Characterization of Movement Disorder Phenomenology in Genetically Proven, Familial Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis.

BACKGROUND: Mutations in granulin (PGRN) and tau (MAPT), and hexanucleotide repeat expansions near the C9orf72 genes are the most prevalent genetic causes of frontotemporal lobar degeneration. Although behavior, language and movement presentations are common, the relationship between genetic subgroup and movement disorder phenomenology is unclear. OBJECTIVE: We conducted a systematic review and meta-analysis of the literature characterizing the spectrum and prevalence of movement disorders in genetic frontotemporal lobar degeneration. METHODS: Electronic databases were searched using terms related to frontotemporal lobar degeneration and movement disorders. Articles were included when cases had a proven genetic cause. Study-specific prevalence estimates for clinical features were transformed using Freeman-Tukey arcsine transformation, allowing for pooled estimates of prevalence to be generated using random-effects models. RESULTS: The mean age at onset was earlier in those with MAPT mutations compared to PGRN (p<0.001) and C9orf72 (p = 0.024). 66.5% of subjects had an initial non-movement presentation that was most likely a behavioral syndrome (35.7%). At any point during the disease, parkinsonism was the most common movement syndrome reported in 79.8% followed by progressive supranuclear palsy (PSPS) and corticobasal (CBS) syndromes in 12.2% and 10.7%, respectively. The prevalence of movement disorder as initial presentation was higher in MAPT subjects (35.8%) compared to PGRN subjects (10.1). In those with a non-movement presentation, language disorder was more common in PGRN subjects (18.7%) compared to MAPT subjects (5.4%). SUMMARY: This represents the first systematic review and meta-analysis of the occurrence of movement disorder phenomenology in genetic frontotemporal lobar degeneration. Standardized prospective collection of clinical information in conjunction with genetic characterization will be crucial for accurate clinico-genetic correlation.

Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders.

BACKGROUND: Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. METHODS: In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. RESULTS: Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size ≥ 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). CONCLUSIONS: These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders.

A randomized, placebo controlled pilot trial of botulinum toxin for paratonic rigidity in people with advanced cognitive impairment.

OBJECTIVE: Evaluate safety and efficacy of Incobotulinumtoxin A in elderly patients with dementia and paratonia. SETTING: University-affiliated hospital, spasticity management Clinic. PARTICIPANTS: Ten subjects were enrolled. INCLUSION CRITERIA: 1) severe cognitive impairment 2) diagnosis of Alzheimer's disease, vascular dementia, or frontotemporal dementia, and 3) score >3 on the paratonic assessment instrument, with posture in an arm(s) interfering with provision of care. EXCLUSION CRITERIA: 1) alternate etiologies for increased tone and 2) injection with botulinum toxin within the 6 months preceding the study. DESIGN: Single center, randomized, double blind, placebo-controlled, crossover trial with two treatment cycles of 16 weeks. Assessments occurred at 2, 6, 12 and16 weeks following injections. Subjects received up to 300 U of Incobotulinumtoxin A in arm(s). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was the modified caregiver burden scale (mCBS); exploratory secondary outcome measures were also performed. Analysis of variance and mixed modeling techniques were used to evaluate treatment effects. RESULTS: Incobotulinumtoxin A treatment produced significant improvement in mCBS total score -1.11 (-2.04 to -0.18) (Treatment effect and 95% CI), dressing sub-score -0.36 (-0.59 to 0.12), and cleaning under the left and right armpits sub-score -0.5 (-0.96 to -0.04), -0.41 (-0.79 to -0.04) respectively. PROM in the left and right elbow increased by 27.67 degrees (13.32-42.02) and 22.07 degrees (9.76-34.39) respectively. PROM in the left and right shoulder increased by 11.92 degrees (5.46-18.38) and 8.58 degrees (3.73-13.43) respectively. No significant treatment effect was found for GAS, VAS and PAINAD scales or change in time to perform care. No adverse drug reactions occurred. CONCLUSIONS: Administration of Incobotulinumtoxin A in elderly people with advanced dementia and paratonia may be an efficacious and safe treatment to increase range of motion and reduce functional burden. Further studies are needed to confirm results. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02212119.

A Patient-Based Needs Assessment for Living Well with Parkinson Disease: Implementation via Nominal Group Technique.

