Friday, 31 January 2014

Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis

PLoS One. 2014 Jan 21;9(1):e85718. doi: 10.1371/journal.pone.0085718. eCollection 2014.
Yu JG, Feng YF, Xiang Y, Huang JH, Savini G, Parisi V, Yang WJ, Fu XA.

Author information
1Department of Ophthalmology, The Central Hospital of Wuhan, Hubei, China.
2Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China.
3The Affiliated Eye Hospital of Wenzhou Medical University, Zhejiang, China.
4G.B. Bietti Eye Foundation-IRCCS, Rome, Italy.


Parkinson disease (PD) is a neurodegenerative process that leads to a selective loss of dopaminergic neurons, mainly in the basal ganglia of the brain. Numerous studies have analyzed the ability of optical coherence tomography (OCT) to detect retinal nerve fiber layer (RNFL) thickness abnormalities and changes in PD, but the results have not always been consistent. Therefore, we carried out a meta-analysis to evaluate the RNFL thickness measured with OCT in PD.

Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PUBMED and EMBASE. For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence interval (CI). The statistical analysis was performed by RevMan 5.0 software. Thirteen case-control studies were included in the present meta-analysis, containing a total of 644 eyes in PD patients and 604 eyes in healthy controls. The results of our study showed that there was a significant reduction in average RNFL thickness in patients with PD compared to healthy controls (WMD = -5.76, 95% CI: -8.99 to -2.53, P = 0.0005). Additionally, differences of RNFL thickness in superior quadrant (WMD = -4.44, 95% CI: -6.93 to -1.94, P = 0.0005), inferior quadrant (WMD = -7.56, 95% CI: -11.33 to -3.78, P<0.0001), nasal quadrant (WMD = -3.12, 95% CI: -5.63 to -0.61, P = 0.01) and temporal quadrant (WMD = -4.63, 95% CI: -7.20 to -2.06, P = 0.0004) were all significant between the two groups.

In view of these results and the noninvasive nature of OCT technology, we surmise that OCT could be a useful tool for evaluating the progression of the Parkinson disease.


Friday, 24 January 2014

Susceptibility loci for pigmentation and melanoma in relation to Parkinson's disease

Neurobiol Aging. 2013 Dec 27. pii: S0197-4580(13)00662-3. doi: 10.1016/j.neurobiolaging.2013.12.020. [Epub ahead of print]
Dong J, Gao J, Nalls M, Gao X, Huang X, Han J, Singleton AB, Chen H; International Parkinson's Disease Genomics Consortium (IPDGC).


Growing evidence suggests that Parkinson's disease (PD) patients have a lower risk for most types of cancer except for melanoma, which has a modest positive association with PD. Pigmentation genes have been hypothesized to contribute to this association. We therefore examined whether genetic susceptibility loci for pigmentation or melanoma was associated with PD risk in 2 large independent datasets. In the Parkinson's Genes and Environment (PAGE) study, we examined 11 single-nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies (GWAS) of pigmentation or melanoma in relation to PD among 808 PD cases and 1623 controls; furthermore, we also examined the colors of hair, eye, or skin and melanoma in relation to PD. In the International Parkinson's Disease Genomic Consortium (IPDGC), we examined a broader selection of 360 pigmentation or melanoma GWAS SNPs in relation to PD among 5,333 PD cases and 12,019 controls. All participants were non-Hispanic Whites. As expected, in the PAGE study, most SNPs were associated with 1 or more pigmentation phenotypes. However, neither these SNPs nor pigmentation phenotypes were associated with PD risk after Bonferroni correction with the exception of rs4911414 at the ASIP gene (p = .001). A total of 18 PD cases (2.2%) and 26 controls (1.6%) had a diagnosis of melanoma with an odds ratio of 1.3 (95% confidence interval: 0.7-2.4). In the IPDGC analysis, none of the 360 SNPs, including rs4911414, were associated with PD risk after adjusting for multiple comparisons. In conclusion, we did not find significant associations between GWAS SNPs of pigmentation or melanoma and the risk for PD.

Thursday, 23 January 2014

Irritable bowel syndrome correlates with increased risk of Parkinson's disease in Taiwan.

Eur J Epidemiol. 2014 Jan 18. [Epub ahead of print]
Lai SW, Liao KF, Lin CL, Sung FC.

