Structural and Functional Changes in Mild Cognitive Impairment in Parkinson's Disease.

Background and Objectives: The pathophysiology of mild cognitive impairment in Parkinson's disease (PD-MCI) is still not fully elucidated. It has been shown in a few studies in the literature that volume loss in the occipital, parietal and frontal cortices and atrophy in the hippocampus of PD-MCI patients can occur in the early stages of PD. The aim of this study was to evaluate the relationship between gray and white matter volumes and different neuropsychological tests and volumetric magnetic resonance imaging parameters in patients with mild cognitive impairment in Parkinson's disease (PD-MCI). Materials and Methods: Twenty-six PD-MCI and twenty-six healthy elderly (HC) were included in this study. Results: We found that Mini Mental State Examination, Trail Making Test Part A, Clock Drawing Test, Benton Line Judgment Orientation Test and pentagon figure-copying scores were impaired in PD-MCI patients due to the decrease in brain volumes. Conclusions: Our study revealed that among PD-MCI patients, there was a more noticeable decline in White matter volume (WMV) based on volumetric Magnetic Resonance Imaging (MRI) compared to the localized loss of GMV. We think that these abnormal neuropsychological tests in PD-MCI patients can be used as pretests in the evaluation of the stage of transition to dementia.

The effect of directional social cues on saccadic eye movements in Parkinson's disease.

There is growing interest in how social processes and behaviour might be affected in Parkinson's disease. A task which has been widely used to assess how people orient attention in response to social cues is the spatial cueing task. Socially relevant directional cues, such as a picture of someone gazing or pointing to the left or the right have been shown to cause orienting of visual attention in the cued direction. The basal ganglia may play a role in responding to such directional cues, but no studies to date have examined whether similar social cueing effects are seen in people with Parkinson's disease. In this study, patients and healthy controls completed a prosaccade (Experiment 1) and an antisaccade task (Experiment 2) in which the target was preceded by arrow, eye gaze or pointing finger cues. Patients showed increased errors and response times for antisaccades but not prosaccades. Healthy participants made most anticipatory errors on pointing finger cue trials, but Parkinson's patients were equally affected by arrow, eye gaze and pointing cues. It is concluded that Parkinson's patients have a reduced ability to suppress responding to directional cues, but this effect is not specific to social cues.

Multicenter study of levodopa carbidopa intestinal gel in Parkinson's disease: the Turkish experience

Background/aim: Our purpose was to determine the efficacy of levodopa carbidopa intestinal gel (LCIG) in a series of Turkish patients with Parkinson's disease (PD). Materials and methods: We had telephone calls with 54 patients from 11 neurology centers who were on LCIG treatment, and 44 patients or their caregivers were included in an eight-item survey between September 2015 and June 2016. The reliability and validity of the survey were evaluated with intraclass correlation coefficients for every question separately. Results: Average age of the patients were 63.48 and the duration of PD was 12.79 years. Average LCIG treatment period was 15.63 months. Percentages of the patients who reported they were 'better' after LCIG treatment were as follows: 80% for time spent off, 55% for dyskinesia, 65% for tremor, 85% for gait disorder, 50% for pain, 50% for sleep disorders, 42.5% for depression, 32.5% for incontinence, and 70% for activities of daily living. Cronbach's alpha was 0.795 and the intraclass correlation coefficient was reliable for the items. Conclusion: As detected by a survey performed by telephone calls with good interrater reliability, patients with PD improve with LCIG treatment in many aspects of the disease.

Assessing Olfactory Function in Parkinson's Disease via Entropy Analysis of Chemosensory Event Related Potentials.

