Parkinsonism & Related Disorders

Editorial Board

2010-08-01

Deep brain stimulation for movement disorders before DBS for movement disorders

Patric Blomstedt, Marwan I. Hariz — 2010-08-01

Abstract: Deep brain stimulation (DBS) is an established surgical treatment for Parkinson’s disease (PD), essential tremor and dystonia. It is generally acknowledged that the development of DBS as we know it today started with the publication of Benabid, Pollak et al in 1987 on thalamic DBS for tremor. This technique gained momentum in the mid-Nineties after that Pollak and Benabid introduced the subthalamic nucleus as a target in advanced PD.This paper reviews the gestational pre-natal era of deep brain stimulation, before 1987. The origin of DBS can be traced back to the practice of intra-operative electrical stimulation, used for target exploration prior to lesioning, during the early years of stereotactic functional neurosurgery. During the 60s, Sem-Jacobsen and others implanted externalised electrodes which were used for intermittent stimulation and evaluation during weeks or months, prior to subsequent ablation of thalamic and other basal ganglia targets. In the early 70s Bechtereva treated PD patients using “therapeutic electrical stimulation” through electrodes implanted for up to 1.5 years. In the late 70s and early 80s the term Deep Brain Stimulation was coined and few groups attempted treatment of Parkinson’s disease, non-Parkinsonian tremor and dystonia with high-frequency stimulation using chronically implanted DBS systems. Cumbersome, un-sophisticated DBS hardware, together with the general decline of all surgery for PD following the introduction of levodopa, may have contributed to the lack of popularity of old-times DBS. It is to the credit of the Grenoble Group to have reinvented, modernised and expanded modern DBS in surgical treatment of movement disorders.

The cause of death in idiopathic Parkinson’s disease

Susan Pennington, Kalyani Snell, Mark Lee, Richard Walker — 2010-08-01

Abstract: Objectives: To identify the cause of death in patients with idiopathic Parkinson’s disease (IPD)Background: Current literature provides little data relating to cause of death in IPD and much is based on the recording of IPD on death certificates.Methods: All patients under the care of a Parkinson’s disease (PD) service who had died between 1999 and 2006 inclusive were identified and further classified into those with IPD according to the UK PD Society Brain Bank Criteria. Details were extracted from the service database and medical notes and further information obtained from the Office for National Statistics (ONS). Corrections were made for data classified using the International Classification of Diseases (ICD) 9 classification (prior to 2001) in order to compare accurately with data classified using ICD 10. Trends in cause of death were identified. Comparative data was obtained from the ONS for a control population.Results: Of 219 patients on the database who had died, 143 were identified as having IPD. They were more likely to be classified as dying from pneumonia, and less likely as malignancy or ischaemic heart disease, than the control population. Pneumonia was a terminal event in 45%. IPD was recorded on the death certificate in only 63% of patients.Conclusion: As expected, pneumonia is very often the terminal event. As previously demonstrated, malignancy is uncommon. Death certificate documentation is inadequate in one third of certificates; this has implications for research.

Lingual protrusion dystonia: Frequency, etiology and botulinum toxin therapy

Christine D. Esper, Alan Freeman, Stewart A. Factor — 2010-08-01

Abstract: The purpose of this study was to examine lingual protrusion dystonia (LPD); its frequency, etiology and response to botulinum toxin therapy. Previous literature suggests that LPD is more frequently the result of heredodegenerative disease and that the use of botulinum toxin therapy in LPD is associated with significant adverse effects. This is a retrospective database and record review from a movement disorder clinic. Of 421 dystonia patients, we identified 17 with LPD (4%). Of these cases, the diagnoses were: primary cranial dystonia (5), primary generalized dystonia (2), tardive dystonia (7), heredodegenerative disease (1), multifactorial (1) and post-infectious (1). All primary cases had concomitant oromandibular dystonia. In some secondary cases the LPD was the only cranial feature. Nine received botulinum toxin injections and 55.6% sustained moderate or marked improvement. Of 89 total botulinum toxin sessions, 66.3% had an excellent response, and 92.1% had some response. 97.8% of the sessions resulted in no significant adverse effects. On one occasion one patient developed severe dysphagia requiring placement of a percutaneous gastrostomy (PEG) tube. We conclude that LPD is rare, most commonly the result of tardive and primary dystonia. Botulinum toxin therapy may be very effective but needs to be utilized with care because of the possibility for the development of dysphagia.