Background. Parkinson's disease (PD) is a neurodegenerative condition with complex subtleties, making it challenging for physicians to fully inform their patients. Given that approximately 50% of Americans access the Internet for health information, the development of a multimedia, web-based application emphasizing targeted needs of people with Parkinson's disease (PwP) has the potential to change patient's lives. Objectives. To determine what information PwP perceive could enhance their quality of life. Methods. Group sessions utilizing nominal group technique (NGT) were conducted. Participants were asked "what information do you want to know about that would help you live well with PD?" Silent generation of ideas preceded discussion followed by anonymous ranking of items. A "summary score" (sum of rank × frequency) was calculated. Results. 36 individual items were collapsed into 9 categories. Coping with emotions, changing relationships, and social implications of PD were ranked as most important. Financial supports and skills for self-advocacy were also highly ranked. Conclusions. Qualitative research methodology was utilized to determine the unmet needs of PwP. Results of this survey will inform the development of a patient-oriented, online resource, the goal will be to provide information and strategies to improve symptom management, reduce disability and address all relevant concerns important to those affected by PD.

Development of a non-motor fluctuation assessment instrument for Parkinson disease.

Patients with Parkinson disease are increasingly recognized to suffer from non-motor symptoms in addition to motor symptoms. Many non-motor symptoms fluctuate in parallel with motor symptoms and in relationship to plasma levodopa levels. Though these symptoms are troublesome and result in reduced quality of life to patients and their caregivers, there has not been an objective method of recognizing and quantifying non-motor fluctuations (NMFs). This study sought to develop a patient-based instrument that would accurately capture the experience of patients with NMFs. Patient-based nominal group technique sessions, focus groups, and expert opinion were utilized in developing this questionnaire.

Benign hereditary chorea.

Benign hereditary chorea (BHC) is a hyperkinetic movement disorder that historically has been characterized as a nonprogressive, dominantly inherited, childhood-onset chorea with normal intelligence. However, in some cases, atypical features were described such that controversy arose regarding whether BHC was a single syndrome. In 2002, a candidate gene, thyroid transcription factor (TITF-1), was identified to cause at least some cases of BHC. Since that time, the classical phenotype has expanded further to include "brain-thyroid-lung syndrome," which, in addition to the neurological symptoms, also manifests variable degrees of thyroid and lung abnormalities. Pathophysiologic mechanisms by which symptoms can occur are postulated to include haploinsufficiency (loss of function) and/or dominant negative effect on wild-type protein. However, genotype-phenotype correlations are complex and there is no clear relationship between mutation size, location or type of mutation, and severity of phenotype. Gross and microscopic pathology has been unremarkable, though immunohistochemistry suggests that BHC may manifest as a result of a reduced complement of migratory interneurons to the striatum and cortex. This chapter reviews the historical literature and current understanding regarding this familial, developmental disorder.

Health-related quality of life in Parkinson disease: correlation between Health Utilities Index III and Unified Parkinson's Disease Rating Scale (UPDRS) in U.S. male veterans.

OBJECTIVE: To apply a scaled, preference-based measure to the evaluation of health-related quality of life (HRQoL) in Parkinson's disease (PD); to evaluate the relationship between disease-specific rating scales and estimated HRQoL; and to identify predictors of diminished HRQoL. BACKGROUND: Scaled, preference-based measures of HRQoL ("utilities") serve as indices of impact of disease, and can be used to generate quality-adjusted estimates of survival for health-economic evaluations. Evaluation of utilities for PD and their correlation with standard rating scales have been limited. METHODS: Utilities were generated using the Health Utilities Index Mark III (HUI-III) on consecutive patients attending a PD Clinic between October 2003 and June 2006. Disease severity, medical, surgical (subthalamic nucleus deep brain stimulation (STN-DBS)), and demographic information were used as model covariates. Predictors of HUI-III utility scores were evaluated using the Wilxocon rank-sum test and linear regression models. RESULTS: 68 men with a diagnosis of PD and a mean age of 74.0 (SD 7.4) were included in the data analysis. Mean HUI-III utility at first visit was 0.45 (SD 0.33). In multivariable models, UPDRS-II score (r2 = 0.56, P < 0.001) was highly predictive of HRQoL. UPDRS-III was a weaker, but still significant, predictor of utility scores, even after adjustment for UPDRS-II (P = 0.01). CONCLUSIONS: Poor self-care in PD reflected by worsening UPDRS-II scores is strongly correlated with low generic HRQoL. HUI-III-based health utilities display convergent validity with the UPDRS-II. These findings highlight the importance of measures of independence as determinants of HRQoL in PD, and will facilitate the utilization of existing UPDRS data into economic analyses of PD therapies.

Long-term effect of unilateral pallidotomy on levodopa-induced dyskinesia.

