Parkinsonism & Related Disorders

Editorial Board

2012-05-01

Prevalence of oropharyngeal dysphagia in Parkinson’s disease: A meta-analysis

J.G. Kalf, B.J.M. de Swart, B.R. Bloem, M. Munneke — 2011-12-05

Abstract: Dysphagia is a potentially harmful feature, also in Parkinson’s disease (PD). As published prevalence rates vary widely, we aimed to estimate the prevalence of oropharyngeal dysphagia in PD in a meta-analysis.We conducted a systematic literature search in February 2011 and two independent reviewers selected the papers. We computed the estimates of the pooled prevalence weighted by sample size.Twelve studies were suitable for calculating prevalence rates. Ten studies provided an estimate based on subjective outcomes, which proved statistically heterogeneous (p < 0.001), with a pooled prevalence estimate with random effect analysis of 35% (95% CI 28–41). Four studies provided an estimate based on objective measurements, which were statistically homogeneous (p = 0.23), with a pooled prevalence estimate of 82% (95% CI 77–87). In controls the pooled subjective prevalence was 9% (95% CI 2–17), while the pooled objective prevalence was 23% (95% CI 13–32). The pooled relative risk was 3.2 for both subjective outcomes (95% CI 2.32–4.41) and objective outcomes (95% CI 2.08–4.98). Clinical heterogeneity between studies was chiefly explained by differences in disease severity.Subjective dysphagia occurs in one third of community-dwelling PD patients. Objectively measured dysphagia rates were much higher, with 4 out of 5 patients being affected. This suggests that dysphagia is common in PD, but patients do not always report swallowing difficulties unless asked. This underreporting calls for a proactive clinical approach to dysphagia, particularly in light of the serious clinical consequences.

An evidence-based approach in the treatment of Huntington’s disease

T.A. Mestre, J.J. Ferreira — 2011-12-19

Abstract: Huntington’s disease (HD) is a neurodegenerative disease with diverse symptoms for which there is no curative or disease-modifying treatment available. Currently, tetrabenazine is the only drug approved for HD by a regulatory agency, and only for the treatment of chorea. In the current review, we present updated results from recent clinical trials and ongoing clinical research efforts to find effective and safe treatments for HD motor, and neuropsychiatric and cognitive symptoms. We used a systematic review approach that included data from well-designed randomised controlled trials. The authors conclude that there is weak evidence to support most of the treatment decisions in HD and thus clinicians may be guided only by expert opinion-based therapeutic recommendations. Ongoing research is considerable and is expected to have an impact in the management of HD in upcoming years.

Direct costs and survival of medicare beneficiaries with early and advanced parkinson’s disease

2011-12-19

Abstract: Background: No recent analysis details Parkinson’s Disease (PD) costs or survival for Medicare beneficiaries. This study assesses excess direct costs and survival in Medicare beneficiaries with early and advanced PD.Methods: Patients with ≥2 PD diagnoses (ICD-9-CM: 332.0), ≥age 65, continuously enrolled in Parts A&B during one-year baseline and study periods were selected from the Medicare 5% sample (N = 3.2 million, 1999–2008). Newly diagnosed patients were defined as having no baseline claims for movement disorder, dementia, Alzheimer’s, bipolar disorder, psychosis, falls or related injuries, ambulatory assistance device (walker or wheelchair), or skilled nursing facility. Controls without PD were demographically matched 1:1. Costs to Medicare were compared via Wilcoxon rank-sum tests and inverse probability weighted multivariate regression. Survival was assessed via Cox proportional hazards analysis.Results: Costs in the year post-diagnosis were higher for newly diagnosed patients (N = 9,201, $7423) than controls ($5024), resulting in excess PD-associated costs of $2399 (p < 0.001). Cumulative excess costs were $28,422 from the year prior to index quarter to five years following (p < 0.01). PD patients receiving their first claim for an ambulatory assistance device (N = 11,294) had excess cumulative costs of $50,923 (p < 0.001) over the same period; those receiving their first claim for a skilled nursing facility (N = 10,152) had excess costs of $102,750 (p < 0.001). Hazard rates of mortality were higher among newly diagnosed PD (1.43, p < 0.001), ambulatory assistance device (2.37, p < 0.001) and skilled nursing facility (3.34, p < 0.001) cohorts than in corresponding non-PD groups.Conclusions: Medicare beneficiaries with PD have substantially and progressively higher costs and mortality compared with controls.

