Parkinson Disease: Tröster AI

Tröster AI. · Department of Neurology (CB 7025), University of North Carolina at Chapel Hill, 3114 Bioinformatics Building, Chapel Hill, NC 27599-7025, USA. · Neuropsychol Rev. · Pubmed #18322801 No free full text.

Abstract: Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are neurodegenerative conditions sharing a disorder of alpha-synuclein metabolism. Temporal differences in the emergence of symptoms and clinical features warrant the continued clinical distinction between DLB and PDD. While DLB and PDD groups' neuropsychological profiles often differ from those in Alzheimer's disease (AD), the diagnostic sensitivity, specificity, and predictive values of these profiles remain largely unknown. PDD and DLB neuropsychological profiles share sufficient similarity to resist accurate and reliable differentiation. Although heterogeneous cognitive changes (predominantly in memory and executive function) may manifest earlier and more frequently than previously appreciated in Parkinson's disease (PD), and executive deficits may be harbingers of dementia, the enthusiasm to uncritically extend the concept of mild cognitive impairment (MCI) to PD should be tempered. Instead, future research might strive to identify the precise neuropsychological characteristics of the prodromal stages of PD, PDD, and DLB which, in conjunction with other potential biomarkers, facilitate early and accurate diagnosis, and the definition of neuroprotective, neurorestorative, and symptomatic treatment endpoints.

Voon V, Kubu C, Krack P, Houeto JL, Tröster AI. · Department of Psychiatry, Toronto Western Hospital, Toronto, Canada. · Mov Disord. · Pubmed #16810676 No free full text.

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced PD is well established. However, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The neuropsychiatric aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. As a companion to the preoperative and postoperative sections of the DBS consensus articles, this article reviews the published literature on the cognitive and neuropsychiatric aspects of DBS for PD. The majority of the observed neuropsychiatric symptoms are transient, treatable, and potentially preventable. Outcome studies, methodological issues, pathophysiology, and preoperative and postoperative management of the cognitive and neuropsychiatric aspects and complications of DBS for PD are discussed.

Burn DJ, Tröster AI. · Department of Neurology, Regional Neurosciences Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE. · J Geriatr Psychiatry Neurol. · Pubmed #15312281 No free full text.

Abstract: This review deals with the range of neuropsychiatric problems that may arise from the use of medical and surgical therapies in the treatment of Parkinson's disease. As new approaches emerge, these problems are diversifying. Well-recognized drug-related complications include hallucinations and psychosis and the so-called dopamine-dysregulation syndrome. The etiology of these problems has not been fully established and is not clearly dose related, while the management can be difficult and needs to be tailored to the individual patient. Cholinergic and dopaminergic drugs may both influence cognitive function. The development of pharmacogenetics could improve the therapeutic ratio of medical approaches to PD in the future. The literature relating to the neuropsychiatric issues complicating the surgical treatment of Parkinson's disease is more recent and frequently suffers from methodological problems, lack of a systematic approach, and adequate patient follow-up. The emergence of neuropsychiatric problems in association with surgery has shed new light upon the pathophysiological mechanisms underpinning these symptoms. Depression, hypomania, euphoria, mirth, and hypersexuality have all been described following deep brain stimulation procedures, although most studies have concentrated upon the depressive features. Anxiety has been described only rarely to date. Fortunately, permanent cognitive complications appear to be rare. The optimal management approach for surgically related neuropsychiatric problems is unknown at present. Prospective multicenter studies would contribute significantly to resolving this therapeutic uncertainty.

Woods SP, Fields JA, Tröster AI. · Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle 98195-6560, USA. · Neuropsychol Rev. · Pubmed #12371602 No free full text.

Abstract: Neuropsychologists are increasingly involved in surgical candidacy evaluations and postoperative neurobehavioral assessments of patients with movement disorders, most notably those with Parkinson's disease (PD). We review here the initial studies regarding neuropsychological outcomes of deep brain stimulation (DBS) within the subthalamic nucleus (STN) for treatment of PD. Overall, these initial investigations provide preliminary support for the cognitive and neurobehavioral safety of STN DBS. Improvements in self-reported symptoms of depression and diminished verbal fluency were the most common findings, whereas changes in global cognitive abilities, memory, attention, and frontal/executive functions were inconsistent and most often described as nominal and/or transient. The generalizability of this literature is hindered by several methodological limitations, including small samples and the absence of appropriate control participants. The clinical and theoretical implications of these initial studies are highlighted and recommendations are offered to guide future research.

