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Introduction: Current treatment of Parkinson's disease (PD) is limited to symptomatic dopaminergic therapy, while no interventions have been shown to slow down disease progression., Areas Covered: The following article highlights a group of PPAR-γ agonists called thiazolidinediones (TZDs), which are currently being tested for a putative disease-modifying benefit in PD, using pioglitazone as a prototypic compound. PPAR-γ is highly expressed in neurons of the substantia nigra and CNS immune cells. Preclinical data in rodent and primate support an effect of TZDs in preventing and/or arresting neurodegeneration and development of motor symptoms. Although no data on the neuroprotective effect of TZDs is currently available, a clinical trial is ongoing where the primary objective is to assess pioglitazone's impact on the progression of PD. The trial is also evaluating the drug's safety concerns., Expert Opinion: The efficacy data from clinical trials must be carefully weighed against the safety concerns. However, given the solid preclinical data, and since the safety data are not yet fully conclusive and limited to the diabetic population, PPAR-γ research in PD can continue with caution. Ideally, drug discovery and development efforts will lead to the identification of new compounds with reduced risk of peripheral side effects.

Background: Despite the benefits of medications and surgical interventions for Parkinson's disease (PD), these treatments are not without complications and neuroprotective strategies are still lacking. Therefore, there is a need for effective alternative approaches to treat motor and non-motor symptoms in PD. During the last decade, several studies have investigated endurance exercise training as a potential treatment for individuals with PD., Objective: This paper reviews the therapeutically beneficial effects of endurance exercise training on motor and non-motor symptoms in PD., Methods: First, we performed a systematic review of the literature on the effects of endurance exercise training on motor and non-motor signs of parkinsonism, functional outcomes including gait, balance and mobility, depression and fatigue, quality of life and perceived patient improvement, cardiorespiratory function, neurophysiological measures, and motor control measures in PD. Second we performed a meta-analysis on the motor section of the UPDRS. Then, we focused on several important factors to consider when prescribing endurance exercise training in PD such as intensity, duration, frequency, specificity and type of exercise. In addition, we identified current knowledge gaps regarding endurance exercise training in PD and made suggestions for future research., Results: A total of eight randomized controlled trials met the inclusion criteria and were reviewed. This systematic review synthesizes evidence that endurance exercise training at a sufficiently high level enhances cardiorespiratory capacity and endurance by improving VO2 max and gait in moderately to mildly affected individuals with PD. However, there is not yet a proven effect of endurance exercise training on specific features of PD such as motor signs of parkinsonism., Conclusion: Endurance exercise training improves physical conditioning in PD patients; however, to date, there is insufficient evidence to include endurance exercise training as a specific treatment for PD. There is a need for well-designed large-scale randomized controlled trials to confirm benefits and safety of endurance exercise training in PD and to explore potential benefits on the motor and non-motor signs of PD.

Objective: Analyze indications for ordering DAT-SPECT scans and the clinical impact of scan results on patients evaluated in a movement disorders practice., Background: DAT-SPECT is FDA approved to evaluate cases of suspected presynaptic dopaminergic deficiency. Little data is available on clinical use and impact of these scans among movement disorders neurologists., Methods: DAT-SPECT scans ordered at the Northwestern University Parkinson's disease (PD) and movement disorders center from 2011-2013 were reviewed. Clinic notes were reviewed for information regarding the indication for ordering each scan, and to assess for any changes in clinical impression or management choices that followed the scan., Results: 83 scans were ordered by four specialists. Scans were commonly ordered to differentiate PD from Essential Tremor (21.7%, n = 18) or from drug-induced parkinsonism (21.7%, n = 18). In 59% (n = 49) of cases, a change in clinical diagnosis or medication regimen occurred within one visit after the scan. The strongest impact was seen for the indication of ET vs. PD in which 72.2% (n = 13) had a change in diagnosis, management, or both., Conclusions: Diagnostic uncertainty in cases of parkinsonism exists even in a tertiary referral center. DAT-SPECT has significant impact on clinical diagnosis and management even in the hands of movement disorders specialists., (© 2015 S. Karger AG, Basel.)

Background: Parkinson's disease (PD) patients with 20 years or more survival (PD-20) are not well characterized., Objective: To evaluate PD-20 patient characteristics and identify areas for improvement of their health care., Methods: The international, multicenter National Parkinson's Foundation Quality Improvement Initiative (NPF-QII) study database was queried to identify PD-20 subjects. Demographic and clinical data were analyzed., Results: We identified 187 PD-20 subjects (55% men) representing 4% (187/4,619) of all NPF-QII participants. Subjects were mean age 69.5 years; mean age at PD onset was 44.0 years. The majority (75% ) had 20-25 years of PD duration, the longest duration being 49 years. They were median Hoehn and Yahr stage 3, and 75% had motor fluctuations. Half (54% ) reported exercising. The majority (89% ) were living at home and required a caregiver (88% ). They were mildly cognitively impaired for age (Montreal Cognitive Assessment estimate 22.6±3.7), with most deficits in verbal fluency and delayed recall. Quality of life (Parkinson's Disease Quality of Life Questionnaire index 36±15% ) was mild to moderately impaired, with most impairment in mobility and activities of daily living. Caregiver strain measured by the Multidimensional Caregiver Strain Index (27±16% ), recorded highest subscores in social constraint. PD-20 subjects aged <70 years versus ≥70 only differed significantly by worse cognition (P <  0.0001)., Conclusions: PD-20 subjects reflect an elite group of PD survivors with early-onset disease and relatively mild cognitive disability despite long disease duration. Interventions for caregivers, mobility, and activities of daily living are areas that could improve caregiver burden and patient quality of life.

Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson's disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD., Competing Interests: The authors have no conflicts of interest to report.

Background: Data on predictors of decline in PD are largely based on de-novo populations and limited to the use of motor outcomes that fail to capture the full scope of disease., Objective: Determine the clinical predictors of decline in early treated PD using a novel multi-domain measure., Methods: Data from NINDS Exploratory Trials in PD Long-Term Study 1 (NET-PD LS1), a multicenter Phase 3 study of creatine in early treated PD, were analyzed. Functional decline was defined by a global outcome metric (GO) that consisted of: Schwab and England ADL scale, PD 39-item Questionnaire, Unified PD Rating Scale, Ambulatory Capacity Score, Symbol Digit Modalities Test, and Modified Rankin Scale. Univariate and multivariate models were used to test the association of predictors of interest with a standardized rank-sum of the GO., Results: 765 of 1741 participants completed five-year assessments and were included. Older age at disease onset (p <  0.0001), higher baseline levodopa equivalent dose (p = 0.01), and worse Scales for Outcomes of Parkinson's Disease Cognition score (p = 0.001) at baseline were the strongest predictors of functional decline in multivariate analysis. PD symptom subtype was not a significant predictor of outcome (p = 0.42). The full model was only a modest predictor of change in GO (R2 = 0.186)., Conclusions: This is the largest study to systematically assess predictors of functional decline in early treated PD over several years, and the first to use a multi-domain outcome measure of decline. Older age at disease onset and worse cognition, and not PD subtype, were predictors of decline.

Objective: To assess costs and effectiveness of deep brain stimulation (DBS) of the internal globus pallidum (GPi) versus subthalamic nucleus (STN) from the provider and societal perspectives for Parkinson's disease (PD) patients in a multicenter randomized trial., Methods: All costs from randomization to 36 months were included. Costs were from Department of Veterans Affairs (VA) and Medicare databases and clinical trial data. Quality adjusted life years (QALYs) were from Quality of Well Being questionnaires., Results: Provider costs were similar for the 144 GPi and 130 STN patients (GPi: $138,044 vs. STN: $131,822; difference = $6,222, 95% confidence interval [CI]: -$42,125 to $45,343). Societal costs were also similar (GPi: $171,061 vs. STN: $167,706; difference = $3,356, 95% CI: -$57,371 to $60,294). The GPi patients had nonsignificantly more QALYs., Conclusions: The QALYs and costs were similar; the level of uncertainty given the sample size suggests that these factors should not direct treatment or resource allocation decisions in selecting or making available either procedure for eligible PD patients., (© 2014 International Parkinson and Movement Disorder Society.)

Opinion Statement: No conventional treatment has been convincingly demonstrated to slow or stop the progression of Parkinson's disease (PD). Dopaminergic therapy is the gold standard for managing the motor disability associated with PD, but it falls short of managing all of the aspects of the disease that contribute to quality of life. Perhaps for this reason, an increasing number of patients are searching for a more holistic approach to healthcare. This is not to say that they are abandoning the standard and effective symptomatic therapies for PD, but rather are complementing them with healthy living, mind-body practices, and natural products that empower patients to be active participants in their healthcare and widen the net under which disease modification might one day be achieved. Despite high rates of utilization of complementary and alternative medicine (CAM) practices, data on efficacy is generally limited, restricting physicians in providing guidance to interested patients. Exercise is now well-established as integral in the management of PD, but mind-body interventions such as Tai Chi that incorporate relaxation and mindfulness with physical activity should be routinely encouraged as well. While no comment can be made about neuroplastic or disease-modifying effects of mind-body interventions, patients should be encouraged to be as active as possible and engage with others in enjoyable and challenging activities such as dance, music therapy, and yoga. Many PD patients also choose to try herbs, vitamins, and neutraceuticals as part of a healthy lifestyle, with the added expectation that these products may lower free radical damage and protect them against further cell death. Evidence for neuroprotection is limited, but patients can be encouraged to maintain a healthy diet rich in "high-power," low-inflammatory foods, while at the same time receiving education that many promising natural products have produced disappointing results in clinical trials. It is vital that the science of holistic medicine reaches a point where all neutraceuticals are investigated with the same rigor as conventional drugs. A number of agents discussed here that have a proposed role in the treatment of neurodegenerative diseases (and PD in particular), including cannabis, mucuna pruriens, and Chinese herbals, deserve more attention from basic science researchers and clinical investigators before they can be either safely utilized or dismissed.

Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments to patients but is also fraught with significant commercial, regulatory, and reimbursement challenges. The Alzheimer's Drug Discovery Foundation (ADDF) and the Michael J. Fox Foundation for Parkinson's Research (MJFF) convened an advisory panel in October 2013 to understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegenerative diseases. Here, we present opportunities on how philanthropy, industry, and government can begin to address these challenges, promote policy changes, and develop targeted funding strategies to accelerate the potential of FDA-approved repurposed drugs.

Importance: Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD., Objective: To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics., Design, Setting, and Participants: A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University., Interventions: Twenty-four hour monitoring of serum melatonin secretion., Main Outcomes and Measures: Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm., Results: Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm., Conclusions and Relevance: Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.

A recent study by Aviles-Olmos and colleagues suggests that 12 months of treatment with the glucagon-like peptide-1 receptor agonist exenatide improves motor and cognitive symptoms in Parkinson's disease (PD), and that the effect persists as long as 12 months after termination of the treatment. Due to the lack of a placebo control, one cannot exclude that the observed differences between patients receiving daily injections of exenatide and non-treated controls are due to a placebo effect. We discuss that large group differences in two independent functional measures remain for at least 12 months following the cessation of exenatide treatment and that this warrants a double-blind placebo-controlled trial with exenatide in PD.

Depression is a major determinant of Health Related Quality of Life in PD, but there is limited data on physician recognition of depression and treatment efficacy. We used data obtained from the QII dataset of the National Parkinson's Foundation database to determine whether there was an association between depressive symptoms and utilization of antidepressants and/or mental health services (MHS) in a large cohort of PD patients. We found that prevalence of depressive symptoms remained high in the PD population despite improved physician recognition and treatment initiation.

Background: Parkinson's disease (PD) patients are hospitalized more frequently than their peers as a result of falls, psychosis, infections and other medical complications. However, patient-specific risk factors for hospitalization are unclear., Objective: To identify rates and risk factors for hospital encounters (Emergency Room [ER] visits or hospitalization) among people with PD., Methods: 3415 PD participants (mean age 67 ± 10 years, disease duration 9 ± 6 years, H&Y 2 47%, H&Y 3 26%) enrolled in the prospective international multicenter NPF-QII Study. One-year follow-up data was available for 1030 patients. Rates and risk factors for hospital encounters were determined at baseline and after one year follow-up., Results: Of 3415 PD participants at study entry, 1120 (33%) reported at least one hospital encounter. Associations were: longer timed up-and-go test (OR: 1.33), increased comorbidities (OR: 1.25), motor fluctuations (OR: 1.32), and deep brain stimulation (DBS) (OR: 2.49). Of these 1120 persons, 311 had follow-up data and 158 (51%) had a repeat encounter one year later, associated with higher H&Y stage, fluctuations, and lower health-related quality-of-life. Of 2295 participants without a hospital encounter at baseline, 719 had follow-up data and 178 (25%) had a first hospital encounter one year later. Risk factors were female gender, comorbidities, lower cognition, fluctuations, and DBS., Conclusions: One-third of people with PD had a hospital encounter each year, and one-half of those had a repeat encounter. These high rates correlated with disease severity, comorbidities and DBS. There is an urgent need to develop programs to reduce PD hospital encounters., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Diffusion tensor imaging could be useful in characterizing movement disorders because it noninvasively examines multiple brain regions simultaneously. We report a multitarget imaging approach focused on the basal ganglia and cerebellum in Parkinson's disease, parkinsonian variant of multiple system atrophy, progressive supranuclear palsy, and essential tremor and in healthy controls. Seventy-two subjects were studied with a diffusion tensor imaging protocol at 3 Tesla. Receiver operating characteristic analysis was performed to directly compare groups. Sensitivity and specificity values were quantified for control versus movement disorder (92% sensitivity, 88% specificity), control versus parkinsonism (93% sensitivity, 91% specificity), Parkinson's disease versus atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson's disease versus multiple system atrophy (94% sensitivity, 100% specificity), Parkinson's disease versus progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy versus progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson's disease versus essential tremor (92% sensitivity, 87% specificity). The brain targets varied for each comparison, but the substantia nigra, putamen, caudate, and middle cerebellar peduncle were the most frequently selected brain regions across classifications. These results indicate that using diffusion tensor imaging of the basal ganglia and cerebellum accurately classifies subjects diagnosed with Parkinson's disease, atypical parkinsonism, and essential tremor and clearly distinguishes them from control subjects., (© 2013 International Parkinson and Movement Disorder Society.)

