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1.  Coordinate-Based Lead Location Does Not Predict Parkinson's Disease Deep Brain Stimulation Outcome 
PLoS ONE  2014;9(4):e93524.
Background
Effective target regions for deep brain stimulation (DBS) in Parkinson's disease (PD) have been well characterized. We sought to study whether the measured Cartesian coordinates of an implanted DBS lead are predictive of motor outcome(s). We tested the hypothesis that the position and trajectory of the DBS lead relative to the mid-commissural point (MCP) are significant predictors of clinical outcomes. We expected that due to neuroanatomical variation among individuals, a simple measure of the position of the DBS lead relative to MCP (commonly used in clinical practice) may not be a reliable predictor of clinical outcomes when utilized alone.
Methods
55 PD subjects implanted with subthalamic nucleus (STN) DBS and 41 subjects implanted with globus pallidus internus (GPi) DBS were included. Lead locations in AC-PC space (x, y, z coordinates of the active contact and sagittal and coronal entry angles) measured on high-resolution CT-MRI fused images, and motor outcomes (Unified Parkinson's Disease Rating Scale) were analyzed to confirm or refute a correlation between coordinate-based lead locations and DBS motor outcomes.
Results
Coordinate-based lead locations were not a significant predictor of change in UPDRS III motor scores when comparing pre- versus post-operative values. The only potentially significant individual predictor of change in UPDRS motor scores was the antero-posterior coordinate of the GPi lead (more anterior lead locations resulted in a worse outcome), but this was only a statistical trend (p<.082).
Conclusion
The results of the study showed that a simple measure of the position of the DBS lead relative to the MCP is not significantly correlated with PD motor outcomes, presumably because this method fails to account for individual neuroanatomical variability. However, there is broad agreement that motor outcomes depend strongly on lead location. The results suggest the need for more detailed identification of stimulation location relative to anatomical targets.
doi:10.1371/journal.pone.0093524
PMCID: PMC3972103  PMID: 24691109
2.  Unilateral deep brain stimulation surgery in Parkinson’s disease improves ipsilateral symptoms regardless of laterality 
Parkinsonism & related disorders  2011;17(10):745-748.
Purpose
Researchers have consistently observed in right-handed individuals across normal and disease states that the ‘dominant’ left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson’s disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side.
Scope
A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right ‘composite scores’, were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557).
Conclusion
While DBS on the ‘dominant’ left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality.
doi:10.1016/j.parkreldis.2011.07.010
PMCID: PMC3791592  PMID: 21856205
Unilateral DBS; STN; GPi; Parkinson’s disease; UPDRS
3.  DBS Candidates That Fall Short on a Levodopa Challenge Test 
The neurologist  2011;17(5):263-268.
Introduction
Candidacy for deep brain stimulation (DBS) in Parkinson disease (PD) is typically assessed by the preoperative motor response to levodopa along with an interdisciplinary evaluation. However, recent cases treated at our institution have achieved good outcomes with DBS despite a sub-30% improvement in motor scores. The aim of this study was to examine the outcomes of DBS in a subset of patients who failed to reach the 30% motor improvement threshold.
Methods
A review of all DBS patients treated at the University of Florida Movement Disorders Center between 2002 and 2009 was performed utilizing a DBS database. All patients with sub-30% improvement in Unified Parkinson Disease Rating Scale Part III after dopaminergic medication administration were included.
Results
Nine patients were identified; DBS was performed for severe dyskinesia (n = 5), “on/off motor” fluctuations (n = 1) and medication-refractory tremor (n = 3). The target symptoms were improved in all patients. Postoperatively, scores on the Unified Parkinson Disease Rating Scale Part II and III and subscores on Parkinson disease questionnaire-39 improved (P < 0.05).
