Thursday, 30 October 2014

Patients with scans without evidence of dopaminergic deficit: A long-term follow-up study.

The more information we get on SWEDDs the better....

Mov Disord. 2014 Oct 28. doi: 10.1002/mds.26018. [Epub ahead of print]
Batla A, Erro R, Stamelou M, Schneider SA, Schwingenschuh P, Ganos C, Bhatia KP.

We previously reported on a cohort of dystonic tremor and patients with scans without evidence of dopaminergic deficit (SWEDDs). We aim to report the long-term clinical and imaging follow-up of these patients.

Patients with at least 5-year follow-up were included. These patients had an asymmetric arm tremor, a previous diagnosis of Parkinson's disease (PD), and a subsequent normal DaTscan. The imaging and clinical follow-up was done on the clinical basis.

Sixteen patients were included. The mean gap between the first and subsequent scans was 5.4 years. Two patients (12.5%) had reduced nigrostriatal uptake on follow-up DaTscan, whereas 14 continued to have normal dopaminergic imaging.


This is the longest follow up of patients with asymmetric rest tremor and normal DaT scans (SWEDDs) reported to date. We show here that only a minority of them show reduced striatonigral uptake over long term follow up.

Tuesday, 28 October 2014

Genetic Movement Disorders in Patients of Jewish Ancestry

Interesting and helpful. Especially for those of us that work in London or other areas where we see a lot of people with Jewish ancestry...

JAMA Neurol. 2014 Oct 27. doi: 10.1001/jamaneurol.2014.1364. [Epub ahead of print]
Inzelberg R, Hassin-Baer S, Jankovic J.

Genetic diseases often cluster in different ethnic groups and may present with recognizable unique clinical manifestations.

To summarize current knowledge about movement disorders overrepresented among patients of Jewish ancestry.

We searched PubMed and the OMIM and Israeli National Genetic Databases for articles published from 1969 through March 31, 2014, using the search terms Parkinson's disease,movement disorders, ataxia, dystonia, chorea, and Creutzfeldt-Jakob with and Jewish. The final reference list was generated by giving priority to articles directly related to the topic, articles with the latest information, and comprehensive but relevant reviews.

About one-third of patients with sporadic Parkinson disease (PD) and more than 40% of patients with familial PD of Ashkenazi Jewish descent likely carry the G2019S mutation in the LRRK2 gene, a mutation in the glucocerebrosidase (GBA) gene, or both. This finding contrasts with only a 10% frequency of these mutations in patients with PD who are of non-Jewish ancestry. A dystonia due to a TOR1A gene mutation is responsible for most early-onset autosomal dominant dystonia, and 90% of Ashkenazi Jews who develop early-onset disease have TOR1A-related dystonia. Familial Creutzfeldt-Jakob disease and cerebrotendinous xanthomatosis tend to cluster among Jews of North African descent, and Machado-Joseph disease is particularly frequent in Yemenite Jews.


Genetic forms of PD are much more common in patients of Ashkenazi Jewish ancestry with sporadic and familial PD than in the non-Jewish population. The recognition of the particular movement disorder phenotype, coupled with information about the ethnic origin of the patients, may point to specific genetic testing and lead to early and correct diagnosis.

Thursday, 23 October 2014

Disease Penetrance of Late-Onset Parkinsonism: A Meta-analysis

JAMA Neurol. 2014 Oct 20. doi: 10.1001/jamaneurol.2014.1909. [Epub ahead of print]
Trinh J, Guella I, Farrer MJ.

Mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13 have been implicated in late-onset familial parkinsonism. However, the estimated disease penetrance of these mutations varies widely.

To compare penetrance of various mutations reported in published genetic studies to improve the understanding of late-onset parkinsonism.

Forty-nine previously published studies, including 709 participants, were included for all original and subsequent articles in ISI Web of Science, PubMed electronic databases, and extracted information about number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014.

Published studies were included if there was information on the ethnicity of the patient or unaffected individual, confirmation of mutation, age of patient or unaffected individual, age at onset, and first motor symptom of patient. Autosomal recessive parkinsonism and genes implicated without significant genetic linkage were excluded from this study.

