Monday, 26 November 2012

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial


Lancet Neurol. 2012 Nov 15. pii: S1474-4422(12)70264-8. doi: 10.1016/S1474-4422(12)70264-8. [Epub ahead of print]

Odekerken VJ, van Laar T, Staal MJ, Mosch A, Hoffmann CF, Nijssen PC, Beute GN, van Vugt JP, Lenders MW, Contarino MF, Mink MS, Bour LJ, van den Munckhof P, Schmand BA, de Haan RJ, Schuurman PR, de Bie RM.

Source
Department of Neurology, Academic Medical Center, Amsterdam, Netherlands.

Abstract
BACKGROUND:
Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS.
METHODS:
We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074.
FINDINGS:
Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups.
INTERPRETATION:
Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease.
FUNDING:
Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.
Copyright © 2012 Elsevier Ltd. All rights reserved.

Thursday, 22 November 2012

Effectiveness of Multidisciplinary Care for Parkinson's Disease: A Randomized, Controlled Trial


Mov Disord. 2012 Nov 19. doi: 10.1002/mds.25194. [Epub ahead of print]
van der Marck MA, Bloem BR, Borm GF, Overeem S, Munneke M, Guttman M.

Source
Radboud University Nijmegen Medical Centre; Nijmegen Centre for Evidence Based Practice, Department of Neurology, Nijmegen, The Netherlands.

Abstract
Multidisciplinary care is considered an optimal model to manage Parkinson's disease (PD), but supporting evidence is limited. We performed a randomized, controlled trial (RCT) to establish whether a multidisciplinary/specialist team offers better outcomes, compared to stand-alone care from a general neurologist. Patients with PD were randomly allocated to an intervention group (care from a movement disorders specialist, PD nurses, and social worker) or a control group (care from general neurologists). Both interventions lasted 8 months. Clinicians and researchers were blinded for group allocation. The primary outcome was the change in quality of life (Parkinson's Disease Questionnaire; PDQ-39) from baseline to 8 months. Other outcomes were the UPDRS, depression (Montgomery-Asberg Depression Scale; MADRS), psychosocial functioning (Scales for Outcomes in Parkinson's disease-Psychosocial; SCOPA-PS), and caregiver strain (Caregiver Strain Index; CSI). Group differences were analyzed using analysis of covariance adjusted for baseline values and presence of response fluctuations. A total of 122 patients were randomized and 100 completed the study (intervention, n = 51; control, n = 49). Compared to controls, the intervention group improved significantly on PDQ-39 (difference, 3.4; 95% confidence interval [CI]: 0.5-6.2) and UPDRS motor scores (4.1; 95% CI: 0.8-7.3). UPDRS total score (5.6; 95% CI: 0.9-10.3), MADRS (3.7; 95% CI: 1.4-5.9), and SCOPA-PS (2.1; 95% CI: 0.5-3.7) also improved significantly. This RCT gives credence to a multidisciplinary/specialist team approach. We interpret these positive findings cautiously because of the limitations in study design. Further research is required to assess teams involving additional disciplines and to evaluate cost-effectiveness of integrated approaches. © 2012 Movement Disorder Society.

Wednesday, 21 November 2012

A New Era of Clinical Dopamine Transporter Imaging Using 123I-FP-CIT


J Nucl Med Technol. 2012 Nov 16. [Epub ahead of print]
Park E.

Source
Department of Nuclear Medicine, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York.

Abstract
(123)I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ((123)I-FP-CIT) was approved for clinical use in 2011 by the Food and Drug Administration. (123)I-FP-CIT is a radioligand for brain dopamine transporter (DAT) imaging that is useful for the differential diagnosis of Parkinson disease (PD) and other diseases that mimic PD. The sensitivity and specificity of (123)I-FP-CIT SPECT for PD diagnosis are more than 90% and equivalent to those of other DAT SPECT methods. In the near future, the clinical indications of DAT imaging are expected to be broadened; for example, including treatment response assessment, disease progression monitoring, and early diagnosis of premotor PD in each individual patient.

Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice


Science. 2012 Nov 16;338(6109):949-53. doi: 10.1126/science.1227157.
Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM.

Source
Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-4283, USA.

Abstract
Parkinson's disease is characterized by abundant α-synuclein (α-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss of midbrain dopamine neurons. However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear. Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α-Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson's-like Lewy pathology in anatomically interconnected regions. Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta, but not in the adjacent ventral tegmental area, and was accompanied by reduced dopamine levels culminating in motor deficits. This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic α-Syn and the cardinal features of Parkinson's disease.

