Michal Gostkowski

Impact of mild cognitive impairment on outcome following deep brain stimulation surgery for Parkinson's disease.

INTRODUCTION Unlike dementia, the effect of mild cognitive impairment (MCI) on outcomes after deep brain stimulation (DBS) in Parkinsons disease (PD) is less clear. We aimed to examine the effect of MCI on short- and long-term DBS outcomes. METHODS To study the effect of MCI type, cognitive domains (attention, language, visuospatial, memory, executive function), and Dementia Rating Scale (DRS) score on immediate postoperative outcomes (postoperative confusion, hospitalization days), PD patients who underwent DBS at our Center from 2006 to 2011 were analyzed. To determine cognitive predictors of intermediate (6-month) and long-term (1-year) post-operative outcomes, the changes in functional and quality-of-life (QOL) scores were analyzed in a smaller group with available preoperative health status measures. RESULTS We identified 130 patients [71% male, mean age: 63 ± 9.1, mean PD duration: 10.7 ± 5.1]. At preoperative assessment, 60% of patients had multiple-domain MCI, 21% had single-domain MCI, and 19% had normal cognition. MCI presence and type as well as DRS performance did not affect immediate outcomes. Attention impairment predicted longer postoperative hospitalization (P = 0.0015) and showed a trend towards occurrence of postoperative confusion (P = 0.089). For intermediate and long-term outcomes we identified 56 patients [73.2% male, mean age: 61.3 ± 9.6, mean PD duration: 10.6 ± 4.7]. Visuospatial impairment showed a trend towards less improvement in 6-month functional score (P = 0.0652), and 1-year QOL score (P = 0.0517). CONCLUSION The presence of MCI did not affect DBS outcomes. However, the types of impaired domains were more detrimental. Detailed cognitive testing can help stratify low- and high-risk patients based on their pattern of cognitive dysfunction.

Comprehensive, Multidisciplinary Deep Brain Stimulation Screening for Parkinson Patients: No Room for “Short Cuts”

Careful, often cumbersome, screening is a fundamental part of DBS evaluation in Parkinsons disease (PD). It often involves a brain MRI, neuropsychological testing, neurological, surgical, and psychiatric evaluation, and “ON/OFF” motor testing. Given that DBS has now been a standard treatment for advanced PD, with clinicians’ improved comfort and confidence in screening and referring patients for DBS, we wondered whether we can now streamline our lengthy evaluation process. We reviewed all PD patients evaluated for DBS at our center between 2006 and 2011 and analyzed the reasons for exclusion and for dropping out despite passing the screening process. A total of 223 PD patients who underwent DBS evaluation had complete charting. Only 131 (58.7%) patients were successfully implanted. Sixty‐one (27.3%) patients were excluded after screening because of significant cognitive decline (32.7%), early disease with room for medication adjustment (29.5%), behavioral dysfunction (21.3%), suspected secondary parkinsonism or atypical parkinsonism syndrome (13.1%), PD, but with poor levodopa response (11.4%), unrealistic goals (9.8%), PD with predominant axial symptoms (6.5%), significant comorbidities (6.5%), or abnormal brain imaging (3.2%). In addition, 31 (13.9%) patients were cleared for surgery, but either chose not have it (18 patients), were lost to follow‐up (12 patients), or were denied by medical insurance (1 patient). Through careful screening, a significant percentage of surgical candidates continue to be identified as less suitable because of a variety of reasons. This underscores the continued need for a comprehensive, multidisciplinary screening process.

A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia.

This phase 2 randomized, double‐blind, placebo‐controlled study evaluated the efficacy and safety of the nicotinic acetylcholine receptor α7 agonist AQW051 in patients with Parkinsons disease and levodopa‐induced dyskinesia.

Socioeconomic Status May Impact Functional Outcome of Deep Brain Stimulation Surgery in Parkinson's Disease

To investigate the association between socioeconomic status and deep brain stimulation (DBS) outcomes in Parkinsons disease (PD).

Dopamine Transporter (DaT) Scan Utilization in a Movement Disorder Center

The aim of this work was to describe utilization patterns of dopamine transporter (DaT) scan and its influence on patient management at a single movement disorders center. DaT scan helps differentiate between neurodegenerative from non‐neurodegenerative parkinsonism and essential tremor (ET). It has been recently approved in the United States in 2011.

Is 6 months of neuroleptic withdrawal sufficient to distinguish drug-induced parkinsonism from Parkinson's disease?

