Long-term effects of bilateral deep brain stimulation of the subthalamic nucleus on depression in patients with Parkinson's disease

ObjectiveTo study the long-term effects of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) on depression in patients with Parkinson's disease (PD) and to discuss the mechanism.MethodsA STN–DBS group (n = 27) and anti-Parkinson's medication control group with paired designing were set up. The evaluation of the depression and motor function was performed a total of six times. Depression was evaluated by the Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HAMD). Motor function was evaluated by the third part of the Unified Parkinson's Disease Rating Scale (UPDRS-III).ResultsCompared with the preoperative and the medication control group, the UPDRS-III scores of the STN–DBS group decreased remarkably within 18 months postoperatively (P ≤ 0.001), and the SDS scores decreased notably within 6 months postoperatively (P ≤ 0.05), and the HAMD scores decreased notably within 3 months postoperatively (P ≤ 0.05). The UPDRS-III scores were strongly correlated with their SDS scores within 6 months postoperatively (P ≤ 0.05), especially at 5 weeks postoperation (P ≤ 0.001). UPDRS-III scores were also strongly correlated with HAMD scores at 5 weeks postoperation (P ≤ 0.05). The mean value of the bilateral voltages was obviously correlated with SDS and HAMD scores (P ≤ 0.05) within 18 months postoperatively.ConclusionThe improvement in motor symptoms resulting from STN–DBS can improve depression in PD patients, but its long-term effects were unremarkable. Within the treatment range, the higher the mean value of bilateral voltages then the more severe was the depression in PD patients.     

Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: Prevalence,depression, and personality

IntroductionDopaminergic medication administered to ameliorate motor symptoms of Parkinson's disease is associated with impulse control disorders, such as pathological gambling, hypersexuality, compulsive buying, and binge eating. Studies indicate a prevalence of impulse control disorders in Parkinson's disease of 6–16%.ObjectiveTo estimate the prevalence of impulsive and compulsive behaviors among Danish patients with Parkinson's disease and to explore the relation of such behavioral disorders to depression and personality.Methods490 patients with Parkinson's disease (303 males), identified through the National Danish Patient Registry, were evaluated with: 1) the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease; 2) the Geriatric Depression Scale; and 3) the NEO-Personality Inventory.Results176 (35.9%) patients reported impulsive and compulsive behaviors sometime during Parkinson's disease (current symptoms in 73, 14.9%). Hereof, 114 (23.3%) reported multiple behavioral symptoms. Patients with behavioral symptoms were significantly younger, were younger at PD onset, had longer disease duration, displayed more motor symptoms, and received higher doses of dopaminergic medication than patients without behavioral symptoms. Furthermore, they reported significantly more depressive symptoms and scored significantly higher on neuroticism and lower on both agreeableness and conscientiousness than patients without behavioral symptoms.ConclusionA history of impulsive and compulsive behaviors are common in Danish patients with Parkinson's disease and have clinical correlates that may allow identification of patients at risk for developing these behaviors.     

Pallidal stimulation in Parkinson's patients with contraindications to subthalamic target: A 3 years follow-up

IntroductionOver a 3-year period, we monitored the efficacy and safety of deep-brain stimulation of the globus pallidus pars interna in patients with advanced Parkinson's disease whose cognitive, psychiatric impairment and/or dopa-resistant axial motor signs made them ineligible for surgery targeting the subthalamic nucleus.MethodsA total of 25 patients were assessed before surgery, 1 year and 3 years after surgery, on the UPDRS and a neuropsychological battery.ResultsWe noted a significant improvement of 65.9% in the Clinical global self-perceived Improvement by Visual Analog Scale and an improvement of 20.6% in the total UPDRS-III motor score at 3 years in the off-dopa condition compared to before surgery. There was an improvement in the treatment's motor complications, as measured by the UPDRS-IV, with a particularly marked reduction of 50% in the Dyskinesia subscore. Cognitive performances remained stable at 1 year but had fallen by the third year. We interpreted this deterioration as due to disease progression.ConclusionBilateral pallidal stimulation in patients with contraindications to subthalamic surgery therefore seems to be effective over the long term in treating motor symptoms, especially dyskinesias, with good neuropsychological safety.     