Fields JA, Tröster AI. · Department of Neurology, University of Kansas Medical Center, Kansas City 66160-7314, USA. · Brain Cogn. · Pubmed #10744924 No free full text.

Abstract: Modern ablative surgery for movement disorders probably results in less frequent and severe cognitive morbidity than seen in early surgical series. Nonetheless, recent studies indicate that neurobehavioral functions commonly compromised in Parkinson's disease (PD) (e.g., executive functions, verbal fluency, and memory) are negatively impacted in some patients by lesion placement. The potential reversibility of cognitive dysfunction after chronic electrical deep brain stimulation (DBS) for PD has lead some to favor this treatment modality over ablation. This paper reviews the initial studies of the cognitive effects of thalamic, pallidal, and subthalamic DBS. These studies suggest that DBS is relatively safe from a cognitive standpoint and that the benefits of motor improvements probably outweigh the cost of minimal cognitive morbidity. This conclusion must be offered with caution, however, given the small numbers of studies to date and their methodological limitations. Neurobehavioral research has yet to adequately address (1) outcome relative to appropriate control groups; (2) effects of electrode placement versus stimulation; (3) laterality- and site-specific effects of DBS; (4) long-term effects of DBS; (5) effects of stimulation parameters; (6) risk factors for cognitive dysfunction with DBS; (7) whether cognitive dysfunction associated with DBS is reversible; and (8) comparative neurobehavioral outcome after DBS and ablation. DBS affords an exciting opportunity to clarify the neurobehavioral role of the basal ganglia.

Norman S, Tröster AI, Fields JA, Brooks R. · Department of Psychology, Xavier University, Cincinnati, Ohio 45207-6511, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #11884652 links to  free full text

Abstract: This study compared the performance of Parkinson's disease (PD) patients with and without depression, patients with depression alone, and normal control subjects on a cognitive screening instrument, the Mattis Dementia Rating Scale (DRS) to evaluate the influences of depression and Parkinson's disease on cognition. PD affects overall level of cognitive functioning and, to a lesser extent, DRS Initiation/Perseveration, Construction, and Attention. Diminished memory was primarily related to depression. Treatment of depression may ameliorate aspects of cognitive dysfunction in the PD patient with depression.

Woods SP, Fields JA, Lyons KE, Koller WC, Wilkinson SB, Pahwa R, Tröster AI. · Department of Psychiatry & Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA. · Acta Neurochir (Wien). · Pubmed #11810392 No free full text.

Abstract: BACKGROUND: The long-term neuropsychological and quality of life (QOL) outcomes of unilateral thalamic deep brain stimulation (DBS) in patients with intractable Parkinson's disease (PD) have not heretofore been described. METHOD: Six patients diagnosed with PD underwent unilateral DBS implantation into a verified thalamic VIM nucleus target. Participants completed presurgical neuropsychological evaluation and follow-up assessment at approximately one year postsurgery. FINDINGS: Compared to their presurgical scores, PD patients exhibited significant improvement on measures of conceptualization, verbal memory, emotional adjustment, and QOL at one-year follow-up. A few nominal declines were observed across the battery of tests. INTERPRETATION: These data provide preliminary support for the long-term neurocognitive safety and QOL improvements following thalamic stimulation in patients with PD.

Hristova A, Lyons K, Tröster AI, Pahwa R, Wilkinson SB, Koller WC. · Department of Neurology, University of Kansas Medical Center, Kansas City, USA. · Clin Neuropharmacol. · Pubmed #11020125 No free full text.

Abstract: We studied the effect and temporal profile of deep brain stimulation (DBS) of the globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease (PD). Four patients with bilateral deep brain stimulators of the globus pallidus and four patients with bilateral deep brain stimulators of the subthalamus were studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6 hours after turning stimulation on. An immediate (15 minutes) and sustained (6 hours) benefit was observed for all the motor manifestations of PD for both stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus is highly effective in reducing all the cardinal motor features of PD.

