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Background The initial COVID-19 pandemic shutdown led to the canceling of elective surgeries throughout most of the USA and Canada. Objective This survey was carried out on behalf of the Parkinson Study Group (PSG) to understand the impact of the shutdown on deep brain stimulation (DBS) practices in North America. Methods A survey was distributed through RedCap® to the members of the PSG Functional Neurosurgical Working Group. Only one member from each site was asked to respond to the survey. Responses were collected from May 15 to June 6, 2020. Results Twenty-three sites participated; 19 (83%) sites were from the USA and 4 (17%) from Canada. Twenty-one sites were academic medical centers. COVID-19 associated DBS restrictions were in place from 4 to 16 weeks. One-third of sites halted preoperative evaluations, while two-thirds of the sites offered limited preoperative evaluations. Institutional policy was the main contributor for the reported practice changes, with 87% of the sites additionally reporting patient-driven surgical delays secondary to pandemic concerns. Pre-post DBS associated management changes affected preoperative assessments 96%; electrode placement 87%; new implantable pulse generator (IPG) placement 83%; IPG replacement 65%; immediate postoperative DBS programming 74%; and routine DBS programming 91%. Conclusion The COVID-19 pandemic related shutdown resulted in DBS practice changes in almost all North American sites who responded to this large survey. Information learned could inform development of future contingency plans to reduce patient delays in care under similar circumstances.

Background Levodopa‐carbidopa intestinal gel (LCIG) is an established treatment for improving motor and some non‐motor symptoms (NMS) in patients with advanced Parkinson's disease (PD). Prospective long‐term data in routine clinical practice are limited. Objective Assess LCIG effectiveness and safety in patients with advanced PD after 12 months during real‐world routine clinical practice. Methods Duodopa/Duopa in patients with advanced Parkinson's disease—a global observational study evaluating long‐term effectiveness (DUOGLOBE) (NCT02611713) is an ongoing, prospective, multinational, observational study of LCIG‐naïve patients treated as part of routine clinical practice; 3 years of follow‐up are planned. The primary outcome is the change in patient‐reported off time. Other assessments include the Unified Dyskinesia Rating Scale (UDysRS), Non‐Motor Symptoms Scale (NMSS), Parkinson's Disease Sleep scale (PDSS‐2), Epworth Sleepiness Scale (ESS), health‐related quality of life (HR‐QoL), caregiver burden, and serious adverse events (SAEs). Outcomes from baseline to month (M) 12 are presented. Results In this 12‐month follow‐up, patients (N = 195) had baseline characteristics similar to other LCIG studies. Significant improvements (mean change to M12) were observed in off time (−3.9 ± 3.6 hr/day, P

Introduction As Parkinson's disease (PD) progresses, the number/frequency of PD medications tend to increase, which is correlated with decreased patient compliance and suboptimal control of PD symptoms. We investigated efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) daytime monotherapy (with or without nighttime oral levodopa-carbidopa) compared with polytherapy (LCIG with ≥1 adjunctive PD therapy) in advanced PD patients. Methods This post hoc descriptive study compared LCIG stable daytime monotherapy with LCIG stable polytherapy in all six phase 3/3b open-label studies from both US and international sites; because of study design variability, pooling data for comparison was not appropriate. Efficacy assessments included PD diary data (mean change from baseline in “Off” time and “On” time with or without troublesome dyskinesia), mean Unified PD Rating Scale scores (Parts II and III), and 39-item Parkinson's Disease Questionnaire (PDQ-39) summary index. Adverse events were also assessed. Results Overall, LCIG daytime monotherapy and polytherapy demonstrated similar efficacy/safety profiles in advanced PD patients, regardless of treatment duration or population. LCIG monotherapy vs. polytherapy groups experienced similar mean decreases in “Off” time (4.6 vs. 4.1 h/day) and similar increases in “On” time without troublesome dyskinesia (4.6 vs. 4.1 h/day). In most studies, PDQ-39 summary index scores were reduced from baseline by ≥5 points, regardless of patient population or study duration. Adverse events not related to the procedure/device were similar in both groups. Conclusion Our data suggest that, for appropriate patients, LCIG monotherapy can provide a more simplified treatment option with similar efficacy and safety., Highlights • Advanced Parkinson's disease (PD) often requires a large number of medications • Levodopa-carbidopa intestinal gel (LCIG) is administered continuously • LCIG monotherapy vs. polytherapy was assessed in six phase 3/3b studies • LCIG monotherapy and polytherapy had similar efficacy and safety profiles • LCIG monotherapy may provide a more simplified treatment option for advanced PD