Asymmetric and Upper Body Parkinsonism in Patients with Idiopathic Normal-Pressure Hydrocephalus

MethodsINPH subjects were selected in consecutive order from a prospectively enrolled INPH registry. Fifty-five INPH patients (37 males) having a positive response to the CSFTT constituted the final sample for analysis. The mean age was 73.7±4.7 years. The pre-tap mean Unified Parkinson''s Disease Rating Scale motor (UPDRS-III) score was 24.5±10.2.ResultsThere was no significant difference between the upper and lower body UPDRS-III scores (p=0.174). The parkinsonian signs were asymmetrical in 32 of 55 patients (58.2%). At baseline, the Timed Up and Go Test and 10-meter walking test scores were positively correlated with the total motor score, global bradykinesia score, global rigidity score, upper body score, lower body score, and postural instability/gait difficulties score of UPDRS-III. After the CSFTT, the total motor score, global bradykinesia score, upper body score, and lower body score of UPDRS-III significantly improved (p<0.01). There was a significant decrease in the number of patients with asymmetric parkinsonism (p<0.05).ConclusionsIn the differential diagnosis of elderly patients presenting with asymmetric and upper body parkinsonism, we need to consider a diagnosis of INPH. The association between gait function and parkinsonism severity suggests the involvement of similar circuits producing gait and parkinsonian symptoms in INPH.     

Efficacy and safety of atypical antipsychotics for psychosis in Parkinson's disease: A systematic review and Bayesian network meta-analysis

IntroductionWe performed a systematic review and Bayesian network meta-analysis to clarify the relative efficacy and safety of pimavanserin compared to atypical antipsychotics for psychosis in Parkinson's disease (PD).MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials, and Japana Centra Revuo Medicina Web were searched for relevant articles until October 31, 2019. Eligible randomized controlled trials were synthesized for efficacy (Brief Psychiatry Rating Scale [BPRS] and Clinical Global Impression Scale [CGI-S]) and safety (Unified Parkinson's Disease Rating Scale part III [UPDRS-III] and dropouts due to adverse events). The mean differences (BPRS, CGI-S, and UPDRS-III) or odds ratios (dropouts due to adverse events) between each active drug and placebo were estimated and summarized as means and 95% credible intervals, respectively.ResultsWe identified 17 relevant trials. Clozapine showed significant efficacy (BPRS, −5.6 [−8.4 to −2.7] and CGI-S, −1.2 [−1.7 to −0.7]), with low impact on motor functions (UPDRS-III, −1.1 [−3.8 to 1.5]), but an increase in dropouts due to adverse events (2.9 [0.9 to 9.6]) as compared to placebo. Pimavanserin also showed significant efficacy (CGI-S, −0.5 [−0.9 to −0.2]) and similar impact on motor functions (UPDRS-III, 0.2 [−1.4 to 1.9]), but a tendency of increase in dropouts due to adverse events (2.2 [0.5 to 12.4]) as compared to placebo.ConclusionsClozapine showed an efficacy with low impact on motor functions that was consistent with previous reports. Although the efficacy of pimavanserin may be inferior to that of clozapine, it had a favorable profile for the treatment of psychosis in PD.     

Parieto-motor functional connectivity is impaired in Parkinson's disease

BackgroundBradykinesia in Parkinson's disease is associated with a difficulty in selecting and executing motor actions, likely due to alterations in the functional connectivity of cortico-cortical circuits.Objective/HypothesisOur aims were to analyse the functional interplay between the posterior parietal cortex and the ipsilateral primary motor area in Parkinson's disease using bifocal transcranial magnetic stimulation, to evaluate its modulation by dopaminergic treatment and its relationship to a simple choice reaction task.MethodsWe studied 12 Parkinson's disease patients with and without dopaminergic treatment and 12 healthy controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area using different conditioning stimulus intensities and interstimulus intervals. Reaction and movement times were studied by a simple choice reaction task.ResultsIn controls, we observed a significant facilitation of motor evoked potential amplitudes at 4 ms interstimulus interval when conditioning stimulus intensity was set to 90% of resting motor threshold. This functional interaction was not observed in Parkinson's disease patients without dopaminergic treatment and was not restored with treatment. Moreover, correlation analyses revealed that Parkinson's disease patients with less impaired parieto-motor interaction were faster in executing reaching movements in a choice reaction time task, suggesting that the functional parieto-motor impairment described here could be related to bradykinesia observed in Parkinson's disease patients.ConclusionsParieto-motor functional connectivity is impaired in Parkinson's disease. The reduced efficacy of this connection could be related to presence of bradykinesia previously observed in Parkinson's disease.     