Conclusions
Although motor response to levodopa remains the primary selection criteria for DBS candidacy in Parkinson disease, patients who do not meet the 30% threshold and have disabling symptoms may still benefit from DBS. Select patients with severe dyskinesia, “on/off” motor fluctuations, and/or medication-refractory tremor may experience significant benefits from DBS and should be considered on a case by case basis through an interdisciplinary team evaluation.
doi:10.1097/NRL.0b013e31822d1069
PMCID: PMC3789884  PMID: 21881468
deep brain stimulation; Parkinson disease; levodopa challenge test; dyskinesia; on-off motor fluctuations; tremor; quality of life
4.  Do Stable Patients With a Premorbid Depression History Have a Worse Outcome After Deep Brain Stimulation for Parkinson Disease? 
Neurosurgery  2011;69(2):357-361.
BACKGROUND
Deep brain stimulation (DBS) has been associated with mood sequelae in a subset of patients operated on in either the subthalamic nucleus or the globus pallidus internus for the treatment of Parkinson disease.
OBJECTIVE
To compare mood and motor outcomes in those with and without a presurgical history of depression.
METHODS
Unilateral subthalamic nucleus or unilateral globus pallidus internus DBS patients followed up for a minimum of 6 months were included. All patients underwent a comprehensive outpatient psychiatric evaluation by a board-certified psychiatrist. Psychiatric diagnoses were based on Diagnostic and Statistical Manual, fourth edition, text revision, nomenclature (American Psychiatric Association, 2000). Motor and mood outcomes were compared.
RESULTS
A total of 110 patients were included. There were no significant differences in baseline variables between the 2 groups. Those with a preoperative history of depression had significantly higher Beck Depression Inventory scores than the nondepression group after DBS (8.97 ± 7.55 vs 5.92 ± 5.71; P = .04). Patients with a depression history had less improvement (11.6%) in pre/post-DBS change when Unified Parkinson Disease Rating Scale motor scores were compared (P = .03) after adjustment for stimulation site and baseline demographic and clinical variables. Patients with a higher levodopa equivalent dose had a worse clinical motor outcome.
CONCLUSION
Patients with a preoperative depression history had higher Beck Depression Inventory scores after DBS and significantly less (albeit small) improvement in pre/post-DBS change in Unified Parkinson Disease Rating Scale motor scores than patients without a history of depression.
doi:10.1227/NEU.0b013e3182160456
PMCID: PMC3593636  PMID: 21415789
DBS; Deep brain stimulation; Depression; DSM; Outcomes; Psychiatry; Psychology
5.  Carbidopa/levodopa dose elevation and safety concerns in Parkinson's patients: a cross-sectional and cohort design 
BMJ Open  2012;2(6):e001971.
Objective
Sinemet, a combination drug containing carbidopa and levodopa is considered the gold standard therapy for the treatment of Parkinson's disease (PD). When approved by the Food and Drug Administration (FDA) in 1988, a maximum daily dosage limit of 800 mg (eight tablets) of the 25/100 carbidopa/levodopa formulation was introduced. Overall, the FDA approval was a historic success; however, the pill limit has been hardcoded into many online medical record systems. This study investigates the 800 mg threshold by using a prospectively collected database of patient information.
Design
A retrospective cohort study: (Part I) cross-sectional, (Part II) longitudinal.
Setting and participants
PD patients at a Movement Disorders Center in a large academic, tertiary medical setting.
Outcome measures
An analysis was performed using carbidopa/levodopa at dosages below and above the 800 mg threshold. A secondary analysis was then performed using two consecutive clinic visits to determine the effects of crossing the 800 mg threshold. Comparisons were made on standardised scales.
Results
There was no significant difference in motor, mood and quality-of-life scores in patients consuming below and above the 800 mg carbidopa/levodopa threshold, though a mild worsening in dyskinesia duration was noted without worsening in dyskinesia pain and disability. In PD patients who crossed the 800 mg threshold between two consecutive clinic visits, a significant improvement in depressive symptoms and quality-of-life measures was demonstrated, and in these patients there was no worsening of motor fluctuations or dyskinesia.
