Linguistic Testing During ON/OFF States of Electrical Stimulation in the Associative Portion of the Subthalamic Nucleus

Introduction: Long‐term studies of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson's disease have shown potential cognitive and linguistic side‐effects. In this pilot study, we examined whether direct monopolar stimulation in the ventral, associative STN would result in language effects. Methods: Three subjects participated in two linguistic tasks targeting language generation (language samples) and language composition (syntactic/grammatical structures). All subjects were tested in ON‐/OFF‐associative stimulation settings. The subjects' Unified Parkinson's Disease Rating Scale scores in ON/OFF medication were taken; all subjects' scores indicated that DBS would be beneficial. Testing was conducted in the associative STN at varying stimulation settings of amplitude (80% of previously determined side‐effect threshold), pulse width, and frequency. Results: Linguistic functioning was affected by electrical stimulation to the associative STN. The data reflected a general decline in linguistic functioning in the ON stimulation setting. Conclusion: Our data support previous findings implicating STN stimulation in cognitive‐linguistic effects. A larger patient group with a blinded methodology is warranted.     

More than meets the Eye—Myelinated axons crowd the subthalamic nucleus

High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a successful treatment for patients with advanced Parkinson's disease (PD). Although its exact mechanism of action is unknown, it is currently believed that the beneficial effects of the stimulation are mediated either by alleviating pathological basal ganglia output patterns of activity or by activation of the axons of passage that arise from the cerebral cortex and other sources. In this study, we show that the anatomical composition of the primate STN provides a substrate through which DBS may elicit widespread changes in brain activity via stimulation of fibers of passage. Using quantitative high‐resolution electron microscopy, we found that the primate STN is traversed by numerous myelinated axons, which occupy as much as 45% of its sensorimotor territory and 36% of its associative region. In comparison, myelinated axons occupy only 27% of the surface areas of the sensorimotor and associative regions of the internal segment of the globus pallidus (GPi), another target for therapeutic DBS in PD. We also noted that myelinated axons in the STN, on average, have a larger diameter than those in GPi, which may render them more susceptible to electrical stimulation. Because axons are more excitable than other neuronal elements, our findings support the hypothesis that STN DBS, even when carried out entirely within the confines of the nucleus, mediates some of its effects by activating myelinated axons of passage. © 2013 International Parkinson and Movement Disorder Society     

Deep brain stimulation of the subthalamic nucleus improves sense of well‐being in parkinson's disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of Parkinson's disease. Although a range of psychiatric and behavioral problems have been documented following deep brain stimulation, the short‐term effects of subthalamic nucleus stimulation on patients' mood have only been investigated in a few studies. Our aim was to compare self‐reported mood in Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON versus OFF. Twenty‐three Parkinson's patients with bilateral deep brain stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients completed a mood visual analogue scale twice. Operated patients were tested with deep brain stimulation of the subthalamic nucleus both ON and OFF. All were assessed on medication. The operated Parkinson's group reported feeling significantly better coordinated, stronger, and more contented with deep brain stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a positive direction when deep brain stimulation of the subthalamic nucleus was ON. When changes in motor scores were taken into account, the operated patients still reported feeling better‐coordinated, but also less gregarious with stimulation ON. Unoperated Parkinson's patients showed no differences on any of these measures between their 2 ratings. Short‐term changes in deep brain stimulation of the subthalamic nucleus have a small and mostly positive effect on mood, which may be partly related to improvements in motor symptoms. The implications for day‐to‐day management of patients with deep brain stimulation of the subthalamic nucleus are discussed. © 2012 Movement Disorder Society     

Weight variation before and after surgery in Parkinson's disease: A noradrenergic modulation?

Changes in the nutritional profile of patients with Parkinson's disease have been reported before and after deep brain stimulation surgery. The major determinants of the weight variation in Parkinson's disease are not yet understood, and the mechanism seems complex. Based on the influence of the sympathetic nervous system in metabolic syndrome obesity, the intent of the present review is to consider the role of noradrenergic modulation on weight variations in Parkinson's disease. In this review the authors raise the following hypothesis: weight variation in Parkinson's disease before and after deep brain stimulation of the subthalamic nucleus could be influenced by noradrenergic interaction between the locus coeruleus, subthalamic nucleus, and hypothalamic nucleus. © 2012 Movement Disorder Society     

Effect of Subthalamic Nucleus Stimulation on Severe Striatal Hand Deformity in Parkinson's Disease: A Case Report

Striatal hand is a deformity encountered in Parkinson's disease and other parkinsonisms. It is characterized by extension that occurs at all the interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar deviation. It can be differentiated from levodopa‐induced dystonia and primary dystonia, since the deformity exists continuously even during sleep. We experienced a case of Parkinson's disease with severe striatal hand deformity which was successfully treated by deep brain stimulation of the subthalamic nucleus (STN‐DBS). Although the precise mechanism remains unclear, rigidity is assumed to contribute to the limb deformities. Based on our experience, it seems possible therefore that the effect of STN‐DBS on the hand deformity was a secondary effect on muscular rigidity. STN‐DBS is assumed to represent a useful treatment option for striatal hand deformity.     