Survival in Parkinson's disease. Relation with motor and non-motor features

BackgroundSurvival in patients with Parkinson's disease is reduced as compared to the general population. We aimed to identify motor and non-motor features that predict mortality in Parkinson's disease.MethodsA broad range of motor and non-motor features were assessed in a hospital-based cohort of 414 patients with Parkinson's disease, who underwent five annual follow-up examinations including vital status assessment. Multivariable Cox's proportional hazards regression analysis was used to evaluate the association between baseline characteristics and mortality risk. Stepwise regression with backward elimination was carried out to determine the best model to predict mortality in Parkinson's disease.ResultsAfter a mean follow-up period of 4.3 years, 49 (11.8%) patients had died. In the stepwise regression model, predictors of mortality in Parkinson's disease were higher age, male sex, cognitive impairment, higher postural instability gait disorder score, and the presence of psychotic symptoms.ConclusionsHigher age, male sex, cognitive impairment, higher postural instability gait disorder score, and the presence of psychotic symptoms are independent predictors of decreased survival in Parkinson's disease. Mortality in Parkinson's disease thus seems to be affected mainly by non-dopaminergic and non-motor features.     

Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations

ObjectiveTo evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinson's disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field.Materials and MethodsWe report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinson's Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinson's Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for the creation of improvement maps and anatomical evaluation.ResultsMedian UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change, but the subdomain activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29%, respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation.ConclusionsBilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief.     

Motor and non-motor features of Parkinson's disease that predict persistent drug-induced Parkinsonism

BackgroundDrug-induced Parkinsonism is common, causes significant morbidity, and can be clinically indistinguishable from idiopathic Parkinson's disease. Additionally, drug-induced Parkinsonism may, in some cases, represent “unmasking” of incipient Parkinson's disease. Clinical features or tests that distinguish degenerative from pharmacologic Parkinsonism are needed.MethodsWe performed a retrospective case-control study of 97 drug-induced Parkinsonism subjects and 97 age-matched patients with Parkinson's disease. We compared the frequency of subjective motor and non-motor complaints, objective motor findings (Unified Parkinson's Disease Rating Scale Part III) and, where available, objective olfactory tests. We also performed a nested case-control study wherein we compared these same features between drug-induced Parkinsonism patients based on whether or not they recovered after changing the offending agent.ResultsNon-motor symptoms including constipation and sexual dysfunction were more common in Parkinson's disease than in drug-induced Parkinsonism. While total motor scores were similar between groups, Postural Instability-Gait Difficulty scores were also higher in Parkinson's disease. Features that were significantly different or showed a trend towards significance in both comparisons included subjective loss of facial expression, dream-enactment behavior, autonomic complaints and Postural Instability-Gait Difficulty scores. Hyposmia was more common in Parkinson's disease and was strongly predictive of persistent drug-induced Parkinsonism after therapy change (odds ratio 30.3, 95% confidence interval: 1.5–500, p = 0.03).ConclusionsA constellation of motor and non-motor features may differentiate unmasked Parkinson's disease from drug-induced Parkinsonism. In particular, olfactory testing may offer a simple and inexpensive method to help predict outcomes in drug-induced Parkinsonism and, potentially, identify a cohort of pre-motor Parkinson's disease.     

Prediction of motor Unified Parkinson's Disease Rating Scale scores in patients with Parkinson’s disease using surface electromyography

ObjectiveParkinson's disease (PD) is a chronic neurodegenerative disorder with increasing prevalence in the elderly. Especially patients with advanced PD often require complex medication regimens due to fluctuations, that is abrupt transitions from ON to OFF or vice versa. Current gold standard to quantify PD-patients’ motor symptoms is the assessment of the Unified Parkinson's Disease Rating Scale (UPDRS), which, however, is cumbersome and may depend upon investigators. This work aimed at developing a mobile, objective and unobtrusive measurement of motor symptoms in PD.MethodsData from 45 PD-patients was recorded using surface electromyography (sEMG) electrodes attached to a wristband. The motor paradigm consisted of a tapping task performed with and without dopaminergic medication. Our aim was to predict UPDRS scores from the sEMG characteristics with distinct regression models and machine learning techniques.ResultsA random forest regression model outnumbered other regression models resulting in a correlation of 0.739 between true and predicted UPDRS values.ConclusionsPD-patients’ motor affection can be extrapolated from sEMG data during a simple tapping task. In the future, such records could help determine the need for medication changes in telemedicine applications.SignificanceOur findings support the utility of wearables to detect Parkinson's symptoms and could help in developing tailored therapies in the future.     