ABSTRACT Background: Drug-induced parkinsonism (DIP) is the second commonest cause of akinetic-rigid syndrome in the western world. Differentiating DIP from Parkinsons disease (PD) may be a challenge to clinicians. One of the factors distinguishing DIP from PD is that discontinuation of the neuroleptic agent in DIP should relieve the symptoms of parkinsonism. The majority of the literature uses the 6-month timeframe between the neuroleptic withdrawal and resolution of the symptoms of parkinsonism. Methods: We report two cases of DIP wherein the symptoms of parkinsonism persisted more than 6-months from withdrawal of the dopamine receptor blocking agent (DRBA) and the results of their ioflupane iodine-123 (DaT) single-photon emission computed tomography (SPECT) scan. DaT scan is a newly approved radiopharmaceutical in the United States indicated for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes. Results: The first case is a patient who developed parkinsonism from risperidone, while the second case developed parkinsonism from metoclopramide. In both cases, parkinsonism persisted 6 months after discontinuation of the DRBA, therefore DaT scan was obtained, showing normal striatal dopamine transporter uptake. Nine months after the discontinuation of the DRBA, parkinsonism was significantly improved in both patients but not completely resolved. Conclusion: Our two cases illustrate the possibility of persistent parkinsonism beyond 6–9 months from the time of neuroleptic withdrawal without evidence of presynaptic dopaminergic neuronal loss that would be suggestive of conversion to PD. We recommend that the official recommendation of the minimum time of neuroleptic withdrawal be modified to at least 1 year before entertaining the diagnosis of PD conversion in patients with exposure to DRBAs.

Predictors of Functional and Quality of Life Outcomes following Deep Brain Stimulation Surgery in Parkinson’s Disease Patients: Disease, Patient, and Surgical Factors

Objective The primary objective was to evaluate predictors of quality of life (QOL) and functional outcomes following deep brain stimulation (DBS) in Parkinsons disease (PD) patients. The secondary objective was to identify predictors of global improvement. Methods PD patients who underwent DBS at our Center from 2006 to 2011 were evaluated by chart review and email/phone survey. Postoperative UPDRS II and EQ-5D were analyzed using simple linear regression adjusting for preoperative score. For global outcomes, we utilized the Patient Global Impression of Change Scale (PGIS) and the Clinician Global Impression of Change Scale (CGIS). Results There were 130 patients in the dataset. Preoperative and postoperative UPDRS II and EQ-5D were available for 45 patients, PGIS for 67 patients, and CGIS for 116 patients. Patients with falls/postural instability had 6-month functional scores and 1-year QOL scores that were significantly worse than patients without falls/postural instability. For every 1-point increase in preoperative UPDRS III and for every 1-unit increase in body mass index (BMI), the 6-month functional scores significantly worsened. Patients with tremors, without dyskinesia, and without gait-freezing were more likely to have “much” or “very much” improved CGIS. Conclusions Presence of postural instability, high BMI, and worse baseline motor scores were the greatest predictors of poorer functional and QOL outcomes after DBS.

Reply to Comment on: Dopamine Transporter (DaT) Scan Utilization in a Movement Disorder Center

Thank you very much for your interest in our study. Different methods for interpreting dopamine transporter (DaT) scans have been described. Our radiologist uses visual assessment for DaT scan interpretation. Although there are reports that quantitative or semiquantitative methods have better accuracy than visual assessment, there are also several reports suggesting comparable accuracy for visual assessment and semiquantitative assessment. Our radiologist classified DaT scan results using the Benamer system (i.e., Grade 1, 2, and 3 for all abnormal scans); however, in our, study we simply combined all abnormal scans regardless of their class or grade. Morphological imaging, such as computed tomography and magnetic resonance imaging of the brain, were not routinely evaluated when reading DaT scans. However, in certain cases, when an atypical pattern of decreased uptake is noted (such as a concern for structural lesions), then morphological images were obtained and compared. Lewy body dementia (LBD) was included as a prescan clinical diagnosis of neurodegenerative parkinsonism in our study. Our center does not routinely use DaT scans to assist in the diagnosis of LBD. However, in our study, 1 patient was suspected of having idiopathic Parkinson’s disease (PD) versus LBD versus another form of dementia, such as Alzheimer’s disease or frontotemporal lobe dementia. The scan for that patient turned out to be abnormal, and the patient was started on carbidopa/levodopa. Tolosa et al. described the possibility that 3 different clinical outcomes can be encountered in patients with drug-induced parkinsonism: (1) full and long-lasting recovery of drug-induced parkinsonism with no subsequent development of PD, (2) persistence and eventual worsening of parkinsonism after discontinuation of the offending drug (drug-induced parkinsonism unmasks PD), and (3) full remission of drug-induced parkinsonism after withdrawal of the offending drug with later reappearance of parkinsonism (drug-induced parkinsonism antedates PD). Rajput et al. reported 2 patients with drug-induced parkinsonism who had completely recovered after stopping the offending drugs and had histopathology findings of Lewy bodies similar to those observed in idiopathic PD. These findings underscore the complexity of the problem. Clearly, further studies involving larger numbers of patients with clinicopathological correlation are needed to determine the sensitivity and specificity of DaT scans.