Conclusions
The data suggest that PD patients have the potential for enhanced clinical benefits when eclipsing the 800 mg carbidopa/levodopa threshold. Many patients will likely need to eclipse the 800 mg threshold and pharmacies and insurance companies should be aware of the requirements that may extend beyond approval limits.
doi:10.1136/bmjopen-2012-001971
PMCID: PMC3533055  PMID: 23233700
6.  Correction: Quantitative Normative Gait Data in a Large Cohort of Ambulatory Persons with Parkinson’s Disease 
PLoS ONE  2012;7(10):10.1371/annotation/d4b5158e-0dd1-4e14-b03a-1af4d5f06c0e.
doi:10.1371/annotation/d4b5158e-0dd1-4e14-b03a-1af4d5f06c0e
PMCID: PMC3525691
7.  Quantitative Normative Gait Data in a Large Cohort of Ambulatory Persons with Parkinson’s Disease 
PLoS ONE  2012;7(8):e42337.
Background
Gait performance is widely evaluated to assess health status in older adult populations. While several investigators have presented normative values for spatiotemporal gait parameters drawn from older adult populations, the literature has been void of large-scale cohort studies, which are needed in order to provide quantitative, normative gait data in persons with Parkinson’s disease. The aim of this investigation was to provide reference values for clinically important gait characteristics in a large sample of ambulatory persons with Parkinson’s disease to aid both clinicians and researchers in their evaluations and treatments of gait impairment.
Methodology/Principal Findings
Gait performance was collected in 310 individuals with idiopathic Parkinson’s disease as they walked across a pressure sensitive walkway. Fourteen quantitative gait parameters were measured and evaluated with respect to Hoehn and Yahr disease staging and gender. Disease duration and age were controlled for in all analyses. Individuals with the greatest Parkinson’s disability walked significantly slower with shorter steps and stride lengths than the mild and moderately affected groups. Further, the most affected patients spent more time with both feet on the ground, and walked with a wider base of support than the moderately disabled patients. No differences were detected between the mild and moderate disability groups on any of the gait parameters evaluated.
Conclusions/Significance
Reference values for 14 gait parameters in a large cohort of ambulatory patients with Parkinson’s disease are provided and these may be highly useful for assessing and interpreting an individual’s gait dysfunction. It is important for clinicians and researchers to appreciate the lack of change in quantitative parameters as PD patients move from mild to moderate gait impairment.
doi:10.1371/journal.pone.0042337
PMCID: PMC3411737  PMID: 22879945
8.  Smile and Laughter Induction and Intraoperative Predictors of Response to Deep Brain Stimulation for Obsessive Compulsive Disorder 
NeuroImage  2010;54S1:S247-S255.
We recently treated six patients for OCD utilizing deep brain stimulation (DBS) of the anterior limb of the internal capsule and the nucleus accumbens region (ALIC-NA). We individually tested leads via a scripted intraoperative protocol designed to determine DBS-induced side effects and mood changes. We previously published qualitative data regarding our observations of induced emotional behaviors in our first five subjects. We have now studied these same behaviors in the full cohort of six patients over two years of follow-up and have examined the relationship of these behaviors to intraoperative mood changes and postoperative clinical outcomes.
Five patients experienced at least one smile response during testing. At higher voltages of stimulation some of these smiles progressed to natural laughter. Smiles and laughter were associated with mood elevation. At stimulation locations at which smiles were observed, voltage and mood were significantly correlated (p=0.0004 for right brain and p<0.0001 for left brain). In contrast, at contacts where smiles were not observed, mood was negatively correlated with voltage (p=0.0591 for right brain and p=0.0086 for left). Smile and laughter-inducing sites were located relatively medial, posterior, and deep in the ALIC-NA.
The presence of stimulation induced laughter predicted improvement in OCD symptoms at two years. The higher the percentage of laugh conditions experienced in an individual patient, the greater the reduction in YBOCS (24 months, p=0.034). Other correlations between clinical outcomes and percent of smile/laugh conditions were not significant. These stimulation-induced behaviors were less frequently observed with one and two-month postoperative test stimulation and were not observed at subsequent test stimulation sessions.