The age-associated cumulative incidence was estimated using the Kaplan-Meier method with age at onset as the time variable; asymptomatic carriers were right censored at the age at last contact or age at death.

Comparative measures were obtained with log-rank tests, and each penetrance estimate was given separately with 95% confidence intervals.

All the assessed autosomal dominant Parkinson disease mutations have significantly different age-dependent cumulative incidences (P < .001). In particular, penetrance of SNCA duplications was comparable to point mutations (log-rank P = .97) and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9 years; 95% CI, 43-49 years). In addition, Israeli Ashkenazi Jewish LRRK2 p.G2019S carriers (mean age at onset, 57.9 years; 95% CI, 54-63 years) were comparable to Tunisian Arab Berbers (mean age at onset, 57.1 years; 95% CI, 45.5-68.7 years) (P = .58), whereas Norwegian carriers (mean age at onset, 63 years; 95% CI, 51.4-74.6 years) were significantly different from the other groups (P < .001).


Parkinson disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations.

Wednesday, 22 October 2014

Nonmotor Symptoms in LRRK2 G2019S Associated Parkinson's Disease

This is an important study that helps us understand more about the non-motor features of LRRK2-associated PD...

PLoS One. 2014 Oct 17;9(10):e108982. doi: 10.1371/journal.pone.0108982. eCollection 2014.
Gaig C, Vilas D, Infante J, Sierra M, García-Gorostiaga I, Buongiorno M, Ezquerra M, Martí MJ, Valldeoriola F, Aguilar M, Calopa M, Hernandez-Vara J, Tolosa E.

Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.
To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients.
The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated.
University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination.

Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD.

Tuesday, 21 October 2014

A Validation Study of Administrative Data Algorithms to Identify Patients with Parkinsonism with Prevalence and Incidence Trends

Neuroepidemiology. 2014 Oct 16;43(1):28-37. [Epub ahead of print]
Butt DA, Tu K, Young J, Green D, Wang M, Ivers N, Jaakkimainen L, Lam R, Guttman M.


Background: Epidemiological studies for identifying patients with Parkinson's disease (PD) or Parkinsonism (PKM) have been limited by their nonrandom sampling techniques and mainly veteran populations. This reduces their use for health services planning. The purpose of this study was to validate algorithms for the case ascertainment of PKM from administrative databases using primary care patients as the reference standard. Methods: We conducted a retrospective chart abstraction using a random sample of 73,003 adults aged ≥20 years from a primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Physician diagnosis in the EMR was used as the reference standard and population-based administrative databases were used to identify patients with PKM from the derivation of algorithms. We calculated algorithm performance using sensitivity, specificity, and predictive values and then determined the population-level prevalence and incidence trends with the most accurate algorithms. Results: We selected, '2 physician billing codes in 1 year' as the optimal administrative data algorithm in adults and seniors (≥65 years) due to its sensitivity (70.6-72.3%), specificity (99.9-99.8%), positive predictive value (79.5-82.8%), negative predictive value (99.9-99.7%), and prevalence (0.28-1.20%), respectively. Conclusions: Algorithms using administrative databases can reliably identify patients with PKM with a high degree of accuracy.

Monday, 20 October 2014

Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques

J Alzheimers Dis Parkinsonism. 2014 Jan 31;4. pii: 137.
Sundman MH, Hall EE, Chen NK.


Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.

Saturday, 18 October 2014

Efficacy of Bisphosphonates against Hip Fracture in Elderly Patients with Stroke and Parkinson Diseases: Meta-analysis of Randomized Controlled Trials

J Stroke Cerebrovasc Dis. 2014 Oct 11. pii: S1052-3057(14)00304-8. doi: 10.1016/j.jstrokecerebrovasdis.2014.06.022. [Epub ahead of print]
Zhang W, Zhu C, Sun M, Ge Y, Yan G.

