Thursday, 21 February 2013

Tai Chi training is effective in reducing balance impairments and falls in patients with Parkinson's disease

J Physiother. 2013 Mar;59(1):55. doi: 10.1016/S1836-9553(13)70148-6.
Tsang WW.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China.

Does Tai Chi improve postural control in patients with Parkinson's disease?
Randomised, controlled trial and blinded outcome assessment.
University clinic in USA.
Individuals with Parkinson's disease (Hoehn and Yahr Stage 1-4) between the age of 40 and 85 years, and ability to walk with or without an assistive device were key inclusion criteria. Mini-Mental State examination score <24 and concurrent participation in other instructor-led exercise programs were key exclusion criteria. Randomisation of 195 participants allocated 65 to each of the Tai Chi, resistance, and stretching groups.
The Tai Chi group underwent a Tai Chi program, the resistance group 8 to 10 leg muscle strengthening exercises, while the stretching group performed stretching exercises involving the upper body and lower extremities. All three groups trained for 24 weeks (60 minutes per session, two sessions per week).
The primary outcomes were two indicators of postural stability - maximum excursion and directional control derived from dynamic posturography. The secondary outcomes were stride length, gait velocity, knee flexion and extension peak torque, functional reach, timed-up-and-go test, and motor section of the Unified Parkinson's Disease Rating Scale (UPDRS III). The outcomes were measured at baseline, at 12 and 24 weeks, and 3 months after termination of the intervention.
185 participants completed the study. At the end of the 24-week training period, the change in maximum excursion in the Tai Chi group was significantly more than that in the resistance group (by 5%, 95% CI 1.1 to 10.0) and the stretching group (by 12%, 95% CI 7.2 to 16.7). Direction control improved significantly more in the Tai Chi group compared with the resistance group (by 11%, 95% CI 3.9 to 17.0) and the control group (by 11%, 95% CI 5.5 to 17.3). The Tai Chi group also had significantly more improvement in stride length and functional reach than the other two groups. The change in knee flexion and extension peak torque, timed-up-and-go test, and UPDRS III score in the Tai Chi group was only significantly more than that in the stretching group, but not the resistance group. The falls incidence was also lower in the Tai Chi group than the stretching group during the 6-month training period (incidence-rate ratio: 0.33, 95% CI 0.16 to 0.71).
Tai Chi training is effective in reducing balance impairments in patients with mild to moderate Parkinson's disease.

Wednesday, 20 February 2013

Cerebrospinal fluid biomarkers in Parkinson disease

Nat Rev Neurol. 2013 Feb 19. doi: 10.1038/nrneurol.2013.10. [Epub ahead of print]
Parnetti L, Castrioto A, Chiasserini D, Persichetti E, Tambasco N, El-Agnaf O, Calabresi P.

Clinica Neurologica, Università di Perugia, Ospedale Santa Maria della Misericordia, 06132 Santa Andrea delle Fratte, Perugia, Italy.

Clinical diagnosis of Parkinson disease (PD) is difficult in early stages of disease, with high risk of misdiagnosis. The long preclinical phase of PD provides the possibility for early therapeutic intervention once disease-modifying therapies have been developed, but lack of biomarkers for early diagnosis and monitoring of disease progression represents a major obstacle to achievement of this goal. Accordingly, research efforts aimed at identification of novel biomarkers have been increasing in the past 5 years. Cerebrospinal fluid (CSF) is an accessible source of brain-derived proteins, which mirror molecular changes that take place in the CNS. In this Review, we discuss evidence from numerous studies that have focused on identification of candidate CSF biomarkers for PD. Notably, molecular pathways related to α-synuclein, tau and β-amyloid peptides have received considerable attention. CSF levels of the protein DJ-1 are also of interest, although further investigation of this candidate marker is required. These studies support the usefulness of a combination of various CSF biomarkers of PD to increase diagnostic accuracy during early phases of the disease, and to differentiate PD from other neurodegenerative disorders.

Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort.

Brain. 2013 Feb;136(Pt 2):392-9. doi: 10.1093/brain/aws318.

Winder-Rhodes SE, Evans JR, Ban M, Mason SL, Williams-Gray CH, Foltynie T, Duran R, Mencacci NE, Sawcer SJ, Barker RA.

Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK.