Importance: We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far., Objective: To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study., Design, Setting, and Participants: Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort., Main Outcomes and Measures: The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol., Results: Slightly, but significantly, lower levels of Aβ1-42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181., Conclusions and Relevance: In this first report of CSF biomarkers in PPMI study subjects,we found that measures of CSF Aβ1-42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression

We conducted an exploratory analysis of the utility of the modified Rankin Scale (mRS) as a global measure of disability in early Parkinson's diesase (PD) using the baseline data from a large cohort of PD patients enrolled in a longitudinal study of creatine. The mRS is scored 0-6 with lower scores reflecting less disability. For the analysis the mRS score was dichotomized at <2 versus ≥2. We explored the association of the mRS with multiple measures of PD-related impairments, including the Unified Parkinson Disease Rating Scale (UPDRS); cognitive function characterized by the Symbol Digit Modalities--verbal, and Scales for Outcomes in Parkinson's disease--cognition (SCOPA-COG); quality of life (Parkinson's disease questionnaire [PDQ-39]) and EuroQOL; Beck Depression Inventory II (BDI); and Total Functional Capacity (TFC). We also investigated the interaction between variables. One thousand seven hundred forty-one patients were included in the analysis of which 374 had a mRS score of 2 or above. In the univariate model, all interested measures except SCOPA-COG (p=0.23) had significant association with mRS (p<0.001) after controlling for confounders. In the multivariate model, UPDRS Part II and III (activities of daily living and motor), BDI, TFC and PDQ-39 were significant (p<0.05). The mRS has a significant association with the wide spectrum of measures of impairment and quality of life in early PD and shows good potential to be a global measure of disability in early PD. The sensitivity of the mRS to change and performance of the scale in more advanced PD will have to be established longitudinally., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation as to whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed., Method: Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n = 11) and patients with PD (n = 15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences., Results: Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n = 20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals., Conclusion: The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system.

Background: Prior studies demonstrated that hesitation-prone persons with Parkinson's disease (PDs) acutely improve step initiation using a novel self-triggered stimulus that enhances lateral weight shift prior to step onset. PDs showed reduced anticipatory postural adjustment (APA) durations, earlier step onsets, and faster 1st step speed immediately following stimulus exposure., Objective: This study investigated the effects of long-term stimulus exposure., Methods: Two groups of hesitation-prone subjects with Parkinson's disease (PD) participated in a 6-week step-initiation training program involving one of two stimulus conditions: 1) Drop. The stance-side support surface was lowered quickly (1.5 cm); 2) Vibration. A short vibration (100 ms) was applied beneath the stance-side support surface. Stimuli were self-triggered by a 5% reduction in vertical force under the stance foot during the APA. Testing was at baseline, immediately post-training, and 6 weeks post-training. Measurements included timing and magnitude of ground reaction forces, and step speed and length., Results: Both groups improved their APA force modulation after training. Contrary to previous results, neither group showed reduced APA durations or earlier step onset times. The vibration group showed 55% increase in step speed and a 39% increase in step length which were retained 6 weeks post-training. The drop group showed no stepping-performance improvements., Conclusions: The acute sensitivity to the quickness-enhancing effects of stimulus exposure demonstrated in previous studies was supplanted by improved force modulation following prolonged stimulus exposure. The results suggest a potential approach to reduce the severity of start hesitation in PDs, but further study is needed to understand the relationship between short- and long-term effects of stimulus exposure.

Background: Freezing of gait (FOG) is a common symptom in patients with advanced Parkinson's disease (PD) representing a major cause of disability and falls. Although the pathophysiology of FOG remains poorly understood, nondopaminergic pathways have been implicated. Treatment studies of levodopa and selegiline have shown limited benefit for FOG. Limited data suggest that amantadine, an N-methyl-D-aspartate receptor antagonist, may be beneficial for FOG in PD., Objective: To examine the relationship between treatment with oral amantadine and FOG in patients with PD., Methods: We conducted a retrospective chart review of PD patients who received amantadine specifically for FOG and had a follow-up assessment of FOG. The primary outcome measure was self-reported effectiveness of amantadine (improvement, worsening, or no change in FOG) based on records from the follow-up assessment., Results: Eleven patients with PD with median age of PD onset of 67 years (range, 51-84 years) and median Hoehn and Yahr stage 3 (range, 2-4) met the study population selection criteria. Ten of 11 patients reported improvement in FOG after initiation of amantadine, whereas FOG worsened in one patient. Median amantadine dosage was 100 mg twice daily, and treatment duration was 20 months (range, 6-66 months). Four patients reported reduction in benefit after 4 months. Three patients reported adverse effects, including blurred vision, visual hallucinations, and peripheral edema; the latter 2 effects resulted in discontinuation of amantadine., Conclusion: Amantadine is associated with self-reported improvement in FOG in PD, but this effect may be transient. Further studies, including a randomized placebo-controlled trial, are needed to better evaluate this association.

The costs of treating Parkinson's disease (PD) are significant. Medication reductions usually occur following deep brain stimulation (DBS), but less is known about the relative costs of DBS targets, the globus pallidum (GPi) or the subthalamic nucleus (STN). This article reports medication costs between best medical therapy (BMT) and DBS over 6 months postintervention and by DBS target over 36 months postsurgery. Prescription use and costs for patients (n = 161) with advanced PD from a multisite randomized trial of BMT and DBS were examined overall and by drug category. Medication adjustment occurred at the discretion of the neurologists. PD medications were extracted from the Department of Veterans Affairs Decision Support System database. Levodopa equivalents (LEDD) were significantly lower for DBS than for BMT patients at 6 months (1101 vs 1398 mg; P = .005), but costs were similar (US$1750 vs US$1589; P = .55). LEDD decreased following GPi and STN DBS (1395-1161 mg, P = .014; and 1347-891 mg, P < .0001, respectively) in the first 6 months, but was lower for STN than for GPi over 36 months following DBS (P = .03). Total PD medication costs per 6-month intervals decreased over 36 months (P < .0001), but did not differ by target (P = .50) in the mixed-model analysis. However, cumulative medication costs over 36 months were lower for the STN than for GPi patients. PD medication use and costs decreased following DBS in either target over 36 months, but cumulative costs were less for STN than for GPi., (Copyright © 2012 Movement Disorder Society.)