The relationship between Parkinson's disease (PD) and olfactory dysfunction has been investigated via psychophysical and electrophysiological assessments. Despite the increasing number of electrophysiological studies focusing on olfactory function, there are still some limitations to observe the chemosensory event-related potentials (CSERP), which are electrophysiological responses of the brain to olfactory and trigeminal stimulations, because of the low sensitivity (low signal-to-noise ratio). Recent studies attempted to establish new techniques to increase the sensitivity for evaluating the CSERP and brain responsiveness. We aimed to inspect CSERP via entropy analysis in assessing chemosensory related brain responses that has been used for the first time. Twelve newly diagnosed and non-medicated PD patients and 12 healthy subjects participated in the study. Psychophysical and electrophysiological evaluation of olfaction were assessed via Sniffin' Sticks Test (SST) and entropy analysis on CSERP in three time windows. The scores of odor threshold, odor identification and total scores of SST were lower (hyposmic) in PD patients compared to healthy subjects. Electrophysiological assessments revealed a significant change in entropy among time windows for olfactory stimulation with phenyl ethyl alcohol and trigeminal stimulation with carbon dioxide (both p < 0.05) in healthy subjects but not in PD patients. Entropy findings indicate that the brain operates in ordered state among healthy subjects in response to olfactory/trigeminal stimuli, whereas the PD patients displayed a chaotic pattern. This pattern in the PD patients suggests the lack of proper smell function. It should be studied if this pattern can be used as a biomarker for PD.

Determinants of 6-minute walk test in people with Parkinson's disease.

BACKGROUND: Most of the previous studies, investigating determinants of 6-minute walk test (6MWT), were conducted on small sample sizes and/or have not explored different aspects such as freezing of gait, physical activity, gender, dual-task cost, and/or have not been able to explain large portion of variation in 6MWT in people with Parkinson's disease. AIMS: This study aimed to investigate the determinants of 6MWT, including aspects that previous studies have not explored. METHODS: In this descriptive cross-sectional study, 6MWT determinants were investigated upon 42 people with Parkinson's disease. After recording participants' demographic data, walking capacity, disease stage, severity of motor symptoms, freezing of gait, balance, physical activity, fear of falling, functional balance, and dual-task cost values were evaluated and grouped into modifiable and unmodifiable variables to investigate possible therapeutic benefits aiming improvement in walking capacity. RESULTS: The mean distance for 6MWT was 401.7 ± 92.7 m. Significant differences between women and men were found for height, walking capacity and speed, fear of falling, and functional balance (p<0.05). Hierarchical regression analysis showed that gender, age, and time since diagnosis significantly explained 52.4% of the variance in 6MWT and disease stage, freezing of gait, dual-task cost, and functional balance added an extra 35.6% to the explained variance. CONCLUSIONS: These results showed that gender, age, disease stage, freezing of gait, dual-task cost, and functional balance values are significant contributors to the variance in 6MWT. Therefore, while planning rehabilitation strategies to improve walking capacity, one should focus on these aspects in people with Parkinson's disease.

The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study.

Cognitive impairment can occur at all stages of Parkinson's disease. Rasagiline is a selective monoamine oxidase type-B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinson's disease. This was a randomized, double-blind, placebo-controlled prospective study. Patients with Parkinson's disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinson's disease dementia. Fifty-five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span-backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit-ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type-B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinson's disease with cognitive impairment.

Is it always necessary to apply botulinum toxin into the lower facial muscles in hemifacial spasm?: a randomized, single-blind, crossover trial.

BACKGROUND: Botulinum toxin (BTX) injections are accepted as safe and efficacious in the treatment of hemifacial spasm (HFS), but it is still debated whether BTX treatment of lower facial muscles should be performed or not. OBJECTIVE: The study aims to evaluate the necessity of BTX administration into lower facial muscles in patients with HFS. METHODS: A randomized, single-blind, crossover, clinical trial was conducted. Twenty-three HFS patients were randomly allocated to two different application methods. The patients were administered BTX type A into both the orbicularis oculi and perioral muscles in the first method and BTX type A into the orbicularis oculi but placebo into the perioral muscles in the second method. Subjects were crossed over to the alternate method when they needed BTX injection with a minimum of 3 months' duration. All the patients underwent both methods with no change in the total dose of BTX. RESULTS: All the patients benefited from BTX treatment regardless of the methods. However, in the patients with severe lower facial muscle involvement, the application of BTX into both orbicularis oculi and lower facial muscles led to better results. CONCLUSION: Our data suggest that BTX application to lower facial muscles might not be necessary in patients with mild lower facial involvement.