Cortical network organization reflects clinical response to subthalamic nucleus deep brain stimulation in Parkinson's disease

The degree of response to subthalamic nucleus deep brain stimulation (STN‐DBS) is individual and hardly predictable. We hypothesized that DBS‐related changes in cortical network organization are related to the clinical effect. Network analysis based on graph theory was used to evaluate the high‐density electroencephalography (HDEEG) recorded during a visual three‐stimuli paradigm in 32 Parkinson''s disease (PD) patients treated by STN‐DBS in stimulation “off” and “on” states. Preprocessed scalp data were reconstructed into the source space and correlated to the behavioral parameters. In the majority of patients (n = 26), STN‐DBS did not lead to changes in global network organization in large‐scale brain networks. In a subgroup of suboptimal responders (n = 6), identified according to reaction times (RT) and clinical parameters (lower Unified Parkinson''s Disease Rating Scale [UPDRS] score improvement after DBS and worse performance in memory tests), decreased global connectivity in the 1–8 Hz frequency range and regional node strength in frontal areas were detected. The important role of the supplementary motor area for the optimal DBS response was demonstrated by the increased node strength and eigenvector centrality in good responders. This response was missing in the suboptimal responders. Cortical topologic architecture is modified by the response to STN‐DBS leading to a dysfunction of the large‐scale networks in suboptimal responders.     

Low frequency stimulation of the nucleus tegmenti pedunculopontini increases cortical metabolism in Parkinsonian patients

Background and purpose: To evaluate the effects of 25‐Hz deep brain stimulation of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity. Methods: Six patients with Parkinson’s disease (PD) who had bilateral stereotactic implantation of PPTg at least 12 months prior to evaluation were included in our study. All underwent, in separate sessions, 18‐FDG‐PET in core assessment programme for intra‐cerebral transplantation as well as motor evaluation [Unified Parkinson’s disease rating scale (UPDRS) – section III] and a battery of cognitive testing. Results: PPTg‐ON (low bipolar contacts, 25 Hz) promoted a significant increase of glucose utilization in bilateral prefrontal areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito‐frontal cortex (BA47), anterior cingulate (BA 25–32), superior frontal gyrus (BA 10) and supramarginal gyrus (BA40); a significant increase of uptake and consumption of FDG also occurred in the left ventral striatum, left subgyral (BA 46), right insula (BA 13) and right superior temporal gyrus (BA 22). PPTg‐ON was associated with a significant decrease of glucose utilization in the left cerebellar anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same patients, PPTg‐ON improved delayed recall (P < 0.05) and executive functions whilst the UPDRS revealed a modest (−21%) and variable treatment effect. Conclusions: Low frequency stimulation of PPTg, a sub‐region of the pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar profile of cognitive improvement associated with a significant increase in FDG consumption in both prefrontal areas and mono‐lateral ventral striatum. These data are consistent with multiple limbic and/or associative domains modulated by PPTg stimulation in our patients with PD.     

Comparison of weight gain and energy intake after subthalamic versus pallidal stimulation in Parkinson's disease

To compare body mass index (BMI) and daily energy intake (DEI) after subthalamic versus pallidal deep brain stimulation (DBS). Weight gain following DBS in Parkinson's disease patients remains largely unexplained and no comparison of subthalamic and pallidal (GPi) stimulation has yet been performed. BMI and DEI, dopaminergic drug administration and motor scores were recorded in 46 patients with PD before STN (n = 32) or GPi (n = 14) DBS and 3 and 6 months after. At M6, BMI had increased by an average of 8.4% in the STN group and 3.2% in the GPi group. BMI increased in 28 STN and 9 GPi patients. This increase was significantly higher in the STN group (P < 0.048) and the difference remained significant after adjustment for reduced dopaminergic medication; 28.6% of GPi patients were overweight at 6 months (14.3% preoperatively) versus 37.5% of STN patients (21.9% preoperatively). Changes in BMI were negatively correlated with changes in dyskinesia in the GPi–DBS group. Food intake did not change in the two groups, either quantitatively or qualitatively. Frequent weight gain, inadequately explained by motor improvement or reduced dopaminergic drug dosage, occurred in subthalamic DBS patients. The difference between groups suggests additional factors in the STN group, such as homeostatic control center involvement. © 2009 Movement Disorder Society     