In advanced Parkinson's disease (PD), a high pill burden is associated with poor compliance, reduced control of symptoms, and decreased quality of life. We assessed the impact of carbidopa-levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on PD-related pill burden.A retrospective cohort analysis was conducted in the IBM MarketScan and Medicare Supplemental databases. Patients with advanced PD, taking only PD medications, and initiating CLES or DBS between 9 January 2015 and 31 July 2019 were identified. CLES patients were matched to DBS patients in a 1:3 ratio based on a propensity score to balance patient characteristics. Pill burden was measured as a 30-day average number of PD-related pills per day and was captured monthly. Pill-free status was evaluated as the percentage of patients receiving CLES or DBS monotherapy. Descriptive statistics were used to compare pill counts and assess the proportion of patients on monotherapy at 6 and 12 months after initiating CLES or DBS.The cohorts included 34 CLES patients matched to 97 DBS patients. A significant reduction in PD-related pill burden was observed at 6 months after initiation of CLES or DBS (∆CLES: -5.62, p 0.0001; ∆DBS: -1.48, p = 0.0022). PD-related pill burden reduction in CLES patients was significantly greater than in matched DBS patients at 6 months (∆: -4.14, p 0.0001), which was sustained at 12 months after initiation. At 12 months, nearly three times more CLES patients were pill free than DBS patients (29.41% and 10.31%, respectively, p = 0.0123).Device-aided therapies such as CLES and DBS are effective in significantly reducing PD-related pill burden. Patients treated with CLES were more likely to achieve pill-free status than patients receiving DBS.

Background: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated. Objective: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms. Methods: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms. Results: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p

OBJECTIVE To the authors’ knowledge, no data have been reported on dopamine fluctuations on subsecond timescales in humans with alcohol use disorder (AUD). In this study, dopamine release was monitored in 2 patients with and 2 without a history of AUD during a “sure bet or gamble” (SBORG) decision-making task to begin to characterize how subsecond dopamine responses to counterfactual information, related to psychological notions of regret and relief, in AUD may be altered. METHODS Measurements of extracellular dopamine levels were made once every 100 msec using human voltammetric methods. Measurements were made in the caudate during deep brain stimulation electrode implantation surgeries (for treatment of movement disorders) in patients who did (AUD, n = 2) or did not (non-AUD, n = 2) have a history of AUD. Participants performed an SBORG decision-making task in which they made choices between sure bets and 50%-chance monetary gamble outcomes. RESULTS Fast changes were found in dopamine levels that appear to be modulated by “what could have been” and by patients’ AUD status. Positive counterfactual prediction errors (related to relief) differentiated patients with versus without a history of AUD. CONCLUSIONS Dopaminergic encoding of counterfactual information appears to differ between patients with and without AUD. The current study has a major limitation of a limited sample size, but these data provide a rare insight into dopaminergic physiology during real-time decision-making in humans with an addiction disorder. The authors hope future work will expand the sample size and determine the generalizability of the current results.