Fields JA, Tröster AI, Wilkinson SB, Pahwa R, Koller WC. · Department of Neurology, University of Kansas Medical Center, Kansas City 66160-7314, USA. · Clin Neurol Neurosurg. · Pubmed #10536904 No free full text.

Abstract: As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.

Fernandez HH, Aarsland D, Fénelon G, Friedman JH, Marsh L, Tröster AI, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. · Department of Neurology, McKnight Brain Institute/University of Florida, Gainesville, Florida 32611, USA. · Mov Disord. · Pubmed #18175343 links to  free full text

Abstract: Psychotic symptoms are a frequent occurrence in Parkinson's disease (PD), affecting up to 50% of patients. The Movement Disorder Society established a Task Force on Rating Scales in PD, and this critique applies to published, peer-reviewed rating psychosis scales used in PD psychosis studies. Twelve psychosis scales/questionnaires were reviewed. None of the reviewed scales adequately captured the entire phenomenology of PD psychosis. While the Task Force has labeled some scales as "recommended" or "suggested" based on the fulfilling-defined criteria, none of the current scales contained all the basic content, mechanistic and psychometric properties needed to capture PD psychotic phenomena and to measure clinical response over time. Different scales may be better for some settings versus others. Since one scale may not be able to serve all needs, a scale used to measure clinical response and change over time [such as the Clinical Global Impression Scale (CGIS)] may need to be combined with another scale better at cataloging specific features [such as the Neuropsychiatric Inventory (NPI) or Schedule for Assessment of Positive Symptoms (SAPS)]. At the present time, for clinical trials on PD psychosis assessing new treatments, the following are recommended primary outcome scales: NPI (for the cognitively impaired PD population or when a caregiver is required), SAPS, Positive and Negative Syndrome Scale (PANSS), or Brief Psychiatric Rating Scale (BPRS) (for the cognitively intact PD population or when the patient is the sole informant). The CGIS is suggested as a secondary outcome scale to measure change and response to treatment over time.

Tröster AI, Woods SP, Morgan EE. · Department of Neurology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7025, USA. · Arch Clin Neuropsychol. · Pubmed #17644304 No free full text.

Abstract: Serial assessments of cognitive functioning in individuals with Parkinson's disease (PD) are commonly used for the detection of incident dementia and neurobehavioral changes associated with treatments using neuromodulation (e.g., deep brain stimulation) and pharmacological agents (e.g., cholinesterase inhibitors). This study provides test-retest stability, expected practice effects, and practice-corrected reliable change indices for several commonly used neuropsychological tests from 62 older adults with mostly mild PD who underwent repeat evaluations approximately 17 months apart. At the group level, results showed adequate test-retest reliability (Spearman's rho range=0.24-0.86) and generally small practice effects (Cohen's d range=0.00-0.50). Application of reliable change indices using 90% confidence intervals showed the expected number of individuals (generally 10% or fewer) with statistically meaningful improvements (range=0-12%) or declines (range=2-8%) in cognitive performance at retest. Limitations discussed include ceiling effects at test baseline, sample homogeneity, interpretative cautions, and generalizability of study results. These data may be useful to researchers and clinicians interested in determining the statistical significance of changes in cognitive test performance in persons with PD over a 1- to 2-year interval.

Huang X, Lee YZ, McKeown M, Gerig G, Gu H, Lin W, Lewis MM, Ford S, Tröster AI, Weinberger DR, Styner M. · Department of Neurology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7025, USA, and University Hospital, Vancouver, British Columbia, Canada. · Mov Disord. · Pubmed #17588238 No free full text.

Abstract: Parkinson's disease (PD) typically manifests with asymmetric motor symptom onset. Ventricular enlargement, a nonspecific measure of brain atrophy, has been associated with cognitive decline in PD, but not with motor symptom asymmetry. Asymmetrical ventricular enlargement on magnetic resonance images was explored in a monozygotic twin pair discordant for PD and in nine healthy monozygotic twin pairs. The left-right lateral ventricular volumetric difference of the PD-twin was greater than that of his twin and all other healthy twins, with the larger ventricle observed contralateral to the more symptomatic side. Moreover, the lateral ventricle asymmetry difference between twin pairs was significantly higher for the discordant PD-twin pair than for the healthy twin pairs. This is the first report to suggest the presence of asymmetrical ventricular enlargement in PD, findings that may be worthy of further study.