Monday, 19 November 2012

Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

Neurobiol Aging. 2012 Nov 12. pii: S0197-4580(12)00530-1. doi: 10.1016/j.neurobiolaging.2012.10.019. [Epub ahead of print]

Pihlstrøm L, Axelsson G, Bjørnarå KA, Dizdar N, Fardell C, Forsgren L, Holmberg B, Larsen JP, Linder J, Nissbrandt H, Tysnes OB, Ohman E, Dietrichs E, Toft M.

Source

Department of Neurology, Oslo University Hospital, Oslo, Norway.

Abstract

Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.

Serum Uric Acid in Patients with Parkinson's Disease and Vascular Parkinsonism: A Cross-Sectional Study

Neuroimmunomodulation. 2012 Nov 14;20(1):19-28. [Epub ahead of print]

Pan M, Gao H, Long L, Xu Y, Liu M, Zou J, Wu A, Wei X, Chen X, Tang B, Wang Q.

Source

Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.

Abstract

Background: Elevation of serum uric acid (UA) is correlated with a decreased risk of Parkinson's disease (PD); however, the association and clinical relevance of serum UA levels in patients with PD and vascular parkinsonism (VP) are unknown. Objective: We performed a cross-sectional study of 160 Chinese patients with PD and VP to determine whether UA levels in patients could predict the outcomes. Methods: Serum UA levels were divided into quartiles and the association between UA and the severity of PD or VP was investigated in each quartile. Results: The serum levels of UA in PD were significantly lower than those in normal subjects and VP. The serum UA levels in PD patients were significantly correlated with some clinical parameters. Strong correlations were observed in male PD patients, but significant correlations were observed only between UA and the non-motor symptoms (NMS) of burden of sleep/fatigue and mood in female PD patients. PD patients in the lowest quartile of serum UA levels had significant correlations between UA and the unified Parkinson's disease rating scale, the modified Hoehn and Yahr staging scale and NMS burden for attention/memory. Conclusion: Our findings support the hypothesis that subjects with low serum UA levels may be more prone to developing PD and indicate that the inverse relationship between UA and severity of PD was robust for men but weak for women. Our results strongly imply that either low serum UA level is a deteriorative predictor or that serum UA level serves as an indirect biomarker of prediction in PD but not in VP patients.

Friday, 16 November 2012

Our systematic review and meta-analysis of risk factors for PD is Open Access

We recently published our comprehensive review of risk factors and early non-motor features for Parkinson's disease in the Annals of Neurology. Parkinson's UK have very kindly supported us to make this paper Open Access, which means that anyone is allowed to read it. You can find it at

http://onlinelibrary.wiley.com/doi/10.1002/ana.23687/abstract


Let me know what you think.

- Alastair Noyce

Tuesday, 13 November 2012

Head injury and Parkinson's disease: A population-based study


Mov Disord. 2012 Nov 9. doi: 10.1002/mds.25143. [Epub ahead of print]
Fang F, Chen H, Feldman AL, Kamel F, Ye W, Wirdefeldt K.

Source
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND:
The epidemiological evidence on head injury and the risk of Parkinson's disease (PD) has been inconsistent.
METHODS:
We examined the relation between previous hospitalization for head injury and PD using a population-based nested case-control design based on the Swedish National Patient Register from 2001 until 2007, including 18,648 PD cases and 93,240 controls, randomly selected from the general population. Exposure was defined as hospitalization for head injury between 1987 and index date.
RESULTS:
Overall, previous hospitalization resulting from head injury was associated with an increased risk of PD; this association appeared to be largely explained by head injuries experienced recently, especially within 1 year before PD ascertainment.
CONCLUSIONS:
Our results do not provide convincing evidence for a causal relationship between head injury later in life and PD. © 2012 Movement Disorder Society.

Ceruloplasmin and iron in Alzheimer's disease and Parkinson's disease: a synopsis of recent studies


Neuropsychiatr Dis Treat. 2012;8:515-21. doi: 10.2147/NDT.S34729. Epub 2012 Nov 2.
Kristinsson J, Snaedal J, Tórsdóttir G, Jóhannesson T.