Unilateral pallidotomy has been effectively used to treat parkinsonism and reduce levodopa induced dyskinesia (LID). We sought to determine the long-term effects of pallidotomy on LID in 10 patients who had initial benefit from pallidotomy but went on to require DBS surgery for symptom progression. The Dyskinesia Rating Scale (DRS) was used to rate and quantify LID in a blinded fashion. Though sample size was small, there was a trend towards a reduction in LID lasting up to 12 years suggesting that posteroventral pallidotomy may provide sustained benefit in reducing LID.

Phenylthiocarbamide (PTC) perception in Parkinson disease.

OBJECTIVE: To examine phenylthiocarbamide (PTC) sensitivity in Parkinson disease (PD) patients and healthy volunteers to determine whether taster status represented a simple vulnerability marker for PD. BACKGROUND: The inability to taste PTC has been associated with a number of medical illnesses not typically associated with taste impairment. Abnormalities in the function/expression of G protein-signaling pathways have been implicated in PTC perception and also in dopamine expression and regulation in PD. No study has yet probed whether PTC tasting is disrupted in PD. METHOD: PTC sensitivity was assessed in a small sample of 36 male PD patients and 20 healthy male comparison subjects using a standardized psychophysical method. RESULTS: A higher proportion of nontasters were found in patients relative to healthy comparison subjects. These differences were not explained by alterations in perception of basic taste intensity or age. Among patients, nontasters and tasters of PTC did not differ with regard to duration of illness, age of onset, severity of motor symptoms, or overall illness severity. CONCLUSIONS: These data suggest an increase in the frequency of PTC nontaster status in PD. As phenotypic variation in PTC sensitivity is genetic in origin, this may represent a surrogate risk factor for the development of PD.

Benign hereditary chorea revisited: a journey to understanding.

Benign hereditary chorea (BHC) has been characterized as an autosomal dominant disorder manifesting nonprogressive chorea without dementia. However, there has been controversy regarding its existence. Diagnosis has been based solely on clinical criteria with many patients and families demonstrating "atypical" features and until recently, no diagnostic test was available for confirmation. Since 2002, mutations in the thyroid transcription factor (TITF-1) gene have been identified as resulting in some cases of BHC. Additionally, the clinical spectrum has expanded to include abnormalities in thyroid and lung with the putative mechanism of disease resulting from gene haploinsufficiency and reduced protein product. This review summarizes both a historical perspective and our current understanding of BHC.

Subthalamic nucleus deep brain stimulation for severe idiopathic dystonia: impact on severity, neuropsychological status, and quality of life.

OBJECT: Medically refractory dystonia has recently been treated using deep brain stimulation (DBS) targeting the globus pallidus internus (GPI). Outcomes have varied depending on the features of the dystonia. There has been limited literature regarding outcomes for refractory dystonia following DBS of the subthalamic nucleus (STN). METHODS: Four patients with medically refractory, predominantly cervical dystonia underwent STN DBS. Intraoperative assessments with the patients in a state of general anesthesia were performed to determine the extent of fixed deformities that might predict outcome. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) preoperatively and 3 and 12 months following surgery by a rater blinded to the study. Mean changes and standard errors of the mean in scores were calculated for each subscore of the two scales. Scores were also analyzed using analysis of variance and probability values were generated. Neuropsychological assessments and quality of life ratings using the 36-Item Short Form Health Survey (SF-36) were evaluated longitudinally. RESULTS: Significant improvements were seen in motor (p = 0.04), disability (p = 0.02), and total TWSTRS scores (p = 0.03). Better outcomes were seen in those patients who did not have fixed deformities. There was marked improvement in the mental component score of the SF-36. Neuropsychological function was not definitively impacted as a result of the surgery. CONCLUSIONS: Deep brain stimulation of the STN is a novel target for dystonia and may be an alternative to GPI DBS. Further studies need to be performed to confirm these conclusions and to determine optimal candidates and stimulation parameters.

Risk factors for the development of pedal edema in patients using pramipexole.