IntroductionCurrently, sub-second monitoring of neurotransmitter release in humans can only be performed during standard of care invasive procedures like DBS electrode implantation. The procedure requires acute insertion of a research probe and additional time in surgery, which may increase infection risk. We sought to determine the impact of our research procedure, particularly the extended time in surgery, on infection risk.MethodsWe screened 607 DBS electrode implantation procedures performed at Wake Forest Baptist Medical Center between January 2011 through October 2020 using International Classification of Diseases (ICD) codes for infection. During this period, 116 cases included an IRB approved 30-minute research protocol, during the DBS electrode implantation surgery, to monitor sub-second neurotransmitter release. We used Fisher’s Exact test (FET) to determine if there was a significant change in the infection rate following DBS electrode implantation procedures that included, versus those that did not include, the neurotransmitter monitoring research protocol.ResultsWithin 30-days following DBS electrode implantation, infection was observed in 7 (1.43%) out of 491 procedures that did not include the research procedure and 2 (1.72%) of the 116 procedures that did include the research procedure. Total infection rates (i.e., not constrained by 30-day time window) for all non-research cases was 28/491 (5.70%) and only 4/116 (3.45%) for research inclusive cases. Notably, all types of infection observed were typical of those expected for DBS electrode implantation.ConclusionTotal infection rates are not statistically different in patients who performed the research procedure (3.45% vs. 5.70%; p = 0.4872, FET) and not statistically different across research and non-research groups within 30-days following the research procedure (1.72% vs. 1.43%; p = 0.684, FET). Our results demonstrate that the research procedures used for sub-second monitoring of neurotransmitter release in humans can be performed without increasing the rate of infection.

Voice and swallowing impairments are common in movement disorders, but their effect on patients' quality of life is not well known. This study was conducted to determine the onset and prevalence of patient-reported dysphonia and dysphagia symptoms in Parkinson's disease (PD), dystonia, Atypical Parkinsonian Syndromes (APS), and Essential Tremor (ET). Patients referred to a movement disorders clinic in a tertiary care academic medical center completed validated voice and swallowing specific Quality of Life (QOL) questionnaires: Voice Handicap Index-10 (VHI-10) and Eating Assessment Tool-10 (EAT-10). Patient demographics and clinical data were also collected. Two hundred and sixty-eight patients (males = 150, females = 118) completed the questionnaires (n was PD = 103, APS = 30, ET = 56, dystonia = 32, other = 47). Prevalence of patient-reported dysphagia symptoms was significantly higher in APS (63%) than PD (26%), ET (25%), and dystonia (31%). Prevalence of patient-reported dysphonia symptoms was significantly lower in ET (14%) compared to PD (34%) and APS (43%). Disease duration was shorter in PD and APS compared to ET and dystonia (p 0.05) before reporting clinically significant dysphonia and dysphagia symptoms indicating an earlier onset of these symptoms. There were significant positive correlations between VHI-10 and EAT-10 scores and disease severity, as indicated by Unified Parkinson's Disease motor scores (p 0.0001) and modified Fahn-Tolosa-Marin Tremor Rating sub-scores (p = 0.0013). Patient-reported dysphonia and dysphagia symptoms were present in one fourth of patients with PD, ET, dystonia, and almost two thirds in APS. Patient-reported QOL measures, such as VHI-10 and EAT-10, can help screen movement disorder patients for dysphonia and dysphagia symptoms.

Summary Objective Deep brain stimulation (DBS) is a treatment for medically refractory essential tremor (ET), but there is a paucity of literature examining the effects of DBS on voice in patients with ET pre-DBS and post-DBS. This study aimed to report a comprehensive evaluation of voice in patients with ET pre-DBS and 6-months post-DBS. Study Design Case series. Methods Five patients receiving DBS for ET underwent voice evaluations pre-DBS and 6-months post-DBS. One patient had concurrent ET of the vocal tract (ETVT). The evaluation included patient-reported, perceptual, acoustic, and phonatory aerodynamic analyses of voice. Voice Handicap Index-10, Grade, Roughness, Breathiness, Asthenia, Strain Scale, perturbation measures, cepstral spectral index of dysphonia, cepstral peak prominence, and mean phonatory airflow measures were also among the data collected. Results Patients with ET presented with minimal changes in perceptual, acoustic, and phonatory aerodynamic parameters. Perceived vocal roughness significantly increased 6-months post-DBS (P = 0.047). The patient with ETVT presented with clinically significant improvement in almost all collected voice parameters 6-months post-DBS. Conclusion This is the first study to provide data encompassing auditory perceptual voice analysis, voice-specific patient-reported quality of life measures, acoustic, and phonatory aerodynamic outcomes in patients pre-DBS and 6-months post-DBS for ET. The results of our preliminary study have implications for the use of a comprehensive voice assessment to identify and measure change in voice outcomes in patients with ET and ETVT pre- and postsurgery.