Timed tests of motor function in Parkinson’s disease

Angus D. Macleod, Carl E. Counsell — 2010-08-01

Abstract: Introduction: Timed tests of motor function in Parkinson’s disease (PD) may be useful for the diagnosis of bradykinesia or to monitor disease progression or treatment response. However, normal ranges have not been established.Aim: To define normal ranges of hand-tapping and timed walking tests in non-parkinsonian controls and compare with PD patients’ performance.Methods: We recruited PD patients and age- and gender-matched controls for a prospective community-based incidence study of parkinsonian disorders in North-East Scotland. We counted the times participants tapped between two counters in 30 s. We also timed a 6m get-up-and-go test. We assessed age and gender effects and calculated 95% reference ranges for controls. We compared PD patients with controls.Results: We recruited 157 controls and 138 newly diagnosed, untreated PD patients (mean ages 75 and 73). The 95% control reference range for tapping scores with the dominant hand was 18–74 taps. Males and younger participants performed significantly better. PD patients performed less well (mean difference 15 taps, p < 0.001) but only 10% had tapping scores below the control range. The 95% control reference range for the get-up-and-go test was 9–27 s. Walking times increased significantly with age, but gender had no effect. PD patients were slower (median difference 4.5s, p < 0.001) but only 17% were slower than the control range.Discussion: Although PD patients performed more slowly than matched controls, timed tests were not helpful diagnostically because few incident patients were outside the normal reference ranges. Further work is needed on their utility in monitoring disease progression.

GST polymorphisms, interaction with smoking and pesticide use, and risk for Parkinson’s disease in a Japanese population

2010-08-01

Abstract: Patients with idiopathic Parkinson’s disease (PD) appear to have reduced capacity for detoxification of certain environmental compounds. The glutathione S-transferases (GSTs) are candidate genes for PD because they are involved in the metabolism of pesticides and cigarette smoke. We investigated the relationship of the seven GST polymorphisms (GSTM1 deletion, GSTT1 deletion, GSTP1 rs1695, GSTO1 rs4925, GSTO1 rs11191972, GSTO2 rs156697 and GSTO2 rs2297235) and PD risk with special reference to the interaction with pesticide use or cigarette smoking among 238 patients with PD cases and 370 controls in a Japanese population. None of the GST polymorphisms were associated with PD. GSTO1 rs4925 and GSTO2 rs2297235 were found to be in strong linkage disequilibrium (D′ = 0.98). Cigarette smoking was significantly associated with decreased risk of PD. However, no interaction of smoking with any of the GST polymorphisms was observed. Self-reported pesticide use was not associated with increased risk of PD. There was no evidence of interaction between self-reported pesticide use and either GST polymorphism. Our results suggest that the tested GST polymorphisms did not play an important role in PD susceptibility in our Japanese population. Our study does not give evidence of interaction between the GST polymorphisms and smoking may although this study provided sufficient statistical power to detect modest interaction. As for interaction between GSTP polymorphisms and pesticide use, the power of this study to detect an interactive effect was low due to a small number of pesticide users. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the GST polymorphisms in PD development.

Sensitivity to reward and punishment in Parkinson’s disease: An analysis of behavioral patterns using a modified version of the Iowa gambling task

Mutsutaka Kobayakawa, Natsuko Tsuruya, Mitsuru Kawamura — 2010-08-01

Abstract: Studies using the Iowa gambling task (IGT) have shown that patients with Parkinson’s disease (PD) make disadvantageous choices characterized by immediate large rewards and delayed larger punishments. These results can be interpreted in two ways: either PD patients are hypersensitive to immediate outcomes and/or insensitive to delayed consequences or PD patients are hypersensitive to rewards and/or insensitive to punishments. In this study, we used a modified IGT in which selection of cards from the disadvantageous decks leads to immediate, small punishments and delayed, smaller rewards and selection of cards from the advantageous decks leads to immediate, large punishments and delayed larger rewards. We then compared the results obtained using this modified IGT with those obtained using the original IGT. If the PD patients were hypersensitive to the immediate outcomes of decisions, they would make disadvantageous choices in both the original and the modified IGTs. Differences between the results of the original and modified tasks would indicate impairments in balancing reward and punishment. In our analysis, PD patients selected advantageous decks and gained as much as normal subjects during the modified IGT, but they selected disadvantageous decks during the original IGT. These results indicate that the decision-making difficulties of PD patients are caused by their inability to balance reward and punishment and their hypersensitivity to reward and/or insensitivity to punishment.