OBJECTIVE: To determine risk factors for pedal edema among patients with Parkinson disease (PD) using pramipexole hydrochloride therapy. DESIGN: A retrospective medical record review. SETTING: Philadelphia Veterans Administration Parkinson's Disease Research, Education and Clinical Center (PADRECC). PATIENTS: All consecutive patients at the PADRECC receiving pramipexole from December 2002 to December 2004. MAIN OUTCOME MEASURES: Bivariable and multivariable logistic regression models were used to identify comorbid illnesses, demographic characteristics, other medications, and PD features associated with increased risk of pedal edema among individuals taking pramipexole. Estimation of time to development of pedal edema in individuals taking pramipexole was performed using Kaplan-Meier survival methods and multivariable Cox proportional hazards models. RESULTS: Two hundred thirty-seven PADRECC patients received pramipexole and met criteria for inclusion in the analysis. Of these, 38 (16%) developed pedal edema. Multivariable regression models identified idiopathic PD (odds ratio [OR], 4.80; 95% confidence interval [CI], 1.54-14.98; P = .007), history of coronary artery disease (OR, 3.35; 95% CI, 1.51-7.46; P = .003), and history of diabetes mellitus (OR, 3.12; 95% CI, 1.01-9.60; P = .05) as strong independent risk factors for development of edema. There was no relationship between dose of pramipexole and incidence and severity of pedal edema. The risk of development of pedal edema was 7.7% (95% CI, 4.5%-12.9%) in the first year after initiation of pramipexole therapy, with more rapid development of edema among those with a history of coronary artery disease. CONCLUSIONS: Pedal edema is a relatively common outcome in patients with PD receiving pramipexole. History of coronary artery disease increases the risk for developing edema.

Long-term outcomes of bilateral subthalamic nucleus stimulation in patients with advanced Parkinson's disease.

BACKGROUND: In patients with advanced Parkinson's disease (PD), deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to improve motor function and decrease medication requirements in the short term. However, the long-term benefits of DBS are not yet established. OBJECTIVE: It was the aim of this study to evaluate long-term outcomes of patients with PD treated with bilateral DBS of the STN. DESIGN AND METHODS: Thirty-three subjects who had bilateral STN DBS were followed prospectively after surgery. We evaluated subjects, using the Unified Parkinson's Disease Rating Scale (UPDRS), preoperatively, 12 months after surgery and at a long-term follow-up visit. Ratings were performed on and off dopaminergic medications. We compared postoperative UPDRS scores, dyskinesia ratings and medication dosages with preoperative values. RESULTS: Twenty-seven subjects had evaluations beyond 18 months (median 33.7 months). Total UPDRS scores in the 'medication-off' state were improved by 37% (p < 0.001) at 12 months and 17.7% (p = 0.0051) at the long-term evaluation. Medication-off state UPDRS part III scores were significantly improved at both 1 year and at the last evaluation (37.6 and 29.3%; p < 0.001). Dopaminergic medication requirements were decreased by 35.3% (p < 0.001) during the first postoperative year and remained below preoperative levels at the long-term evaluation. Average duration of 'off' time remained decreased by about 40% at both 1 year and at the time of last evaluation. Subjects had a sustained reduction in dyskinesia severity (88.6% at 1 year and 68.8% at last evaluation). CONCLUSIONS: In this cohort of subjects with advanced PD, bilateral STN stimulation improved 'off' medication motor function, reduced time spent in the medication-off state and reduced medication requirements for up to 4 years after surgery. We conclude that STN DBS is an effective long-term therapy for selected patients with advanced PD.

Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinson's disease (PD) who have failed medical management. However, a recent summary of clinical evidence on the effectiveness of STN DBS is lacking. We report the results of such a systematic review and meta-analysis. A comprehensive review of the literature using Medline and Ovid databases from 1993 until 2004 was conducted. Estimates of change in absolute Unified Parkinson's Disease Rating Scale (UPDRS) scores after surgery were generated using random-effects models. Sources of heterogeneity were explored with meta-regression models, and the possibility of publication bias was evaluated. Patient demographics, reduction in medication requirements, change in dyskinesia, daily offs, quality of life, and a ratio of postoperative improvement from stimulation compared to preoperative improvement by medication from each study were tabulated and average scores were calculated. Adverse effects from each study were summarized. Thirty-seven cohorts were included in the review. Twenty-two studies with estimates of standard errors were included in the meta-analysis. The estimated decreases in absolute UPDRS II (activities of daily living) and III (motor) scores after surgery in the stimulation ON/medication off state compared to preoperative medication off state were 13.35 (95% CI: 10.85-15.85; 50%) and 27.55 (95% CI: 24.23-30.87; 52%), respectively. Average reduction in L-dopa equivalents following surgery was 55.9% (95% CI: 50%-61.8%). Average reduction in dyskinesia following surgery was 69.1% (95% CI: 62.0%-76.2%). Average reduction in daily off periods was 68.2% (95% CI: 57.6%-78.9%). Average improvement in quality of life using PDQ-39 was 34.5% +/- 15.3%. Univariable regression showed improvements in UPDRS III scores were significantly greater in studies with higher baseline UPDRS III off scores, increasing disease duration prior to surgery, earlier year of publication, and higher baseline L-dopa responsiveness. Average baseline UPDRS III off scores were significantly lower (i.e., suggesting milder disease) in later than in earlier studies. In multivariable regression, L-dopa responsiveness, higher baseline motor scores, and disease duration were independent predictors of greater change in motor score. No evidence of publication bias in the available literature was found. The most common serious adverse event related to surgery was intracranial hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of the available literature indicates that STN DBS improves motor activity and activities of daily living in advanced PD. Differences between available studies likely reflect differences in patient populations and follow-up periods. These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies.