This chapter presents a case of medication-refractory primary generalized dystonia presenting with disabling symptoms of cervical dystonia and dystonic bilateral arm tremors. This case posed a challenge in the choice of the appropriate target for deep brain stimulation (DBS) because the targeting of the globus pallidus interna improves dystonia symptoms but may have a less predictable response to tremor. DBS targeting the ventral intermedius may not in many cases improve dystonia symptoms but can effectively control tremor. The authors describe a case in which they employed a systematic approach including implanting multiple leads in different DBS targets. This approach resulted in a favorable outcome for this patient in dystonia and in dystonic tremor.

Aim: A Delphi expert consensus panel proposed that fulfilling ≥1 of the ‘5-2-1 criteria’ (≥five-times daily oral levodopa use, ≥two daily hours with ‘Off’ symptoms or ≥one daily hour with troublesome dyskinesia) suggests advanced Parkinson’s disease (PD). Patients & methods: DUOdopa/Duopa in Patients with Advanced PD – a GLobal OBservational Study Evaluating Long-Term Effectiveness (DUOGLOBE) – is a single-arm, postmarketing, observational, long-term effectiveness study of levodopa–carbidopa intestinal gel (LCIG) for advanced PD. Results: This 6-month interim analysis (n = 139) affirms that most (98%) enrolled patients fulfill ≥1 of the 5-2-1 criteria. These patients responded favorably to LCIG treatment. Safety was consistent with other LCIG studies. Conclusion: In advanced PD patients, the 5-2-1 criteria generally aligns with clinician assessment. Clinical Trial Registration: NCT02611713 ( ClinicalTrials.gov )

Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease.This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396.Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation.This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes.Boston Scientific.

OBJECTIVE To determine the effects of globus pallidus interna (GPi) deep brain stimulation (DBS) on speech and voice quality of patients with primary, medically refractory dystonia. METHODS Voices of 14 patients aged ≥18 years (males = 7 and females = 7) with primary dystonia (DYT1 gene mutation dystonia = 4, cervical dystonia = 6, and generalized dystonia = 4) with bilateral GPi DBS were assessed. Five blinded raters (two fellowship-trained laryngologists and three speech/language pathologists) evaluated audio recordings of each patient pre- and post-DBS. Perceptual voice quality was rated using the Grade, Roughness, Breathiness, Asthenia, and Strain scale and changes in speech intelligibility were assessed with the Clinical Global Impression scale of Severity instrument. Inter-rater and intrarater reliability rates for perceptual voice ratings were assessed using the kappa coefficient. RESULTS Voice quality parameters showed mean improvements in Grade (P < 0.0001), Roughness (P = 0.0043), and Strain (P < 0.0001) 12 months post-DBS. Asthenia increased from baseline to 6 months (P = 0.0022) and declined significantly from 6 to 12 months (P = 0.0170). Breathiness did not change significantly over time. Speech intelligibility also improved from 6 to 12 months (P = 0.0202) and from pre-DBS to 12 months post-DBS (P = 0.0022). Grade and Strain ratings had nearly perfect and substantial inter-rater agreement (0.84 and 0.71, respectively). CONCLUSIONS Voice and speech intelligibility improved after bilateral GPi DBS for dystonia. GPi DBS may emerge as a potential treatment option for patients with medically refractory laryngeal dystonia.