Incidence and mortality of Parkinson’s disease in older Canadians

2011-12-26

Abstract: Objective: To estimate the age-specific incidence of Parkinson’s disease (PD) in elderly persons in the Canadian province of British Columbia (BC). All-cause and injury mortalities and relative risk of death for those persons with PD were also examined.Methods: A historical cohort study was conducted using 5 provincial administrative databases from 1991/92 to 2000/2001. A series of algorithms based on the databases were created for case ascertainment of PD for persons 65 years or older. Crude and age-specific incidence and mortality rates were calculated using person-years of follow-up as the denominator. The impact of PD on all-cause and injury mortalities was examined using multivariate Cox regression models to provide adjusted hazard ratios.Results: 10,910 incidence cases over 6,051,682 person-years of follow-up were identified. The crude annual incidence rate was 252 per 100,000 person-years. Over the nine year period, age standardized incidence for males ranged from 207 to 396 per 100,000 person-years and 127 to 259 per 100,000 person-years for females. Persons with PD were at a 43% greater risk of all-cause mortality and specifically, 51% greater risk of injury mortality.Conclusions: Incidence of PD is substantially higher in advanced age with age adjusted increases for both all-cause and injury mortalities. These findings also highlight falls as a primary factor for injury mortality in PD.

First neuropathological description of a patient with Parkinson’s disease and LRRK2 p.N1437H mutation

2011-12-08

Abstract: The c.4309A>C mutation in the LRRK2 gene (LRRK2 p.N1437H) has recently been reported as the seventh pathogenic LRRK2 mutation causing monogenic Parkinson’s disease (PD). So far, only two families worldwide have been identified with this mutation. By screening DNA from seven brains of PD patients, we found one individual with seemingly sporadic PD and LRRK2 p.N1437H mutation. Clinically, the patient had levodopa-responsive PD with tremor, and developed severe motor fluctuations during a disease duration of 19 years. There was severe and painful ON-dystonia, and severe depression with suicidal thoughts during OFF. In the advanced stage, cognition was slow during motor OFF, but there was no noticeable cognitive decline. There were no signs of autonomic nervous system dysfunction. Bilateral deep brain stimulation of the subthalamic nucleus had unsatisfactory results on motor symptoms. The patient committed suicide. Neuropathological examination revealed marked cell loss and moderate alpha-synuclein positive Lewy body pathology in the brainstem. There was sparse Lewy pathology in the cortex. A striking finding was very pronounced ubiquitin-positive pathology in the brainstem, temporolimbic regions and neocortex. Ubiquitin positivity was most pronounced in the white matter, and was out of proportion to the comparatively weaker alpha-synuclein immunoreactivity. Immunostaining for tau was mildly positive, revealing non-specific changes, but staining for TDP-43 and FUS was entirely negative. The distribution and shape of ubiquitin-positive lesions in this patient differed from the few previously described patients with LRRK2 mutations and ubiquitin pathology, and the ubiquitinated protein substrate remains undefined.

Apathy and depression in Parkinson’s disease: The Belgrade PD study report

Lj Ziropadja, E. Stefanova, M. Petrovic, T. Stojkovic, V.S. Kostic — 2011-12-14

Abstract: Apathy and depression are among the most common psychiatric and behavioral disorders associated with Parkinson’s disease (PD). The objective of this study was to examine the prevalence and demographic and clinical correlates of apathy and depression in a clinical population-based sample of patients with PD and to assess whether apathy may present as a primary behavioral disturbance independent from depression and cognitive impairment. A series of 360 PD patients underwent psychiatric investigation with the Starkstein’s Apathy Scale (AS), and the 17-item Hamilton Depression Rating Scale (HDRS-17), motor scoring with Hoehn and Yahr (HY) staging, and the Unified Parkinson’s Disease Rating Scale (UPDRS); and cognitive screening with the Mini-Mental State Examination (MMSE) on the same day. Apathy coexisted with depression in 133 (36.9%) of PD patients, compared with depression without apathy in 16 (4.4%), apathy without depression in 84 (23%), and neither apathy nor depression in 127 PD patients (35.2%). Apathy was associated with higher axial UPDRS impairment score, lower MMSE score, higher l-dopa dosage, and earlier HY stages, while depression was predicted by the more advanced HY stages and younger age of PD patients. These findings suggest that apathy and depression may be separable in PD, although both are common in patients with PD. Therefore these two conditions should be systematically screened and considered in the care and management of PD.