Author information
School of Medicine, China Medical University, Taichung, Taiwan


This study investigated whether an association exists between irritable bowel syndrome (IBS) and the risk of Parkinson's disease. This is a retrospective cohort study using the dataset of the Taiwan National Health Insurance Program from 2000 to 2010. We identified 23,875 patients (aged 20 years or older) with newly diagnosed IBS as the IBS group and 95,500 subjects without IBS as the non-IBS group for comparison. The main outcome was incident Parkinson's disease compared between both groups by the end of 2010. We measured the hazard ratio (HR) to evaluate the association between IBS and Parkinson's disease. The overall incidence of Parkinson's disease in the IBS group was 1.76-fold higher than that in the non-IBS group (16.4 vs. 9.33 per 10,000 person-years). The multivariable Cox proportional hazards regression analysis revealed that the adjusted HR of Parkinson's disease associated with IBS was 1.48 (95 % CI 1.27, 1.72), compared with the non-IBS group. Age, women, hypertension, dementia, cerebrovascular disease and depression were also significantly associated with Parkinson's disease. Patients with irritable bowel syndrome are at an increased risk of developing Parkinson's disease. Further studies are required to explore the pathophysiological connection between these disorders.

Wednesday, 22 January 2014

Which target is best for patients with Parkinson's disease? A meta-analysis of pallidal and subthalamic stimulation

J Neurol Neurosurg Psychiatry. 2014 Jan 20. doi: 10.1136/jnnp-2013-306090. [Epub ahead of print]
Sako W, Miyazaki Y, Izumi Y, Kaji R.

Author information
Center for Neurosciences, The Feinstein Institute for Medical Research, , Manhasset, New York, USA.


There is a growing body of evidence demonstrating that deep brain stimulation (DBS) of globus pallidus internus (GPi DBS) and subthalamic nucleus (STN DBS) are effective treatment for patients with Parkinson's disease (PD). However, it remains controversial whether the best stimulation target for a PD patient is GPi or STN.

A computer literature search of PubMed was carried out. We included randomised studies with direct comparison between targets. The outcome of unified PD rating scale (UPDRS) III was expressed as the standardised mean difference (SMD) between targets in baseline to endpoint change. Pooled risk ratio (RR) between targets was also used to assess adverse events.

Four studies, comprising a total sample size of 502 PD patients (254 GPi DBS, 248 STN DBS), were included in this meta-analysis. The overall effect of GPi DBS on UPDRS III was not significantly different from STN DBS (SMD=0.19, 95% CI -0.2 to 0.58, p=0.34, four studies, n=448). This result was heterogeneous (p=0.03, I2=66%). In terms of adverse events, depression was significantly less frequent in patients with GPi DBS than STN DBS with homogeneous studies (pooled RR=0.53, 95% CI 0.31 to 0.90, p=0.02, three studies, n=479, I2=48%).

The effect of GPi DBS was similar to STN DBS except for depression, however, only three studies described depression as adverse events. We need additional randomised trials with direct comparison between targets based on unified scoring of adverse events.

Sunday, 12 January 2014

Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders

Mov Disord. 2014 Jan 2. doi: 10.1002/mds.25776. [Epub ahead of print]
Gelpi E, Navarro-Otano J, Tolosa E, Gaig C, Compta Y, Rey MJ, Martí MJ, Hernández I, Valldeoriola F, Reñé R, Ribalta T.

Author information
Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.


Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD.

Saturday, 11 January 2014

Association of homocysteine with ventricular dilatation and brain atrophy in Parkinson's disease

Mov Disord. 2014 Jan 6. doi: 10.1002/mds.25798. [Epub ahead of print]
Sapkota S, Gee M, Sabino J, Emery D, Camicioli R.

Author information
Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.