Source
Department of Pharmacology and Toxicology, University of Iceland, Reykjavik, Iceland.
Abstract
Ceruloplasmin (Cp) concentration and oxidative activity in serum are lowered in Parkinson's disease (PD). In most PD patients, iron increases in the substantia nigra in the midbrain. In PD, the low Cp concentration and activity in serum and the high iron amounts in the substantia nigra appears to be correlated. An hereditary background is common in PD and variations in the Cp gene that have been found in PD are associated with high iron levels in the substantia nigra. Variations in Cp synthesis and in the incorporation of copper into the Cp molecule are essential features of PD. In Alzheimer's disease (AD), the Cp activity in serum is lowered but not the concentration, except in the advanced stages of the disease. Generally, iron is not increased in the AD brain. In the AD brain, iron accumulates in neuritic plaques and in neurofibrillary tangles. There is also increased risk of iron-mediated tissue damage, which may possibly be counteracted by Cp. At the same time, the AD brain is short in copper, which presumably results in the deficient activity of many copper enzymes in the brain, in addition to Cp. Lowered Cp activity in serum most likely stems from lessened incorporation of copper in the Cp molecule and similar incorporation defects might also apply to other copper enzymes in AD.

Symptoms and Quality of Life in Late Stage Parkinson Syndromes: A Longitudinal Community Study of Predictive Factors


PLoS One. 2012;7(11):e46327. Epub 2012 Nov 7.
Higginson IJ, Gao W, Saleem TZ, Chaudhuri KR, Burman R, McCrone P, Leigh PN.

Source
Cicely Saunders Institute, King's College London, London, United Kingdom.

Abstract
BACKGROUND:
Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes.
METHODS:
We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders.
FINDINGS:
Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores.
INTERPRETATION:
The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention.

Wednesday, 7 November 2012

Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias in Parkinson's disease


Parkinsons Dis. 2012;2012:943159. doi: 10.1155/2012/943159. Epub 2012 Oct 17.
Guridi J, González-Redondo R, Obeso JA.

Source
Department of Neurosurgery and Neurology, Clinica Universidad de Navarra, 31008 Pamplona, Spain.

Abstract
Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood.

Prevalence and Pharmacological Factors Associated With Impulse-Control Disorder Symptoms in Patients With Parkinson Disease


Clin Neuropharmacol. 2012 Nov 1. [Epub ahead of print]
Perez-Lloret S, Rey MV, Fabre N, Ory F, Spampinato U, Brefel-Courbon C, Montastruc JL, Rascol O.

Source
*Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, Toulouse, France; †INSERM Centre d'Investigation Clinique CIC 9203, Toulouse, France; ‡Services de Neurologie, CHU Toulouse, France; §Department of Neurology, CHU Bordeaux, France; and ∥INSERM U 1027 Equipe de PharmacoEpidémiologie, Toulouse, France.

Abstract
BACKGROUND:
Impulse-control disorders (ICDs) occur in patients with Parkinson disease (PD), especially in younger patients on dopamine therapies.
OBJECTIVE:
To assess the prevalence of ICD symptoms and its pharmacological correlations in a sample of French patients with PD and without PD (poststroke).
METHODS:
Outpatients with PD and without PD (poststroke) were screened for compulsive behaviors related to hypersexuality, compulsive shopping, pathological gambling, or compulsive eating by means of the Questionnaire for Impulse-Control Disorders-short version. Full medical history and Unified Parkinson's Disease Rating Scale scores were also recorded. Dose of dopamine agonists were converted to defined daily doses (DDDs), according to the World Health Organization Anatomical Therapeutic Chemical classification system classification system.
RESULTS:
Two hundred three patients with PD and 52 patients without PD were recruited (mean ± SD age, 67 ± 1 vs 69 ± 2, P = 0.4; males: 62% vs 55% P = 0.2). Symptoms of ICDs were reported by 0% of poststroke patients and 25% of the patients with PD (P < 0.001). Hypersexuality was reported by 10% of the patients with PD, compulsive shopping by 6%, pathological gambling by 3%, and compulsive eating by 14%. A logistic regression analysis found that age younger than 68 years (odds ratio [OR], 3.3; 95% confidence interval, 1.6-6.6) and exposure to dopamine agonists (OR, 20.3; 95% confidence interval, 2.7-65.0) or monoaminooxidase-B inhibitor (OR, 3.7; 95% confidence interval, 1.1-12.6) were significant factors associated with increased ICD frequency. Patients with ICD symptoms were exposed to higher dopamine doses than those without them (1.6 ± 0.1 vs 1.0 ± 0.1 daily-defined doses; P < 0.001). A dose-response pharmacodynamic model disclosed a significant nonlinear dose-response relationship between dopamine agonists and frequency of ICD symptoms (P < 0.01).
CONCLUSIONS:
Impulse-control disorder symptoms were more frequent in the patients with PD than in the poststroke patients with PD. Impulse-control disorder symptoms were related to younger age and exposure to monoaminooxidase-B inhibitors, and showed a nonlinear dose-response relationship with dopamine agonists.