Effects of Pilates and Elastic Taping on Balance and Postural Control in Early Stage Parkinson's Disease Patients: A Pilot Randomised Controlled Trial.

INTRODUCTION: The purpose of this study is to investigate the effects of Pilates training and elastic taping on balance and postural control in patients with early stage Parkinson's Disease (PD). METHOD: Patients were randomly divided into Pilates, elastic taping, and control (wait list) groups. Pilates training was performed for 6 weeks, twice a week and 60 minutes per session. In elastic taping group, in addition to Pilates training, elastic taping was applied to the upper back twice a week for 6 weeks with the aim of postural correction. In order to evaluate the postural control before and after the training, Berg Balance Scale, Trunk Impairment Scale, the tests of NeuroCom Balance Master performance test device as Limits of stability (LOS), Sit-to Stand, Walk Across and Tandem Walking Tests were performed. RESULTS: The data of 20 patients (6 male in Pilates group, 2 female and 6 male in elastic taping group, 3 female and 3 male in control group) were analyzed. Reaction times in LOS test decreased significantly and walking speed in Walk Across test increased significantly after 6 weeks in Pilates and elastic taping groups. In elastic taping group, the postural sways of Tandem Walk test were decreased significantly and, the rising index in Sit-to-Stand test increased significantly after 6 weeks (Wilcoxon Test, p<0.05). CONCLUSION: We believe that Pilates is a feasible rehabilitation strategy for PD, and it has a remedial effect on the dynamic balance and postural control for these patients. We also think that elastic taping could be applied for supporting the right posture.

Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease.

In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.

Auditory brain oscillatory responses in drug-naïve patients with Parkinson's disease.

Parkinson's Disease (PD) is a common neurodegenerative disorder affecting the function of dopaminergic cells in basal ganglia. Besides the motor symptoms, tremor, and dysfunction of sensory systems. In the literature, there was limited studies which investigates the basic sensorial processing in PD. Therefore, we aimed to establish the sensorial processing of simple auditory stimulations in naïve PD comparing to healthy controls (HC) via delta, theta, and alpha brain oscillatory responses. 12 naïve PD and 12 HC participated to the study. Brain responses recorded via the 64-channel electroencephalography (EEG) system in an electromagnetically and acoustically isolated room. The auditory stimuli (1500 Hz, 60 dB SPL, 500 ms) were delivered to the subjects via a headphone. The inter-stimulus interval was ranged between 2.5-4.5 s. The peak-to-peak maximum amplitudes were measured in the delta, theta and alpha frequency bands on 11 electrodes (including the frontal, central and parietal areas) for the statistical analysis in which one-way ANOVA test was employed for the comparisons between PD and HC. For the delta oscillatory responses, PD group has bigger amplitudes in frontal, central and parietal areas in comparison with HC. For the theta and alpha oscillatory responses, PD group has bigger amplitudes in parietal areas in comparison with HC. As a result, amplitudes of brain oscillatory responses in PD group were significantly bigger than the HC. In this context, decreased inhibitory mechanisms of cortical auditory processing due to the dysfunction of the dopaminergic activity may lead the increased evoked responses in PD group.

The difference of mild cognitive impairment in Parkinson's disease from amnestic mild cognitive impairment: Deeper power decrement and no phase-locking in visual event-related responses.