Intraoperative stimulation-induced laughter may predict long-term OCD response to DBS. Identifying other potential response predictors for OCD will become increasingly important as more patients are implanted with DBS devices. A larger study is needed to better delineate the relationship between induced intraoperative and postoperative emotional behavior and clinical outcome in patients treated with DBS therapy.
doi:10.1016/j.neuroimage.2010.03.009
PMCID: PMC2907450  PMID: 20226259
9.  Do Patient's Get Angrier Following STN, GPi, and Thalamic Deep Brain Stimulation 
NeuroImage  2010;54S1:S227-S232.
Objective
The objective of the study was to examine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), the globus pallidus internus (GPi), and/or the ventralis intermedius thalamic nucleus (Vim) was associated with making patients angrier pre to post-surgical intervention.
Background
Secondary outcome analysis of the NIH COMPARE Parkinson's Disease DBS trial revealed that participants were angrier and had more mood and cognitive side effects following DBS. Additionally blinded on/off analysis did not change anger scores. The sample size was small but suggested that STN DBS may have been worse than GPi in provoking anger. We endeavored to examine this question utilizing a larger dataset (the UF INFORM database), and also we included a third surgical target (Vim) which has been utilized for a different disease, essential tremor.
Methods
Consecutive patients from the University of Florida Movement Disorders Center who were implanted with unilateral DBS for Parkinson's Disease (STN or GPi) or Essential Tremor (Vim) were included. Patients originally implanted at outside institutions were excluded. Pre- and 4-6 month postoperative Visual Analog Mood Scales (VAMS) scores for all three groups were compared; additionally, pre- and 1-3 month scores were compared for STN and GPi patients. A linear regression model was utilized to analyze the relationship between the VAMS anger score and the independent variables of age, years with symptoms, Mini-mental status examination (MMSE) score, handedness, ethnicity, gender, side of surgery, target of surgery, baseline Dementia Rating Scale (DRS) total score, baseline Beck Depression Index (BDI) score, micro and macro electrode passes, and years of education. Levodopa equivalent dosages and dopamine agonist use was analyzed for a potential impact on anger scores.
Results
A total of 322 unilateral DBS procedures were analyzed, with STN (n= 195), Vim (n=71), and GPi (n=56) making up the cohort. An ANOVA analysis was used to detect significant differences among the three targets in the changes pre- to post-operatively. Similar to the COMPARE dataset, at four months the only subscore of VAMS to reveal a significant difference between the three targets was the angry subscore, with GPi revealing a mean (standard) change of 2.38 (9.53), STN 4.82 (14.52), and Vim -1.17 (11.51) (p-value = 0.012). At 1-3 months postop, both STN and GPi groups were significantly angrier (p= 0.004), but there was no significant difference between the two groups. However, GPi patients were significantly more confused as compared to STN patients (p= 0.016). The linear regression model which sought independent explanatory variables revealed a relationship between the VAMS anger score and the surgical target and the disease duration. The mean changes for STN and GPi DBS pre- to post were 11.67 (p= 0.001) and 8.21 (p= 0.022) units more than those with Vim, respectively. For every year added of disease duration, the VAMS anger score increased by 0.24 (p= 0.022). For the GPi and STN groups, number of microelectrode passes was significantly associated with angry score changes (p= 0.014), with the anger score increasing 2.29 units per microelectrode pass. Independent variables not associated with the VAMS anger score included the surgery side, handedness, gender, ethnicity, education, age at surgery, MMSE, DRS, and BDI scores. Although the STN group significantly decreased in LED when compared to GPi, there was no relationship to anger scores. Similarly dopamine agonist use was not different between STN and GPi groups, and did not correlate with the VAMS anger score changes.