Tuesday, 6 November 2012

Cerebrospinal fluid amyloid-β and phenotypic heterogeneity in de novo Parkinson's disease

J Neurol Neurosurg Psychiatry. 2012 Oct 31. [Epub ahead of print]

Alves G, Pedersen KF, Bloem BR, Blennow K, Zetterberg H, Borm GF, Dalaker TO, Beyer MK, Aarsland D, Andreasson U, Lange J, Tysnes OB, Zivadinov R, Larsen JP.


Source

The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.

Abstract

BACKGROUND:

In Parkinson's disease (PD), the motor presentation characterised by postural instability/gait difficulties (PIGD) heralds accelerated motor, functional and cognitive decline, as compared with the more benign tremor-dominant (TD) variant. This makes the PIGD complex an attractive target for the discovery of prognostic biomarkers in PD.

OBJECTIVE:

To explore in vivo whether variability in brain amyloid-β (Aβ) metabolism affects the initial motor presentation in PD.

METHODS:

We quantified cerebrospinal fluid (CSF) concentrations and ratios of Aβ42, Aβ40 and Aβ38 using a triplex immunoassay in 99 patients with de novo PD with the PIGD phenotype (n=39) or the TD phenotype (n=60). All patients underwent standardised assessments of motor and neuropsychological function and cerebral MRI. 46 age-matched normal controls served as external reference.

RESULTS:

Patients with PD with the PIGD phenotype had significantly reduced CSF Aβ42, Aβ38, Aβ42/40 and Aβ38/40 levels compared with patients with the TD phenotype and controls. CSF marker levels in patients with PD-TD did not differ from those in controls. Multivariate regression models demonstrated significant associations of CSF Aβ markers with severity of PIGD and lower limb bradykinesia in patients with PD, independently from age, MRI white matter hyperintensities and cognition. No associations were found between CSF markers and other motor features.

CONCLUSIONS:

Motor heterogeneity in de novo PD independently relates to CSF Aβ markers, with low levels found in patients with the PIGD presentation. This suggests that disturbed Aβ metabolism has an effect on PD beyond cognition and may contribute to the variable rate of motor and functional decline in PD.

Monday, 5 November 2012

Parkinson's UK Conference

I'm taking a couple of days out from seeing study participants to attend the Parkinson's UK conference in York. It's a beautiful sunny but cold autumn day in the North of England - my favourite kind of day. There's lots of molecular biology on the menu so hopefully I can keep pace. I'm just looking forward to hearing about all the fantastic work that's being supported by Parkinson's UK and that's going on all round the country and beyond.

- Alastair Noyce

Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder

Neurology. 2012 Oct 31. [Epub ahead of print]

Dang-Vu TT, Gagnon JF, Vendette M, Soucy JP, Postuma RB, Montplaisir J.

Source

From the Center for Advanced Research in Sleep Medicine (T.T.D.-V., J.-F.G., M.V., R.B.P., J.M.), Hôpital du Sacré-Cœur de Montréal; Department of Exercise Science and Center for Studies in Behavioral Neurobiology (T.T.D.-V.), Concordia University, Montréal, Canada; Cyclotron Research Centre (T.T.D.-V.), University of Liege; Department of Neurology (T.T.D.-V.), Centre Hospitalier Universitaire de Liège, Belgium; Department of Psychology (J.-F.G.), Université du Québec à Montréal; Montreal Neurological Institute (P.S.), McGill University, Montréal; Department of Nuclear Medicine (J.P.-S.), Centre Hospitalier de l'Université de Montréal; Department of Neurology (R.B.P.), Montreal General Hospital; and Department of Psychiatry (J.M.), University of Montreal, Canada.

Abstract

OBJECTIVES:

Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with (99m)Tc-ethylene cysteinate dimer (ECD).