Stroke and Parkinson disease cause disability and immobilization that increase the risk for fractures. The purpose of the present research was to clarify the efficacy of 3 different bisphosphonates against hip fracture in elderly patients with these neurologic diseases. A literature search was performed in Medline, Embase, CBMdisc, and the Cochrane Library until March 1, 2014, with respect to strictly conducted randomized controlled trials (RCTs) and a meta-analysis was conducted. Every study was evaluated using the Jadad scale. Eight RCTs met the criteria including 5 RCTs for stroke and 3 for Parkinson disease. According to the results of RCTs, the relative risks (95% confidence interval [CI]) for hip fracture with bisphosphonates treatment compared with control treatment were .20 (.07-.54) for stroke and .26 (.13-.52) for Parkinson disease. Overall, the total relative risk (95% CI) for hip fracture with bisphosphonates treatment was .24 (.14-.42), suggesting hip fracture risks with bisphosphonates treatment were reduced significantly in elderly patients compared with the control group in the 2 neurologic diseases (heterogeneity, .86; P = 1.00 and overall effect, 4.99; P < .0001). Meanwhile, after bisphosphonates treatment, bone mineral density, intact parathyroid hormone, and 1,25-dihydroxyvitamin D increased, and serum ionized calcium, urinary deoxypyridinoline decreased compared with the placebo group. No severe adverse events were reported for bisphosphonates treatment. The results of a meta-analysis of strictly conducted RCTs suggest that there is efficacy against hip fracture with bisphosphonates treatment in patients with stroke and Parkinson disease.

Friday, 17 October 2014

7 tesla magnetic resonance imaging: A closer look at substantia nigra anatomy in Parkinson's disease

Mov Disord. 2014 Oct 12. doi: 10.1002/mds.26043. [Epub ahead of print]
Lehéricy S, Bardinet E, Poupon C, Vidailhet M, François C.

A hallmark of Parkinson's disease (PD) is the progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Dopaminergic denervation is commonly imaged using radiotracer imaging in target structures such as the striatum. Until recently, imaging made only a modest contribution to detecting neurodegenerative changes in the substantia nigra (SN) directly. Histologically, the SN is subdivided into the ventral pars reticulata and the dorsal pars compacta, which is composed of dopaminergic neurons. In humans, dopaminergic neurons, which are known to accumulate neuromelanin, form clusters of cells (nigrosomes) that penetrate deep into the SN pars reticulata (SNr). The SNr contains higher levels of iron than the SNc in normal subjects. Neuromelanin and T2*-weighted imaging therefore better detect the SNc and the SNr, respectively. The development of ultra-high field 7 Tesla (7T) magnetic resonance imaging (MRI) provided the increase in spatial resolution and in contrast that was needed to detect changes in SN morphology. 7T MRI allows visualization of nigrosome-1 as a hyperintense signal area on T2*-weighted images in the SNc of healthy subjects and its absence in PD patients, probably because of the loss of melanized neurons and the increase of iron deposition. This review is designed to provide a better understanding of the correspondence between the outlines and subdivisions of the SN detected using different MRI contrasts and the histological organization of the SN. The recent findings obtained at 7T will then be presented in relation to histological knowledge.

Thursday, 16 October 2014

Imaging prodromal Parkinson disease: The Parkinson Associated Risk Syndrome Study

Eagerly awaited results from the PARS study...

Neurology. 2014 Oct 8. pii: 10.1212/WNL.0000000000000960. [Epub ahead of print]
Jennings D, Siderowf A, Stern M, Seibyl J, Eberly S, Oakes D, Marek K; For the PARS Investigators.

The purpose of this study is to evaluate the relative risk of abnormal dopamine transporter (DAT) imaging for subjects with and without hyposmia and the feasibility of acquiring a large, community-based, 2-tiered biomarker assessment strategy to detect prodromal Parkinson disease (PD).

In this observational study, individuals without a diagnosis of PD, recruited through 16 movement disorder clinics, underwent tier 1 assessments (olfactory testing, questionnaires). Tier 2 assessments (neurologic examination, DAT imaging, and other biomarker assessments) were completed by 303 subjects. The main outcome of the study is to compare age-expected [123I]β-CIT striatal binding ratio in hyposmic and normosmic subjects.