Acceleration of syllable repetition in Parkinson's disease is more prominent in the left-side dominant patients

Andrea Flasskamp, Sonja A. Kotz, Uwe Schlegel, Sabine Skodda — 2011-12-14

Abstract: Background: In Parkinson's disease (PD), abnormalities of speech rate have been observed in spontaneous speech, reading tasks and syllable repetition tasks. Impaired temporal speech patterns have been contributed to dysfunctional basal ganglia circuits, but little is known about a possible differential role of right and left basal ganglia concerning speech production, although neurodegeneration in PD typically follows an asymmetrical pattern. The aim of our study was to reveal a possible influence of lateralized basal ganglia dysfunction on speech timing in PD.Patients and methods: 60 patients with PD (30 with predominant symptoms on the left-side PD_L and 30 with predominant symptoms on the right side PD_R) and 40 healthy controls were tested. Participants had to repeat a single syllable in a self chosen steady pace. Additionally, the participants performed a reading task in order to measure speaking rate related to connected speech.Results: Syllable repetition showed a significant instability in both PD groups as compared to controls. However, the PD_L group performed in a much higher pace with further significant pace acceleration in the course of the syllable repetition task. This pattern showed a further correlation to axial motor symptoms. No correlations were seen between parameters of syllable repetition and the reading task.Conclusions: Lateralization of basal ganglia dysfunction in PD seems to differentially impact the stability of spontaneous syllable repetition pace. Our data suggest a crucial role of the right basal ganglia in the maintenance of isochronous speech rhythms at least in patients with additional axial motor symptoms.

Short and valid assessment of apraxia in Parkinson’s disease

2011-12-19

Abstract: Background: Valid assessment of apraxia in usually non-apraxic Parkinson’s disease helps to delineate atypical parkinsonism frequently associated with apraxia. Furthermore, in a subgroup of late Parkinson’s disease apraxia, typically the ideomotor subtype, may gradually superimpose onto parkinsonian motor symptoms contributing to defective manual skill. Here we evaluate the utility of a brief, standardized test, the apraxia screen of TULIA (AST).Methods: Seventy five Parkinson’s disease patients were tested with the AST. Parkinsonian motor deficits were measured using Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III and difficulties in activities of daily living (ADL) by modified MDS-UPDRS part II (eating, dressing, personal hygiene, and writing).Results: No association was found between the AST and MDS-UPDRS part III, indicating that AST discriminates well (discriminative validity) between apraxia and parkinsonism. Furthermore, AST was associated with ADL and Hoehn & Yahr stage (convergent validity).Conclusions: AST is a short and valid test to rule out or detect apraxia in Parkinson’s disease.

Common polymorphisms in dystonia-linked genes and susceptibility to the sporadic primary dystonias

2011-12-15

Abstract: Genes involved in familial dystonia syndromes (DYT genes) are ideal candidates for investigating whether common genetic variants influence the susceptibility to sporadic primary dystonia. To date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1, have been assessed. We therefore employed a haplotype-tagging strategy to comprehensively assess if common polymorphisms in eight DYT genes (TOR1A, TAF1, GCH1, THAP1, MR-1 (PNKD), SGCE, ATP1A3 and PRKRA) confer risk for sporadic primary dystonia. The 230 primary dystonia cases were matched for age and gender to 228 controls, recruited from movement disorder clinics in Brisbane, Australia and the Australian electoral roll. All subjects were genotyped for 56 tagging SNPs and genotype associations were investigated. Modest genotypic associations (P<0.05) were observed for three GCH1 SNPs (rs12147422, rs3759664 and rs10483639) when comparing all cases against controls. Associations were also seen when the cases were stratified based on presentation. Overall, our findings do not support the hypothesis that common TOR1A variants affect susceptibility for sporadic primary dystonia, and that it is unlikely that common variants around the DYT genes confer substantial risk for sporadic primary dystonia. Further work is warranted to follow up the GCH1 SNPs and the subgroup analyses.