Event-related oscillatory responses reflect the cognitive status in many neuropsychiatric conditions including mild cognitive impairment (MCI). In this study, a total of 30 patients with amnestic MCI (aMCI) and 25 patients with MCI of Parkinson's disease (PD-MCI) were compared with 28 aged-, gender-, education-matched healthy control (HC) participants using visual event-related delta, theta, alpha oscillatory responses by methods of event-related spectral perturbation and inter-trial coherence. PD-MCI and aMCI groups commonly share a decreased theta power, but all electrophysiological deviations from the controls were more prominent in PD-MCI than aMCI in all frequency bands. Additionally, decreased phase-locking in all studied frequency bands was encountered only in PD-MCI group, but it was preserved in aMCI. These findings indicate that visual networks in PD-MCI are more severely affected than aMCI. Reduced phase-locking in PD-MCI may possibly relate to dysfunctioning subcortical modulating centers that take a role in the generation of event-related responses.

A Novel and Mosaic WDR45 Nonsense Variant Causes Beta-Propeller Protein-Associated Neurodegeneration Identified Through Whole Exome Sequencing and X chromosome Heterozygosity Analysis.

Beta-propeller protein-associated neurodegeneration (BPAN) is an X-linked rare dominant disorder of autophagy. The role of WDR45 has been implicated in BPAN almost exclusively in females possibly due to male lethality. Characterization of distinctive clinical manifestations and potentially the complex genetic determinants in rare male patients remain crucial for deciphering BPAN and other X-linked dominant diseases. We performed whole exome sequencing (WES) followed by segregation analysis and identified a novel nonsense and mosaic variant in WDR45, namely NM_007075.3:c.873C>G; p.(Tyr291*) in an affected male at the age of 34. His biphasic medical history was compatible with BPAN, which was characterized by delayed psychomotor development, intellectual disability, and progression into dystonia parkinsonism in his twenties. The variant had an apparently mosaic pattern both in whole exome and Sanger sequencing findings. In order to figure out if mosaicism was restricted to this variant or related to a chromosomal level mosaicism, we used our in-house WES data from 129 unrelated individuals to calculate the threshold values of male and female X chromosome heterozygosity (XcHet) in WES data for our pipeline. A background level of heterozygous variants on X chromosome excluding the pseudoautosomal loci is an observed phenomenon in WES analysis and this level has been used as a quality measure. Herein, we suggest utilization of this measure for detection of digital anomalies of the X chromosome in males by potentially observing a higher XcHet value than the threshold value. This approach has revealed a variant level mosaicism in the affected male, which was further supported with cytogenetic analyses.

Technical Case Report of Deep Brain Stimulation: Is it Possible Single Electrode Reach to Both of Subthalamic Nucleus and Ventral Intermediate Nucleus in One Stage?

BACKGROUND: The primary target of this operation is Ventral Intermediate Nucleus (VIM); however VIM - Subthalamic Nucleus (STN) were tried to be reached with one electrode, adjusting the angle well, the coronal section; medial of VIM can partially reach the STN. Using the properties of the electrode; we believe we could act on a wide area. METHODS: An analysis was performed on one patient who underwent VIM Deep Brain Stimulation (DBS) in 3 periods (pre - peri - post-operation). RESULTS: A 53 - year - old woman diagnosed with Parkinson's disease 8 years earlier including symptoms of severe tremor on the right than left underwent bilateral DBS VIM. Obtaining a satisfactory improvement of tremor, the patient did well, and postoperative complications were not observed. The patient was discharged from hospital on postoperative thirty day. CONCLUSIONS: It is certain that more research and experience are needed. However, we believe that the two targets can reach the same point and the second operations for another target can be avoided.We believe that this initiative is advantageous and promising regarding patient and cost.