BACKGROUND. We report the 12-month clinical and imaging data on the effects of bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic nuclei (STN) of advanced Parkinson's disease (PD) patients. METHODS. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2-GAD delivery into the STN compared with sham surgery and were followed for 12 months in open-label fashion. Subjects were assessed with clinical outcome measures and 18F-fluorodeoxyglucose (FDG) PET imaging. RESULTS. Improvements under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in the AAV2-GAD group compared with the sham group continued at 12 months [time effect: F(4,138) = 11.55, P < 0.001; group effect: F(1,35) = 5.45, P < 0.03; repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced dyskinesias significantly declined at 12 months in the AAV2-GAD group (P = 0.03; post-hoc Bonferroni test), while the sham group was unchanged. Analysis of all FDG PET images over 12 months revealed significant metabolic declines (P < 0.001; statistical parametric mapping RMANOVA) in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group compared with the sham group. Across all time points, changes in regional metabolism differed for the two groups in all areas, with significant declines only in the AAV2-GAD group (P < 0.005; post-hoc Bonferroni tests). Furthermore, baseline metabolism in the prefrontal cortex (PFC) correlated with changes in motor UPDRS scores; the higher the baseline PFC metabolism, the better the clinical outcome. CONCLUSION. These findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL REGISTRATION. ClinicalTrials.gov NCT00643890. FUNDING. Neurologix Inc.

OBJECTIVE To study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function. RESEARCH DESIGN AND METHODS Regional brain volumes and ischemic lesion volumes in 1,366 women, aged 72–89 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Cross-sectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined. RESULTS The 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01) but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits. CONCLUSIONS Diabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetes-related deficits in cognitive function.

Summary Background Gene transfer of glutamic acid decarboxylase ( GAD ) and other methods that modulate production of GABA in the subthalamic nucleus improve basal ganglia function in parkinsonism in animal models. We aimed to assess the effect of bilateral delivery of AAV2- GAD in the subthalamic nucleus compared with sham surgery in patients with advanced Parkinson's disease. Methods Patients aged 30–75 years who had progressive levodopa-responsive Parkinson's disease and an overnight off-medication unified Parkinson's disease rating scale (UPDRS) motor score of 25 or more were enrolled into this double-blind, phase 2, randomised controlled trial, which took place at seven centres in the USA between Nov 17, 2008, and May 11, 2010. Infusion failure or catheter tip location beyond a predefined target zone led to exclusion of patients before unmasking for the efficacy analysis. The primary outcome measure was the 6-month change from baseline in double-blind assessment of off-medication UPDRS motor scores. This trial is registered with ClinicalTrials.gov, NCT00643890. Findings Of 66 patients assessed for eligibility, 23 were randomly assigned to sham surgery and 22 to AAV2- GAD infusions; of those, 21 and 16, respectively, were analysed. At the 6-month endpoint, UPDRS score for the AAV2- GAD group decreased by 8·1 points (SD 1·7, 23·1%; p GAD group showed a significantly greater improvement from baseline in UPDRS scores compared with the sham group over the 6-month course of the study (RMANOVA, p=0·04). One serious adverse event occurred within 6 months of surgery; this case of bowel obstruction occurred in the AAV2- GAD group, was not attributed to treatment or the surgical procedure, and fully resolved. Other adverse events were mild or moderate, likely related to surgery and resolved; the most common were headache (seven patients in the AAV2- GAD group vs two in the sham group) and nausea (six vs two). Interpretation The efficacy and safety of bilateral infusion of AAV2- GAD in the subthalamic nucleus supports its further development for Parkinson's disease and shows the promise for gene therapy for neurological disorders. Funding Neurologix.