Deuschl G, Herzog J, Kleiner-Fisman G, Kubu C, Lozano AM, Lyons KE, Rodriguez-Oroz MC, Tamma F, Tröster AI, Vitek JL, Volkmann J, Voon V. · Department of Neurology, Christian-Albrechts-Universität Kiel, Kiel, Germany. · Mov Disord. · Pubmed #16810719 No free full text.

Abstract: 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.

Lang AE, Houeto JL, Krack P, Kubu C, Lyons KE, Moro E, Ondo W, Pahwa R, Poewe W, Tröster AI, Uitti R, Voon V. · Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada. · Mov Disord. · Pubmed #16810718 No free full text.

Abstract: Numerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a 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 (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making.

Parsons TD, Rogers SA, Braaten AJ, Woods SP, Tröster AI. · Department of Neurology, School of Medicine, University of North Carolina at Chapel Hill, NC 27599-7025, USA. · Lancet Neurol. · Pubmed #16781988 No free full text.

Abstract: BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) is an increasingly common treatment for Parkinson's disease. Qualitative reviews have concluded that diminished verbal fluency is common after STN DBS, but that changes in global cognitive abilities, attention, executive functions, and memory are only inconsistently observed and, when present, often nominal or transient. We did a quantitative meta-analysis to improve understanding of the variability and clinical significance of cognitive dysfunction after STN DBS. METHODS: We searched MedLine, PsycLIT, and ISI Web of Science electronic databases for articles published between 1990 and 2006, and extracted information about number of patients, exclusion criteria, confirmation of target by microelectrode recording, verification of electrode placement via radiographic means, stimulation parameters, assessment time points, assessment measures, whether patients were on levodopa or dopaminomimetics, and summary statistics needed for computation of effect sizes. We used the random-effects meta-analytical model to assess continuous outcomes before and after STN DBS. FINDINGS: Of 40 neuropsychological studies identified, 28 cohort studies (including 612 patients) were eligible for inclusion in the meta-analysis. After adjusting for heterogeneity of variance in study effect sizes, the random effects meta-analysis revealed significant, albeit small, declines in executive functions and verbal learning and memory. Moderate declines were only reported in semantic (Cohen's d 0.73) and phonemic verbal fluency (0.51). Changes in verbal fluency were not related to patient age, disease duration, stimulation parameters, or change in dopaminomimetic dose after surgery. INTERPRETATION: STN DBS, in selected patients, seems relatively safe from a cognitive standpoint. However, difficulty in identification of factors underlying changes in verbal fluency draws attention to the need for uniform and detailed reporting of patient selection, demographic, disease, treatment, surgical, stimulation, and clinical outcome parameters.

Tröster AI, Fields JA, Paolo AM, Koller WC. · Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. · J Neurol Sci. · Pubmed #16769085 No free full text.

Abstract: The apolipoprotein E (APOE) epsilon4 allele has been associated with an increased risk of Alzheimer's disease (AD) and weaker episodic memory among elderly. Although this APOE allele has been linked to earlier onset of Parkinson's disease (PD), an association with dementia in PD has been only inconsistently demonstrated. Given the heterogeneity of cognitive impairment patterns in PD, this study sought to determine whether an association exists between APOE genotype and specific cognitive deficits in PD. The neuropsychological test performance of 42 PD patients without an epsilon4 allele (PD-Non4) and of 20 with at least one epsilon4 allele (PD-epsilon4) was compared to that of 146 elderly control subjects (NC). The PD groups were comparable in overall severity of cognitive impairment and disease duration, but the PD-epsilon4 group was younger, had an earlier disease onset, and contained a higher proportion of persons with dementia. Both PD groups showed wide-ranging cognitive impairments relative to NC. Once age differences between groups were controlled for, the PD groups generally did not differ from each other in cognitive performance. However, only the PD-Non4 group demonstrated working memory/attention impairments (digit span, visual span, Trailmaking test) relative to the NC group. Results suggest that the APOE genotype may influence the cognitive phenotype of PD, and specifically that absence of the epsilon4 allele is associated with working memory impairment. Additionally, results are consistent with prior findings showing an association between the epsilon4 allele and earlier onset of PD and presence of dementia.