People with Parkinson's disease (PD) frequently have difficulties with generating anticipatory postural adjustments (APAs) for forward propulsion and lateral weight transfer when initiating gait. This impairment has been attributed to deficits in motor planning and preparation. This study examined the preparation of APAs prior to an imperative cue to initiate forward stepping. A startling acoustic stimulus (SAS) was used to probe the state of preparation of the APA in eight PD (off medication) and seven matched control subjects. Subjects performed visually cued trials involving a pre-cue light instructing them to prepare to step, followed 3.5 s later by a go-cue light to rapidly initiate stepping. In random trials, a SAS (124 dB) was presented at -1,500, -1,000, -500, -250, -100, or 0 ms before the go-cue. Subjects also performed self-initiated steps. Ground reaction forces (GRFs), center of pressure (CoP) changes, and electromyographic (EMG) signals were recorded. The SAS triggered APAs in 94 ± 11% (PD) and 96 ± 8% (control) of trials at latencies 89 ± 4 ms (PD) and 97 ± 3 ms (control) earlier than Control trials. The temporal profile of APA preparation was similar between groups. However, peak EMG, GRF, and mediolateral CoP amplitudes were reduced in PD. SAS-evoked APAs at 0 ms matched Control trial APAs and were enhanced compared with self-initiated stepping. These results demonstrate that people with mild to moderate PD can plan and prepare the appropriate APA sequence prior to the expected cue to initiate gait; however, the prepared APAs are underscaled in magnitude.

During the initiation of stepping, anticipatory postural adjustments (APAs) for lateral weight transfer and propulsion normally precede the onset of locomotion. In Parkinson's disease (PD), impaired step initiation typically involves altered APA ground force production with delayed step onset and deficits in stepping performance. If, as in stance and gait, sensory information about lower limb load is important for the control of stepping, then perturbations influencing loading conditions could affect the step initiation process. This study investigated the influence of changes in lower limb loading during step initiation in patients with PD and healthy control subjects. Participants performed rapid self-triggered step initiation with the impending single stance limb positioned over a pneumatically actuated platform. In perturbation trials, the stance limb ground support surface was either moved vertically downward (DROP) or upward (ELEVATE) by 1.5 cm shortly after the onset of the APA phase. Overall, PD patients demonstrated a longer APA duration, longer time to first step onset, and slower step speed than controls. In both groups, the DROP perturbation reinforced the intended APA kinetic changes for lateral weight transfer and resulted in a significant reduction in APA duration, increase in peak amplitude, and earlier time to first step onset compared with other conditions. During ELEVATE trials that opposed the intended weight transfer forces both groups rapidly adapted their stepping to preserve standing stability by decreasing step length and duration, and increasing step height and foot placement laterally. The findings suggested that sensory information associated with limb load and/or foot pressure modulates the spatial and temporal parameters of posture and locomotion components of step initiation in interaction with a centrally generated feedforward mode of neural control. Moreover, impaired step initiation in PD may at least acutely be enhanced by augmenting the coupling between posture and locomotion.

Recent data suggests that isradipine, a dihydropyridine calcium channel blocker, is neuroprotective in preclinical models of parkinsonism. Isradipine has not been systematically studied in patients with Parkinson's disease (PD). The aim of this study was to evaluate safety and tolerability of isradipine controlled release (CR) in patients with early PD. Qualified subjects (n = 31) received isradipine CR, titrated from 5 to 20 mg daily dose over 8 weeks as tolerated. Eighty-one percent of subjects completed the study. Tolerability of isradipine CR was dose dependent: 94% for 5 mg dose; 87% for 10 mg; 68% for 15 mg; and 52% for 20 mg. Isradipine had no significant effect on blood pressure or PD motor disability. The two most common reasons for dose reduction were leg edema (7) and dizziness (3). There was no difference in isradipine tolerability between subjects with and without dopaminergic treatment, or with and without hypertension., (© 2010 Movement Disorder Society.)

Cognitive impairment is common in Parkinson's disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen for dementia and mild cognitive impairment in clinical trials of PD where cognition is not the primary outcome. This Task Force conducted a systematic literature search for cognitive assessments previously used in a PD population. Scales were then evaluated for their appropriateness to screen for cognitive deficits in clinical trials, including brief administration time (<15 minutes), assessment of the major cognitive domains, and potential to detect subtle cognitive impairment in PD. Five scales of global cognition met the predetermined screening criteria and were considered for review. Based on the Task Force's evaluation criteria the Montreal Cognitive Assessment (MoCA), appeared to be the most suitable measure. This Task Force recommends consideration of the MoCA as a minimum cognitive screening measure in clinical trials of PD where cognitive performance is not the primary outcome measure. The MoCA still requires further study of its diagnostic utility in PD populations but appears to be the most appropriate measure among the currently available brief cognitive assessments. Widespread adoption of a single instrument such as the MoCA in clinical trials can improve comparability between research studies on PD., (© 2010 Movement Disorder Society.)