Carriers of mutations in the glucocerebrosidase gene (GBA) are at increased risk of developing Parkinson's disease. The frequency of GBA mutations in unselected Parkinson's disease populations has not been established. Furthermore, no previous studies have investigated the influence of GBA mutations on the natural history of Parkinson's disease using prospective follow-up. We studied DNA from 262 cases who had been recruited at diagnosis into one of two independent community-based incidence studies of Parkinson's disease. In 121 cases, longitudinal data regarding progression of motor disability and cognitive function were derived from follow-up assessments conducted every 18 months for a median of 71 months. Sequencing of the GBA was performed after two-stage polymerase chain reaction amplification. The carrier frequency of genetic variants in GBA was determined. Baseline demographic and clinical variables were compared between cases who were either GBA mutation carriers, polymorphism carriers or wild-type homozygotes. Cox regression analysis was used to model progression to major motor (Hoehn and Yahr stage 3), and cognitive (dementia) end-points in cases followed longitudinally. We show that in a representative, unselected UK Parkinson's disease population, GBA mutations are present at a frequency of 3.5%. This is higher than the prevalence of other genetic mutations currently associated with Parkinson's disease and indicates that GBA mutations make an important contribution to Parkinson's disease encountered in the community setting. Baseline clinical characteristics did not differ significantly between cases with and without GBA sequence variants. However, the hazard ratio for progression both to dementia (5.7, P = 0.003) and Hoehn and Yahr stage 3 (4.2, P = 0.003) were significantly greater in GBA mutation carriers. We also show that carriers of polymorphisms in GBA which are not generally considered to increase Parkinson's disease risk are at significantly increased risk of progression to Hoehn and Yahr stage 3 (3.2, P = 0.004). Our results indicate that genetic variation in GBA has an important impact on the natural history of Parkinson's disease. To our knowledge, this is the first time a genetic locus has been shown to influence motor progression in Parkinson's disease. If confirmed in further studies, this may indicate that GBA mutation status could be used as a prognostic marker in Parkinson's disease. Elucidation of the molecular mechanisms that underlie this effect will further our understanding of the pathogenesis of the disease and may in turn suggest novel therapeutic strategies.

Tuesday, 19 February 2013

C9orf72 repeat expansions are a rare genetic cause of parkinsonism.

Brain. 2013 Feb;136(Pt 2):385-91. doi: 10.1093/brain/aws357.

Lesage S, Le Ber I, Condroyer C, Broussolle E, Gabelle A, Thobois S, Pasquier F, Mondon K, Dion PA, Rochefort D, Rouleau GA, Dürr A, Brice A; French Parkinson’s Disease Genetics (PDG) Study Group.

INSERM UMR_S975-CNRS UMR 7225, Université Pierre et Marie Curie, Centre de recherche de l'Institut du Cerveau et de la Moëlle épinière-CRICM, Hôpital de la Salpêtrière, 47, Boulevard de l'Hôpital, 75651 Paris cedex 13, France. 

The recently identified C9orf72 gene accounts for a large proportion of amyotrophic lateral sclerosis and frontotemporal lobar degenerations. As several forms of these disorders are associated with parkinsonism, we hypothesized that some patients with Parkinson's disease or other forms of parkinsonism might carry pathogenic C9orf72 expansions. Therefore, we looked for C9orf72 repeat expansions in 1446 unrelated parkinsonian patients consisting of 1225 patients clinically diagnosed with Parkinson's disease, 123 with progressive supranuclear palsy, 21 with corticobasal degeneration syndrome, 43 with Lewy body dementia and 25 with multiple system atrophy-parkinsonism. Of the 1446 parkinsonian patients, five carried C9orf72 expansions: three patients with typical Parkinson's disease, one with corticobasal degeneration syndrome and another with progressive supranuclear palsy. This study shows that (i) although rare, C9orf72 repeat expansions may be associated with clinically typical Parkinson's disease and also with other parkinsonism; (ii) in several patients, parkinsonism was levodopa-responsive and remained pure, without associated dementia, for >10 years and (iii) interestingly, all C9orf72 repeat expansion carriers had positive family histories of parkinsonism, degenerative dementias or amyotrophic lateral sclerosis. This study also provides the tools for identifying parkinsonian patients with C9orf72 expansions, with important consequences for genetic counselling.

Monday, 18 February 2013

Levodopa challenge test and (123) I-metaiodobenzylguanidine scintigraphy for diagnosing Parkinson's disease.

Acta Neurol Scand. 2013 Feb 15. doi: 10.1111/ane.12104. [Epub ahead of print]

Asayama S, Wate R, Kaneko S, Asayama T, Oki M, Tsuge A, Nagashima M, Morita J, Nakamura S, Nakamura M, Nishii M, Fujita K, Saito A, Nakano S, Ito H, Kusaka H.