Conclusions
STN and GPi DBS for Parkinson's disease were associated with significantly higher anger scores pre- to post-DBS as compared to Vim for essential tremor. Anger score changes in STN and GPi patients seem to be associated with microelectrode passes, suggesting it may be a lesional effect. PD patients with longer disease durations may be particularly susceptible, and this should be kept in mind when discussing the potential of DBS surgery for an individual patient. Essential tremor patients who on average have much longer disease durations did not get angrier. The changes in anger scores were not related to LED change or dopamine agonist use. Whether the induction of anger is disease specific or target specific is not currently known, however our data would suggest that PD patients implanted in STN or GPi are at a potential risk. Finally, on closer inspection of the COMPARE DBS data VAMS anger scores did not change on or off DBS, suggesting that anger changes may be more a lesional effect rather than a stimulation induced one(Okun et al., 2009).
doi:10.1016/j.neuroimage.2010.09.077
PMCID: PMC3014411  PMID: 20932923
Subthalamic nucleus; globus pallidus; ventralis intermedius nucleus; deep brain stimulation; anger; Parkinson's disease; tremor
10.  Effect of Deep Brain Stimulation on Parkinson's Nonmotor Symptoms following Unilateral DBS: A Pilot Study 
Parkinson's Disease  2011;2011:507416.
Parkinson's disease (PD) management has traditionally focused largely on motor symptoms. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are effective treatments for motor symptoms. Nonmotor symptoms (NMSs) may also profoundly affect the quality of life. The purpose of this pilot study was to evaluate NMS changes pre- and post-DBS utilizing two recently developed questionnaires. Methods. NMS-Q (questionnaire) and NMS-S (scale) were administered to PD patients before/after unilateral DBS (STN/GPi targets). Results. Ten PD patients (9 STN implants, 1 GPi implant) were included. The three most frequent NMS symptoms identified utilizing NMS-Q in pre-surgical patients were gastrointestinal (100%), sleep (100%), and urinary (90%). NMS sleep subscore significantly decreased (−1.6 points ± 1.8, P = 0.03). The three most frequent NMS symptoms identified in pre-surgical patients using NMS-S were gastrointestinal (90%), mood (80%), and cardiovascular (80%). The largest mean decrease of NMS scores was seen in miscellaneous symptoms (pain, anosmia, weight change, and sweating) (−7 points ± 8.7), and cardiovascular/falls (−1.9, P = 0.02). Conclusion. Non-motor symptoms improved on two separate questionnaires following unilateral DBS for PD. Future studies are needed to confirm these findings and determine their clinical significance as well as to examine the strengths/weaknesses of each questionnaire/scale.
doi:10.4061/2011/507416
PMCID: PMC3246796  PMID: 22220288
11.  A Case of Mania following Deep Brain Stimulation for Obsessive Compulsive Disorder 
Deep brain stimulation (DBS) of the basal ganglia is an effective treatment for select movement disorders, including Parkinson's disease, essential tremor and dystonia. Based on these successes, DBS has been explored as an experimental treatment for medication-resistant neuropsychiatric disease. During a multiyear experience employing DBS to treat patients for obsessive compulsive disorder (OCD) we encountered several unanticipated stimulation-induced psychiatric side effects. We present a case of a young woman treated for OCD with DBS of the anterior limb of the internal capsule and nucleus accumbens region, who subsequently manifested a manic episode. We aim to discuss the case details, treatment and potential neuroanatomical underpinnings of this response.
doi:10.1159/000319960
PMCID: PMC2969111  PMID: 20714212
Obsessive compulsive disorder; Deep brain stimulation, side effects; Neuropsychiatric mania
12.  Differential Response of Dystonia and Parkinsonism following Globus Pallidus Internus Deep Brain Stimulation in X-Linked Dystonia-Parkinsonism (Lubag) 
Background
X-linked dystonia-parkinsonism (XDP; DYT3; Lubag) is an adult-onset hereditary progressive dystonia/parkinsonism which is typically minimally responsive to pharmacological treatment.
Case Report
We report a 63- year-old man with a diagnosis of XDP who underwent bilateral globus pallidus internus deep brain stimulator (GPi-DBS) placement. His course initially began with right hand tremor and dystonia at age 57 and progressed to also include bradykinesia and rigidity. The patient tolerated the procedure without significant complications. GPi-DBS improved his right hand dystonia, but did not significantly improve his parkinsonism.