High‐frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease

Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico‐basal ganglia regions of partially bilateral DA‐ lesioned rats. We recorded neural activity with a multiple‐channel single‐unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6‐OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6‐OHDA lesioned rats, and restored operational behavior‐related neural responses in cortico‐basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion‐induced impairment of RT performance is associated with changes in neural activity in the cortico‐basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long‐lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico‐basal ganglia circuits. © 2009 Wiley‐Liss, Inc.     

脑深部电刺激对帕金森病患者基底节环路的影响及其作用机制

目的研究双侧丘脑底核(STN)慢性电刺激术(DBS)对晚期帕金森病(PD)患者静止期脑局部糖代谢的影响,并探讨DBS的作用机制.方法对7例进行双侧STNDBS的晚期PD患者,在术前和术后1个月电刺激条件下,分别进行18F-脱氧葡萄糖(FDG)/PET检查和UPDRS评分,并通过SPM99统计学软件进行数据分析,研究双侧STNDBS对PD患者脑内代谢的影响.结果双侧STN DBS使PD患者临床症状明显改善,同时脑局部糖代谢也发生了明显变化双侧豆状核、脑干(中脑、脑桥)、双侧顶枕部、运动前区(BA6)及扣带回的脑代谢增加;前额叶底部、海马的脑代谢减少(P＜0.05).结论双侧STN DBS可能通过兴奋STN轴突的方式,使轴突投射区域的基底节上行和下行通路代谢改善,并增加相应的额叶高级运动中枢的代谢,使PD患者临床症状改善.     

Bilateral subthalamic nucleus deep brain stimulation improves certain aspects of postural control in Parkinson's disease, whereas medication does not.

Postural control requires precise integration of sensory inputs and motor output, but clinical assessments of postural control do not differentiate between these. Previously, we found that this differentiation is important in Parkinson's disease (PD) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability. In this study, we address several questions that emerged from that work in 28 different patients with PD off and on medication, before and after bilateral subthalamic nucleus deep brain stimulation (B‐STN DBS): (1) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory‐deprived conditions? (2) Are more specific measures of motor aspects of postural control using dynamic posturography (postural movement velocity [MV] and reaction time [RT]) abnormal in PD as seen clinically using the Postural Instability and Gait Disorder score of the Unified Parkinson's Disease Rating Scale? (3) What is the effect of B‐STN DBS versus medication on sensory versus motor aspects of postural instability in PD? The results included (1) substantially more patients (39%) versus controls (5%) exhibited postural instability in conditions of limited sensory feedback; (2) postural MV and postural RT were abnormal off medication preoperatively (N_subset = 23; P < 0.001 for both); (3) B‐STN DBS improved abnormal sensory aspects of postural instability (P < 0.05) and postural MV (P = 0.005), whereas medication did not. Neither B‐STN DBS nor medication improved postural RT. For the group as a whole, STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control (P = 0.003). © 2006 Movement Disorder Society     

BDNF provides many routes toward STN DBS‐mediated disease modification

The concept that subthalamic nucleus deep brain stimulation (STN DBS) may be disease modifying in Parkinson's disease (PD) is controversial. Several clinical trials that enrolled subjects with late‐stage PD have come to disparate conclusions on this matter. In contrast, some clinical studies in early‐ to midstage subjects have suggested a disease‐modifying effect. Dopaminergic innervation of the putamen is essentially absent in PD subjects within 4 years after diagnosis, indicating that any neuroprotective therapy, including STN DBS, will require intervention within the immediate postdiagnosis interval. Preclinical prevention and early intervention paradigms support a neuroprotective effect of STN DBS on the nigrostriatal system via increased brain‐derived neurotrophic factor (BDNF). STN DBS‐induced increases in BDNF provide a multitude of mechanisms capable of ameliorating dysfunction and degeneration in the parkinsonian brain. A biomarker for measuring brain‐derived neurotrophic factor‐trkB signaling, though, is not available for clinical research. If a prospective clinical trial were to examine whether STN DBS is disease modifying, we contend the strongest rationale is not dependent on a preclinical neuroprotective effect per se, but on the myriad potential mechanisms whereby STN DBS‐elicited brain‐derived neurotrophic factor‐trkB signaling could provide disease modification. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease

Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS‐exacerbated dysarthria. We use the unilateral, 6‐hydroxydopamine (6‐OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism‐associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism‐associated changes in each of these metrics, the subthalamic stimulated 6‐OHDA rat is a good model of DBS‐induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. © 2015 Wiley Periodicals, Inc.     