Validation of a new scale to assess olfactory dysfunction in patients with Parkinson’s disease

2012-01-09

Abstract: Bakckground: Olfactory dysfunction is present in up to 90% of Parkinson’s disease (PD) patients. It is usually evaluated by means of objective standardized tests; however no self-administered scales have been developed for olfactory dysfunction bedside assessment. We present validation of a new scale to assess this symptom in PD patients.Methods: Seventy-five PD patients and 25 control subjects were evaluated using a Hyposmia Rating Scale developed in-house, combined with the extended Sniffin’ Sticks test.Results: Total score of the 6-item Hyposmia Rating Scale showed significant correlation with threshold, discrimination, identification and total Sniffin’ Sticks test scores (r = 0.53; r = 0.60; r = 0.57; r = 0.65 respectively, p < 0.001 for all values). Area under the curve of the receiver operating curve for the ability of Hyposmia Rating Scale to discriminate patients with Sniffin’ Sticks test total scores below or above the cut-off point was 80 ± 6% (p < 0.001). Considering Sniffin’ Sticks test as the gold standard method for olfactory dysfunction detection, an affirmative response to a single screening question about smelling ability problems showed 35% sensitivity (95%CI = 23–47%) and 100% specificity. The best cut-off point for Hyposmia Rating Scale was 22.5 with a sensitivity of 70% (60–81%) and a specificity of 85% (65–100%).Conclusion: The Hyposmia Rating Scale here presented may offer a simple, cost-effective, time-saving and reliable approach to evaluate olfactory dysfunction in PD patients.

Group I nonreciprocal inhibition in restless legs syndrome secondary to chronic renal failure

2011-12-26

Abstract: Background: Neurophysiological investigations disclosed spinal cord hyperexcitability in primary restless legs syndrome (p-RLS). Uremic RLS (u-RLS) is the most common secondary form, but its pathophysiological mechanisms remain unsettled. Aim of this study was to explore spinal cord excitability by evaluating group I nonreciprocal (Ib) inhibition in u-RLS patients in comparison with p-RLS patients and healthy subjects.Methods: Eleven u-RLS patients undergoing long-term hemodialysis treatment, nine p-RLS patients and ten healthy subjects were studied. Soleus H reflex latency (HR-L), ratio, and Ib inhibition were evaluated. Ib inhibition was tested measuring the amplitude changes in soleus H reflex following stimulation of the synergist gastrocnemius medialis (GM) nerve at rest. Nerve conduction studies were performed in the uremic patients.Results: The ratio did not differ in the three groups. The u-RLS patients showed a normal Ib inhibition comparable with the healthy group, whereas the p-RLS group had evidence of a reduced active inhibition compared with both u-RLS patients (P = 0.04) and controls (P = 0.007), prominently at 5 ms (P = 0.007) and at 6 ms (P = 0.02) of conditioning-test interval. Neurophysiological examination disclosed abnormalities ranging from higher HR-L to clear-cut polyneuropathy in most u-RLS patients.Conclusions: Unlike p-RLS patients, u-RLS patients had normal Ib inhibition, suggesting a regular supraspinal control of Ib spinal interneurons. Subclinical peripheral nerve abnormalities were detected in most uremic patients. Peripherally disrupted sensory modulation may represent the major pathophysiological determinant of uremic RLS.

Apolipoprotein E gene (APOE) genotype in Wilson’s disease: Impact on clinical presentation

T. Litwin, G. Gromadzka, A. Członkowska — 2012-01-05

Abstract: Background: Wilson’s disease (WD), an inherited copper metabolism disorder that leads to pathological tissue copper accumulation and secondary organ damage, is caused by mutations in the ATP-ase 7B gene (ATP7B). The apolipoprotein E gene (APOE) alleles ε2, ε3, and ε4 produce three different apoE isoforms with different biological effects, which can determine risks of many human diseases, including neurodegenerative and liver disease. This study aimed to evaluate the impact of APOE genotype on the variability of WD phenotypic expression.Methods: We analyzed data on 383 WD consecutive patients in the WD registry. The APOE genotypes (APOE ε3/ε3 (wild-type), APOE ε2-positive, and APOE ε4-positive) were determined and the APOE genotype effect on the phenotypic WD presentation was assessed in all symptomatic WD patients, as well as in patient subgroups divided according to sex and ATP7B genotype.Results: APOE genotype had no impact on WD presentation in the general population of symptomatic patients. However, APOE ε4-positive women tended to present WD symptoms earlier than women possessing the wild-type APOE ε3/ε3 genotype (24.2 vs. 27.9 years; p = 0.08). The effect of the APOE ε4-positive genotype was more pronounced in ATP7B p.H1069Q homozygous women, in whom disease symptoms started almost 6 years earlier (23.6 vs. 29.9 years; p < 0.05) than in APOE ε3/ε3 women.Conclusions: In women, APOE ε4-positive genotype is associated with earlier onset of WD symptoms, particularly among ATP7B p.H1069Q homozygous patients. Further studies are needed to understand the mechanisms of these gender-dependent phenotypic effects.