METHODS:

Twenty patients with IRBD were scanned at baseline during wakefulness using (99m)Tc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process.

RESULTS:

Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients.

CONCLUSIONS:

(99m)Tc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.

Sleep and Parkinson's disease: A review of case-control polysomnography studies

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25197. [Epub ahead of print]

Peeraully T, Yong MH, Chokroverty S, Tan EK.

Source


National Neuroscience Institute, Department of Neurology, Singapore General Hospital, Singapore, Singapore.

Abstract

The link between Parkinson's disease (PD) and certain primary sleep disorders has yet to be clarified. We performed a systematic review of case-control polysomnography studies to evaluate the relationship between PD and sleep disorders. A PubMed literature search and bibliography review yielded 15 case-control polysomnography studies in patients with PD. Studies differed by recruitment methods, duration of polysomnography monitoring, and sleep parameters measured. Subjective sleepiness was greater in patients than controls (50%-66% vs 2.9%-12%) despite lack of objective increase in daytime sleepiness by mean sleep latency testing. The 4 case-control polysomnography studies investigating rapid eye movement behavior disorder support a higher prevalence in PD (0%-47% vs 0%-1.8% in controls), although differences in diagnostic criteria hamper interpretation. The preponderance of evidence did not support an increased incidence of obstructive sleep apnea (27%-60% vs 13%-65%) or periodic leg movements of sleep in patients compared to controls. Adequately powered, prospective studies with uniform methodology and healthy controls are needed to further address the association and pathophysiological significance between PD and sleep problems. © 2012 Movement Disorder Society.

Sunday, 4 November 2012

Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25226. [Epub ahead of print]

Mata IF, Checkoway H, Hutter CM, Samii A, Roberts JW, Kim HM, Agarwal P, Alvarez V, Ribacoba R, Pastor P, Lorenzo-Betancor O, Infante J, Sierra M, Gómez-Garre P, Mir P, Ritz B, Rhodes SL, Colcher A, Van Deerlin V, Chung KA, Quinn JF, Yearout D, Martinez E, Farin FM, Wan JY, Edwards KL, Zabetian CP.

Source

Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA; Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.

Abstract

BACKGROUND:

Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear.

METHODS:

We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals.

RESULTS:

Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10(-4) ; rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10(-4) ).

CONCLUSIONS:

Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry. © 2012 Movement Disorder Society.

Long-term course of substantia nigra hyperechogenicity in Parkinson's disease

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25193. [Epub ahead of print]

Behnke S, Runkel A, Kassar HA, Ortmann M, Guidez D, Dillmann U, Fassbender K, Spiegel J.

Source

Department of Neurology, Saarland University, Homburg/Saar, Germany.

Abstract

A hyperechogenicity of the (SN+) in transcranial sonography corroborates the diagnosis of idiopathic Parkinson's disease (iPD). Although it is thought to represent a biomarker of the disease that is independent of disease severity and progression, differing results have been reported describing a positive correlation of the size and advancing clinical stage. In 50 parkinsonian patients, transcranial ultrasound and clinical examination was performed twice with a mean time interval of 6.4 years. SN+ did not change in size significantly between the first and second examination, whereas clinical parkinsonian symptoms-as determined by the motor part of the UPDRS-significantly worsened (P < 0.001). We found a highly significant intraindividual correlation in SN+ sizes between both examinations (P < 0.001). The size of SN+ did not correlate with the UPDRS part III at the time of first or second ultrasound examination. Progression of motor symptoms between the first and second investigation did not correlate with the size of SN+ at baseline. Furthermore, even in the subgroup of patients with an interval of ≥8 years between examinations, there was no significant change in SN+ size. SN+ represents a largely stable biomarker in iPD and does not reflect disease progression. The size of SN+ does not predict the further course of the disease. © 2012 Movement Disorder Society.

Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's disease

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25192. [Epub ahead of print]

Berg D, Behnke S, Seppi K, Godau J, Lerche S, Mahlknecht P, Liepelt-Scarfone I, Pausch C, Schneider N, Gaenslen A, Brockmann K, Srulijes K, Huber H, Wurster I, Stockner H, Kiechl S, Willeit J, Gasperi A, Fassbender K, Gasser T, Poewe W.

Source

Center of Neurology, Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany.