A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias

2010-08-01

Abstract: Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson’s disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of M. pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decarboxylase inhibitor (DDCI) benserazide (MPE+BZ), LD+BZ and LD alone without BZ in the hemiparkinsonian rat model of PD. A battery of behavioral tests assessed by blinded investigators served as outcome measures in these randomized trials. In experiment 1, animals that received LD+BZ or MPE+BZ at high (6mg/kg) and medium (4mg/kg) equivalent doses demonstrated significant alleviation of parkinsonism, but, developed severe dose-dependent DID. LD+BZ at low doses (2mg/kg) did not provide significant alleviation of parkinsonism. In contrast, MPE+BZ at an equivalent low dose significantly ameliorated parkinsonism. In experiment 2, MPE without any additives (12mg/kg and 20mg/kg LD equivalent dose) alleviated parkinsonism with significantly less DID compared to LD+BZ or MPE+BZ. In experiment 3, MPE without additives administered chronically provided long-term anti-parkinsonian benefits without causing DID. In experiment 4, MPE alone provided significantly more behavioral benefit when compared to the equivalent dose of synthetic LD alone without BZ. In experiment 5, MPE alone reduced the severity of DID in animals initially primed with LD+BZ. These findings suggest that M. pruriens contains water-soluble ingredients that either have an intrinsic DDCI-like activity or mitigate the need for an add-on DDCI to ameliorate parkinsonism. These unique long-term anti-parkinsonian effects of a parenterally administered water extract of M. pruriens seed powder may provide a platform for future drug discoveries and novel treatment strategies in PD.

Affective and cognitive theory of mind in patients with parkinson’s disease

2010-08-01

Abstract: Theory of Mind (ToM), which is the ability to infer other people’s mental states such as beliefs or desires, is an important prerequisite for social interaction. Affective and cognitive subcomponents of ToM can be impaired selectively in neurological and psychiatric disorders. This study examines ToM in 21 Parkinson’s disease (PD) patients and 21 healthy control (HC) subjects, using the computerized “Yoni task” that assesses affective and cognitive ToM abilities and an extensive battery of neuropsychological tests. Furthermore, questionnaires to assess health-related quality of life and depressive symptoms were applied and correlations to ToM were investigated. Compared to the control subjects, PD patients scored lower on both the affective (PD: 76% versus HC: 89%; p = 0.006) and cognitive (PD: 80% versus HC: 92%; p = 0.002) ToM subscales but not on control items (PD: 90% versus HC: 95%; p = 0.077). The ToM abilities were not associated with other cognitive functions, depressive symptoms or clinical data. However, affective ToM was correlated with health-related quality of life (p = 0.01). Parkinson patients are impaired in affective as well as cognitive ToM. These deficits are largely independent from other cognitive impairments, depressive symptoms and motor impairment. The relationship of affective ToM to the health-related quality of life of PD patients points to a clinical relevance of this issue and suggests that ToM dysfunctions must be regarded as an important non-motor feature of Parkinson’s disease.

A case control study on bone mineral density in Chinese patients with Parkinson’s disease

Kuen Lam, Martin Li, Vincent Mok, Andrew Hui, Jean Woo — 2010-08-01

Abstract: Although previous studies showed that patients with Parkinson’s disease (PD) have low bone mineral density (BMD), there is little data on factors predisposing PD patients to low BMD. We compared the BMD of 108 PD patients (58 females) with an average age of 68 (range 42–83) years with that of 216 sex- and age-matched controls, adjusting for other covariate factors (exercise levels, estrogen status, dietary calcium intake, smoking, drinking, body mass index, and percentage of body fat). The mean BMD in the hip and lumbar spine of male PD patients did not differ significantly from those of male controls. On the other hand, the mean BMD in femoral neck was significantly lower in female PD patients than in controls (0.53 ± 0.11 g/cm2 versus 0.58 ± 0.10 g/cm2, P = 0.005). Compared with controls, female PD patients experienced menopause much earlier (47 years versus 50 years, P = 0.028). The percentage of body fat was also lower in female PD patients (33% versus 36%, P = 0.02). A lower BMD in the hip in female PD patients was associated with an increased number of months after menopause (P = 0.004) and lower percentage of body fat (P = 0.025). We concluded that female patients with PD have lower hip BMD, but this association appears largely attributable to differences in percentage body fat and years since menopause. After multivariate adjustment, PD no longer remained independently associated with reduced BMD in female patients.