Parkinson's disease (PD) patients are treated with levodopa (l-dopa) to help stabilize their impaired motor abilities; however, l-dopa leads to increased homocysteine (Hcy) levels, which may have a deleterious effect on brain structure and function. The purpose of this study was to examine the impact of increased Hcy concentration on global brain atrophy as determined by magnetic resonance imaging in PD patients and controls. The effect of high Hcy level on ventricular dilatation (percentage of intracranial volume [%ICV]) and total tissue volume (%ICV) was examined at baseline and longitudinally at 36 months. Age, sex, education, and l-dopa duration (in PD patients) were included as covariates. Elevated Hcy levels correlated positively with ventricular dilatation (%ICV) in the whole sample (P = 0.004) and in the PD group (P = 0.008). At baseline, adults with a high Hcy level (>14 μmol/L) had higher ventricular volume (%ICV) than adults with a low Hcy level (≤14 μmol/L) in the whole sample (P = 0.006) and in the PD group (P = 0.03), which persisted over 36 months in both the whole sample (P = 0.004) and the PD group (P = 0.03). PD patients with high Hcy concentrations had a greater rate of ventricular enlargement (%ICV) over time compared with those with low Hcy concentration (P = 0.02). Elevated Hcy concentration was associated with increased ventricular dilatation (%ICV) in PD patients. A larger sample with a broader age range and longer follow-up is needed to establish the consequences of high Hcy level, including interactions with genetic and environmental risk factors, in PD.

Friday, 10 January 2014

Predictors of cognitive impairment in an early stage Parkinson's disease cohort

Further evidence that the MoCA is a better screening test than the MMSE in early PD (and it is free, with permission!).

Mov Disord. 2014 Jan 6. doi: 10.1002/mds.25748. [Epub ahead of print]
Hu MT, Szewczyk-Królikowski K, Tomlinson P, Nithi K, Rolinski M, Murray C, Talbot K, Ebmeier KP, Mackay CE, Ben-Shlomo Y.

Author information
Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, University of Oxford, Oxford, United Kingdom; Department of Clinical Neurology, John Radcliffe Hospital, Oxford, United Kingdom; Oxford Parkinson's Disease Centre, Oxford, United Kingdom.


The impact of Parkinson's disease (PD) dementia is substantial and has major functional and socioeconomic consequences. Early prediction of future cognitive impairment would help target future interventions. The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and fluency tests were administered to 486 patients with PD within 3.5 years of diagnosis, and the results were compared with those from 141 controls correcting for age, sex, and educational years. Eighteen-month longitudinal assessments were performed in 155 patients with PD. The proportion of patients classified with normal cognition, mild cognitive impairment (MCI), and dementia varied considerably, depending on the MoCA and MMSE thresholds used. With the MoCA total score at screening threshold, 47.7%, 40.5%, and 11.7% of patients with PD were classified with normal cognition, MCI, and dementia, respectively; by comparison, 78.7% and 21.3% of controls had normal cognition and MCI, respectively. Cognitive impairment was predicted by lower education, increased age, male sex, and quantitative motor and non-motor (smell, depression, and anxiety) measures. Longitudinal data from 155 patients with PD over 18 months showed significant reductions in MoCA scores, but not in MMSE scores, with 21.3% of patients moving from normal cognition to MCI and 4.5% moving from MCI to dementia, although 13.5% moved from MCI to normal; however, none of the patients with dementia changed their classification. The MoCA may be more sensitive than the MMSE in detecting early baseline and longitudinal cognitive impairment in PD, because it identified 25.8% of those who experienced significant cognitive decline over 18 months. Cognitive decline was associated with worse motor and non-motor features, suggesting that this reflects a faster progressive phenotype.

Thursday, 9 January 2014

Thoughts on selected movement disorder terminology and a plea for clarity

Tremor Other Hyperkinet Mov (N Y). 2013 Dec 16;3. pii: tre-03-203-4656-2.
Walker RH.

Author information
Department of Neurology, James J. Peters Veterans Affairs Medical Center, Bronx, New York ; Department of Neurology, Mount Sinai School of Medicine, New York City, New York, United States of America.


Description of the phenomenology of movement disorders requires precise and accurate terminology. Many of the terms that have been widely used in the literature are imprecise and open to interpretation. An examination of these terms and the assumptions implicit in their usage is important to improve communication and hence the definition, diagnosis, and treatment of movement disorders. I recommend that the term dyskinesia should be used primarily in the settings of Parkinson's disease and tardive dyskinesia, in which its clinical implications are relatively clear; it should not be used in other situations where a precise description could more usefully facilitate diagnosis and treatment. In general dyskinesia should be used in the singular form. Extrapyramidal is based upon obsolete anatomical concepts, is uninformative, and should be discarded. The term abnormal involuntary movements (AIMs) is similarly vague and uninformative, although is unlikely to be eliminated from the psychiatric literature. Movement disorder neurologists as teachers, clinicians, article reviewers, and journal editors have the responsibility to educate our colleagues regarding appropriate usage and the importance of employing correct descriptors.