Tier 1 assessments were mailed to 9,398 eligible subjects and returned by 4,999; 669 were hyposmic. Three hundred three subjects (203 hyposmic, 100 normosmic) completed baseline evaluations. DAT deficit was present in 11% of hyposmic subjects compared with 1% of normosmic subjects. Multiple logistic regression demonstrates hyposmia (odds ratio [OR] 12.4; 95% confidence interval [CI] 1.6, 96.1), male sex (OR 5.5; 95% CI 1.7, 17.2), and constipation (OR 4.3; 95% CI 1.6, 11.6) as factors predictive of DAT deficit. Combining multiple factors (hyposmia, male sex, and constipation) increased the percentage of subjects with a DAT deficit to >40%.


Subjects with DAT deficit who do not meet criteria for a diagnosis of PD can be identified by olfactory testing. Sequential biomarker assessment may identify those at risk of PD. Selecting hyposmic individuals enriches the population for DAT deficit, and combining hyposmia with other potential risk factors (male sex, constipation) increases the percentage of subjects with a DAT deficit compatible with prodromal PD.

Tuesday, 14 October 2014

Safinamide for the treatment of Parkinson's disease.

Expert Rev Clin Pharmacol. 2014 Oct 10:1-13. [Epub ahead of print]
Kandadai RM, Jabeen SA, Kanikannan MA, Borgohain R.

Parkinson's disease (PD) is a neurodegenerative disease caused by a complex interaction of loss of dopaminergic and non-dopaminergic neurotransmitter systems. Drugs acting on the dopaminergic pathways are the mainstay of treatment for motor symptoms today. Safinamide (NW-1015) is a novel drug with multiple actions. It is a monoamine oxidase B inhibitor and improves dopaminergic transmission. In addition, it has antiglutamatergic effects and can thus reduce dyskinesias, which is a side effect limiting most dopaminergic therapy. In Phase III trials, safinamide has been found to be a useful adjunctive to dopamine agonists in early PD and has been shown to increase time without increasing troublesome dyskinesias when used as an adjunct to levodopa in patients with advanced PD. A possible neuroprotective role in inhibiting PD disease progression is envisaged and warrants future studies.

Sunday, 12 October 2014

Under-reporting of Parkinson's disease on death certificates: A population-based study (NEDICES).

This is an important observation given that other studies use death certificates to estimate prevalence and for case finding....

J Neurol Sci. 2014 Oct 2. pii: S0022-510X(14)00644-3. doi: 10.1016/j.jns.2014.08.048. [Epub ahead of print]
Benito-León J, Louis ED, Villarejo-Galende A, Romero JP, Bermejo-Pareja F.

Parkinson's disease is frequently omitted as a cause of death from death certificates. A limitation of previous studies that attempted to assess the validity of death certificates is that population-dwelling cases, with milder, undiagnosed Parkinson's disease were likely excluded. As a result, those studies likely overestimated the validity of death certificates because they did not include these milder cases. We assessed the validity of death certificates in a prospective population-based study (NEDICES), which includes previously undiagnosed Parkinson's disease cases detected during the assessment.

3926 community-dwelling elderly subjects with and without Parkinson's disease were followed during a median of 12.6years, after which the death certificates of those who died were examined. We calculated the proportion of cases of clinically diagnosed Parkinson's disease for whom a diagnosis of Parkinson's disease was certified as the basic cause of death on death certificates.

1791 (45.6%) of the 3926 participants died over a median follow-up of 7.1years, including 82 (73.9%) deaths among 111 participants with Parkinson's disease. Parkinson's disease was rarely certified as the basic cause of death (14.6%). Gender, disease stage and the period during which the study was conducted (i.e., 1994 to 2007) did not influence the likelihood that Parkinson's disease would be reported.


Our findings reinforce the notion that the reporting of Parkinson's disease on death certificates remains poor. This suggests a lack of awareness of the importance of Parkinson's disease as a cause of death.

