rich region expressing several proteins important for dopamine neuron homeostasis. We used a haplotyping approach to determine whether common genetic variation in the IGF2-INS-TH cluster influences the risk of idiopathic Parkinson's disease in a Caucasian case-control group recruited from Brisbane, Australia. Three tagging polymorphisms, the SNPs, rs680 and rs689 and the microsatellite, HUMTH01, were genotyped in 215 cases and 215 age- and gender-matched controls. Eight common haplotypes accounted for 91% of the genetic variation in our control group and one haplotype, IGF2-INS-TH*6, was significantly under-represented among the cases with idiopathic Parkinson's disease (OR = 0.42, 95% CI = 0.25-0.72, P-value = 0.001). Analysis of the individual polymorphisms showed that the IGF2-rs680 alternate 'A' allele accounted for the majority of the protective effect. Our findings suggest that common genetic variants in the IGF2-INS-TH cluster modify susceptibility to idiopathic Parkinson's disease.

Huang Y, Halliday GM, Vandebona H, Mellick GD, Mastaglia F, Stevens J, Kwok J, Garlepp M, Silburn PA, Horne MK, Kotschet K, Venn A, Rowe DB, Rubio JP, Sue CM. · Prince of Wales Medical Research Institute, University of New South Wales, Australia. · Mov Disord. · Pubmed #17427941 No free full text.

Abstract: We determined the prevalence of two common leucine-rich repeat kinase 2 (LRRK2) gene mutations in Australian patients with Parkinson's disease (PD). Of 830 affected patients, eight were heterozygous for the G2019S mutation, and two were heterozygous for the R1441H (4,322 G > A) mutation. In addition, one familial patient had a novel A1442P (4,324 G > C) mutation. Haplotype analysis showed that all LRRK2 G2019S-positive individuals carried the common founder haplotype 1 and a putative founder haplotype for the R1441H mutation carriers. Clinically, patients with LRRK2 mutations had typical levodopa responsive Parkinsonism with tremor being the commonest presenting feature. Patients with the G2019S mutation in our series had a similar age of onset of symptoms when compared with patients with other LRRK2 mutations or sporadic PD, although they were more likely to have a family history of PD (2.4% of Australian patients with familial PD and 0.3% of Australian patients with sporadic PD). Our results demonstrate that the G2019S mutation carriers share the same ancestors who migrated to Australia originally from Europe and that other LRRK2 mutations (R1441H and A1442P) can be found in this population.

Price S, Paviour D, Scahill R, Stevens J, Rossor M, Lees A, Fox N. · Dementia Research Center (UCL), Institute of Neurology, London, UK. · Neuroimage. · Pubmed #15488416 No free full text.

Abstract: Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) are neurodegenerative diseases with distinctive pathological appearances. Early clinical diagnosis can be difficult. MRI may help differentiate PSP from PD, but the differences are often only obvious with advanced disease. It would be useful to have an unbiased assessment of difference to guide visual assessment of MRI as an aid to clinical diagnosis. Voxel-based morphometry (VBM) offers nonbiased, observer-independent morphometric MRI analysis. Our objectives were to assess structural differences between PSP, PD, and normal controls and test the clinical utility of the results. T1-weighted MR images in 12 patients with clinically diagnosed PSP, 12 with PD, and 12 age- and sex-matched controls were normalized to a common stereotaxic space and segmented into gray matter (GM) and white matter (WM) then analyzed using VBM. MRI scans were reviewed by a neuroradiologist blinded to the clinical diagnosis and assigned to the "non-PSP" or "PSP" group based on regional differences highlighted using VBM. VBM revealed significant group differences between PSP and PD as well as PSP and controls, with tissue reduction demonstrated in the region of the cerebral peduncles and midbrain. With these regional differences as a guide, neuroradiological diagnosis achieved a sensitivity of 83% and a specificity of 79%. VBM did not detect dramatic changes in frontal regions despite significant frontal cognitive decline in the PSP group. Pathology in the basal ganglia rather than tissue loss in the frontal lobes could be responsible for this. This information may help in the differentiation of PSP in clinical practice.