What does the Dementia Rating Scale-2 measure? The relationship of neuropsychological measures to DRS-2 total and subscale scores in non-demented individuals with Parkinson's disease.

OBJECTIVE: The Dementia Rating Scale-2 (DRS-2) is recommended for assessing global cognition in Parkinson's disease (PD) by the Movement Disorder Society. However, empirical evidence is limited regarding the degree to which the DRS-2 corresponds to traditional neurocognitive domains (i.e., construct validity) in PD. Thus, this study aims to determine the construct validity of the DRS-2 in a non-demented sample of PD patients. METHOD: Patients with PD (n = 359; mean age = 64.50 ± 8.53, education = 14.97 ± 2.73, disease duration = 8.48 ± 4.87, UPDRS Part III motor scale scores = 25.23 ± 10.17) completed the DRS-2 as part of a comprehensive neuropsychological assessment consisting of attention/working memory, executive function, language, delayed recall, and visuoperceptual-spatial skills.Bootstrapped bias-corrected Spearman rho's correlations andhierarchical linear regressions were performed to examine construct validity of DRS-2 total and subscale scores. RESULTS: Speeded measures of set-shifting, rapid word generation to letter and semantic cues, and simple visuoperceptual skills largely accounted for variance in DRS-2 total scores. Most DRS-2 subscale scores showed weak relationships with theoretically related neuropsychological measures. CONCLUSIONS: DRS-2 total scores reflect impairment across a range of cognitive domains (i.e., executive, language, and visuoperception), while DRS-2 subscale scores have limited construct validity. Together, the DRS-2 does not appear to have utility beyond screening for global cognition in PD.

Cognitive subtypes in individuals with essential tremor seeking deep brain stimulation.

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET (N = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches (K-means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group (N = 64), Low Memory Multi-Domain group (N = 41), and Cognitively Normal group (N = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

Frequency of suicidal ideation and associated clinical features in Lewy body dementia.

INTRODUCTION: Neuropsychiatric disturbance is common in individuals with Lewy body dementia (LBD). Despite this, there is minimal research regarding suicide risks in this population. METHODS: This study was a retrospective review of a prospectively-collected database at a tertiary movement disorders clinic. Database participants with an LBD diagnosis at their most recent visit and at least one complete Beck Depression Inventory-II (BDI-II) were included. Additional measures included demographics and measures of cognition, psychiatric symptoms, motor function, and the Parkinson Disease Questionnaire-39. The frequency of suicidal ideation was assessed using question 9 of the BDI-II. Features associated with a BDI-II score greater than zero were assessed using logistic regression. RESULTS: The database included 95 individuals with LBD and at least one BDI-II (visit years 2010-2020). Most participants were older men who identified as white. Eighteen individuals (18.9%; 95% CI 12.3%-28.0%) reported thoughts of killing themselves without an intent to carry them out (BDI-II = 1). No participants reported a desire or plan to kill themselves. The presence of SI was associated with measures of depression, anxiety, and emotional well-being, but not with demographics, measures of disease severity, or other psychiatric concerns. CONCLUSION: These findings emphasize the importance of routine screening for psychiatric symptoms in LBD and intervention when such concerns are identified. Interventions could include pharmacologic (e.g. depression treatment) and non-pharmacologic (e.g. firearm screening) approaches. More research is needed to assess suicidal ideation and suicide risks in large and more diverse LBD populations. Prospective studies should include measures of additional potential contributors to suicidality.

The UF Deep Brain Stimulation Cognitive Rating Scale (DBS-CRS): Clinical Decision Making, Validity, and Outcomes.