Saturday, 11 October 2014

Risk of Parkinson's disease following severe constipation: A nationwide population-based cohort study

Large study assessing the risk of PD in those with constipation. Adds to the increasing body of literature in this field...

Parkinsonism Relat Disord. 2014 Sep 28. pii: S1353-8020(14)00363-0. doi: 10.1016/j.parkreldis.2014.09.026. [Epub ahead of print]
Lin CH, Lin JW, Liu YC, Chang CH, Wu RM.

Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample.

551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models.

After an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14-5.03), 3.83 (2.51-5.84), and 4.22 (2.95-6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43-3.33), 5.22 (4.61-5.92), and 10.47 (9.46-11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant.


Our study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner.

Thursday, 9 October 2014

Uric acid relates to dopamine transporter availability in Parkinson's disease.

Acta Neurol Scand. 2014 Oct 7. doi: 10.1111/ane.12295. [Epub ahead of print]
Moccia M, Pappatà S, Erro R, Picillo M, Vitale C, Amboni M, Longo K, Palladino R, Barone P, Pellecchia MT.

Diagnosing Parkinson's disease (PD) and tracking its progression may require the combination of reliable biomarkers. Among them, both serum uric acid (UA) and dopamine transporter (DaT) binding deserve more investigations.

We aimed to investigate the relationship between serum UA levels and DaT availability in newly diagnosed, drug-naïve PD patients, by means of semiquantitative [(123) I]FP-CIT-SPECT.

We recruited 52 newly diagnosed, drug-naïve PD patients, and performed serum UA dosage and [(123) I]FP-CIT-SPECT.

Pearson's correlation analysis showed that UA levels were significantly higher in patients with higher averaged, ipsilateral and contralateral DaT binding in caudate, putamen, and striatum.


We showed, for the first time, by regional semiquantitative analysis of DaT binding in PD patients that UA levels significantly correlates with the severity of dopaminergic impairment in caudate, putamen, and striatum. This study broadens our knowledge on the importance of UA as a biomarker of PD.

Tuesday, 7 October 2014

Parkinson's disease beyond 20 years

Not only does this help us prognosticate but it may also tell us a lot about the mechanisms that underpin PD...

J Neurol Neurosurg Psychiatry. 2014 Oct 3. pii: jnnp-2014-308786. doi: 10.1136/jnnp-2014-308786.
Cilia R, Cereda E, Klersy C, Canesi M, Zecchinelli AL, Mariani CB, Tesei S, Sacilotto G, Meucci N, Zini M, Ruffmann C, Isaias IU, Goldwurm S, Pezzoli G.

A very limited number of studies report data on the clinical features of Parkinson's disease (PD) 20 years after onset and beyond.

To characterise PD 20 years after onset, investigating the impact of age at onset and disease duration on the clinical picture and the predictors of outcomes in patients reaching the 20-year time point.

We conducted a retrospective, cross-sectional study and a longitudinal study. All case visits of patients with a disease duration ≥20 years (N=401) were stratified by disease duration (20-22, 23-25, ≥26 years) and by age at onset (cut-off, 50 years). Patients with a disease duration of 20-22 years (N=320) were prospectively followed up for a median of 45 months (IQR 23-89) for the new occurrence of fracture, percutaneous endoscopic gastrostomy, institutionalisation, confinement to a wheelchair or bed and death.

Older age at onset and longer disease duration were independently associated with a higher prevalence of major motor and non-motor milestones of disease disability (no interaction observed). In the longitudinal study, the most frequent outcomes were death (N=92), confinement to a wheelchair or bed (N=67) and fracture (N=52). Mortality was associated with the gender: male, older age, dysphagia, orthostatic hypotension, postural instability, fractures and institutionalisation. Fracture was associated with postural instability. Predictors of permanent confinement to a wheelchair or bed were older age, postural instability and institutionalisation. Comorbid dementia at the 20-year examination did not predict any of the outcomes.


Age at onset and disease duration are independent determinants of the clinical features of PD beyond 20 years. Non-motor symptoms depend more on age at onset rather than the disease duration itself. Non-levodopa-responsive axial symptoms are the main predictors of all relevant outcomes.