Demonstration of Early Cognitive Impairment in Parkinson's Disease with Visual P300 Responses.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Cognitive changes in PD are less observable than motor symptoms; thus, research on cognitive processes, which are known to be impaired from the early stages of PD, is minimal. The purpose of this study is to research the brain dynamics of cognitively normal PD patients and healthy elderly controls using event-related potentials (ERPs) and to evaluate their relationships with neuropsychological tests. METHODS: Eighteen cognitively normal PD patients and 18 age-, gender-, and education-matched healthy controls were included in the study. Detailed neuropsychological tests were applied to all participants. Electroencephalography (EEG) was performed according to the international 10-20 system, and a classical visual oddball paradigm was used in the experiments. ERP responses in the 0.5 to 25 Hz frequency range were examined. P300 amplitude and latency values were measured from the F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, and O2 electrode sites. In addition, the correlations between P300 responses and neuropsychological test scores were analyzed. RESULTS: Significant differences were found between the P300 amplitudes of cognitively normal PD patients and healthy elderly controls [F(1,31)=9.265; p=0.005]. P300 amplitudes were significantly lower for PD patients at the F3, FZ, Cz, C4, Pz, and P4 electrode sites than for healthy elderly controls. Moderate correlations were found between Stroop test score and P4 amplitude, digit span forward and C3 and Pz amplitude, and digit span backward and O1 amplitude. CONCLUSION: The major finding of this study was the detection of cognitive changes by electrophysiological methods in PD patients who were indicated to be cognitively normal by neuropsychological tests. These finding suggests that cognitive changes in PD patients, which are not yet reflected in neuropsychological tests, may be detected by electrophysiological methods in earlier stages.

Decrease of Delta Oscillatory Responses in Cognitively Normal Parkinson's Disease.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. This study aims to compare sensory-evoked oscillations (SEOs) and event-related oscillations (EROs) of visual modality in cognitively normal PD patients and healthy controls. Sixteen PD and 16 age-, gender-, and education-matched healthy controls participated in the study. A simple flashlight was used for SEO and a classical visual oddball paradigm was used for target ERO. Oscillatory responses in the delta frequency range (0.5-3.5 Hz) were examined. Significantly lower delta ERO and SEO responses were found in PD patients than healthy controls. Delta ERO responses were decreased at all frontal, central and parietal locations, whereas delta SEO responses were decreased over mid and right central locations in PD. According to the notion that SEO reflects the activity of sensory networks and ERO reflects cognitive networks, these findings indicate that PD patients have impairments in both cognitive and sensory networks of visual modality. Decreased delta ERO responses indicate that the subliminal cognitive changes in PD can be detected by electrophysiological methods. These results demonstrate that brain oscillatory responses have the potential to be studied as a biomarker for visual cognitive and sensory networks in PD.

Comparison of preseptal and pretarsal injections of botulinum toxin in the treatment of blepharospasm and hemifacial spasm.

Although the beneficial effect of subcutaneous injections of botulinum toxin type A (BTX-A) is well known in both blepharospasm and hemifacial spasm, the position of the injection sites around the orbicularis oculi may influence the effectiveness and side effects. Here we report results of preseptal and pretarsal BTX-A injections in 53 patients (25 blepharospasm and 28 hemifacial spasm) in whom we used both injection techniques successively. Pretarsal injections were used in 102 out of 186 treatments in blepharospasm group and in 84 out of 202 treatments in hemifacial spasm group. Pretarsal BTX-A treatment produced significantly higher response rate and longer duration of maximum response in both patient groups. This technique was also associated with a lower frequency of major side effects such asptosis. We concluded that injections of BTX-A into the pretarsal, rather than the preseptal portion of the orbicularis oculiis more effective for treatment of involuntary eyelid closure due to contractions of this muscle.

Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study.

We studied the excitability of the motor cortex in patients with migraine without aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex and recording of the first dorsal interosseous muscle, we measured thresholds, latencies and amplitudes of motor evoked potentials and duration of cortical silent periods in patient groups and in controls (n = 20). No differences were found between groups for threshold, latency and amplitude values. However, the duration of the cortical silent period was longer in CM patients, being significantly different from both controls and MWOA. We suggest that either this difference in cortical excitability may develop during transformation from MWOA to CM or different pathophysiological mechanisms may play a role in these two headache syndromes.

Cortical relay time for long latency reflexes in patients with definite multiple sclerosis.