We recently treated six patients for OCD utilizing deep brain stimulation (DBS) of the anterior limb of the internal capsule and the nucleus accumbens region (ALIC-NA). We individually tested leads via a scripted intraoperative protocol designed to determine DBS-induced side effects and mood changes. We previously published qualitative data regarding our observations of induced emotional behaviors in our first five subjects. We have now studied these same behaviors in the full cohort of six patients over 2 years of follow-up and have examined the relationship of these behaviors to intraoperative mood changes and postoperative clinical outcomes. Five patients experienced at least one smile response during testing. At higher voltages of stimulation, some of these smiles progressed to natural laughter. Smiles and laughter were associated with mood elevation. At stimulation locations at which smiles were observed, voltage and mood were significantly correlated (p=0.0004 for right brain and p

Patients with Parkinson's disease (PD) and essential tremor (ET) tend to lose weight progressively over years. Weight gain following deep brain stimulation (DBS) of the subthalamic nucleus (STN) for treatment of PD has been documented in several studies that were limited by small sample size and exclusive focus on PD patients with STN stimulation. The current study was undertaken to examine weight change in a large sample of movement disorder patients following DBS. A retrospective review was undertaken of 182 patient charts following DBS of the STN, ventralis intermedius nucleus of the thalamus (VIM), and globus pallidus internus (GPi). Weight was collected preoperatively and postoperatively up to 24 months following surgery. Data were adjusted for baseline weight and multivariate linear regression was performed with repeated measures to assess weight change. Statistically significant mean weight gain of 1.8 kg (2.8% increase from baseline, p = 0.0113) was observed at a rate of approximately 1 kg per year up to 24 months following surgery. This gain was not predicted by age, gender, diagnosis, or stimulation target in a multivariate model. Significant mean weight gain of 2.3 kg (p = 0.0124) or 4.2% was observed in our PD patients. Most patients with PD and ET gain weight following DBS, and this gain is not predicted by age, gender, diagnosis, or stimulation target.

Object Microelectrode recording (MER) and macrostimulation (test stimulation) are used to refine the optimal deep brain stimulation (DBS) lead placement within the operative setting. It is well known that there can be a microlesion effect with microelectrode trajectories and DBS insertion. The aim of this study was to determine the impact of intraoperative MER and lead placement on tremor severity in a cohort of patients with essential tremor. Methods Consecutive patients with essential tremor undergoing unilateral DBS (ventral intermediate nucleus stimulation) for medication-refractory tremor were evaluated. Tremor severity was measured at 5 time points utilizing a modified Tremor Rating Scale: 1) immediately before MER; 2) immediately after MER; 3) immediately after lead implantation; 4) 6 months after DBS implantation in the off-DBS condition; and 5) 6 months after implantation in the on-DBS condition. To investigate the impact of the MER and DBS lead placement, Wilcoxon signed-rank tests were applied to test changes in tremor severity scores over the surgical course. In addition, a generalized linear mixed model including factors that potentially influenced the impact of the microlesion was also used for analysis. Results Nineteen patients were evaluated. Improvement was noted in the total modified Tremor Rating Scale, postural, and action tremor scores (p < 0.05) as a result of MER and DBS lead placement. The improvements observed following lead placement were similar in magnitude to what was observed in the chronically programmed clinic setting parameters at 6 months after lead implantation. Improvement in tremor severity was maintained over time even in the off-DBS condition at 6 months, which was supportive of a prolonged microlesion effect. The number of macrostimulation passes, the number of MER passes, and disease duration were not related to the change in tremor severity score over time. Conclusions Immediate improvement in postural and intention tremors may result from MER and DBS lead placement in patients undergoing DBS for essential tremor. This improvement could be a predictor of successful DBS lead placement at 6 months. Clinicians rating patients in the operating room should be aware of these effects and should consider using rating scales before and after lead placement to take these effects into account when evaluating outcome in and out of the operating room.

After more than 2 decades since it was introduced, deep brain stimulation (DBS) has gained widespread popularity as a surgical treatment for medically refractory symptoms of Parkinson disease, essential tremor, and dystonia. In this chapter, authors review the benefits, risks, indications, limitations, and targets for DBS in patients with Parkinson disease, essential tremor, and dystonia. A brief outline of the DBS procedure and programming is also given.

