Wednesday, 31 July 2013
Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy-a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group.
Tuesday, 30 July 2013
Sunday, 28 July 2013
Saturday, 27 July 2013
Relationship of olfactory function with olfactory bulbus volume, disease duration and Unified Parkinson's disease rating scale scores in patients with early stage of idiopathic Parkinson's disease
Friday, 26 July 2013
Nicotine increases lifespan and rescues olfactory and motor deficits in a Drosophila model of Parkinson's disease
Thursday, 25 July 2013
Wednesday, 24 July 2013
Tuesday, 23 July 2013
Measurement of costs and scales for outcome evaluation in health economic studies of Parkinson's disease
Thursday, 18 July 2013
Rasagiline adjunct therapy in patients with Parkinson's disease: Post hoc analyses of the PRESTO and LARGO trials
Wednesday, 17 July 2013
A Single-Center, Cross-Sectional Prevalence Study of Impulse Control Disorders in Parkinson Disease: Association With Dopaminergic Drugs
Tuesday, 16 July 2013
Monday, 15 July 2013
Friday, 12 July 2013
Thursday, 11 July 2013
Monday, 8 July 2013
Sunday, 7 July 2013
Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems.
Saturday, 6 July 2013
Drivers with Parkinson's disease: are the symptoms of PD associated with restricted driving practices?
Friday, 5 July 2013
Depressive symptoms in Parkinson's disease are related to reduced [123I]FP-CIT binding in the caudate nucleus
J Neurol Neurosurg Psychiatry. 2013 Jun 29. [Epub ahead of print]
Vriend C, Raijmakers P, Veltman DJ, van Dijk KD, van der Werf YD, Foncke EM, Smit JH, Berendse HW, van den Heuvel OA.
Department of Psychiatry, VU University Medical Center, , Amsterdam, The Netherlands.
Depression is a common neuropsychiatric symptom in Parkinson's disease (PD). In previous research, PD-related depression was associated with striatal dopaminergic deficits, presumably due to degeneration of brainstem dopaminergic projections. Segregated areas of the striatum are crucially involved in various parallelly arranged cortical-striatal-thalamocortical circuits and serve functions in, among others, motor control or emotion. This suggests regional specificity of dopaminergic deficits in the striatum in motor and depressive symptoms in PD.
In this cross-sectional retrospective study, we correlated severity scores of depressive and motor symptoms in 100 non-demented PD patients (median Hoehn & Yahr stage: 2) with dopamine loss in specific regions of the striatum as measured by [123I]FP-CIT SPECT tracer binding to the dopamine transporter (DaT).
Depressive symptoms were related to lower DaT binding in the right caudate nucleus, while motor symptoms were associated with decreased DaT binding in the right putamen. This double dissociation was most pronounced in early-stage PD patients.
These results suggest that depressive symptoms in PD are associated with dopamine loss in the caudate nucleus, possibly related to degeneration of dopaminergic projections from the ventral tegmental area, while motor symptoms are associated with low dopamine signalling to the putamen and loss of nigrostriatal projections. This is consistent with the neuroanatomy of partially segregated cortical-striatal-thalamocortical circuits and supports the role of dysfunctional associative and motivational circuits in PD-related depression.
PLoS One. 2013 Jun 20;8(6):e66639. Print 2013.
Jugel C, Ehlen F, Taskin B, Marzinzik F, Müller T, Klostermann F.
Department of Neurology, Charité - University Medicine, Campus Benjamin Franklin, Berlin, Germany.
Severe polyneuropathy has been observed in a number of patients treated for Parkinson's disease with Levodopa/Carbidopa intestinal gel infusion. This may reflect a rare individual complication or a systematic side effect.
To investigate whether peripheral nerve function differed between patients with oral treatment versus Levodopa/Carbidopa intestinal gel infusion.
In an observational design, data from median, tibial, and peroneal neurography were prospectively assessed and compared between patients with conventional drug treatment (n = 15) and with Levodopa/Carbidopa intestinal gel infusion (n = 15). The groups were matched for age and disease duration. In view of the medical risk profile for polyneuropathy, comorbidity and basic serological parameters were assessed.