To more efficiently communicate the results of neuropsychological assessment to interdisciplinary teams, the University of Florida Neuropsychology Service developed a Deep Brain Stimulation-Cognitive Rating Scale (DBS-CRS). This tool condensed results of a 3-h exam into a five-point scale ranging from 1 (least) to 5 (most) cognitive concern for DBS surgery. In this study, we evaluated the role of the DBS-CRS in clinical decisions by the interdisciplinary team to proceed to surgery, its relationship to objective neuropsychological scores, and its predictive utility for clinical outcome. We retrospectively examined 189 patients with Parkinson's disease who were evaluated for DBS candidacy (mean age 64.8 [SD 9.2], disease duration 8.9 years [SD 5.0], UPDRS-Part III off medication 38.5 [SD 10.5], Dementia Rating Scale-II 135.4 [SD 6.0]). Approximately 19% of patients did not proceed to surgery, with neuropsychological red flags being the most commonly documented reason (57%). Patients who underwent DBS surgery had significantly better DBS-CRS scores than those who did not (p < 0.001). The two strongest and unique neuropsychological contributors to DBS-CRS ratings were delayed memory and executive function, followed by language and visuoperception, based on hierarchical linear regression that accounted for 77.2% of the variance. In terms of outcome, DBS-CRS scores were associated with higher quality of life, less severe motor symptoms, and better daily functioning 6 months following DBS surgery. Together, these findings support the construct and predictive validity of the DBS-CRS as a concise tool for effectively communicating pre-DBS cognitive concerns to an interdisciplinary team, thereby aiding decision making in potential DBS candidates.

Spatiotemporal gait parameters and tremor distribution in essential tremor.

BACKGROUND: Essential Tremor is characterized by an action tremor of the upper extremities, which may or may not be accompanied by a head, voice, leg or trunk tremor. Problems with gait and balance have also been identified in persons with Essential Tremor. Therefore, understanding gait performance is an important area of focus for clinicians and researchers. RESEARCH QUESTION: We sought to 1) conduct a factor analysis on a broad spectrum of spatiotemporal gait parameters 2) build upon the normative database of gait measures in persons with Essential Tremor 3) understand the influence of age on gait speed in persons with Essential Tremor and 4) identify the relationships between gait performance and clinical measures of disease severity. METHODS: Gait data and Tremor Rating Scale scores were retrospectively collected from one hundred and forty-two ambulatory participants with a diagnosis of Essential Tremor. A factor analysis was used to characterize spatiotemporal gait parameters and regression models were applied to associate tremor scores to gait performance factors. RESULTS: Three domains of gait performance factors were identified in persons with Essential Tremor. Specifically, we observed a pace, rhythm, and stability factor. In sum, these factors accounted for 91.9% of the variance in gait performance. Only the pace and stability factors were associated with disease severity, suggesting these factors are most sensitive to disease severity compared to the rhythm factor. Our linear regression analysis revealed a significant influence of age on gait speed. Gait speed decreased with age significantly by 0.64 cm/s/year. SIGNIFICANCE: Reference values for 12 gait parameters will be highly useful for assessing gait performance in individuals with Essential Tremor. Our observations suggest that a clinical assessment of gait and balance would be an important measure to consider in routine clinical practice when treating persons with Essential Tremor.

Platelet-rich plasma does not decrease blood loss in total knee arthroplasty.

This study was designed to assess the use of platelet-rich plasma (PRP) during primary total knee arthroplasty (TKA). The authors hypothesized that this would result in less blood loss and greater hemoglobin and hematocrit levels at discharge and would potentially decrease the length of hospital stay. Leukocyte rich PRP was used during the procedure and at wound closure. Two surgeons performed all procedures in a similar fashion. Two different TKA implants were used. Each surgeon used the same implant throughout the study. A limited medial parapatellar approach was used and drains were used at closure. No tranexamic acid preparations were used. Continuous passive motion machines were used in all patients during their hospital stay. A total of 102 consecutive TKAs were performed. The study group (n=46) consecutively received the PRP injections during the TKA, whereas the control group (n=47) did not. Hemoglobin and hematocrit levels were obtained pre- and postoperatively. Estimated blood loss was recorded during surgery, and the auto-collection reinfusion drain system output was measured. The length of hospital stay was collected and recorded. The study showed that hemoglobin and hematocrit levels were not different when comparing study and control groups. Age and sex differences were insignificant. Finally, no statistical difference was seen for the estimated blood loss and hospital stay between the 2 groups. Platelet-rich plasma use during TKA does not decrease hospital stay or reduce estimated blood loss in the perioperative period.

Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS.

OBJECTIVE: To study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson's disease (PD). BACKGROUND: There are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction. METHODS: A standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III), the Hamilton depression (HAM-D) and anxiety rating scales (HAM-A), the Yale-Brown obsessive-compulsive rating scale (YBOCS), the Apathy Scale (AS), and the Young mania rating scale (YMRS) were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed. RESULTS: Thirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi). There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV) did not change. No between group differences were observed in the cohort of bilateral cases. CONCLUSIONS: There were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach.

Coordinate-based lead location does not predict Parkinson's disease deep brain stimulation outcome.

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.

Influence of hypertension on neurocognitive domains in nondemented Parkinson's disease patients.

Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson's disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity. Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables. Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson's Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function. Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.

Cerebral venous infarction: a potentially avoidable complication of deep brain stimulation surgery.

OBJECT: Despite numerous reports on the morbidity and mortality of deep brain stimulation (DBS), cerebral venous infarction has rarely been reported. We present four cases of venous infarct secondary to DBS surgery. METHODS: The diagnosis of venous infarction was based on 1) delayed onset of new neurologic deficits on postoperative day 1 or 2; 2) significant edema surrounding the superficial aspect of the implanted lead, with or without subcortical hemorrhage on CT scan. RESULTS: Four cases (0.8% per lead, 1.3% per patient) of symptomatic cerebral venous infarction were identified out of 500 DBS lead implantation procedures between July 2002 and August 2009. All four patients had Parkinson's disease. Their DBS leads were implanted in the subthalamic nucleus (n = 2), and the globus pallidus internus (n = 2). Retrospective review of the targeting confirmed that the planned trajectory passed within 3 mm of a cortical vein in two cases for which contrast-enhanced preoperative magnetic resonance (MR) imaging was available. In the other two cases, contrasted targeting images were not obtained preoperatively. CONCLUSION: Cerebral venous infarction is a potentially avoidable, but serious complication. To minimize its incidence, we propose the use of high-resolution, contrast-enhanced, T1-weighted MR images to delineate cerebral venous anatomy, along with careful stereotactic planning of the lead trajectory to avoid injury to venous structures.

Taking a better history for behavioral issues pre- and post-deep brain stimulation: issues missed by standardized scales.

OBJECTIVES: To screen for potentially underreported behavioral changes in patients with idiopathic Parkinson's disease (PD) pre- and post-deep brain stimulation (DBS), a retrospective data base review was performed. METHODS: In total, 113 patients who underwent unilateral or bilateral DBS at the University of Florida in either subthalamic nucleus or globus pallidus internus for PD were screened for behavioral issues by asking about the presence or absence of seven neuropsychiatric symptoms (panic, fear, paranoia, anger, suicidal flashes, crying, and laughing). RESULTS: There was a high prevalence of fear (16.3%), panic (14.0%), and anger (11.6%) at baseline in this cohort. In the first six months following DBS implantation, anger (32.6%), fear (26.7%), and uncontrollable crying (26.7%) were the most frequent symptoms reported. Those symptoms also were present following six months of DBS surgery (30.2%, 29.1%, and 19.8%, respectively). New uncontrollable crying occurred more in the acute postoperative stage (less than or equal to six months) (p = 0.033), while new anger occurred more in the chronic postoperative stage (greater than six months) (p = 0.017). The frequency of uncontrollable laughing significantly increased with bilateral DBS (p = 0.033). CONCLUSIONS: Many of the neuropsychiatric issues were identified at preoperative baseline and their overall occurrence was more than expected. There was a potential for worsening of these issues post-DBS. There were subtle differences in time course, and in unilateral vs. bilateral implantations. Clinicians should be aware of these potential behavioral issues that may emerge following DBS therapy, and should consider including screening questions in preoperative and postoperative interviews. Standardized scales may miss the presence or absence of these clinically relevant issues.