Huang X, Chen P, Kaufer DI, Tröster AI, Poole C. · Department of Neurology, University of North Carolina School of Medicine, Chapel Hill 27599-7025, USA. · Arch Neurol. · Pubmed #16476806 links to  free full text

Abstract: OBJECTIVE: To understand the relationship of apolipoprotein E (APOE) polymorphism to dementia in Parkinson disease (PD) because the APOE epsilon4 allele is linked to Alzheimer disease. DATA SOURCE: We reviewed MEDLINE, BIOSIS Previews, and ISI Web of Science from January 1, 1966, to May 7, 2004, supplemented by citation analysis from retrieved articles. STUDY SELECTION: Case-control studies using clinical or pathologic criteria for PD and dementia, and with complete APOE genotype frequencies data. DATA EXTRACTION: We compared estimated prevalence odds ratios for dementia in PD in relation to each allele. We also looked for evidence of heterogeneity and publication bias and performed a stratified analysis on several study characteristics. DATA SYNTHESIS: Data analyses suggest publication bias and heterogeneity of source data for the epsilon4 allele (homogeneity P = .2; Begg and Mazumdar, P = .06; and Egger et al, P = .1). The estimated odds ratios for development of dementia in PD are 1.6 for epsilon4 (95% confidence interval, 1.0-2.5); 1.3 for epsilon2 (95% confidence interval, 0.73-2.4); and 0.54 for epsilon3 (95% confidence interval, 0.18-1.6). The odds ratio estimates for epsilon4 were higher for studies published in 1996 or later (2.3 vs 1.0) and for studies conducted outside North American sites (2.4 vs 1.2). CONCLUSIONS: The APOE epsilon4 allele appears to be associated with a higher prevalence of dementia in PD. Publication bias and heterogeneous source data may, however, confound this conclusion. Confirmatory studies that use standardized and validated diagnostic criteria for dementia in PD are needed.

Woods SP, Rippeth JD, Conover E, Carey CL, Parsons TD, Tröster AI. · Department of Psychiatry, University of California, San Diego, CA 92103, USA. · Clin Neuropsychol. · Pubmed #16393919 No free full text.

Abstract: It has been argued that neuropsychological studies generally possess adequate statistical power to detect large effect sizes. However, low statistical power is problematic in neuropsychological research involving clinical populations and novel interventions for which available sample sizes are often limited. One notable example of this problem is evident in the literature regarding the cognitive sequelae of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in persons with Parkinson's disease (PD). In the current review, a post hoc estimate of the statistical power of 30 studies examining cognitive effects of STN DBS in PD revealed adequate power to detect substantial cognitive declines (i.e., very large effect sizes), but surprisingly low estimated power to detect cognitive changes associated with conventionally small, medium, and large effect sizes. Such wide spread Type II error risk in the STN DBS cognitive outcomes literature may affect the clinical decision-making process as concerns the possible risk of postsurgical cognitive morbidity, as well as conceptual inferences to be drawn regarding the role of the STN in higher-level cognitive functions. Statistical and methodological recommendations (e.g., meta-analysis) are offered to enhance the power of current and future studies examining the neuropsychological sequelae of STN DBS in PD.

Tröster AI, Fields JA, Wilkinson S, Pahwa R, Koller WC, Lyons KE. · Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. · Stereotact Funct Neurosurg. · Pubmed #14745208 No free full text.

Abstract: BACKGROUND/AIMS: Subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) improves motor symptoms and quality of life (QOL). Because depression is a potent correlate of QOL, and STN-DBS may be associated with changes in mood, this study sought to determine whether QOL improvement is a direct or indirect consequence of motor improvement. METHODS: 26 patients with PD, free of dementia and major depression, who consecutively underwent bilateral, microelectrode-guided STN-DBS, underwent preoperative and 3-month postoperative neuropsychological evaluation, including measures of QOL (PD Questionnaire -39) and depressive symptoms (Beck Depression Inventory). RESULTS: Motor score in the Unified Parkinson's Disease Rating Scale (UPDRS Part III) improved significantly with STN-DBS relative to preoperative 'on' and 'off' scores, as did QOL and depressive symptoms. Extent of QOL improvement tended to be associated with improvement in motor score from presurgical on to postsurgical on stimulation and on medication state. QOL improvement was significantly related to amelioration of depressive symptoms. Partial correlations revealed that the association between QOL improvement and depression remained significant when influence of motor improvement on QOL and depression was controlled for. The motor-QOL association was no longer significant when effects of depression were controlled for. CONCLUSIONS: Significant QOL improvements after STN-DBS are associated with improved motor 'on' state and depressive symptoms. The influence of motor improvement on QOL may be largely indirect by reducing depression.