Great MSA awareness video from MSAT

MSA Trust from Media Trust on Vimeo.

Increased plasma oligomeric alpha-synuclein in patients with lysosomal storage diseases.

Neurosci Lett. 2014 Sep 26. pii: S0304-3940(14)00778-2. doi: 10.1016/j.neulet.2014.09.041. [Epub ahead of print]
Pchelina SN, Nuzhnyi EP, Emelyanov AK, Boukina TM, Usenko TS, Nikolaev MA, Salogub GN, Yakimovskii AF, Zakharova EY.

A link between lysosomal storage diseases (LSDs) and neurodegenerative disorders associated with accumulation of presynaptic protein alpha-synuclein has been shown. Particularly, Gaucher disease (GD) patients with a deficiency of the lysosomal enzyme glucocerebrosidase (GBA) and carriers of GBA mutations are at increased risk of Parkinson's disease (PD). It remains unclear whether this link is due to increased alpha-synuclein oligomerization. Here we show that level of oligomeric alpha-synuclein form, associated with PD development, is increased in plasma of GD patients (n=41, median=22.9pg/mL, range1.57-444.58pg/mL; controls (n=40, median=6.02pg/mL, range 1.05-103.14pg/mL, p<0.0001). This difference is absent in GD patients receiving enzyme replacement therapy (ERT) for more than 5 years. Moreover, the levels of alpha-synuclein oligomers in plasma are also higher in patients with other LSDs (Niemann-Pick type C, Krabbe disease, Wolman disease) compared to the median value in controls. Therefore, we suggest that mutations in the GBA gene and at least in several other LSDs genes may be associated with an increase in oligomeric alpha-synuclein in plasma. ERT applied for recovering of GBA functions in GD treatment might decrease formation of plasma oligomeric alpha-synuclein.

Monday, 6 October 2014

Dance As An Intervention For People With Parkinson's Disease: A Systematic Review And Meta-Analysis

Neurosci Biobehav Rev. 2014 Sep 27. pii: S0149-7634(14)00236-X. doi: 10.1016/j.neubiorev.2014.09.009. [Epub ahead of print]

Sharp K, Hewitt J.

Recent studies suggest dance may be able to improve motor and non-motor disabilities in Parkinson's disease patients. A systematic review and meta-analysis of randomised controlled trials (RCT's) regarding the effectiveness of dance compared with no intervention and other exercise interventions was performed. Five trials were included and methodological quality and mean or standardised mean differences were calculated. Dance significantly improved UPDRS motor scores (-10.73, CI -15.05 to -6.16; P=0.004), berg balance (0.72, CI 0.31 to 1.44; P=0.0006) and gait speed (0.14m/s CI 0.02 to 0.26; P=0.02) when compared with no intervention. When compared with other exercise interventions significant improvements in berg balance (3.98, CI 1.52 to 6.44, P=0.002) and quality of life (PDQ-39) (-4.00, CI -7.13 to -0.87, P=0.01) were found. Dance demonstrates short term clinically meaningful benefits in Parkinson's disease. Future RCT's should be well designed and determine the long term effects of dance, which dose and type of dance is most effective and how dance compares to other exercise therapies.

Sunday, 5 October 2014

A Survey of Parkinson's Disease Patients: Most Bothersome Symptoms and Coping Preferences

J Parkinsons Dis. 2014 Sep 30. [Epub ahead of print]
Uebelacker LA, Epstein-Lubow G, Lewis T, Broughton MK, Friedman JH.

Background: Treatment for Parkinson's disease (PD) is symptomatic. Health professionals must therefore understand which of the many motor and non-motor problems that patients experience are the most troublesome, and what types of assistance patients believe would best help them cope with these problems. 

Objective: To identify and understand potential issues of importance to patients with Parkinson's Disease. 

Methods: We conducted surveys with 75 patients with PD in a Movement Disorders Program. We asked about: the two most bothersome PD-related problems, methods for coping with these problems, what motor and non-motor PD-related problems patients needed the most help with, and what a comprehensive assistance program for PD patients and caregivers should include. We used qualitative data analysis techniques to summarize responses. 