Abstract

BACKGROUND:

SN hyperechogenicity (SN+), determined by transcranial sonography, has been proposed as a risk factor for Parkinson's disease (PD). Recently, we reported a 17.4-fold increased risk for PD in individuals with SN+ older than 50 years within 3 years.

METHODS:

This is the second follow-up of a prospective, longitudinal, three-center observational study after 5 years. Of the initial 1,847 at baseline PD-free participants 50 years or older, 1,271 underwent the 5-year reassessment.

RESULTS:

Within 5 years, 21 individuals developed incident PD. Participants with SN+ at baseline had a more than 20.6 times increased risk to develop PD in this time span than those without this echo feature.

CONCLUSION:

We thus confirm our finding of the 3-year follow-up examination in a longer observation time and higher number of individuals with incident PD and suggest SN+ as an important risk marker for PD. © 2012 Movement Disorder Society.

Sonographic abnormality of the substantia nigra in melanoma patients

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25233. [Epub ahead of print]

Rumpf JJ, Weise D, Fricke C, Wetzig T, Simon JC, Classen J.


Source

Department of Neurology, University of Leipzig, Leipzig, Germany.

Abstract

BACKGROUND:

Evidence derived from large epidemiological studies suggests an association between Parkinson's disease (PD) and malignant melanoma. Transcranial sonography of the midbrain reveals an extended echogenic substantia nigra (SN) area in a high proportion of patients with PD. This characteristic, in the context of PD, may signal degeneration of dopaminergic nigrostriatal projection neurons. Demonstration of an increased prevalence of abnormal echogenic SN in melanoma patients could add weight to the hypothesis of an underlying common pathogenic pathway of both diseases.

METHODS:

This was a cross-sectional observational study. Transcranial sonography of the SN region was performed on 31 patients suffering from malignant melanoma and 29 healthy participants. In addition, patients and controls were screened for motor and non-motor symptoms of PD.

RESULTS:

The echogenic SN area was abnormally extended in 42% of melanoma patients versus 7% of control subjects (χ(2) = 9.811, P = .002). Mean echogenic SN area (SN[R, L]) was significantly larger in melanoma patients than in controls (patients, 0.21 ± 0.07 cm(2) ; controls, 0.15 ± 0.04 cm(2) [mean ± SD]; unpaired t test, P < .001).

CONCLUSIONS:

These findings provide additional evidence in favor of a common pathogenic pathway of PD and malignant melanoma and raise the possibility that their association is closer than previously assumed. © 2012 Movement Disorder Society.

Copyright © 2012 Movement Disorder Society.

Friday, 2 November 2012

Fatigue in Parkinson's disease: Motor or non-motor symptom?


Parkinsonism Relat Disord. 2012 Oct 26. pii: S1353-8020(12)00385-9. doi: 10.1016/j.parkreldis.2012.10.009. [Epub ahead of print]
Fabbrini G, Latorre A, Suppa A, Bloise M, Frontoni M, Berardelli A.

Source
Department of Neurology and Psychiatry, "Sapienza" University of Rome, Viale dell'Università 30, 00185 Rome, Italy; Neuromed Institute (IRCSS), Pozzilli (IS), Italy.

Abstract
Fatigue is one of the most disabling symptoms in patients with Parkinson's disease (PD), with a significant impact on patients' quality of life. Clinical studies using ad hoc questionnaires showed that in PD fatigue is associated with non-motor as well motor symptoms. Neurophysiological observations suggest that motor mechanisms play a role in the pathophysiology of fatigue but there is no clear correlation between fatigue measured with clinical instruments and fatigue assessed with neurophysiological tests. Neuroimaging studies show that fatigue is associated with an involvement of non-dopaminergic or extrastriatal dopaminergic pathways. It is conceivable that both motor and non-motor mechanisms underlie the pathophysiology of fatigue.

Thursday, 1 November 2012

Over 700 now...

It's great to see that over 700 of our participants have continued in the study so far and I think this number will be close to 1000 when we finish the re-survey period. 

I had a fruitful trip to South East London last week, and I am seeing participants in South West London today (and yesterday) and North London tomorrow. November will see me travelling around the UK seeing as many participants as possible. 

It's wonderful to meet people and hear about their motivations for joining the study.

- Alastair Noyce

The BRAIN test: a keyboard-tapping test to assess disability and clinical features of multiple sclerosis

Okay. Not strictly Parkinson's research but the BRAIN tap test comes from the PREDICT-PD team. Here we show that the BRAIN test can be u...