DePold Hohler A, Ransom BR, Chun MR, Tröster AI, Samii A. · Department of Neurology, Madigan Army Medical Center, Tacoma, WA, USA. · Parkinsonism Relat Disord. · Pubmed #14499207 No free full text.

Abstract: Corticobasal degeneration (CBD) is a movement disorder characterized by early apraxia and asymmetric parkinsonism that responds poorly to anti-Parkinson medications. There are clinical manifestations reflecting dysfunction in both the cerebral cortex and the basal ganglia. Patients typically present between the sixth and seventh decades. Previously, the youngest clinically diagnosed individual was 40 years old. Here we describe a 34-year-old woman who meets the clinical diagnostic criteria for CBD with onset of symptoms at age 28. In this patient, the first symptom was an 'uncooperative' right hand. This was soon followed by right hand dystonia. Symptoms progressed rapidly, and she developed generalized bradykinesia, rigidity, and corticospinal tract signs with preservation of the initial asymmetry. Her symptoms did not respond to a daily dose of 1200 mg of immediate release levodopa. Extensive laboratory workup and brain imaging were normal. Neuropsychological evaluation revealed mild deficits consistent with frontal-subcortical dysfunction. The chronic, progressive course, asymmetric limb rigidity, apraxia, focal dystonia, and lack of response to levodopa suggest CBD. To our knowledge, this is the youngest reported case of clinically probable CBD.

Lyons KE, Wilkinson SB, Tröster AI, Pahwa R. · Department of Neurology, University of Miami Medical Center, Miami, Fla., USA. · Stereotact Funct Neurosurg. · Pubmed #12890979 No free full text.

Abstract: OBJECTIVE: To determine the long-term efficacy and safety of globus pallidus internus (GPi) stimulation for Parkinson's disease (PD). BACKGROUND: We previously reported 3-month data for 5 patients who underwent GPi stimulation for PD. We now report long-term data on these 5 patients and 4 additional patients. METHODS: Nine PD patients, 5 men and 4 women, with an average age of 49 years and disease duration of 10 years, underwent GPi stimulation. Six patients had staged bilateral implants and 3 patients had unilateral implants. The mean follow-up was 48.5 months. All patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) and completed 2-day diaries before and after surgery. RESULTS: There was a 21% improvement in UPDRS Part II (activities of daily living; ADL) scores and a 37% improvement in UPDRS Part III (motor) scores when the longest follow-up in the 'stimulation-on/medication-off' state was compared to the 'medication-off' state at baseline. The UPDRS Part II (ADL) scores improved by 30% and the UPDRS Part III (motor) scores improved by 39% when the longest follow-up in the 'stimulation-on/mediation-on' state was compared to the 'medication-on' state at baseline. As measured by patient diaries, 'on' time increased from 25 to 59% and 'on with dyskinesia' decreased from 42 to 15%. Surgical- and device-related complications included transient hemiparesis in the operating room, postoperative seizures, and implantable pulse generator and lead problems. There were seven device-related events requiring additional surgical procedures. CONCLUSIONS: GPi stimulation continues to be effective for the long-term treatment of the disabling symptoms of PD; however, the physician and patient should be aware that device-related problems are not uncommon and additional surgery may be necessary.

Tröster AI, Woods SP, Fields JA. · Department of Psychiatry and Behavioral Sciences and Department of Neurological Surgery, University of Washington, Seattle, Washington 98195-6560, USA. · Appl Neuropsychol. · Pubmed #12788681 No free full text.