High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex relieves musculoskeletal pain in patients with Parkinson's disease: A randomized controlled trial

BackgroundPain is common in Parkinson's disease, and there is no effective treatment. We conducted a clinical trial to determine whether high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex alleviates musculoskeletal pain in patients with Parkinson's disease.MethodsIn this single-center and double-blind trial, 52 patients with Parkinson's disease and musculoskeletal pain were randomly allocated to 26-member groups receiving 5 sessions of either 20-Hz repetitive transcranial magnetic stimulation or sham stimulation over the primary motor cortex. The participants underwent assessments in the “ON” medication state at baseline, after the fifth session, and at 2- and 4-week follow-up timepoints. The primary outcomes were pain scores on a numeric rating scale. The secondary outcomes were scores on clinical scales assessing motor symptoms, depression, anxiety, autonomic symptoms, sleep quality, and the overall severity of Parkinson's disease.ResultsAnalyses revealed significant group × time interactions for numeric rating scale pain scores (p < 0.001), motor symptom scores (p < 0.001), depression scores (p = 0.009), anxiety scores (p = 0.013), and overall disease severity scores (p < 0.001). Post hoc analyses confirmed that the repetitive transcranial magnetic stimulation group, but not the sham stimulation group, exhibited significant improvements in numeric rating scale pain scores, motor symptom scores, depression scores, anxiety scores, and overall disease severity scores.ConclusionHigh-frequency repetitive transcranial magnetic stimulation over the primary motor cortex may be an effective adjunct therapy for alleviating musculoskeletal pain in patients with Parkinson's disease.     

Reaction Times and Visuospatial Processing in Parkinson's Disease

Abstract

Three motor reaction time tasks which differed in visuospatial complexity but not in motor demands were completed by a group of Parkinson's disease patients and a group of matched control subjects. Response initiation times increased with visuospatial difficulty, whereas movement times remained within a similar range. The two groups differed in response initiation and movement execution times across all reaction time conditions. However, there was no disproportionate increase in response initiation times between an initial nonspatial condition and more complex visuospatial conditions in Parkinson disease patients, and the patients did not make more errors than control subjects. The results do not give support to the hypothesis of a generalised visuospatial deficit in Parkinson's disease.     

Closed-loop programming using external responses for deep brain stimulation in Parkinson's disease

IntroductionDeep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD). Clinicians face various challenges in adjusting stimulation parameters and configurations in clinical DBS settings owing to inexperience, time constraints, and recent advances in DBS technology that have expanded the number of possible contact configurations. We aimed to assess the efficacy of a closed-loop algorithm (CLA) for the DBS-programming method using external motion sensor-based motor assessments in patients with PD.MethodsIn this randomized, double-blind, crossover study, we enrolled 12 patients who underwent eight-ring-contact DBS lead implantations bilaterally in the subthalamic nucleus. The DBS settings of the participants were programmed using a standard of care (SOC) and CLA method. The clinical effects of both programming methods were assessed in a randomized crossover fashion. The outcomes were evaluated using the Unified Parkinson's Disease Scale part III (UPDRS-III) and sensor-based scores for baseline (medication-off/stimulation-off) and both programming methods. The number of programming steps required for each programming method was also recorded.ResultsThe UPDRS-III scores and sensor-based scores were significantly improved by SOC and CLA settings compared to the baseline. No statistical difference was observed between SOC and CLA. The programming steps were significantly reduced in the CLA settings compared to those in the SOC. No serious adverse events were observed.ConclusionCLA can optimize DBS settings prospectively with similar therapeutic benefits as that of the SOC and reduce the number of programming steps. Automated optimization of DBS settings would reduce the burden of programming for both clinicians and patients.     