Performance of repetitive finger movements is an important clinical measure of disease severity in patients with Parkinson's disease (PD) and is associated with a dramatic deterioration in performance at movement rates near 2 Hz and above. The mechanisms contributing to this rate-dependent movement impairment are poorly understood. Since clinical and experimental testing of these movements involve prolonged repetition of movement, a loss of force-generating capacity due to peripheral fatigue may contribute to performance deterioration. This study examined the contribution of peripheral fatigue to the performance of unconstrained index finger flexion movements by measuring maximum voluntary contractions (MVC) immediately before and after repetitive finger movements in patients with PD (both off- and on-medication) and matched control subjects. Movement performance was quantified using finger kinematics, maximum force production, and electromyography (EMG). The principal finding was that peak force and EMG activity during the MVC did not significantly change from the pre- to post-movement task in patients with PD despite the marked deterioration in movement performance of repetitive finger movements. These findings show that the rate-dependent deterioration of repetitive finger movements in PD cannot be explained by a loss of force-generating capacity due to peripheral fatigue, and further suggest that mechanisms contributing to impaired isometric force production in PD are different from those that mediate impaired performance of high-rate repetitive movements., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To pilot a data-driven quality care program in National Parkinson Foundation (NPF) Centers of Excellence., Background: Evidence from comparative effectiveness research (CER) can be used to guide decisions regarding health care and to improve quality and efficiency of care. We propose to develop the infrastructure required to conduct CER across an extensive network of NPF Centers of Excellence., Methods: We present the staged planning for a pilot study which will demonstrate the development and implementation of the infrastructure that will be needed for a large standardized patient-centered, clinical practice database for PD. This database will support CER and drive quality improvement studies., Results: We describe the infrastructure for the ongoing pilot feasibility testing in a subset of six NPF Centers of Excellence, and we discuss the impact that the data (available in 2010) could have in guiding PD management., Conclusion: This preliminary experience will facilitate the longitudinal tracking of therapies and of outcomes in PD clinical practice. Further, we are hopeful that the information will provide insight into PD that will extend beyond the clinical trials population (the population included in most available PD databases). This prospective standardized real-world multi-center clinical practice database will aim to identify positive health outcomes associated with treatment approaches, and to identify variations in clinical outcomes that may suggest improvements in best clinical practice patterns., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Approximately two thirds of Parkinson's disease (PD) patients exhibit bothersome pain symptoms that oftentimes go unrecognized. In this study, 14 patients with PD volunteered to complete a computerized version of the McGill Pain Questionnaire using the PAINReportIt interactive software to assess the feasibility of acquiring real-time pain data in a clinical setting. 100% of the subjects completed >90% of questions in an average of 19.9 min; however, some subjects (n = 4, 28.6%) required physical assistance. 92.9% (n = 13) of subjects supported use of PAINReportIt across all measures. PAINReportIt was feasible as a data-collection modality among our PD cohort, and with modifications may be used as both an investigative instrument and clinical tool for the evaluation of PD-related pain syndromes., (Copyright 2009 Elsevier Ltd. All rights reserved.)

In young healthy adults, syncopated finger movements (movements between consecutive beats) are characterized by a frequency-dependent change in phase at movement rates near 2 Hz. A similar frequency-dependent phase transition is observed during bimanual anti-phase (asymmetric) tasks in healthy young adults, but this transition frequency is significantly lowered in both patients with Parkinson's disease (PD) and older adults. To date, no study has examined the transition frequency associated with unimanual syncopated movements in patients with PD or older adults. This study examined the effects of movement frequency on the performance of unconstrained syncopated index finger flexion movements in patients with PD, older adult subjects matched to patients with PD, and young adult subjects. Syncopated movements were paced by an acoustic tone that increased in frequency from 1 to 3 Hz in 0.25 Hz increments. Movement phase was quantified and the movement frequency where subjects transitioned from syncopation to synchronization was compared between groups. The principal finding was a marked impairment in the ability of patients with PD to perform syncopated movements when off medication. Medication did not significantly improve performance. In addition, the transition frequency for older adult subjects was lower than young adult subjects. These findings demonstrate that, similar to bimanual tasks, the coordination dynamics associated with unimanual syncopated finger movements transition from a stable to an unstable pattern at significantly lower frequencies in patients with PD and older adults compared to young adults.