Abstract: Verbal fluency declines are commonly reported after pallidotomy in patients with Parkinson's disease. However, it is not clear whether there is an interaction between side of surgery and task format (lexical vs. semantic) or whether error rates (perseverations, intrusions, rule violations) increase after surgery. This study examined verbal fluency before and approximately 4 months after unilateral pallidotomy. The left and right pallidotomy groups were matched on key demographic, cognitive, and disease variables. Pallidotomy resulted in a decline in lexical but not semantic verbal fluency, and this decline was most evident in the left-sided surgery group. Error rates (perseverations, intrusions, and rule violations) were not affected by pallidotomy. Findings support the role of left frontal-basal ganglionic circuits in word retrieval processes and/or lexical search and access.

Woods SP, Tröster AI. · Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA. · J Int Neuropsychol Soc. · Pubmed #12570354 No free full text.

Abstract: To identify the cognitive characteristics predictive of incident dementia in Parkinson's disease (PD), we examined the baseline neuropsychological profiles of 18 initially non-demented patients with PD who met diagnostic criteria for dementia (PDD) at one-year follow-up. PDD participants' baseline neuropsychological test scores were compared to the baseline performance of 18 patients with PD who did not meet criteria for dementia at one-year follow-up (PDND) and 18 normal controls (NC). The three groups were matched on baseline demographic and disease variables. Relative to the PDND group, the incident PDD participants demonstrated significantly poorer performance on digits backward (Wechsler Memory Scale-Revised), word list learning and recognition (California Verbal Learning Test), and perseverative errors on the Wisconsin Card Sorting Test. Each of these baseline neuropsychological variables exhibited adequate diagnostic classification accuracy in predicting PDD and PDND group membership at follow-up. These results suggest that subtle frontal/executive dysfunction is evident during the immediate PDD prodrome and may be of prognostic value in identifying PD patients at risk for dementia. Accordingly, neuropsychological evaluation may facilitate early identification of PDD and thereby inform appropriate dispositional planning.

Tröster AI, Woods SP, Fields JA, Hanisch C, Beatty WW. · Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington, Seattle, WA, USA. · Brain Cogn. · Pubmed #12464190 No free full text.

Abstract: Declines in verbal fluency are consistently reported in patients with Parkinson's disease (PD) after pallidal surgery. In the present study, the clustering and switching components of semantic or category fluency (oral naming of items obtainable in supermarkets) were examined at baseline and four months after unilateral deep brain stimulation or pallidotomy in 45 patients with PD (30 left, 15 right pallidal surgery). Post-operative declines were observed for supermarket fluency total score and switching, but not for average cluster size. These findings support the proposal that semantic fluency decrements after pallidal surgery reflect a disruption of frontal-basal ganglia circuits mediating efficient shifting between semantic categories, or perhaps efficient access to categories, rather than a degradation of semantic stores.

Higginson CI, Fields JA, Tröster AI. · Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, USA. · Neuropsychiatry Neuropsychol Behav Neurol. · Pubmed #11417665 No free full text.

Abstract: OBJECTIVE: The purpose of the current study was to address whether improvement in anxious symptoms after surgical treatment of Parkinson disease (PD) reflects a true reduction in anxiety as opposed to an epiphenomenon of parkinsonian symptom amelioration. BACKGROUND: Recent research suggests that anxiety is common in PD. An association between surgical intervention for PD and anxiety reduction has been reported; however, it is not clear which specific symptoms of anxiety improve. METHOD: Thirty-nine PD patients completed the Beck Anxiety Inventory (BAI) approximately 1 month before and 4 months after surgery. Twenty-four participants underwent unilateral pallidotomy, 10 underwent deep brain stimulating electrode implantation of the internal segment of the globus pallidus, 4 underwent thalamic deep brain stimulating electrode implantation, and 1 underwent left thalamotomy. RESULTS: Statistically significant reductions were found postoperatively in terms of BAI total score as well as neurophysiologic, autonomic, and subjective factors from the BAI. The panic factor did not significantly change after surgery, possibly secondary to limited power afforded by the sample size. CONCLUSIONS: Results suggest that surgical intervention for PD is associated with reduction in anxiety symptoms distinct from symptoms of PD. In other words, improvement in anxious symptoms reflects a true reduction in anxiety rather than simply being an epiphenomenon of parkinsonian symptom amelioration.