Changes in Glucose Metabolism in Cerebral Cortex and Cerebellum Correlate With Tremor and Rigidity Control by Subthalamic Nucleus Stimulation in Parkinson's Disease: A Positron Emission Tomography Study

Objective. Employing [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess the correlation between the effect of deep brain stimulation (DBS) on the subthalamic nucleus (STN) and the regional cerebral metabolic rate of glucose (rCMRGlc) in advanced Parkinson's disease patients (N = 8). Materials and Methods. On the basis of patients’ diary records, we performed FDG‐PET during the off‐period of motor activity with on‐ or off‐stimulation by STN‐DBS on separate days and analyzed the correlation between changes in motor symptoms and alterations in the rCMRGlc. Result. When FDG‐PET was performed, the motor score on the unified Parkinson's disease rating scale (UPDRS) was 64% lower with on‐stimulation than with off‐stimulation (p < 0.001, Wilcoxon single‐rank test). STN‐DBS increased the rCMRGlc in the posterior part of the right middle frontal gyrus, which corresponded to the premotor area, and the right anterior lobe of the cerebellum (p < 0.005, paired t‐test). No region exhibited a decrease in rCMRGlc. Among the items of the UPDRS motor score, the changes in resting tremor and rigidity of the left extremities showed a significant correlation with the changes in rCMRGlc observed in the right premotor area (p < 0.02 and p < 0.05, respectively, Spearman's rank correlation). Conclusions. STN‐DBS either activates the premotor area or normalizes the deactivation of the premotor area. These FDG‐PET findings obtained are consistent with the idea that STN‐DBS modifies the activities of neural circuits involved in motor control.     

Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson's disease: A [15O] H2O PET study

Patients with advanced Parkinson's disease (PD) develop disabling axial symptoms, including gait disturbances, freezing and postural instability poorly responsive to levodopa replacement therapy. The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement sleep]. Recent reports suggested that PPN modulation with deep brain stimulation (DBS) may be beneficial in the treatment of axial symptoms. However, the mechanisms underlying these effects are still unknown. We used [¹⁵O] H₂O PET to investigate regional cerebral blood flow in three patients with advanced PD who underwent a new experimental surgical procedure with implantation of unilateral PPN‐DBS. Patients were studied Off‐medication with stimulator Off and On, both at rest and during a self‐paced alternating motor task of the lower limbs. We used SPM2 for imaging data analysis, threshold P < 0.05 corrected at the cluster level. Stimulation induced significant regional cerebral blood flow increment in subcortical regions such as the thalamus (P < 0.006), cerebellum (P < 0.001), and midbrain region (P < 0.001) as well as different cortical areas involving medial sensorimotor cortex extending into caudal supplementary motor area (BA 4/6; P < 0.001). PPN‐DBS in advanced PD resulted in blood flow and presumably neuronal activity changes in subcortical and cortical areas involved in balance and motor control, including the mesencephalic locomotor region (e.g. PPN) and closely interconnected structures within the cerebello‐(rubro)‐thalamo‐cortical circuit. Whether these findings are associated with the DBS‐PPN clinical effect remains to be proven. However, they suggest that PPN modulation may induce functional changes in neural networks associated with the control of lower limb movements. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Long‐term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson's disease

We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN‐DBS) or internal pallidum (GPi‐DBS) on health‐related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP) questionnaires were available for analysis in a subgroup of n = 20/20 patients with GPi‐DBS and n = 45/49 patients with STN‐DBS at baseline, 6 and 36 months. The SIP provides a physical dimension and a psychosocial dimension sum score and 12 category scores: Alertness/Intellectual Behavior (AIB), Ambulation (A), Body Care and Movement (BCM), Communication (C), Eating (E), Emotional Behavior (EB), Home Management (HM), Mobility (M), Recreation and Pastimes (RP), Sleep and Rest (SR), Social Interaction (SI), and Work (W). Motor functioning was assessed by means of the Unified Parkinson's Disease Rating Scale and diaries. At 6 months significant improvements in off‐period motor symptoms and activities of daily living were paralleled by significant reductions in the total, physical, and psychosocial SIP score in both treatment groups. At 3 years, sustained improvements were observed in the physical dimension score, BCM, E, M, RP after STN‐DBS and M, SI after GPi‐DBS. All other SIP subscores approached baseline values, but were still the same or better (except C) whereas motor functioning remained stable after 36 months. STN‐DBS and GPi‐DBS led to significant early improvements in HrQoL. Despite sustained motor improvements many of these initial benefits were lost after 3 years. This may reflect either progression of the disease or adaptive changes in the subjective perception of health‐related wellbeing over time. © 2009 Movement Disorder Society     