Department of Neurology, Kansai Medical University, Moriguchi, Osaka, Japan.


To explore the possibility of a generally applicable tool for the immediate diagnosis of Parkinson's disease (PD) in its early stage, we compared the sensitivity and specificity of an acute levodopa challenge test with that of (123) I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy.

A consecutive series of 45 patients with extrapyramidal symptoms were recruited to the acute levodopa challenge and evaluated for improvement by use of the Unified Parkinson's Disease Rating Scale motor scores. Of these patients, 32 of them were also examined by MIBG scintigraphy. The patients were followed up for at least 24 months, and 22 patients were diagnosed as having clinically definite PD.

The sensitivity and specificity of the acute levodopa challenge test to predict clinical diagnosis of PD were 81.8% and 81.8%, respectively, which were better than those obtained by MIBG scintigraphy (62.5% and 62.5%). In both early- and middle-stages of PD, the test gave better sensitivity than MIBG scintigraphy.

Considering that the well-established and frequently referred clinical diagnostic criteria require longitudinal observation for at least 24 months, the acute levodopa challenge test can be used as an immediate diagnostic tool for PD with sensitivity and specificity comparable to those of MIBG.

Nocturnal hypertension and dysautonomia in patients with Parkinson's disease: are they related?

J Neurol. 2013 Feb 15. [Epub ahead of print]

Berganzo K, Díez-Arrola B, Tijero B, Somme J, Lezcano E, Llorens V, Ugarriza I, Ciordia R, Gómez-Esteban JC, Zarranz JJ.

Autonomic and Movement Disorders Unit, Neurology Service, Basque Health Service (Osakidetza), Cruces University Hospital, Plaza de Cruces s/n, Barakaldo, 48903, Spain.

Orthostatic hypotension and supine hypertension frequently coexist in Parkinson's disease (PD) patients, leading to visceral damage and increased mortality rates. The aim of this paper is to analyze the frequency and association of both conditions in a sample of outpatients with PD. A total of 111 patients, diagnosed with PD, were studied. Disease duration, treatment, cardiovascular risk factors, UPDRS I-IV and Scopa Aut scale scores were reported. Subjects underwent 24-h ambulatory blood pressure (BP) monitoring and were assessed for orthostatic hypotension. We compared our results with those published in 17,219 patients using the same protocol and the same type of device. Overall, 71.1 % had no proper circadian rhythm. This frequency was significantly higher than that of the control population (48 %). The prevalence of the nondipper or riser patterns was higher in patients with orthostatic hypotension (77.8 vs. 66.7 %). There was a correlation between nightly increases in diastolic blood pressure and changes in BP during the orthostatic test. Patients taking higher doses of treatment had less decreases in SBP (cc:-0.25; p = 0.007) and DBP (cc:-0.33; p < 0.001) at night, however there was no relation with drug type. The majority of patients with Parkinson's disease show an altered circadian rhythm of blood pressure. Patients with a non-dipper or riser pattern on 24 h ABPM exhibited a higher prevalence of autonomic disorders (orthostatic hypotension) and received higher doses of dopaminergic treatment. A day-night variation in diastolic blood pressure was the most important marker of these findings.

Wednesday, 13 February 2013

PREDICT-PD follow up survey closing...

Approximately 1100 of our original 1326 participants have completed the year one follow-up survey and tapping test. The retention rate is therefore upwards of 80%, which is tremendous.

Despite the bad weather, 120 of our participants have been seen in person as well. More will be seen from March onwards.

I am visiting Austria for 4 weeks now to learn transcranial sonography in the Neurology department at the University of Innsbruck. It is going well so far and I will post updates on this blog.

- Alastair Noyce

Monday, 4 February 2013

Next-generation sequencing in understanding complex neurological disease

Expert Rev Neurother. 2013 Feb;13(2):215-227.
Handel AE, Disanto G, Ramagopalan SV.

Department of Physiology, Anatomy and Genetics and Medical Research Council Functional Genomics Unit, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK.

Next-generation sequencing techniques have made vast quantities of data on human genomes and transcriptomes available to researchers. Huge progress has been made towards understanding the basis of many Mendelian neurological conditions, but progress has been considerably slower in complex neurological diseases (multiple sclerosis, migraine, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and so on). The authors review current next-generation sequencing methodologies and present selected studies illustrating how these have been used to cast light on the genetic etiology of complex neurological diseases with specific focus on multiple sclerosis. The authors highlight particular pitfalls in next-generation sequencing experiments and speculate on both clinical and research applications of these sequencing platforms for complex neurological disorders in the future.