BACKGROUND: Long latency reflexes (LLR) include afferent sensory, efferent motor and central transcortical pathways. It is supposed that the cortical relay time (CRT) reflects the conduction of central transcortical loop of LLR. Recently, evidence related to the cortical involvement in multiple sclerosis (MS) has been reported in some studies. Our aim was to investigate the CRT alterations in patients with MS. METHODS: Upper extremity motor evoked potentials (MEP), somatosensory evoked potentials (SEP) and LLR were tested in 28 patients with MS and control subjects (n=22). The patients with MS were classified according to the clinical form (relapsing-remitting [R-R] and progressive groups). The MS patients with secondary progressive and primary progressive forms were considered as the "progressive" group. CRT for LLR was calculated by subtracting the peak latency of somatosensory evoked potentials (SEP) and that of motor evoked potentials (MEP) by transcranial magnetic stimulation from the onset latency of the second component of LLR (LLR2) (CRT = LLR2 - [MEP latency + N20 latency]) RESULTS: Cortical relay time was calculated as 7.4 +/- 0.9 ms in control subjects. Cortical relay time was prolonged in patients with MS (11.2 +/- 2.9 ms) (p<0.0001). The latencies of LLR, MEP and SEP were also prolonged in patients with MS. Cortical relay time was not correlated with disease severity and clinical form in contrast to other tests. CONCLUSIONS: Our findings suggested that CRT can be a valuable electrophysiological tool in patients with MS. Involvement of extracortical neural circuits between sensory and motor cortices or cortical involvement due to MS may cause these findings.

Cortical silent period and motor evoked potentials in patients with multiple sclerosis.

In order to determine the importance of central motor conduction time (CMCT) and silent period (SP) in patients with multiple sclerosis (MS), we enrolled this clinical and electrophysiological study. Additionally, we planned to compare the correlation between electrophysiological findings and clinical status. We examined 58 patients with definite MS and 31 controls. Patients were classified as relapsing-remitting (N: 37), secondary progressive (N: 21) groups. Eleven out of 58 patients with MS had no neurological findings (subclinical patients). We evaluated CMCT and the duration of SP. Prolonged CMCT latency was shown in 75.2% of patients. We observed SP abnormalities in 69% of patients. In subclinical patients, SP abnormalities (six of 11) were observed more common than CMCT (two of 11). The duration of SP was extremely prolonged in MS patients with cerebellar dysfunction. When the both electrophysiological parameters are taken into account, the abnormality ratio was determined as 89.7%. Our results indicate that CMCT and SP analysis are complementary tests in evaluating motor pathways of patients with MS. We observed a relationship between cerebellar dysfunction and SP prolongation. It is suggested that, SP can be applied in patients with pure cerebellar dysfunction and it can be a valuable test in subclinical cases with MS.

Low-frequency repetitive transcranial magnetic stimulation for dyskinesia and motor performance in Parkinson's disease.

Dyskinesias are one of the most frequent and disabling complications of the long-term treatment of Parkinson's disease (PD). Although the cause is not completely understood, it appears that an imbalance between excitatory and inhibitory inputs from the basal ganglia to the motor cortex leads to overactivation of motor and premotor areas. Overactivation of the supplementary motor area (SMA) has been observed in neuroimaging studies in dyskinetic PD patients. We investigated the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the SMA on levodopa-induced dyskinesias (LID) and motor performance in PD. We tested whether longer duration (10days) and higher number of total pulses (1800 pulses) would enhance the beneficial effect. Seventeen dyskinetic PD patients were randomly assigned to real rTMS or sham (placebo) rTMS, and 1Hz rTMS or sham rTMS was applied over the SMA for 10 consecutive days. Patients were assessed at baseline and 1day after the last rTMS with a levodopa challenge test, and video recordings were taken. Dyskinesias and motor performance were rated off-line by two blinded raters using video recordings. After 10days of treatment with rTMS, we observed that 1Hz rTMS delivered over the SMA had decreased LID lasting for 24hours without a change in motor performance, whereas sham rTMS induced no significant change in dyskinesia scores. These results support a possible therapeutic effect of low-frequency rTMS in LID. However, in order to suggest rTMS as an effective treatment, long-term observations and further investigations with a larger patient population are essential.