Anhedonia in Parkinson's disease patients with and without pathological gambling: A case-control study

Psychiatry Res. 2013 Dec 16. pii: S0165-1781(13)00776-2. doi: 10.1016/j.psychres.2013.12.013. [Epub ahead of print]
Pettorruso M, Martinotti G, Fasano A, Loria G, Di Nicola M, De Risio L, Ricciardi L, Conte G, Janiri L, Bentivoglio AR.


Anhedonia is present in Parkinson's Disease (PD) as well as in addictive behaviors. Pathological Gambling (PG) and other Impulse Control Disorders (ICDs) have emerged as iatrogenic complications associated with dopamine replacement therapy. We studied 154 PD patients, divided into three groups: 11 with PG, 23 with other ICDs (compulsive buying, hypersexuality, binge eating), 120 without ICDs. All patients underwent a thorough clinical, neuropsychological and psychiatric evaluation. The PG-group, compared to the ICDs-group and PD-controls, reported a significantly higher incidence of anhedonia (45% vs. 9% vs. 14% respectively), higher Snaith-Hamilton Pleasure Scale (SHAPS) scores (2.0±1.3 vs. 1.0±1.1 vs. 1.0±1.2), higher levels of impulsivity traits as measured by the Barratt Impulsiveness Scale (70.0±10.6 vs. 64.8±11 vs. 60.9±9.3) and more severe frontal dysfunctions (Frontal Assessment Battery, FAB: 12.4±4.9 vs. 15.5±1.6 vs. 14.4±3). A model for PG (incorporating anhedonia, impulsivity levels and frontal impairment) is discussed in the context of the pathophysiology of addictive behaviors. The impairment of hedonic capacity, possibly resulting from an underlying neuropsychological dysfunction, might facilitate loss of control over reward-related behavior, thus favoring the shift towards predominantly habit-based compulsive behaviors.

Wednesday, 8 January 2014

Alimentary, my dear Watson? The challenges of enteric α-synuclein as a Parkinson's disease biomarker

Mov Disord. 2013 Dec 26. doi: 10.1002/mds.25789. [Epub ahead of print]
Visanji NP, Marras C, Hazrati LN, Liu LW, Lang AE.

Author information
Morton and Gloria Shulman Movement Disorders Centre and the Edmund J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada.


An accurate early diagnostic test for Parkinson's disease (PD) is a critical unmet need. Recently, independent groups using different histological techniques have reported that the presence of alpha-synuclein (α-syn) in colonic biopsy tissue is able to distinguish living patients with PD from those without the disease. In addition, a further study has suggested that the presence of α-syn in colonic biopsy tissue may be evident in early or even prodromal PD. However, several questions remain regarding the translation of these findings into using the assessment of α-syn deposition in the enteric nervous system as a diagnostic biomarker for prodromal PD. Here we address critical issues related to the location and quantification of enteric α-syn, detection of α-syn with currently available histological techniques, timing of detection of α-syn deposition, and, most crucially, whether enteric α-syn can distinguish those with PD from both healthy individuals and individuals with other related diseases. We conclude that, although enteric α-syn is a very exciting prospect, further studies will be vital to determine whether enteric α-syn deposition has the potential to be the biomarker for prodromal PD that the field so desperately seeks. © 2013 International Parkinson and Movement Disorder Society.

Tuesday, 7 January 2014

Nizatidine ameliorates gastroparesis in Parkinson's disease: A pilot study

Mov Disord. 2013 Dec 27. doi: 10.1002/mds.25777. [Epub ahead of print]
Doi H, Sakakibara R, Sato M, Hirai S, Masaka T, Kishi M, Tsuyusaki Y, Tateno A, Tateno F, Takahashi O, Ogata T.

Author information
Pharmaceutical Unit, Sakura Medical Center, Toho University, Sakura, Japan.


The objective of this work was to perform an open trial of the effects of nizatidine (NZT), a selective histamine H2-receptor antagonist and a cholinomimetic, on gastroparesis in Parkinson's disease (PD) patients, using objective parameters given by a gastric emptying study using a 13 C-sodium acetate expiration breath test.

Twenty patients with PD were enrolled in the study. There were 13 men and 7 women; aged 68.0 ± 7.72 years; disease duration 5.50 ± 3.62 years. All patients underwent the breath test and a gastrointestinal questionnaire before and after 3 months of administration of NZT at 300 mg/day. Statistical analysis was performed by Student t test.