Small intestinal bacterial overgrowth in Parkinson's disease

BackgroundRecent studies reported a high prevalence of small intestinal bacterial overgrowth (SIBO) in Parkinson's disease (PD), and a possible association with gastrointestinal symptoms and worse motor function. We aimed to study the prevalence and the potential impact of SIBO on gastrointestinal symptoms, motor function, and quality of life in a large cohort of PD patients.Methods103 Consecutive PD patients were assessed using the lactulose-hydrogen breath test; questionnaires of gastrointestinal symptoms and quality of life (PDQ-39); the Unified PD Rating Scale (UPDRS) including “on”-medication Part III (motor severity) score; and objective and quantitative measures of bradykinesia (Purdue Pegboard and timed test of gait). Patients and evaluating investigators were blind to SIBO status.Results25.3% of PD patients were SIBO-positive. SIBO-positive patients had a shorter mean duration of PD (5.2 ± 4.1 vs. 8.1 ± 5.5 years, P = 0.007). After adjusting for disease duration, SIBO was significantly associated with lower constipation and tenesmus severity scores, but worse scores across a range of “on”-medication motor assessments (accounting for 4.2–9.0% of the variance in motor scores). There was no association between SIBO and motor fluctuations or PDQ-39 Summary Index scores.ConclusionsThis is the largest study to date on SIBO in PD. SIBO was detected in one quarter of patients, including patients recently diagnosed with the disease. SIBO was not associated with worse gastrointestinal symptoms, but independently predicted worse motor function. Properly designed treatment trials are needed to confirm a causal link between SIBO and worse motor function in PD.     

Medication errors in Parkinson's disease inpatients in the Basque Country

IntroductionParkinson's disease (PD) medication errors, including both missing dopaminergic drug doses and antidopaminergic usage, have been suggested as risk factors for prolonged hospital stays. The objective of this study was to evaluate the prevalence of such errors in PD patients admitted to public acute-care hospitals in the Basque Country over a two year period and their association with clinically relevant adverse health outcomes, such as length of hospital stay and mortality.MethodsAll PD patients admitted to any of the 11 public acute-care hospitals in the Basque Country in 2011–2012 were included. Medication errors involved incorrect timing or the complete omission of administration for dopaminergic drugs, and the administration of centrally acting antidopaminergics. A logistic regression and a competing risk analysis were applied to verify whether those errors affected intrahospital mortality and length of stay.ResultsThe study included 1628 patients admitted 2546 times. Medication errors, affecting almost one third of admissions and half of patients, were associated with higher mortality: inappropriately omitted dopaminergic drug doses OR = 1.92 CI 95% (1.34–2.76); inappropriate antiemetic administration OR = 2.15 CI 95% (1.36–3.39); and inappropriate antipsychotic administration OR = 1.91 CI 95% (1.33–1.73). Inappropriately omitted doses and both inappropriate antipsychotic and antiemetic administration were associated with a significant 4-day increase in median hospital stay.ConclusionMedication errors (missing dopaminergic drug doses and centrally acting antidopaminergic use) are not only associated with increased length of hospital stays in PD patients, but also with a higher mortality rate.     

Cortical and motor responses to acute forced exercise in Parkinson's disease

IntroductionStudies in animal models of Parkinson's disease (PD) have suggested that the rate of exercise performance is important in treatment efficacy and neuroprotection. In humans with PD, lower-extremity forced-exercise (FE) produced global improvements in motor symptoms based on clinical ratings and biomechanical measures of upper extremity function.MethodsfMRI was used to compare the underlying changes in brain activity in PD patients following the administration of anti-parkinsonian medication and following a session of FE.ResultsNine individuals with PD completed fMRI scans under each condition: off anti-PD medication, on anti-PD medication, and off medication + FE. Unified Parkinson's Disease Rating Motor Scale scores improved by 50% in the FE condition compared to the off-medication condition. The pattern of fMRI activation after FE was similar to that seen with anti-PD medication. Direct comparison of the fMRI activation patterns showed high correlation between FE and anti-PD medication.ConclusionThese findings suggest that medication and FE likely utilize the same pathways to produce symptomatic relief in individuals with PD.     

