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1.  Randomized trial of deep brain stimulation for Parkinson disease 
Weaver, Frances M. | Follett, Kenneth A. | Stern, Matthew | Luo, Ping | Harris, Crystal L. | Hur, Kwan | Marks, William J. | Rothlind, Johannes | Sagher, Oren | Moy, Claudia | Pahwa, Rajesh | Burchiel, Kim | Hogarth, Penelope | Lai, Eugene C. | Duda, John E. | Holloway, Kathryn | Samii, Ali | Horn, Stacy | Bronstein, Jeff M. | Stoner, Gatana | Starr, Philip A. | Simpson, Richard | Baltuch, Gordon | De Salles, Antonio | Huang, Grant D. | Reda, Domenic J. | Ippolito, Dolores | Barnett, Tammy | Bukowski, Ken | Carlson, Kimberly | Christine, Barbara | DeNicolo, Rosemarie | Jimenez, Joyce | Motyka, Jan | Patel, Unnati | Simon, Theresa | Thakkar, Bharat | Woolson, Robert | Fye, Carol | Gagne, William | Sheehy, Paul | O'Leary, Timothy | Atassi, Farah | Bello, Cecilia | Bunting-Perry, Lisette | Conn, Tina | Cugley, Alice | Eubank, Nanette | Fincher, Linda | Franks, Romay | Harris, Tammy | Haselman, Mariann | Heath, Susan | Hirsch, Miriam | Janovsky, Virginia | Lanier, Elaine | Lloyd, Mary | Loehner, Susan | O'Connor, Susan | Ordonez, Ligaya | Maccarone, Heather | Massey-Makhoul, Kelli | Matthews, Mary | Meyn, Elizabeth | Mimura, Keiko | Morrow, Wes | Searles, Tammy | Valotta, Jamye | Vasthare, Usha | Volz, Monica | Ward, Constance | Warker, Rebecca | Watson, Heidi | Willson, Pamela | Baron, Mark | Brodsky, Matthew | Calabrese, Vincent | Campbell, Gordon | Colcher, Amy | Farag, Emad | Henry, Eva | Hou, Jyh-Gong | Kang, Gail | Kleiner-Fisman, Galit | Kraakevik, Jeff | Nutt, John | Ostrem, Jill | Sarwar, Aliya | Subramanian, Indu | Vanek, Zeba | Carne, William | Erikson, Tom | Kreutzer, Jeffrey | Mendez, Mario | Moberg, Paul | Ragland, John | Seel, Ronald | Soety, Elizabeth | Storzbach, Daniel | Troster, Alexander | York, Michele | Jaggi, Jurg | Stroupe, Kevin | Koller, William
Neurology  2012;79(1):55-65.
Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial.
Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson's Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function.
Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] −16.4 to −10.8; p < 0.001) and STN (42.5 to 29.7; 95% CI −15.8 to −9.4; p < 0.001); improvements were similar between targets and stable over time (p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (p = 0.01); other neurocognitive measures showed gradual decline overall.
The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life.
Classification of Evidence:
This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology® 2012;79:55–65
PMCID: PMC3385495  PMID: 22722632
2.  Validation of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) 
As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson’s disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD.
The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored.
The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling=0.95, sexual behavior=0.97, buying=0.87, eating=0.88, punding=0.78, hobbyism=0.93, walkabout=0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling=0.95, sexual behavior=0.96, buying=0.87, eating=0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96% and 94%, respectively.
Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.
PMCID: PMC2848971  PMID: 19452562
Parkinson’s disease; impulse control disorders; dopamine dysregulation syndrome; punding; pathological gambling
3.  Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease 
Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.
To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy.
Design, Setting, and Patients
Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (<70 years vs ≥70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage ≥2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006.
Bilateral deep brain stimulation of the subthalamic nucleus (n=60) or globus pallidus (n=61). Patients receiving best medical therapy (n=134) were actively managed by movement disorder neurologists.
Main Outcome Measures
The primary outcome was time spent in the “on” state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.
Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P<.001). Motor function improved significantly (P<.001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (≥5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P<.001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P<.001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.
In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.
Trial Registration Identifier: NCT00056563
PMCID: PMC2814800  PMID: 19126811
4.  Montreal Cognitive Assessment Performance in Patients with Parkinson’s Disease with “Normal” Global Cognition According to Mini-Mental State Examination Score 
To examine Montreal Cognitive Assessment (MoCA) performance in patients with Parkinson’s disease (PD) with “normal” global cognition according to Mini-Mental State Examination (MMSE) score.
A cross-sectional comparison of the MoCA and the MMSE.
Two movement disorders centers at the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center.
A convenience sample of 131 patients with idiopathic PD who were screened for cognitive and psychiatric complications.
Subjects were administered the MoCA and MMSE, and only subjects defined as having a normal age- and education-adjusted MMSE score were included in the analyses (N = 100). As previously recommended in patients without PD, a MoCA score less than 26 was used to indicate the presence of at least mild cognitive impairment (MCI).
Mean MMSE and MoCA scores ± standard deviation were 28.8 ± 1.1 and 24.9 ± 3.1, respectively. More than half (52.0%) of subjects with normal MMSE scores had cognitive impairment according to their MoCA score. Impairments were seen in numerous cognitive domains, including memory, visuospatial and executive abilities, attention, and language. Predictors of cognitive impairment on the MoCA using univariate analyses were male sex, older age, lower educational level, and greater disease severity; older age was the only predictor in a multivariate model.
Approximately half of patients with PD with a normal MMSE score have cognitive impairment based on the recommended MoCA cutoff score. These results suggest that MCI is common in PD and that the MoCA is a more sensitive instrument than the MMSE for its detection.
PMCID: PMC2754699  PMID: 19170786
cognitive impairment; Parkinson’s disease; Mini-Mental State Examination; Montreal Cognitive Assessment; neuropsychology
5.  Long-Term Follow-Up of Impulse Control Disorders in Parkinson’s Disease 
Recent studies have linked dopamine agonist (DA) usage with the development of impulse control disorders (ICDs) in Parkinson’s disease (PD). Little is known about optimal management strategies or the long-term outcomes of affected patients. To report on the clinical interventions and long-term outcomes of PD patients who developed an ICD after DA initiation. Subjects contacted by telephone for a follow-up interview after a mean time period of 29.2 months. They were administered a modified Minnesota Impulse Disorder Interview for compulsive buying, gambling, and sexuality, and also self-rated changes in their ICD symptomatology. Baseline and follow-up dopamine replacement therapy use was recorded and verified by chart review. Of 18 subjects, 15 (83.3%) participated in the follow-up interview. At follow-up, patients were receiving a significantly lower DA levodopa equivalent daily dosage (LEDD) (Z = -3.1, P = 0.002) and a higher daily levodopa dosage (Z = -1.9, P = 0.05), but a similar total LEDD dosage (Z = -0.47, P = 0.64) with no changes in Unified Parkinson’s Disease Rating Scale motor score (Z = -1.3, P = 0.19). As part of ICD management, 12 (80.0%) patients discontinued or significantly decreased DA treatment, all of whom experienced full or partial remission of ICD symptoms by self-report, and 10 (83.3%) of whom no longer met diagnostic criteria for an ICD. For PD patients who develop an ICD in the context of DA treatment, discontinuing or significantly decreasing DA exposure, even when offset by an increase in levodopa treatment, is associated with remission of or significant reduction in ICD behaviors without worsening in motor symptoms.
PMCID: PMC2651355  PMID: 17960796
dopamine agonist; gambling; impulse control disorders; Parkinson’s disease

Results 1-5 (5)