Results: The most bothersome problems cited were: tremors, lack of mobility, pain, imbalance, lack of energy/fatigue, having to give up previously enjoyed activities, dysarthria, and anxiety or depression. Frequently cited ways to cope with different types of problems included medications, physical activity, instrumental or practical support, and emotional support. When asked specifically about which non-motor problems elicited the most need for help, respondents most commonly mentioned depression and anxiety, "nothing," or cognitive problems. Participants suggested that a comprehensive assistance program for people with PD and their caregivers should include education, physical activity, and emotional support. 

Conclusions: Results from this survey highlight the diversity of patient experiences with PD, and the importance of strategies for coping with both motor and non-motor symptoms associated with Parkinson's Disease (in addition to medications).

Saturday, 4 October 2014

Does a specialist unit improve outcomes for hospitalized patients with Parkinson's disease?

Really like this idea! General wards (medical, surgical and even neurological) can be very unsuitable for managing the range of problems that patients with PD are admitted for (motor, non motor, psychological/psychiatric, medication change). Dedicated units (if cost effective) could have very big impact! Looking forward to seeing more about this in the future.

Parkinsonism Relat Disord. 2014 Sep 18. pii: S1353-8020(14)00337-X. doi: 10.1016/j.parkreldis.2014.09.015. [Epub ahead of print]
Skelly R, Brown L, Fakis A, Kimber L, Downes C, Lindop F, Johnson C, Bartliff C, Bajaj N.

Suboptimal management of Parkinson's disease (PD) medication in hospital may lead to avoidable complications. We introduced an in-patient PD unit for those admitted urgently with general medical problems. We explored the effect of the unit on medication management, length of stay and patient experience.

We conducted a single-center prospective feasibility study. The unit's core features were defined following consultation with patients and professionals: specially trained staff, ready availability of PD drugs, guidelines, and care led by a geriatrician with specialty PD training. Mandatory staff training comprised four 1 h sessions: PD symptoms; medications; therapy; communication and swallowing. Most medication was prescribed using an electronic Prescribing and Administration system (iSOFT) which provided accurate data on time of administration. We compared patient outcomes before and after introduction of the unit.

The general ward care (n = 20) and the Specialist Parkinson's Unit care (n = 24) groups had similar baseline characteristics. On the specialist unit: less Parkinson's medication was omitted (13% vs 20%, p < 0.001); of the medication that was given, more was given on time (64% vs 50%, p < 0.001); median length of stay was shorter (9 days vs 13 days, p = 0.043) and patients' experience of care was better (p = 0.01).


If replicated and generalizable to other hospitals, reductions in length of stay would lead to significant cost savings. The apparent improved outcomes with Parkinson's unit care merit further investigation. We hope to test the hypothesis that specialized units are cost-effective and improve patient care using a randomized controlled trial design.

Early automatic detection of Parkinson's disease based on sleep recordings

RBD is clearly a risk factor for PD but I don't think all patients pass through idiopathic RBD en-route to clinically probable PD. The role of 'loss of REM sleep atonia' or RSWA needs to be better understood...

J Clin Neurophysiol. 2014 Oct;31(5):409-15. doi: 10.1097/WNP.0000000000000065.
Kempfner J, Sorensen HB, Nikolic M, Jennum P.

Idiopathic rapid-eye-movement (REM) sleep behavior disorder (iRBD) is most likely the earliest sign of Parkinson's Disease (PD) and is characterized by REM sleep without atonia (RSWA) and consequently increased muscle activity. However, some muscle twitching in normal subjects occurs during REM sleep.

There are no generally accepted methods for evaluation of this activity and a normal range has not been established. Consequently, there is a need for objective criteria.

In this study we propose a full-automatic method for detection of RSWA. REM sleep identification was based on the electroencephalography and electrooculography channels, while the abnormal high muscle activity was detected from the electromyography channels, in this case the submentalis combined with left and right anterior tibialis. RSWA was identified by considering it an outlier problem, in which the number of outliers during REM sleep was used as a quantitative measure of muscle activity.