Conflict-dependent dynamic of subthalamic nucleus oscillations during moral decisions

Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the neural mechanisms of judgement and decision-making, all these works focused on the cerebral cortex, without investigating the role of subcortical structures such as the basal ganglia. Besides being an effective therapeutic tool, deep brain stimulation (DBS) allows local field potential (LFP) recordings through the stimulation electrodes thus providing a physiological “window” on human subcortical structures. In this study we assessed whether subthalamic nucleus LFP oscillations are modulated by processing of moral conflictual, moral nonconflictual, and neutral statements. To do so, in 16 patients with Parkinson's disease (8 men) bilaterally implanted with subthalamic nucleus (STN) electrodes for DBS, we recorded STN LFPs 4 days after surgery during a moral decision task. During the task, recordings from the STN showed changes in LFP oscillations. Whereas the 14–30 Hz band (beta) changed during the movement executed to perform the task, the 5–13 Hz band (low-frequency) changed when subjects evaluated the content of statements. Low-frequency band power increased significantly more during conflictual than during nonconflictual or neutral sentences. We conclude that STN responds specifically to conflictual moral stimuli, and could be involved in conflictual decisions of all kinds, not only those for moral judgment. LFP oscillations provide novel direct evidence that the neural processing of conflictual decision-making spreads beyond the cortex to the basal ganglia and encompasses a specific subcortical conflict-dependent component.     

Influence of deep brain stimulation and levodopa on sensory signs in Parkinson's disease

To examine the effects of levodopa (L ‐dopa) and deep brain stimulation of the subthalamic nucleus (STN‐DBS) on sensory symptoms and signs in Parkinson's disease (PD). Seventeen patients with PD were included. (1) Presence of sensory symptoms and (2) effects of L ‐dopa and STN‐DBS on sensory symptoms and signs [assessed by quantitative sensory testing (QST)] were examined 6 months after starting STN‐DBS. In addition, in 12 of these patients, presence of sensory symptoms prior and post STN‐DBS was compared. Pain was most frequently nociceptive. In about 30–40%, pain and sensory symptoms were associated with PD motor symptoms. In most of these cases, pain responded to L ‐dopa. Intensity of pain was reduced post STN‐DBS compared to pre STN‐DBS. L ‐Dopa had no influence on detection thresholds, whereas STN‐DBS improved thermal detection thresholds. However, thermal and mechanical pain thresholds were uninfluenced by L ‐dopa or STN‐DBS. Although some patients reported an improvement of pain with STN‐DBS or L ‐dopa, objectively pain sensitivity as assessed by QST was not altered by STN‐DBS or L ‐dopa suggesting that there is no evidence for a direct modulation of central pain processing by L ‐dopa or STN‐DBS. © 2010 Movement Disorder Society     

MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease

Objective: To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. Results: One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. Conclusions: This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.     

Rapid response of parkinsonian tremor to STN‐DBS changes: Direct modulation of oscillatory basal ganglia activity?

Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor and other cardinal symptoms in Parkinson's disease (PD), the precise mechanisms of action of DBS are still unclear. We analyzed the time course of resting tremor amplitude and frequency during discontinuation and subsequent reinitiation of STN‐DBS in nine PD patients, using a computerized three‐dimensional motion analysis combined with surface electromyography. Following discontinuation of STN‐DBS, resting tremor amplitude rapidly increased, reaching maximum amplitude after 2 min (mean ± 95%CI: 34.3 ± 13.8 mm; P < 0.01), subsequently stabilizing at a medium level. Reinitiation of stimulation after 30 min resulted in rapid, nearly complete suppression of tremor activity within 1 min (1.4 ± 1.3 mm; P < 0.01) and, furthermore, increased tremor frequency within a few seconds in seven of nine patients. These findings support the hypothesis that STN‐DBS acts by direct interference with the neurotransmission of basal ganglia networks involved in tremor. © 2009 Movement Disorder Society