Pardoprunox as adjunct therapy to levodopa in patients with Parkinson’s disease experiencing motor fluctuations: Results of a double-blind, randomized, placebo-controlled, trial

2012-02-10

Abstract: Aims: To determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson’s disease (PD) experiencing motor fluctuations.Methods: Patients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary efficacy variable was the change from baseline to study endpoint in total daily OFF time, based on patient diaries. Secondary analyses included the change in ON time without troublesome dyskinesias, UPDRS-ADL + Motor ON, UPDRS-ADL OFF and PDQ-39. Subgroup analyses explored the impact of pardoprunox on dyskinesias (UPDRS items 32 + 33), depression (Hospital Anxiety Depression Scale) and pain (Visual Analogue Scale).Results: Pardoprunox significantly reduced OFF time versus placebo (−1.62 h/day versus −0.92 h/day, respectively, p = 0.0215). Compared to placebo, pardoprunox improved ON time without troublesome dyskinesias (p = 0.0386), UPDRS-ADL + Motor ON (p = 0.0003), and UPDRS-ADL OFF (p < 0.0001), while no significant difference was observed on PDQ-39. A high drop-out rate due to adverse events (AEs) (pardoprunox, 37%; placebo, 12%) suggested that the selected dose range may have been too high, and/or titration was too rapid.Conclusions: Pardoprunox decreased OFF time and increased ON time without troublesome dyskinesias in levodopa-treated PD patients. The high drop-out rate at the selected doses justifies the investigation of lower doses. The impact of pardoprunox on dyskinesias and non-motor symptoms deserves further investigation.

Assessment of appropriate medication administration for hospitalized patients with Parkinson’s disease

2012-01-11

Abstract: Background: For Parkinson’s disease (PD) patients, adherence to a regular PD medication schedule is important in achieving optimal symptom control. There are few published studies quantifying PD medication administrations in hospitalized PD patients.Methods: Hospitalization records for 100 veterans with idiopathic PD and admitted to our center were reviewed to determine the on time rate and contraindicated medication doses. A barcode based computerized medication administration system within the electronic medical record provided information of the exact time the medication was given to a patient.Results: Eighty-nine idiopathic PD patients met study inclusion criteria. Among them, 87 were on levodopa monotherapy or in combination with other PD medications. Two patients were on dopamine agonists only. A total of 3873 doses of PD medications were prescribed during hospitalization. Among 675 incorrect medication administrations, 322 doses were omitted, 300 doses late by ≥30 min, and 53 doses given early by ≥30 min. Contraindicated medications were prescribed for 19 patients. The correct administration percentage was lower during the first 2 days post-admission compared to subsequent days (mean 74.6% vs. 82.8%) and higher for patients who had neurological consultations (mean 85.5% vs. 76.5%). Correct administration rates were better for patient-based medication schedules (85.6%) than with hospital-based schedules (77.5%), but did not achieve statistical significance.Conclusion: Adherence to regular PD medication dosing schedules during hospitalization is problematic, but improves with specialist consultation. Staff involved in the admission process for PD patients should work to safeguard against disruption of the prescribed home dosing schedule.

The Q10 questionnaire for detection of wearing-off phenomena in Parkinson’s disease

Pablo Martinez-Martin, Basilio Hernandez, on behalf of the Q10 Study Group — 2012-01-13

Abstract: In Parkinson’s disease (PD), wearing-off can be difficult to detect as it is very variable and may affect motor and non-motor symptoms. The Wearing-Off Questionnaire, WOQ-32 (Stacy et al., 2005), was introduced to help identify wearing-off and proved to be very efficient. Two short versions of the questionnaire (WOQ-19 or QUICK and WOQ-9) were later developed to decrease the respondent burden without loss of efficacy in terms of sensitivity. The objective of the present study was to check the ability of a new 10-item QUICK version, Q10, to identify patients with wearing-off. Q10 items were selected from the QUICK validation study data set through statistical analysis and it was then tested on a sample of 162 PD patients, 64.8% with wearing-off. Sensitivity, specificity, and accuracy were 96%, 63%, and 85% respectively with one positive response and 90%, 70%, and 83% respectively with two positive responses. The correlation with the gold standard (neurologist diagnosis of wearing-off) was substantial (kappa = 0.62–0.64). Comparison with the QUICK and WOQ-9 shows that the Q10 can be a new tool for detection of wearing-off with satisfactory properties and a good balance between brevity and performance.