The proposed method was able to automatically separate all iRBD test subjects from healthy elderly controls and subjects with periodic limb movement disorder.


The proposed work is considered a potential automatic method for early detection of PD.

Thursday, 2 October 2014

Formulations of hormone therapy and risk of Parkinson's disease

Mov Disord. 2014 Sep 25. doi: 10.1002/mds.26037. [Epub ahead of print]
Lundin JI, Ton TG, LaCroix AZ, Longstreth WT, Franklin GM, Swanson PD, Smith-Weller T, Racette BA, Checkoway H.


Hormone therapy (HT) is a class of medications widely prescribed to women in the Western world. Evidence from animal models and in vitro studies suggests that estrogen may protect against nigrostriatal system injury and increase dopamine synthesis, metabolism, and transport. Existing epidemiologic research indicates a possible reduced risk of Parkinson's disease (PD) associated with HT use. The objective of this study was to evaluate PD risk associated with specific HT formulations. Neurologist-confirmed cases and age-matched controls were identified from Group Health Cooperative (GHC) of Washington State. Final analysis included 137 female cases and 227 controls. Hormone therapy use was ascertained from the GHC pharmacy database, further classified as conjugated estrogens, esterified estrogens, and progestin. Ever use of HT formulation demonstrated a suggested elevated risk with esterified estrogen use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8), and no risk associated with conjugated estrogen use (OR, 0.6; 95% CI, 0.6-1.3). Restricting this analysis to prescriptions that included progestin further elevated the risk associated with esterified estrogen use (OR, 6.9; 95% CI, 2.1-22.9); again, no risk was associated with conjugated estrogen use (OR, 1.7; 95% CI, 0.6-5.0). The findings from this study suggest an increase in PD risk associated with esterified estrogen use combined with progestin, and no risk associated with conjugated estrogen with progestin. These findings could have important implications for choice of HT in clinical practice.

Wednesday, 1 October 2014

Reduced alpha-synuclein in cerebrospinal fluid in synucleinopathies: Evidence from a meta-analysis

All the rage...

Mov Disord. 2014 Sep 25. doi: 10.1002/mds.26036. [Epub ahead of print]
Sako W, Murakami N, Izumi Y, Kaji R.

Alpha-synuclein plays a key role in the pathology of synucleinopathies including Parkinson's disease (PD) and multiple system atrophy (MSA). However, whether alpha-synuclein level in cerebrospinal fluid (CSF) could distinguish synucleinopathies from progressive supranuclear palsy (PSP) is still a contentious issue. A comprehensive literature search yielded nine eligible studies. We expressed the between-group difference of the concentration of alpha-synuclein in CSF as the standardized mean difference. The proportion of variation attributable to heterogeneity was computed and expressed as I2 . Nine studies involved 537 controls, 843 PD, 130 MSA, and 98 PSP patients. The overall effect of PD on alpha-synuclein in CSF was significantly different from normal control or disease control (standardized mean difference = -0.67, P < 0.00001). These studies were heterogeneous (I2 = 40%). Alpha-synuclein in CSF in MSA was significantly reduced relative to controls with heterogeneous studies (standardized mean difference = -0.75, P < 0.0001; I2 = 62%). In contrast, no significant difference of alpha-synuclein in CSF was observed between PSP and controls with heterogeneous studies (standardized mean difference = -0.28, P = 0.13; I2 = 53%). Alpha-synuclein in CSF was significantly reduced in synucleinopathies compared with PSP ("PD vs. PSP": standardized mean difference = -0.38, P = 0.001; "MSA vs. PSP": standardized mean difference = -0.66, P < 0.00001). The included studies were homogeneous (I2 = 0%). Our study showed that alpha-synuclein levels in CSF in synucleinopathies was significantly lower than in PSP. This finding provides insights into the pathophysiological difference between synucleinopathies and PSP as well as possibility of development of a tool for differential diagnosis between MSA and PSP using enzyme-linked immunosorbent assay (ELISA) and similar methods.