Impact of discontinuing tremor suppressing medications following thalamic deep brain stimulation.

BACKGROUND: Many essential tremor patients continue to require tremor suppressing medications following deep brain stimulation. The true incidence of medication usage in the years following surgery remains unclear, and the use of medications has not been included in the post-operative analyses of tremor severity and also quality of life. METHODS: Among 28 essential tremor patients treated with deep brain stimulation at a single center between January 2002 and April 2010, we analyzed the prevalence and dosage of pre-operative tremor suppressing medications versus post-operative medications at 12 and 36 months following surgery. We also assessed the influence of medication continuation on clinical outcome measures, such as the Fahn-Tolosa-Marin Tremor Rating Scale, and the 36 item short-form health quality of life survey. RESULTS: Both unilateral and bilateral deep brain stimulation resulted in a decrease in primidone use (p = 0.0082, 0.046, respectively), and bilateral deep brain stimulation patients used less tremor suppressing medications 36 months following surgery (p = 0.02). The decision to discontinue primidone after surgery resulted in a non-significant long-term improvement in tremor motor score (23 points versus 15 points, p = 0.19), and did not significantly influence the physical and mental composite quality of life scores (p = 0.81, 0.23, respectively). CONCLUSIONS: Bilateral deep brain stimulation effectively eliminated the need for tremor suppressing medications, while unilateral stimulation was not as effective in reducing medication usage. Clinicians and patients should be aware that discontinuation of primidone after surgery may worsen tremor in unilateral deep brain stimulation cases, but discontinuation will not likely impact quality of life.

Carbidopa/levodopa dose elevation and safety concerns in Parkinson's patients: a cross-sectional and cohort design.

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.

Quantitative normative gait data in a large cohort of ambulatory persons with Parkinson's disease.

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.

The prevalence of fatigue following deep brain stimulation surgery in Parkinson's disease and association with quality of life.

Fatigue is a common and disabling nonmotor symptom seen in Parkinson's disease (PD). While deep brain stimulation surgery (DBS) improves motor symptoms, it has also been associated with non-motor side effects. To date no study has utilized standardized instruments to evaluate fatigue following DBS surgery. Our objective was to determine the prevalence of fatigue following DBS surgery in PD its impact on quality of life and explore predictive factors. We recruited 44 PD subjects. At least one year following DBS placement, we administered the Fatigue Severity Scale (FSS), the Parkinson's Disease Questionnaire (PDQ-39), the Beck Depression Inventory, the Beck Anxiety Inventory, the UPDRS, and a neuropsychological battery. Fifty-eight percent of subjects had moderate to severe fatigue. Fatigue was significantly associated with quality of life, depression, and anxiety. Depression preoperatively was the only predictive factor of fatigue. Fatigue is common following DBS surgery and significantly impacts quality of life.

GPi and STN deep brain stimulation can suppress dyskinesia in Parkinson's disease.

OBJECTIVES: To compare subthalamic nucleus (STN) to globus pallidus internus (GPi) deep brain stimulation (DBS) for control of motor fluctuations and for potential dyskinesia-suppressing qualities. METHODS: We conducted a retrospective database review of all patients who underwent GPi or STN DBS for idiopathic Parkinson's disease. Direct dyskinesia suppression (dDS) was defined as improvement in dyskinesia subscore of the unified Parkinson's disease rating scale (UPDRS) part IV (items 32-34), despite lack of reduction in dopaminergic medication dosage. We analyzed the data using methods appropriate for a case-control study. RESULTS: A total of 133 patients were evaluated. At the last evaluation Dyskinesia scores and motor fluctuations significantly improved in both the GPi (p < 0.0001) and STN groups (p < 0.0001). The GPi group was more likely than the STN group to experience dDS (odds ratio = 1.95, 95% CI = 0.556, 3.21). However, the association between DBS target and dDS was not statistically significant (Pearson chi-square = 2.286, p = 0.131). CONCLUSIONS: The overall clinical outcome of STN and GPi DBS for control of dyskinesia and motor fluctuations was similar. STN and GPi DBS both had some direct dyskinesia suppression effects.

Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome.

OBJECTIVE: Impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS) are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD) and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on ICD/DDS frequency and dopaminergic medication usage. METHODS: A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED), and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement) were examined. RESULTS: 28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively. CONCLUSIONS: Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.

Worsening essential tremor following deep brain stimulation: disease progression versus tolerance.

A major concern regarding ventralis intermedius nucleus deep brain stimulation for essential tremor has been the loss of surgical efficacy over time in a minority of patients. Some experts have ascribed the worsening tremor to tolerance, while other evidence has suggested that disease progression may play a role. Suboptimal lead placement has also been reported to be a factor in worsening tremor following deep-brain stimulation; however, most authors consider this phenomenon to manifest within a few months of the actual surgery. We aimed to dissect the tolerance versus disease progression issue by analysing preoperative versus long-term post-surgical Fahn-Tolosa-Marin Tremor Rating Scale scores both on and off stimulation among 28 patients who underwent ventralis intermedius nucleus deep brain stimulation and 21 age-matched controls. Of the 28 patients in the treatment arm of the cohort, seven (25%) demonstrated evidence of tremor progression, and had a 34% increase in the tremor score off stimulation at the 36 month follow-up compared with a 32% increase among controls (P = 0.67). In one of the seven patients there was evidence of suboptimal lead placement given the lateral position of the lead, and the motor side effects during threshold testing. This patient demonstrated a loss of stimulation benefit between 24 and 36 months, which may have been more indicative of tolerance. The other six subjects (86%) maintained stimulation benefit throughout the follow-up period, despite worsening tremor off stimulation (at a comparable rate to that of controls), making disease progression the most likely explanation. The data suggest that deep brain stimulation tolerance may be over-reported in the literature, and that a tolerance versus disease progression work-up should include: examining the trend in off stimulation scores, accounting for image based lead locations, and during programming sessions checking for thresholds which may elicit clinical benefits and side effects.

Low-Frequency Deep Brain Stimulation for Dystonia: Lower is Not Always Better.

BACKGROUND: It has been observed that low-frequency stimulation (LFS) may be effective for dystonia, and the use of LFS may alleviate the need for frequent battery changes in a subset of patients. The aim of this study was to analyze LFS as a strategy to treat deep brain stimulation (DBS) patients with various dystonias. METHODS: Subjects had to receive a minimum of 6 months of clinical follow-up at the University of Florida, and were required to have a minimum of 3 months on a LFS trial. Twenty-seven dystonia DBS patients were retrospectively analyzed from the UF-INFORM database. RESULTS: Thirteen subjects met inclusion criteria. Of the 13 subjects, all had bilateral internal pallidum (GPi) DBS, and five (38.5%) remained with at least one side on LFS settings at their last follow up (average follow up 24 months, range 6-46 months). Within the first 6 months, six (46%) subjects remained on LFS and seven (54%) were changed to high-frequency stimulation (HFS). Those who remained on LFS settings at 6 months were characterized by shorter disease durations than those on HFS settings. There were no significant differences in dystonia severity (Unified Dystonia Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale) at baseline between the two settings. The estimated battery life for LFS (79.9±30.5) was significantly longer than for HFS settings (32.2±13.1, p<0.001). DISCUSSION: LFS was ultimately chosen for 38.5% of all subjects. Although this study failed to yield solid predictive features, subjects on LFS tended to have shorter disease durations.

DBS candidates that fall short on a levodopa challenge test: alternative and important indications.

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.