Deep brain stimulation: postoperative issues.

Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.

Falling risk factors in Parkinson's disease.

OBJECTIVE: To identify falling risk factors that are potentially modifiable among individuals who have idiopathic Parkinson's disease. DESIGN: A between group comparison of 19 fallers and 21 nonfallers who have Parkinson's disease, across an array of variables that have been identified as falling risk factors among the elderly and among those who have Parkinson's disease. RESULTS: Several variables were demonstrated significantly to distinguish fallers: disease duration and severity; dyskinesias associated with the use of dopaminergic agents; freezing; postural instability; depression; fear of falling; impaired fine motor control and motor planning in the feet; decreased proximal strength and muscular endurance in the legs; and a higher level of disability. CONCLUSIONS: Several of these variables can be viewed a potentially modifiable during a future intervention trial that aims to reduce falls in those who have Parkinson's disease using multidimensional risk factor modification.

Alterations of striatal neurons in benign hereditary chorea.

Benign hereditary chorea (BHC) recently has been associated with mutations in TITF-1 gene, although a pathological study of an individual with BHC and a TITF-1 mutation revealed no significant gross or microscopic abnormalities using standard methods. Immunohistochemical staining of striatal tissue from a BHC-affected postmortem brain was performed using antibodies against neurotransmitters of interneurons whose tangential migration is mediated by TITF-1. There was a loss of most TITF-1-mediated striatal interneurons in the BHC specimen compared to four matched control brains.

Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease.

UNLABELLED: We studied the correlation of striatal dopamine transporter (DAT) imaging with anxiety and depression symptoms in Parkinson's disease (PD). METHODS: Patients with idiopathic PD (n = 76) and age-matched healthy volunteers (n = 46) underwent SPECT brain scans with (99m)Tc-TRODAT-1, a radiolabeled tropane that selectively binds to the DAT. TRODAT-1 distribution volume ratios, a reflection of DAT availability, were calculated from the SPECT scan data for 6 regions of interest (ROIs) in the caudate and putamen. The association between neuropsychiatric symptoms (anxiety, depression, and fatigue) and DAT availability was explored for both subject groups, and the impact of disease severity on this association was examined in the PD group. RESULTS: PD patients showed lower DAT availability than did healthy volunteers in all examined regions (for all ROIs, P < 0.001). In PD patients, higher individual affective measures (for anxiety, r = -0.30 and P = 0.01; and for depression, r = -0.24 and P = 0.05) and total affect scores (r = -0.31; P = 0.01) were associated with diminished left anterior putamen DAT availability. The association between total affect scores and DAT availability was present only in the subset of patients with less severe PD (r = -0.35; P = 0.04), but subjects with the highest DAT availability did not show high total affect scores. No association between neuropsychiatric measures and DAT availability was found in the controls. CONCLUSION: These preliminary findings suggest that decreased DAT availability may be necessary for but not invariably associated with the development of affective symptoms in PD. This suggestion is consistent with previous research showing a link between depression and basal ganglia impairment, particularly involving the left hemisphere, and extends this finding to include anxiety.

Subthalamic nucleus deep brain stimulation for parkinson's disease after successful pallidotomy: clinical and electrophysiological observations.

Unilateral pallidotomy is an effective treatment for contralateral parkinsonism and dyskinesia, yet symptoms progress in many patients. Little is known about whether such patients obtain a useful response to subsequent bilateral subthalamic nucleus deep brain stimulation (STN DBS). Changes in Unified Parkinson's Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores, medication requirements, and dyskinesias were measured. Clinical outcomes were compared to patients with de novo STN DBS. Neuronal recordings were performed. STN DBS resulted in a significant reduction in UPDRS Motor scores (42.1%; 95% confidence interval [CI], 26.9-57.4; P = 0.03), comparable with de novo STN DBS surgery (41%; 95% CI, 26-46%; P < 0.001). There was also less change in dyskinesia duration and disability scores (P = 0.017, 0.005). There were no side-to-side differences clinically or in the STN neuronal firing rates and patterns. Bilateral STN DBS is safe and efficacious in improving motor symptoms in patients with prior pallidotomy.