Performance of repetitive hand movements in patients with Parkinson's disease (PD) is characterized by slowness, reduced movement amplitude, and hesitation or arrests in ongoing movement. Currently, the factors and mechanisms contributing to impaired performance of these types of movement remain poorly understood. This study examined the effects of movement frequency and medication on the performance of unconstrained index finger flexion movements in patients with PD and matched control subjects. Movements were synchronized with an auditory tone as the frequency of the tone was increased from 1 to 3 Hz in 0.25 Hz increments. Movement performance was quantified based upon finger kinematics and electromyography (EMG) recorded from the index finger flexors and extensors. The principal finding was that patients with PD showed a dramatic reduction in movement amplitude, an increase in movement frequency, and a loss of phase when the movement frequency reached or exceeded 2 Hz. This deficit was not significantly improved with medications. In contrast, all control subjects could synchronize to 3 Hz. These findings show that movement frequency is a major determinant of hypokinesia during repetitive movements and may contribute to hesitations and movement arrest during clinical testing of bradykinesia in the upper limb of patients with PD., ((c) 2009 Movement Disorder Society.)

Background and Purpose: Anticipatory postural adjustments (APAs) for lateral weight transfer and stability precede and accompany gait initiation. Individuals with Parkinson's disease (PD) show altered APA characteristics with delays in initiating stepping that may reflect impaired interactions between posture and locomotion. The purpose of this study was to determine the short-term effects of a single session of repetitive robotic assistance training with the APA on rapid step initiation in individuals with PD in the medications "on" state and healthy control individuals. Ground reaction forces and step kinematics were recorded., Methods: Subjects first performed baseline trials of unassisted self-paced rapid forward stepping. Next, a training acquisition series involved 50 trials with a lateral pull applied to the pelvis by a robotic system to assist with the early phase of the APA during stepping. To assess potential retention effects of training, unassisted stepping trials were evaluated immediately after acquisition trials (immediate retention) and one week later (one-week retention)., Results: Overall, the subjects with PD had a longer APA duration (P < 0.03), and longer first step duration (P < 0.04) than the healthy control individuals. Compared with baseline, APA duration was shorter (P < 0.001) and step onset time became earlier (P < 0.001) for acquisition trials but these effects were not retained. Step duration, which became shorter (P < 0.001) during the late acquisition trials (P = 0.002), demonstrated immediate retention (P < 0.001) and one-week retention (P < 0.001)., Conclusion: Posture-assisted training, affecting the interaction between posture and locomotion, may have therapeutic potential for improving movement performance in individuals with PD.

The management of early Parkinson's disease (PD) involves the treatment of motor symptoms and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews motor symptom efficacy data for the newest PD treatment options, as well as for established therapies. Safety and tolerability data are also reviewed. Part 2 of the article reviews key findings relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms., (Copyright 2009 S. Karger AG, Basel.)

The management of early Parkinson's disease (PD) involves the treatment of motor symptoms, and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews efficacy and safety data for the newest PD treatment options, as well as for established therapies. Part 2 of the article, presented here, reviews key data relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms., (Copyright 2009 S. Karger AG, Basel.)

Anticipatory postural adjustments (APAs) for lateral weight transfer and stability precede and accompany voluntary stepping. Patients with Parkinson's disease (PD) show delays in step initiation with altered APA characteristics that may reflect impaired interactions between posture and locomotion. The purpose of this study was to examine the influence of a lateral postural assist on step initiation in patients with early stage PD while off medication and healthy controls. Subjects performed self-paced rapid forward steps. In one condition (ASSIST), the APA was assisted at onset with a lateral pull applied to the pelvis by a motor-driven robotic system. Ground reaction forces and whole body kinematics were recorded to characterize the APA and step characteristics. Overall, PD subjects had a longer APA duration (P < 0.01) and longer first step duration (P < 0.027) than Control subjects. With the ASSIST, the APA duration for both groups was shorter (P < 0.001), the step onset time was earlier (P < 0.001), and the speed of the first step became faster for PD subjects. Postural assistance affecting the interaction between posture and locomotion may have therapeutic potential for improving movement function in patients with PD., (Copyright 2006 Movement Disorder Society.)

We evaluated the long-term effects of subthalamic nucleus (STN) stimulation on health-related quality of life (HRQL) in patients with advanced Parkinson's disease (PD). STN stimulation improves motor function and decreases medication requirements in patients with advanced PD. The impact of STN stimulation on HRQL is less well established, especially beyond 1 year after surgery. We report HRQL outcomes for 18 patients with advanced PD. Patients were evaluated with the Parkinson's Disease Questionnaire-39 (PDQ-39), the Medical Outcome Study Short Form (SF-36), and the EuroQol visual analogue scale (VAS) before surgery, 6 months postoperatively, and at a long-term follow-up visit (mean, 35.9 months; range, 18-57 months after surgery). Preoperative scores on HRQL measures were compared to results obtained at short- and long-term follow-up evaluations. The VAS and all domains of the PDQ-39 except for cognition, communication, and social support showed marked improvements at 6 months after surgery. At the long-term follow-up, there were sustained improvements in the VAS (63% improvement; P = 0.0009) and in several domains of the PDQ-39 [mobility: 20%, P = 0.01; activities of daily living (ADL): 29%, P = 0.005; emotional well-being: 26%, P = 0.02; stigma: 43%, P = 0.003; and bodily discomfort: 35%, P = 0.007]. At the long-term evaluation, only the vitality domain of the SF-36 was significantly improved from baseline (16%; P = 0.01). In this selected group of patients, many of the short-term gains in HRQL persist beyond 18 months after STN implantation. Benefits in nonmotor aspects of HRQL such as bodily discomfort and stigma appear to be among the most durable.