Deep brain stimulation (DBS) of the basal ganglia is an effective treatment for select movement disorders, including Parkinson’s disease, essential tremor and dystonia. Based on these successes, DBS has been explored as an experimental treatment for medication-resistant neuropsychiatric disease. During a multiyear experience employing DBS to treat patients for obsessive compulsive disorder (OCD) we encountered several unanticipated stimulation-induced psychiatric side effects. We present a case of a young woman treated for OCD with DBS of the anterior limb of the internal capsule and nucleus accumbens region, who subsequently manifested a manic episode. We aim to discuss the case details, treatment and potential neuroanatomical underpinnings of this response.

To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)).Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified.47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout).Significant improvements in motor scores (p0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p0.05) and a trend for significance following lead placement (p0.08) but long term outcome was similar.This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

Attempts to modulate brain activity for therapeutic purposes by stimulating various cortical and subcortical areas, have been made since the 19th century. Bartholow was one of the first to describe in detail, a case of brain stimulation in 1874 [13]. However, it was not until a century later, when in 1987, Benabid and Pollack proved that chronic high frequency deep brain stimulation (DBS) of thalamus could be used as a safe and effective way of treating the tremor of Parkinson’s disease (PD) [11,19]. A timeline of important milestones in the history of brain stimulation is shown in Fig. 1. In this article we will discuss the currently approved and the experimental uses of DBS. In addition we will give a brief overview of the proposed mechanisms by which DBS is currently thought to modulate brain activity. Sometimes referred to as a ‘brain pacemaker’, DBS involves placement of intracranial electrodes (Fig. 2) which can be connected to a subcutaneously and subclavicularly implanted pulse generator (IPG). The IPG allows noninvasive adjustments of current amplitude, frequency, pulse width and polarity by means of a hand

To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS.A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain.Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain.In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain.

Microelectrode recording (MER) and macrostimulation (test stimulation) are used to refine the optimal deep brain stimulation (DBS) lead placement within the operative setting. It is well known that there can be a microlesion effect with microelectrode trajectories and DBS insertion. The aim of this study was to determine the impact of intraoperative MER and lead placement on tremor severity in a cohort of patients with essential tremor.Consecutive patients with essential tremor undergoing unilateral DBS (ventral intermediate nucleus stimulation) for medication-refractory tremor were evaluated. Tremor severity was measured at 5 time points utilizing a modified Tremor Rating Scale: 1) immediately before MER; 2) immediately after MER; 3) immediately after lead implantation; 4) 6 months after DBS implantation in the off-DBS condition; and 5) 6 months after implantation in the on-DBS condition. To investigate the impact of the MER and DBS lead placement, Wilcoxon signed-rank tests were applied to test changes in tremor severity scores over the surgical course. In addition, a generalized linear mixed model including factors that potentially influenced the impact of the microlesion was also used for analysis.Nineteen patients were evaluated. Improvement was noted in the total modified Tremor Rating Scale, postural, and action tremor scores (p0.05) as a result of MER and DBS lead placement. The improvements observed following lead placement were similar in magnitude to what was observed in the chronically programmed clinic setting parameters at 6 months after lead implantation. Improvement in tremor severity was maintained over time even in the off-DBS condition at 6 months, which was supportive of a prolonged microlesion effect. The number of macrostimulation passes, the number of MER passes, and disease duration were not related to the change in tremor severity score over time.Immediate improvement in postural and intention tremors may result from MER and DBS lead placement in patients undergoing DBS for essential tremor. This improvement could be a predictor of successful DBS lead placement at 6 months. Clinicians rating patients in the operating room should be aware of these effects and should consider using rating scales before and after lead placement to take these effects into account when evaluating outcome in and out of the operating room.