Conclusion
DBS may be a therapeutic option for select cases of XDP, but its specificindications must be carefully discussed, as the available cases have had mixed responses. Whether other targets may be more effective is not known.
doi:10.1159/000319961
PMCID: PMC2969112  PMID: 20714213
X-linked dystonia-parkinsonism; Globus pallidus internus; Cognitive impairment; Medication-resistant parkinsonism
13.  Binge Eating in Parkinson Disease: Prevalence, Correlates, and the Contribution of Deep Brain Stimulation 
Of 96 Parkinson’s disease (PD) patients at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge eating disorder (BED). Eight (8.3%) exhibited subthreshold BED. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, buying in 11.5%, hypersexuality in 1.0%, and mania in 1.0% of patients. More overeaters met psychometric criteria for at least one additional impulse control disorder (67% vs. 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% vs. 41%). More overeaters had a history of subthalamic DBS (44% vs. 14%). History of DBS was the only independent predictor of overeating.
doi:10.1176/appi.neuropsych.23.1.56
PMCID: PMC3075093  PMID: 21304139
Parkinson’s disease; binge eating; impulse control disorders
14.  The Frequency of Nonmotor Symptoms among Advanced Parkinson Patients May Depend on Instrument Used for Assessment 
Parkinson's Disease  2011;2011:290195.
Background. Nonmotor symptoms (NMS) of Parkinson's disease (PD) may be more debilitating than motor symptoms. The purpose of this study was to determine the frequency and corecognition of NMS among our advanced PD cohort (patients considered for deep brain stimulation (DBS)) and caregivers. Methods. NMS-Questionnaire (NMS-Q), a self-administered screening questionnaire, and NMS Assessment-Scale (NMS-S), a clinician-administered scale, were administered to PD patients and caregivers. Results. We enrolled 33 PD patients (23 males, 10 females) and caregivers. The most frequent NMS among patients using NMS-Q were gastrointestinal (87.9%), sleep (84.9%), and urinary (72.7%), while the most frequent symptoms using NMS-S were sleep (90.9%), gastrointestinal (75.8%), and mood (75.8%). Patient/caregiver scoring correlations for NMS-Q and NMS-S were 0.670 (P < 0.0001) and 0.527 (P = 0.0016), respectively. Conclusion The frequency of NMS among advanced PD patients and correlation between patients and caregivers varied with the instrument used. The overall correlation between patient and caregiver was greater with NMS-Q than NMS-S.
doi:10.4061/2011/290195
PMCID: PMC3144664  PMID: 21808724
15.  Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus 
Journal of neurology  2009;256(8):1321-1329.
While deep brain stimulation (DBS) surgery is a well-accepted treatment for Parkinson disease (PD) that improves overall quality of life (QoL), its effects across different domains of QoL are unclear. The study reported here directly compared the effects of unilateral DBS in subthalamic nucleus (STN) or globus pallidus (GPi) on QoL in 42 non-demented patients with medication-refractory PD. Patients were enrolled in the COMPARE trial, a randomized clinical trial of cognitive and mood effects of STN versus GPi DBS conducted at the University of Florida Movement Disorders Center. Patients underwent motor, mood, verbal fluency and QoL (Parkinson disease questionnaire: PDQ-39) measures before and 6 months following surgery. Groups experienced motor and mood improvements that did not differ by target. Patients with STN DBS evidenced a slight decrement on letter fluency. On average, all patients endorsed better overall QoL after surgery. However, despite similar motor and mood improvements, GPi patients improved more than STN patients (38 vs. 14%, respectively; P = 0.03). Patients reported better QoL on subscales of mobility, activities of daily living (ADLs), emotional well-being, stigma, cognition and discomfort, but not on those of social support and communication. Improvements on the mobility, ADLs, stigma and social support subscales were greater amongst GPi patients. In regression analyses, only depression changes independently predicted changes in overall QoL as well as emotional well-being and social support changes. Within the STN group only, declining category fluency scores correlated with poorer QoL on the communication subscale. Unilateral DBS in both STN and GPi improved QoL overall and in disparate domains 6 months after surgery. Patients receiving GPi DBS reported greater improvements that cannot be explained by differential mood or motor effects; however, verbal fluency changes may have partially contributed to lesser QoL improvements amongst STN patients.
doi:10.1007/s00415-009-5121-7
PMCID: PMC3045861  PMID: 19363633
Cognition; Deep brain stimulation; Depression; Parkinson disease; Quality of life
16.  Cognition and Mood in Parkinson Disease in STN versus GPi DBS: The COMPARE Trial 
Annals of neurology  2009;65(5):586-595.