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., (Copyright 2006 S. Karger AG, Basel.)

We describe the case of a 28-year-old obtunded woman who presented with bilateral anterior parietal lobe cortical hemorrhages associated with thrombosis of the superior sagittal sinus, both transverse and sigmoid sinuses, and multiple cortical veins draining into the sagittal sinus. Initial heparin therapy was not effective. A combination of AngioJet rheolytic catheter thrombectomy, balloon angioplasty, and continuous direct superior sagittal sinus recombinant tissue plasminogen activator infusion led to venous recanalization with a successful clinical outcome, without worsening of the preexisting intracranial hemorrhages.

This postmortem study correlated intraoperative subthalamic nucleus (STN) deep brain stimulation (DBS) placement and postoperative magnetic resonance imaging (MRI) with autopsy findings in a patient who died suddenly 4 days postoperatively from a pulmonary embolism. The study demonstrates that (1) MRI stereotactic localization combined with microelectrode recording (MER) is an accurate way to target STN; (2) multiple MER tracts do not cause significant injury to the brain; and (3) postoperative MRI accurately demonstrates location of the DBS electrodes., (Copyright 2003 Movement Disorder Society)

Object: Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD., Methods: In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods., Conclusions: This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.

The etiology of parkinsonism is varied. Symptomatic parkinsonism is seen in the setting of genetic disorders, infectious processes, structural lesions, and as a result of concomitant medications. A thorough history and good examination will differentiate PD from the diverse group of conditions that can mimic it.

The treatment of essential tremor with thalamic deep brain stimulation (DBS) is considered to be more effective and to cause less morbidity than treatment with thalamotomy. Nonetheless, implantation of an indwelling electrode, connectors, and a generator is associated with specific types of morbidity. The authors describe three patients who required revision of their DBS systems due to lead breakage. The connector between the DBS electrode and the extension wire, which connects to the subclavicular pulse generator, was originally placed subcutaneously in the cervical region to decrease the risk of erosion through the scalp and to improve cosmesis. Three patients presented with fractured DBS electrodes that were located in the cervical region near the connector, necessitating reoperation with stereotactic retargeting and placement of a new intracranial electrode. At reoperation, the connectors were placed subgaleally over the parietal region. Management of these cases has led to modifications in the operative procedure designed to improve the durability of DBS systems. The authors recommend that surgeons avoid placing the connection between the DBS electrode and the extension wire in the cervical region because patient movement can cause microfractures in the electrode. Such microfractures require intracranial revision, which may be associated with a higher risk of morbidity than the initial operation. The authors also recommend considering prophylactic relocation of the connectors from the cervical area to the subgaleal parietal region to decrease the risk of future DBS electrode fracture, which would necessitate a more lengthy procedure to revise the intracranial electrode.

Essential tremor can be suppressed with chronic, bilateral deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim), the cerebellar receiving area of the motor thalamus. The goal in this study was to correlate the location of the electrodes with the clinical efficacy of DBS in a patient with essential tremor. The authors report on a woman with essential tremor in whom chronic bilateral DBS directed to the ventral thalamus produced adequate tremor suppression until her death from unrelated causes 16 months after placement of the electrodes. Neuropathological postmortem studies of the brain in this patient demonstrated that both stimulators terminated in the Vim region of the thalamus, and that chronic DBS elicited minor reactive changes confined to the immediate vicinity of the electrode tracks. Although the authors could not identify neuropathological abnormalities specific to essential tremor, they believe that suppression of essential tremor by chronic DBS correlates with bilateral termination of the stimulators in the Vim region of the thalamus.

Deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim) is a safe and effective treatment for essential tremor. Bipolar disorder and essential tremor had each been reported to occur in association with Klinefelter syndrome but the three diseases have been reported to occur together in only one patient. The genetic basis and natural history of these disorders are not completely understood and may be related rather than coincidental. The authors report on a 23-year-old man with Klinefelter syndrome (47,XXY) and bipolar disorder who was treated successfully with unilateral DBS of the thalamic Vim for essential tremor.

Although the clinical manifestations of PD remain similar to those described by Parkinson in the nineteenth century, knowledge of associated findings has increased dramatically. The ability to characterize the myriad of findings associated with PD enables clinicians to care better for patients with PD. Knowledge of the associated symptoms as well as the cardinal manifestations allows clinicians to target treatment to specific symptoms and thereby improve the quality of life of those affected with PD.

The authors assess the accuracy of targeting nucleus ventralis intermedius (Vim) with fast spin echo inversion recovery (FSE/IR) magnetic resonance imaging (MRI) in 18 successful deep brain stimulator (DBS) implants for medically refractory tremor. FSE/IR-MRI-derived coordinates are compared to the final coordinates employed for DBS lead placement, selected with intraoperative neurophysiology. The authors conclude that FSE/IR MRI is sufficiently reliable to serve as the sole means of anatomically targeting Vim for DBS lead placement. An independent computer workstation is not required for accurate targeting; however, intraoperative neurophysiology remains essential., (Copyright 2000 S. Karger AG, Basel)