The impact of and the factors associated with drooling in Parkinson's disease

2010-08-01

Abstract: We administered a 7-question survey on drooling to PD patients and age-matched controls. Each subject was assigned a drooling severity score and categorized as a “drooler” or a “non-drooler”. The age, disease duration, motor scores, quality of life (PDQ-39), and levodopa equivalent daily dosage (LEDD) were compared between PD droolers vs. PD non-droolers.58 PD patients and 51 age-matched controls participated. In PD patients, the mean: disease duration was 10.96 years (SD 8.66) and UPDRS on motor score was 30.76 (SD 10.57). The drooling severity score was significantly different between patients vs. controls (3.41 vs. .58; p < .01). 14% of controls vs. 59% of patients were droolers (p < .01). PD droolers scored worse on the ADL subscale of the PDQ-39 (p = .031). Furthermore, PD droolers had significant difficulty speaking (7.27% vs. 0%; p < .01); eating (3.64% vs. 0%; p = .01); and socially interacting (12.73% vs. 0%; p < .01) compared to PD non-droolers. Interestingly, the hallucination component of the UPDRS Part I was significantly correlated with being a drooler (p = .016). None of the other variables have significant effect on drooling severity scores. There is a high prevalence of drooling among PD patients compared to controls.PD droolers had worse quality of life and had more difficulty speaking, eating and socially interacting compared to PD non-droolers. Experiencing hallucinations was the only factor that correlated with being a drooler and it may be confounded by medications.

Botulinum toxin type A in simple motor tics: Short-term and long-term treatment-effects

2010-08-01

Abstract: To determine the short-term and long-term treatment-effects of botulinum toxin type A in simple motor tics, we analyzed 15 consecutive patients (18 tics) with simple motor tics that were treated every 3 months with injections of BTX-A. Efficacy (rated on a 4-level scale) and duration of effect of the first 2 and last 2 (if treated 5 times or more) treatments were recorded, as well as latency of response, changes of premonitory urges (PMUs) and possible side effects.Total number of treatments for each tic varied from 2 to 50 (mean 11, median 6). In 16 of 18 tics (89%) short-term efficacy was reported successful (good or moderate). Long-term efficacy was reported in 12 tics of which 11 showed similar or even increased beneficial effects. Premonitory urge (PMU) was reported in 8 patients (53%). PMU, if present, lessened or disappeared after treatment with BTX-A. A permanent remission of the treated tic was seen in 3 patients with a maximum follow-up of 10 years.BTX-A appears a safe and effective treatment for simple motor tics and retains its efficacy after long-term treatment. BTX may also induce permanent remission of the treated tics and effects of BTX are not restricted to merely motor behaviour.

Whatever the disease duration, stimulation of the subthalamic nucleus improves Parkin disease

2010-08-01

Younger age, shorter disease duration, absence of levodopa-resistant axial signs, and normal cognition, have been reported to predict the best postoperative clinical improvement following high-frequency stimulation of subthalamic nucleus (STN) . Furthermore, recent studies suggest that STN stimulation is particularly effective in patients with early-onset genetic parkinsonism . However, it is unclear whether patients with Parkin combined with extremely long disease duration can still be suitable candidates for surgery.

Familial frontotemporal dementia with parkinsonism associated with the progranulin c.C1021T (p.Q341X) mutation

2010-08-01

The frontotemporal lobe degenerations (FTLD) are a complex group of neurodegenerative disorders associated with a broad clinical spectrum, ranging from predominantly cognitive (frontotemporal dementia, progressive primary aphasia) to predominantly motor syndromes (corticobasal degeneration, progressive supranuclear palsy syndrome), and mixed syndromes such as frontotemporal dementia with motor neuron disease (reviewed in ). The brain pathology of FTLD is characterized by degeneration of the frontal and temporal lobes with formation of various types of neuronal and glial protein aggregates . FTLD are etiologically heterogeneous and different inherited forms have been characterized, among which those caused by mutations in the microtubule associated protein tau (MAPT) and the progranulin (GRN) genes are the most common. Mutations in the GRN gene [OMIM 138945] are an important cause of autosomal dominant FTLD with tau-negative pathology . Here we report an Italian family with rapidly progressing frontotemporal dementia with parkinsonism associated with the GRN c.C1021T mutation.

Differences between familial and sporadic Parkinson’s disease

2010-08-01

Parkinson’s disease (PD) is a disorder of older individuals, hence finding an affected family member from a previous generation becomes rather difficult in large majority of PD patients. Many a times the diagnosis made by the family physician/non-movement disorders specialist is incorrect in case of PD . It is important to identify clinical features in a person with PD which may suggest familial PD to prompt intense search for familial occurrence and hence investigate more vigorously for genetic factors. Known genetic mutations are rare in Indian PD patients necessitating the need for search of novel genes . In the current study we examined the phenotypic differences, if any, between familial and sporadic PD to help differentiate between the two.