Objective
There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this prospective blinded randomized trial was to compare the cognitive and mood effects of unilateral subthalamic nucleus (STN) vs. unilateral globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with Parkinson disease (PD).
Methods
Fifty-two subjects with moderate-to-advanced PD were randomized to either unilateral STN or GPi DBS. Right or alternatively left sided stimulation was chosen to address the side of the body with the most bothersome symptoms. The co-primary outcome measures were the change in the 8 subscales of the Visual Analog Mood Scale (VAMS), and the change in the 2 versions of verbal fluency (i.e. semantic and letter), at 7 months post-DBS in the optimal setting compared to the pre-DBS state. In addition, at 7 months post-DBS, after subjects underwent initial evaluation off medications and on optimized DBS therapy, they were tested in four randomized and counterbalanced conditions (optimal DBS, ventral DBS, dorsal DBS, and off DBS) while remaining off medication. Secondary outcome measures then compared the differences in the VAMS items and verbal fluency subscales within the 4 DBS conditions at 7 months, and the change in the VAMS items and verbal fluency subscales from the pre-DBS state to the other 3 DBS conditions (ventral, dorsal and off ) at 7 months.
Results
Forty-five subjects (23 GPi and 22 STN) completed the protocol. The study revealed no significant difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes from pre- to post-DBS in the optimal setting (Hotelling's T2 test: p=0.16 and 0.08 respectively). When comparing the 4 DBS conditions at 7 months, subjects in both targets were less “happy”, less “energetic” and more “confused” when stimulated ventrally to the optimal stimulation site. When comparing the other 3 DBS conditions (ventral, dorsal and off DBS) to the pre-DBS state, the STN group showed a larger deterioration of letter verbal fluency scores than the GPi group, especially in the off DBS state. A 12-point mean improvement in the UPDRS motor subscale was seen post DBS, but there was no significant difference between targets.
Interpretations
There were no significant differences in in the co-primary outcome measures of mood and cognition between STN and GPi in the optimal DBS state.. However, adverse mood effects were noted when stimulating ventrally to the optimal site in both targets. Furthermore, a worsening for letter verbal fluency was noted in the 3 non-optimal post-DBS states in the STN target only. The persistence of deterioration in verbal fluency in the off DBS state at 7 months is, suggestive of a surgical rather than a stimulation-induced effect at the STN target. STN and GPi DBS resulted in similar motor improvement.
doi:10.1002/ana.21596
PMCID: PMC2692580  PMID: 19288469
GPi; STN; DBS; Mood; Cognition; Side Effects; verbal fluency; motor; UPDRS
18.  The four As associated with pathological Parkinson disease gamblers: anxiety, anger, age, and agonists 
Several studies have related pathological gambling in PD to dopamine agonist therapy. A mail-in survey was sent to PD patients seen at the University of Florida Movement Disorders Center to determine gambling frequency and behavior, and any lifestyle or environmental factors associated with compulsive gambling in PD. 462 surveys were sent and 127 completed surveys were returned, of which ten were from patients who met criteria for compulsive gambling. All ten were taking dopamine agonists coincident with the compulsive gambling. Compulsive gamblers were younger, and psychological distress measures revealed that compulsive gamblers exhibited higher levels of anxiety, anger, and confusion. Thus in this cohort, we have uncovered the several characteristics of the most likely PD compulsive gambler, namely: (young) age, “angry”, “anxious”, and using a (dopamine) agonist.
PMCID: PMC2654528  PMID: 19300546
Parkinson; gambling; compulsive behavior; dopamine agonist; anxiety

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