A DNA resequencing array for genes involved in Parkinson’s disease

2012-01-13

Abstract: Parkinson’s disease (PD) is aetiologically complex with both familial and sporadic forms. Familial PD results from rare, highly penetrant pathogenic mutations whereas multiple variants of low penetrance may contribute to the risk of sporadic PD. Common variants implicated in PD risk appear to explain only a minor proportion of the familial clustering observed in sporadic PD. It is therefore plausible that combinations of rare and/or common variants in genes already implicated in disease pathogenesis may help to explain the genetic basis of PD.We have developed a CustomSeq Affymetrix resequencing array to enable high-throughput sequencing of 13 genes (44 kb) implicated in the pathogenesis of PD. Using the array we sequenced 269 individuals, including 186 PD patients and 75 controls, achieving an overall call rate of 96.5% and 93.6%, for two respective versions of the array, and >99.9% accuracy for five samples sequenced by capillary sequencing in parallel. We identified modest associations with common variants in SNCA and LRRK2 and a trend suggestive of an overrepresentation of rare variants in cases compared to controls for several genes. We propose that this technology offers a robust and cost-effective alternative to targeted sequencing using traditional sequencing methods, and here we demonstrate the potential of this approach for either routine clinical investigation or for research studies aimed at understanding the genetic aetiology of PD.

Genetic analysis of HLA-DRA region variation in Taiwanese Parkinson’s disease

2012-01-13

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder comprising both motor and cognitive disability. The pathogenesis of the disease is still unclear; however, neuroinflammation seemed to play a role. A recent genome-wide association study (GWAS) reported an association between HLA-DRA rs3129882 and the development of PD in Caucasian populations. In this study, we observe no association between this single nucleotide polymorphism and PD in a Taiwanese population. The possible reasons include different ethnicity with genomic differences and environmental factors in different geographical regions.

Comparison of REM sleep behaviour disorder variables between patients with progressive supranuclear palsy and those with Parkinson’s disease

Takashi Nomura, Yuichi Inoue, Hiroshi Takigawa, Kenji Nakashima — 2011-11-24

Abstract: Purpose: Rapid eye movement (REM) sleep behaviour disorder (RBD) is an important indicator of underlying synucleinopathies. However, the frequency of RBD in tauopathies such as progressive supranuclear palsy (PSP) remains unclear. In this study, we compared RBD-related symptoms and polysomnographic (PSG) findings between patients with PSP and those with Parkinson’s disease (PD).Methods: We conducted clinical interviews of 20 patients with PSP, 93 patients with PD and their caregivers regarding RBD-related symptoms, and conducted PSG recordings on all the subject patients. We then compared the clinical backgrounds, PSG parameters, and frequency of RBD-related symptoms between the two groups.Results: PSP patients had more severe symptoms of Parkinsonism and cognitive impairment, and took lower doses of dopaminergic agents compared with PD patients. The PSP group had lower values for both estimated total sleep time and sleep efficiency on PSG compared with the PD group (p = 0.002, p = 0.021, respectively). The PSP group also included a significantly smaller number of patients having REM sleep without atonia (RWA) compared with the PD group (n = 5, 20.0% vs. n = 56, 60.2%, p = 0.003). None of the PSP patients were experiencing RBD-related symptoms at the time of the investigation, while 30 PD patients (32.3%) had RBD-related symptoms.Discussion: The existence of RWA as well as RBD-related symptoms was less frequent in patients with PSP versus patients with PD. Differences in brain stem pathology and/or disease course between the two disorders might influence this difference.

