Saturday, 22 December 2012

Serum urate and the risk of Parkinson's disease: results from a meta-analysis

Can J Neurol Sci. 2013 Jan;40(1):73-9.
Shen C, Guo Y, Luo W, Lin C, Ding M.

Department of Neurology, Second Affiliated Hospital.

Objective: Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD. Methods: We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender. Results: Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72). Conclusions: In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.

Cohort Profile: A population-based cohort to study non-motor symptoms in parkinsonism (EPIPARK)

Int J Epidemiol. 2012 Dec 19. [Epub ahead of print]
Kasten M, Hagenah J, Graf J, Lorwin A, Vollstedt EJ, Peters E, Katalinic A, Raspe H, Klein C.

Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany, Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Luebeck, Luebeck, Germany, Department of Neurology, Westkuestenklinikum Heide, Heide, Germany, Department of Clinical Epidemiology, University of Luebeck, Luebeck, Germany and Department of Public Health, University of Luebeck, Luebeck, Germany.

Parkinson's disease is increasingly viewed as a complex disorder including a range of typical non-motor symptoms in addition to the cardinal motor signs. This cohort was set up in 2010 to investigate the specificity of non-motor symptoms for Parkinson's disease. For this, we included several control groups with decreasing contrast from Parkinson's disease patients. Group definitions ranged from healthy control subjects to those with suspected early motor signs of parkinsonism. Using a mailed questionnaire, we screened 5838 inhabitants of Lübeck, Germany, out of a target population of 10 000 citizens, enquiring about motor impairment, pain, quality of life, comorbidities, somatization and demographics. Based on this information, participants were assigned to screening groups, and selected participants were invited for in-person examination (n = 623). The examination included cognitive examinations, transcranial ultrasound, a brief psychiatric interview and a standardized motor examination that was used to assign examination groups. In addition, all participants answered questionnaires addressing depression, anxiety, sleep and quality of life. The first-year follow-up examination was performed either in person using the same protocol or via mailed questionnaires. This study is ongoing and publications are in preparation, but you may contact the first author ( with suggestions for collaboration or data requests.

Tuesday, 18 December 2012

Impulse control disorders in Parkinson's disease: Crossroads between neurology, psychiatry and neuroscience

Behav Neurol. 2012 Dec 14. [Epub ahead of print]
Bugalho P, Oliveira-Maia AJ.

Department of Neurology, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal Department of Neurology and CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.

Non-motor symptoms contribute significantly to Parkinson's disease (PD) related disability. Impulse control disorders (ICDs) have been recently added to the behavioural spectrum of PD-related non-motor symptoms. Such behaviours are characterized by an inappropriate drive to conduct repetitive behaviours that are usually socially inadequate or result in harmful consequences. Parkinson disease impulse control disorders (PD-ICDs) have raised significant interest in the scientific and medical community, not only because of their incapacitating nature, but also because they may represent a valid model of ICDs beyond PD and a means to study the physiology of drive, impulse control and compulsive actions in the normal brain. In this review, we discuss some unresolved issues regarding PD-ICDs, including the association with psychiatric co-morbidities such as obsessive-compulsive disorder and with dopamine related side effects, such as hallucinations and dyskinesias; the relationship with executive cognitive dysfunction; and the neural underpinnings of ICDs in PD. We also discuss the contribution of neuroscience studies based on animal-models towards a mechanistic explanation of the development of PD-ICDs, specifically regarding corticostriatal control of goal directed and habitual actions.

New concepts in the early and preclinical detection of Parkinson's disease: therapeutic implications

Expert Rev Neurother. 2012 Dec;12(12):1429-38. doi: 10.1586/ern.12.144.
Akhtar RS, Stern MB.

Parkinson's Disease and Movement Disorders Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Parkinson's disease is a chronic neurodegenerative disorder leading to progressive motor impairment for which there is no cure. Currently, the diagnosis is made by the presence of cardinal motor features and several associated non-motor symptoms. However, at this point, the underlying neuropathological changes are already underway, and efforts in basic and clinical research have converged to suggest that Parkinson's disease actually begins well before symptom onset. As a result, the identification and development of disease-modifying therapies is difficult. In this review, we begin by summarizing what is known of disease pathogenesis in the context of early symptomatology. We then discuss the Parkinson's at-risk syndrome and highlight how this conceptual framework can be a useful for studies of early disease biomarkers and putative disease-modifying neurotherapeutics. With this framework, we discuss several clinical assessments, radiological studies and molecular assays that may be useful in early disease detection.

Monday, 17 December 2012

Neuropathological findings in benign tremulous Parkinsonism

Mov Disord. 2012 Dec 12. doi: 10.1002/mds.25220. [Epub ahead of print]
Selikhova M, Kempster PA, Revesz T, Holton JL, Lees AJ.

Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, University College London, London, United Kingdom; Department of Neurology, Russian State Medical University, Moscow, Russia.

Benign tremulous parkinsonism, a tremor dominant syndrome with a relatively slow rate of deterioration, is recognized by clinicians although its pathological basis is not well understood. A systematic review of Queen Square Brain Bank donors was carried out to determine the natural history and pathology of individuals who had tremor dominant parkinsonism with mild non-tremor components and minimal gait disability for at least 8 years. We identified 16 cases of pathologically proved benign tremulous Parkinson's disease (PD); another 5 individuals conformed to the definition but did not have the pathology of PD. Patients with verified benign tremulous PD had less severe neuronal loss in the substantia nigra than controls (χ(2) : P = .003). Twelve of these had been correctly diagnosed with PD at their first neurological evaluation, whereas the other 4 were originally thought to have another tremor disorder. The only consistent distinguishing feature of the 5 pathologically disproved cases, who may have had either essential tremor with associated rest tremor or dystonic tremor, was a failure to develop unequivocal bradykinesia within a decade of onset of tremor at rest. Our findings support the existence of a distinct subgroup of benign tremulous PD. The slower rate of clinical progression correlates with less severe nigral cell loss at postmortem, although many of these patients transgress the benign tremulous parkinsonism definition by the final third of their disease course and develop the common features of advanced PD. © 2012 Movement Disorder Society.

Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder

Mov Disord. 2012 Dec 12. doi: 10.1002/mds.25246. [Epub ahead of print]

Unger MM, Ekman R, Björklund AK, Karlsson G, Andersson C, Mankel K, Bohne K, Tebbe JJ, Stiasny-Kolster K, Möller JC, Mayer G, Kann PH, Oertel WH.

Philipps-University Marburg, Department of Neurology, Marburg, Germany; Saarland University, Department of Neurology, Homburg, Germany. 

Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD).
We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients.
The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations.
Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain-gut axis. © 2012 Movement Disorder Society.

Thursday, 6 December 2012

Patients with rest-tremor and scans with ipsilateral dopaminergic deficit

J Neurol. 2012 Nov 30. [Epub ahead of print]

Aguirregomozcorta M, Stamelou M, Antonini A, Schwingenschuh P, Prvulovich L, Edwards MJ, Dickson JC, Bhatia KP.


Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.


Dopamine transporter imaging is typically abnormal in Parkinson's disease and shows reduced striatal uptake, which is typically greater contralateral to the clinically more affected side. However, tremor-dominant Parkinson's disease patients may have significantly lower uptake in the striatum ipsilateral to the rest-tremor compared to akinetic-rigid PD patients, implying a possible role of an ipsilateral deficit in the generation of rest-tremor.We report here three patients with rest-tremor and the unexpected finding of an ipsilateral presynaptic dopaminergic deficit with normal uptake contralateral to the rest-tremor in dopamine transporter imaging. We divided them in two groups, with and without a corresponding structural lesion in brain imaging. These data may suggest a role of ipsilateral dopaminergic deficit in the generation of rest-tremor. An explanation of these findings could be damage of crossed dopaminergic fibres from the substantia nigra to thalamus, which can cause motor impairment ipsilateral to dopamine depletion experimentally. This is speculative but there is no doubt that these cases exist and we encourage others to report similar cases, as this may assist in the better understanding of the yet unknown pathophysiology of rest-tremor.

Wednesday, 5 December 2012

Switch from selegiline to rasagiline is beneficial in patients with Parkinson's disease

J Neural Transm. 2012 Nov 30. [Epub ahead of print]

Müller T, Hoffmann JA, Dimpfel W, Oehlwein C.


Department of Neurology, St. Joseph-Hospital, Gartenstr. 1, 13088, Berlin, Germany.


The objective of this study is to demonstrate that application of rasagiline instead of selegiline with concomitant determination of L-amphetamine and L-methamphetamine in plasma is safe and well tolerated and influences sleep, mood, and motor behavior in patients with Parkinson's disease on a stable drug therapy. 30 patients, who took 7.5 mg selegiline daily for at least 3 months, were switched to 1 mg rasagiline. Then they were followed over an interval of 4 months. The remaining drug therapy remained stable. This changeover was safe and well tolerated. L-Amphetamine and L-methamphetamine only appeared during selegiline treatment. Motor behavior, motor complications, mood and sleep improved during rasagiline administration. Amphetamine-like derivatives of selegiline could contribute to sleep disturbances, which may be involved in worsening of mood. Motor behavior and motor complications probably became better due to the additional glutamate receptor antagonizing properties of rasagiline in this open label study.

A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients

J Neurol Sci. 2012 Nov 28. pii: S0022-510X(12)00581-3. doi: 10.1016/j.jns.2012.10.024. [Epub ahead of print]

Schneider JS, Gollomp SM, Sendek S, Colcher A, Cambi F, Du W.


Dept. of Pathology, Anatomy and Cell Biology and Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA 19107, USA.


The present single center, double-blind, delayed start study was conducted to examine possible symptomatic and disease-modifying effects of GM1 ganglioside in Parkinson's disease (PD). Seventy-seven subjects with PD were randomly assigned to receive GM1 for 120weeks (early-start group) or placebo for 24weeks followed by GM1 for 96weeks (delayed-start group). Washout evaluations occurred at 1 and 2years after the end of treatment. Seventeen additional subjects who received standard-of-care were followed for comparative information about disease progression. Primary outcome was change from baseline Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. At week 24, the early-start group had significant improvement in UPDRS motor scores vs. a significant worsening of scores in the delayed-start group. The early-start group also showed a sustained benefit vs. the delayed-start group at week 72 and at week 120. Both groups had significant symptom worsening during washout. This study provides evidence that GM1 use for 24weeks was superior to placebo for improving motor symptoms and that extended GM1 use (up to 120weeks) resulted in a lower than expected rate of symptom progression. The data from this small study suggest that GM1 may have symptomatic and potentially disease modifying effects on PD.

Tuesday, 4 December 2012

Now to the North West to see participants...

Spending a week at my family home in order to see 15 or so participants in the area. Beautiful winter sun has given way to wet windiness now and I'm relieved to be off the motorbike and into a car! Pictures from yesterdays trip into the Welsh countryside to see a couple of participants.

A look back at the Welsh coast and Snowdonia from Anglesey. 

Finding my way around single track roads in North Wales.

Plain English - Low body mass index and life prognosis in Parkinson's disease

Over the last few years we have seen research that suggests being underweight has a negative or detrimental effect on survival with diseases...