To examine in a pilot study inappropriate crying and laughing (also termed pseudobulbar affect (PBA)) and underlying mood disturbances in a large clinic based population of Parkinson's disease and movement disorder patients.PBA is characterized by uncontrollable laughter without mirth, or alternatively crying without the feeling of sadness. It is a common condition affecting more than one million people with neurological diseases. While PBA has been studied in many neurological diseases, little is known about its prevalence in movement disorders, or its relationship to more chronic mood disturbances. We carried out this pilot study to examine this relationship.Seven hundred and nineteen out of 860 consecutive patients who visited our Movement Disorders Center met inclusion criteria (i.e.or = 18 years of age, formal diagnosis by a movement disorder specialist, completion of PBA questionnaire, and absence of brain surgery including deep brain stimulation). All subjects were interviewed for symptoms of PBA during their visit. In addition, 661 of these patients completed both the Visual Analog Mood Scale (VAMS) and Beck Depression Inventory I (BDI-I).Thirty-seven of the 719 reported PBA symptoms; 75.7% (28/37) had pathological 'crying', 13.5% (5/37) had pathological 'laughing' and 10.8% (4/37) had both. The prevalence of PBA in individual diagnostic categories was: 4.7% (18/387) of idiopathic Parkinson's disease (PD), 2.7% (2/74) of primary dystonia, 3.1% (2/65) of essential tremor (ET), 7.8% (8/108) of patients with other forms of Parkinsonism, 21.7% (5/23) of psychogenic movement disorders, 0% (0/18) of patients with combined PD and ET, and 4.5% (2/44) of other movement disorders. Patients with PBA had a higher total BDI score (P=0.0278) and VAMS 'tiredness' score (P=0.0109). In patients on antidepressant therapy the prevalence of PBA was 7.1% compared to 2.7% in the group not on therapy (P=0.0094).PBA was present in most movement disorders, but especially prevalent in parkinsonism. PBA patients in this cohort had more chronic depressive symptoms and tiredness.

Selecting the appropriate candidate for deep brain stimulation (DBS) may be the most important factor to determine the success of surgery (1, 2, 3, 4). The proc ess of patient selection appears to vary widely among DBS centers in different regions of the world. The majority of large centers prefer a multidisciplinary approach involving a neurologist, a neurosurgeon, a psychologist, a psychia trist, and a nurse specialist (5) This chapter focuses on reviewing the factors involved in selecting appropriate DBS candidates for Parkinson's disease (PD) as well as other movement and neuropsychiatric disorders.

Objective: The goal of this study was to examine patient outcomes after their initial evaluation in the Movement Disorders (MD) Clinic at our institution for possible normal pressure hydrocephalus (NPH). We attempted to identify predictive factors that lead to the clinical diagnosis of NPH and ultimately to pursuit of ventriculoperitoneal shunt (VPS) placement, as well as those that lead to positive post-surgical outcomes. Background First, we wanted to review patient outcomes after VPS placement for NPH at our institution. Second, given current limitations in successfully identifying optimal surgical candidates among patients with possible NPH, we wanted to review the clinical and radiological data utilized for decision-making with each patient to see if certain factors were more predictive of positive outcome. Design/Methods: This was a retrospective chart review of patients evaluated in MD Clinic for gait disturbance between January 2007 and October 2010. Outcomes were based on the patients9 postoperative assessments in Neurosurgery and/or MD Clinic and Clinical Global Impression (CGI) scale scores. Results: Fourteen of 25 patients initally evaluated in MD Clinic for gait disturbance and possible NPH ultimately underwent VPS placement, 12 of those at our institution. Of those, 11 had post-operative CGIs between 1 (very much improved) and 3 (minimally improved). Only one patient had no change after surgery. In the patients that underwent high-volume lumbar puncture (LP) as part of evaluation for possible NPH, a higher percent change in gait speed and lower post-LP CGI were associated with surgery, but not necessarily with more positive post-surgical outcome. Conclusions: In general, patients undergoing VPS placement for probable NPH after evaluation in MD Clinic had positive outcomes, with improvement in gait dysfunction. However, measures such as percent change in gait speed after high-volume lumbar puncture, frequently used to predict response to VPS, were not necessarily predictive of the degree of improvement after surgery. Disclosure: Dr. Tate has nothing to disclose. Dr. Siddiqui has nothing to disclose.