NZT was well tolerated by all patients and none had abdominal pain or other adverse effects. NZT significantly shortened Tmax (13 C) (the peak time of the 13 C-dose-excess curve) (P < 0.05).

Although this is a pilot study, we found a significant shortening of gastric emptying time after administration of NZT in PD patients.

Monday, 6 January 2014

Autonomic dysfunction according to disease progression in Parkinson's disease

Parkinsonism Relat Disord. 2013 Dec 16. pii: S1353-8020(13)00434-3. doi: 10.1016/j.parkreldis.2013.12.001. [Epub ahead of print]
Kim JB, Kim BJ, Koh SB, Park KW.


Although autonomic dysfunction is common in patients with Parkinson's disease (PD), few data are available regarding its pattern and quantitative severity with increasing Hoehn and Yahr (H&Y) stage. We conducted autonomic function tests to quantify autonomic dysfunction in PD patients and to elucidate its possible relationship with disease progression.

We performed autonomic function tests including Valsalva ratio, heart rate response to deep breathing, quantitative sudomotor axon reflex test, and head-up tilt test in 66 patients with PD. We compared clinical characteristics and results of autonomic function tests between stages, and correlated the proportion of abnormal patients in each test with their H&Y stage. In addition, logistic regression analyses were conducted to examine the contribution of increasing H&Y stage to impairments of each domain of the autonomic nervous system.

We found that PD patients with higher disease stage tended to have impairments in cardiovagal and sudomotor domains of the autonomic nervous system. Cardiovagal function was the domain most influenced by disease progression. Our findings also demonstrated that the pattern of sudomotor impairment in PD was similar to that in patients with peripheral autonomic neuropathy.


Our study demonstrates that autonomic dysfunction is not only common in early stage PD but it increases in severity with increasing disease stage. Given that the patterns of sudomotor impairments in PD are similar to those in peripheral neuropathy, our data support a previous hypothesis that pathophysiology of PD involves both the central and peripheral nervous systems.

Thursday, 2 January 2014

Prevalence of cancer in Parkinson's disease related to R1441G and G2019S mutations in LRRK2

Mov Disord. 2013 Dec 19. doi: 10.1002/mds.25778. [Epub ahead of print]
Ruiz-Martínez J, de la Riva P, Rodríguez-Oroz MC, Mondragón Rezola E, Bergareche A, Gorostidi A, Gago B, Estanga A, Larrañaga N, Sarasqueta C, López de Munain A, Martí Massó JF.

Author information
Department of Neurology, University Hospital Donostia, San Sebastián, Spain; Center for Biomedical Research in Neurodegenerative Diseases Network (CIBERNED), San Sebastián, Spain; Neurosciences Area, Biodonostia Institute, San Sebastián, Spain.

An inverse relationship between Parkinson's disease (PD) and cancer has been described. However, the association between cancers and genetic forms of PD, in particular the R1441G mutation in the LRRK2 gene, is not well known. The objective of this work was to analyze cancer prevalence in PD patients with R1441G or G2019S mutations in LRRK2, and in idiopathic PD (iPD). A total of 732 patients with PD (70 and 25 carriers of R1441G or G2019S mutations, respectively), and 177 controls, were linked using a population-based cancer registry of the Spanish province of Gipuzkoa. Cancer prevalence was not significantly higher in PD-G2019S carriers (20%) than in PD-R1441G carriers (14.3%), iPD (13.8%), or controls (12.5%). With the exception of a high prevalence of hematological cancers (crude odds ratio of 7.1) in the R1441G group, specific cancer types were not increased in PD mutation carriers. In both the carrier and iPD groups, cancers were diagnosed after the onset of PD. PD patients had a similar prevalence of cancer to control subjects. There was no increased association between G2019S or R1441G mutations and any type of cancer. Although there was a higher prevalence of hematological cancers in the R1441G group, the low number of such cancers overall makes this finding of uncertain significance. There was a slightly higher but not statistically significant prevalence of non-skin cancers in the G2019S group, suggesting that further study to evaluate the association should be undertaken prior to ascribing an increased cancer risk to this population. © 2013 International Parkinson and Movement Disorder Society.

© 2013 Movement Disorder Society.

Plain English - LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic

This research study compared patients with Parkinson's who carry the commonest gene mutation associated with the disease (called LRRK2),...