Factors related to extended hospital stays following deep brain stimulation for Parkinson's disease

ObjectivePatients with Parkinson's disease (PD) are typically discharged from the hospital the day following deep brain stimulation (DBS) surgery; however, factors extending hospital stay are largely unknown. This study examined potential factors that might have corresponded to increased post-operative stays following unilateral DBS surgery.MethodsA retrospective review was performed on 115 unilateral PD DBS patients. Age, gender, number of microelectrode passes, duration and severity of illness, and pre-operative neuropsychological scores were considered as possible contributors to length of stay.ResultsMost patients (79%) had a hospital stay of one day following surgery. The most frequent reasons for delayed discharge (>1 day) included mental status change (N = 6) and hemorrhage (N = 5). Those with delayed discharge had significantly lower pre-surgical cognitive screening scores (Mini-Mental State Evaluation; MMSE), higher pre-surgical “on” medication motor score, and more microelectrode passes than those with immediate discharge. In correlation analyses, increasing length of hospital stay was significantly associated with more microelectrode passes, higher pre-surgical “on” medication motor scores, and decreasing MMSE scores. When the significant variables from the preliminary analyses were entered into a Poisson regression model, a greater number of microelectrode passes as well as lower MMSE scores remained significant predictors of increased length of stay.ConclusionsThe number of microelectrode passes utilized for DBS surgery as well as a patient's general cognitive status may be important factors related to extended hospital stay. UPDRS “on” medication motor score may also provide some predictive power for immediate post-operative morbidity in unilateral DBS patients.     

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD.ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD.MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing.ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD.ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.     

Restless legs syndrome in Korean patients with drug-naïve Parkinson's disease: A nation-wide study

BackgroundRestless legs syndrome is a common neurologic disorder, and there is increasing evidence for a dopaminergic link between Parkinson's disease and restless legs syndrome. However, most previous studies did not take into account the effects of dopaminergic medication. We conducted a nation-wide, cross-sectional study to determine the prevalence and clinical characteristics of restless legs syndrome in Korean drug-naïve Parkinson's disease patients.MethodsOne hundred and fifty-one drug-naïve patients with Parkinson's disease were enrolled from 18 centers in South Korea over the course of one year. Clinical profiles of parkinsonism, restless legs syndrome, psychiatric symptoms, and laboratory data were collected. The findings of subjects with and without restless legs syndrome were compared.ResultsThe prevalence of restless legs syndrome in drug-naïve patients with Parkinson's disease was 16.5%. Subjects with restless legs syndrome had a higher mean Hoehn and Yahr stage and more severe limb parkinsonism, especially tremor. There was, however, no difference in iron metabolism between patients with and without restless legs syndrome. Analysis demonstrated that Beck's depression inventory score was associated with the severity of restless legs syndrome.ConclusionOur study demonstrated an increased prevalence of restless leg syndrome in drug-naïve patients with Parkinson's disease than in the general population. Based on the association between parkinsonism and restless legs syndrome, and the unique characteristics of restless legs syndrome in patients with Parkinson's disease, we suggest that the pathophysiology of restless legs syndrome in Parkinson's disease differs from that in patients without Parkinson's disease.     

Longitudinal changes in movement-related functional MRI activity in Parkinson's disease patients

IntroductionFunctional brain imaging has shown alterations in the basal ganglia, cortex and cerebellum in Parkinson's disease patients. However, few functional imaging studies have tested how these changes evolve over time. Our study aimed to test the longitudinal progression of movement-related functional activity in Parkinson's disease patients.MethodsAt baseline, 48 Parkinson's disease patients and 16 healthy controls underwent structural and functional magnetic resonance imaging during a joystick motor task. Patients had repeated imaging after 18-months (n = 42) and 36-months (n = 32). T-tests compared functional responses between Parkinson's disease patients and controls, and linear mixed effects models examined longitudinal differences within Parkinson's disease. Correlations of motor-activity with bradykinesia, rigidity and tremor were undertaken. All contrasts used whole-brain analyses, thresholded at Z > 3.1 with a cluster-wise P < 0.05.ResultsBaseline activation was significantly greater in patients than controls across contralateral parietal and occipital regions, ipsilateral precentral gyrus and thalamus. Longitudinally, patients showed significant increases in cerebellar activity at successive visits following baseline. Task-related activity also increased in the contralateral motor, parietal and temporal areas at 36 months compared to baseline, however this was reduced when controlling for motor task performance.ConclusionWe have shown that there are changes over time in the blood-activation level dependent response of patients with Parkinson's disease undertaking a simple motor task. These changes are observed primarily in the ipsilateral cerebellum and may be compensatory in nature.