Role of genetic polymorphisms of the dopaminergic system in Parkinson’s disease patients with impulse control disorders

2011-11-23

Abstract: Background: The mechanisms underlying the development of impulse control disorders (ICDs) like compulsive gambling, buying, sexual, and eating behaviors in Parkinson’s disease (PD) are debated. We assessed whether allelic variants of dopamine D2 receptors (DRD2), catechol-O-methyltransferase (COMT) and dopamine transporter (DAT) were associated with the development of ICDs in PD.Method: We enrolled 89 idiopathic PD patients (48 without ICDs and 41 with ICDs). All patients were screened with the Minnesota Impulsive Disorders Interview (MIDI) and fulfilled DSM-IV criteria for the ICD positive cohort. Differences in the frequency of the genotypes between ICDs and non-ICDs groups were assessed using the χ2 test.Results: Genotyping was performed for variants of the DRD2 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 (3′ UTR 40bp VNTR). Variants of DRD2 Taq1A, COMT and DAT1 were not associated with the risk of developing ICDs.Conclusion: In our study, there were no differences in the frequency of variant of DRD2 Taq1A, COMT and DAT1 between the two groups. Polymorphisms of dopaminergic genes do not play a relevant role in the development of ICD in PD suggesting that ICD originate from inability to filter inappropriate behaviors triggered by dopaminergic therapy.

The utility of laser-generated visual-cueing in parkinsonian patients with gait freezing

J.A. Van Gerpen — 2011-08-29

I read with interest and appreciation the recently published article, “Laserlight Cues for Gait Freezing in Parkinson’s Disease: An Open-Label Study” by Donovan et al. Like these authors, colleagues and I have long sought to make visual-cueing a practical aid for relieving freezing of gait (FOG) in parkinsonian patients. Over eight years ago, we developed a swivel-mounted, type 3A laser, which can be attached to any walker or cane with Velcro™, so that patients can have a constant, laser-generated visual cue. This cue can be adjusted to approximate their normal stride, to utilize for ambulation outside of their home. Previously, placing strips of tape on the floor of their home to serve as a visual cue has been a standard recommendation for parkinsonian patients with FOG , and other investigators have concluded that laser-generated visual-cueing is ineffective at attenuating FOG . As with Donovan et al. , my colleagues and I have conducted studies, which bring this pessimistic assessment into question .

The utility of laser-generated visual-cueing in Parkinsonian patients with gait freezing

2011-09-30

We appreciate the thoughtful comments and questions from Dr. J.A. Van Gerpen regarding our study, “Laserlight Cues for Gait Freezing in Parkinson's Disease: An Open-Label Study” by Donovan et al. . Our study showed that a laserlight visual cue was associated with a modest reduction in freezing of gait (FOG) in Parkinson's disease (PD) patients, and with a significant reduction in the frequency of falls. Because our study focused only on FOG in PD patients, results from that study cannot be used to assess whether or not a laserlight visual cue will improve FOG in non-PD patients. Non-ambulatory patients were excluded from our study. Dr. Van Gerpen suggests that instructing patients to continuously look at the visual cue and to slightly lean forward over the walker might improve efficacy. We agree that this is possible, although one also could hypothesize potentially deleterious effects. Because we did not provide such instructions to our subjects, our data do not address this question. Future studies to compare different methods and in different patient groups will be necessary to clarify these issues and to optimize the use of visual cues for overcoming FOG.

Withdrawal of visual feedback in essential tremor

A. Gironell, R. Ribosa-Nogué, J. Pagonabarraga — 2011-12-22

We read with interest the review article on non-pharmacological interventions for essential tremor (ET) by O’Connor and Kini . The authors concluded that many rehabilitation interventions are of little efficacy and that evidence is poor. One form of physical therapy not mentioned in this review is withdrawal of visual feedback. Many patients with ET report improvements when they withdraw their vision when tremor interferes with an activity they are performing.

Correspondence related to published paper non-pharmacological and non-surgical interventions for tremor: A systematic review

Rory J. O’Connor, Manohar U. Kini — 2012-02-29

We read with interest Gironell et al’s response to our review of non-pharmacological and non-surgical interventions for tremor . Their work is of importance to all concerned with elucidating the mechanism of tremor in neurological conditions.

Erratum to ‘Propofol-induced paroxysmal dystonia’ [Parkinsonism Relat Disord, vol. 18 (2012) 115–116]

2012-05-01

The publisher regrets that the printed version of the above article was published as an Editorial instead of a Letter to the Editor. The correct and final version follows.