Axonal neuropathy was common in both patient groups. However, although group differences in risk factors for polyneuropathy were not evident, neurographic abnormalities were more severe in the patients treated with Levodopa/Carbidopa intestinal gel infusion than in the orally treated patients. In the group with Levodopa/Carbidopa intestinal gel infusion, the degree of neuropathic change correlated with weight lost since therapy initiation and with the drug dose. In contrast to the axonal abnormalities, conduction velocity was found normal in both groups.
The results are compatible with the promotion of axonal neuropathy by Levodopa/Carbidopa intestinal gel infusion. This could be due to the intrinsically high levodopa doses associated with the therapy and/or malnutritional effects from intestinal drug application. The results should be corroborated by a larger longitudinal and controlled trial.
Thursday, 4 July 2013
CSF α-synuclein improves diagnostic and prognostic performance of CSF tau and Aβ in Alzheimer's disease
Acta Neuropathol. 2013 Jun 29. [Epub ahead of print]
Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J.
Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Alzheimer's disease (AD) and Lewy body diseases (LBD), e.g., Parkinson's disease (PD) dementia and dementia with Lewy bodies (DLB), are common causes of geriatric cognitive impairments. In addition, AD and LBD are often found in the same patients at autopsy; therefore, biomarkers that can detect the presence of both pathologies in living subjects are needed. In this investigation, we report the assessment of α-synuclein (α-syn) in cerebrospinal fluid (CSF) and its association with CSF total tau (t-tau), phosphorylated tau181 (p-tau181), and amyloid beta1-42 (Aβ1-42) in subjects of the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 389), with longitudinal clinical assessments. A strong correlation was noted between α-syn and t-tau in controls, as well as in patients with AD and mild cognitive impairment (MCI). However, the correlation is not specific to subjects in the ADNI cohort, as it was also seen in PD patients and controls enrolled in the Parkinson's Progression Markers Initiative (PPMI; n = 102). A bimodal distribution of CSF α-syn levels was observed in the ADNI cohort, with high levels of α-syn in the subjects with abnormally increased t-tau values. Although a correlation was also noted between α-syn and p-tau181, there was a mismatch (α-syn-p-tau181-Mis), i.e., higher p-tau181 levels accompanied by lower α-syn levels in a subset of ADNI patients. We hypothesize that this α-syn-p-tau181-Mis is a CSF signature of concomitant LBD pathology in AD patients. Hence, we suggest that inclusion of measures of CSF α-syn and calculation of α-syn-p-tau181-Mis improves the diagnostic sensitivity/specificity of classic CSF AD biomarkers and better predicts longitudinal cognitive changes.
Genotype and phenotype in Parkinson's disease: Lessons in heterogeneity from deep brain stimulation.
Mov Disord. 2013 Jul 1. doi: 10.1002/mds.25535. [Epub ahead of print]
Angeli A, Mencacci NE, Duran R, Aviles-Olmos I, Kefalopoulou Z, Candelario J, Rusbridge S, Foley J, Pradhan P, Jahanshahi M, Zrinzo L, Hariz M, Wood NW, Hardy J, Limousin P, Foltynie T.
Sobell Department of Motor Neuroscience, University College London (UCL) Institute of Neurology, Queen Square, London, United Kingdom.
Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD. The consequent genetic subgroups of patients were compared with respect to phenotype, levodopa (l-dopa), and DBS responsiveness. An unprecedented number (29%) of patients tested positive for at least 1 of the currently known PD genes. Patients with Parkin mutations presented at the youngest age but had many years of disease before needing DBS, whereas glucocerebrosidase (GBA) mutation carriers reached the threshold of needing DBS earlier, and developed earlier cognitive impairment after DBS. DBS cohorts include large numbers of gene positive PD patients and can be clinically instructive in the exploration of genotype-phenotype relationships.
© 2013 The Authors. Movement Disorders published by Wiley on behalf of The Movement Disorder Society.
Wednesday, 3 July 2013
J Neurol. 2013 Jun 29. [Epub ahead of print]
Böttcher T, Rolfs A, Meyer B, Grossmann A, Berg D, Kropp P, Benecke R, Walter U.
Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany.
Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson's disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %; p < 0.001, p < 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN pars compacta, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD, n = 4; early PD, n = 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.