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.

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.

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.

Do patient's get angrier following STN, GPi, and thalamic deep brain stimulation.

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-operative and 4- to 6-month post-operative Visual Analog Mood Scale (VAMS) scores for all three groups were compared; additionally, pre-operative and 1- to 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 macroelectrode passes, and years of education. Levodopa equivalent dosages and dopamine agonist use were 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 was used to detect significant differences among the three targets in the changes pre- to post-operatively. Similar to the COMPARE dataset, at 4 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=0.012). At 1-3 months post-operation, 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-operation 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 that it may be a lesional effect. PD patients with longer disease duration 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 of a lesional effect rather than a stimulation induced one (Okun et al., 2009).

Smile and laughter induction and intraoperative predictors of response to deep brain stimulation for obsessive-compulsive disorder.

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 2 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 2 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 1 and 2-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.

Binge eating in Parkinson's disease: prevalence, correlates and the contribution of deep brain stimulation.

Of 96 Parkinson's disease patients surveyed at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge-eating disorder. Eight (8.3%) exhibited subthreshold binge eating. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, compulsive 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% versus 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% versus 41%). More overeaters had a history of subthalamic deep brain stimulation (DBS; 44% versus 14%). History of DBS was the only independent predictor of overeating.

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.

Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial.

OBJECTIVE: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease. METHODS: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS). RESULTS: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets. INTERPRETATION: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.

Should we consider Vim thalamic deep brain stimulation for select cases of severe refractory dystonic tremor.

Dystonic tremor, which may present with many different clinical presentations (rhythmic oscillations, abnormal posture, pain, and/or a null point) has proven to be a challenge for the clinician to effectively treat. Although recent studies have demonstrated excellent outcomes in select cases following deep brain stimulation (DBS) of the internal globus pallidus, the optimal target for dystonia and particularly for dystonic tremor remains unknown. We report 3 cases of dystonic tremor which were successfully addressed through the use of ventral intermediate nucleus (Vim) DBS. We also review the literature concerning the efficacy of Vim DBS for addressing dystonia. This case series illustrates the potential use of Vim DBS for select cases of dystonic tremor.

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.

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 specific indications must be carefully discussed, as the available cases have had mixed responses. Whether other targets may be more effective is not known.

Prevalence of Twiddler's syndrome as a cause of deep brain stimulation hardware failure.

We reviewed our deep brain stimulation patient database to describe hardware complications which resulted from implantable pulse generator mobility, a phenomenon referred to as Twiddler's syndrome. A prospectively collected database of adverse events for all patients operated on at the University of Florida was queried searching for hardware malfunctions. Of 362 total leads implanted in 226 patients since 2002, there were 17 hardware malfunctions. Three of them were due to Twiddler's syndrome, representing 1.3% of patients (3 of 226 patients) and 1.4% of leads (5 of 362 leads). The subjects had characteristic presentations including re-emergence of symptoms, pain along the path of the hardware, abnormal impedances/current drain and radiographic signs of twisting/fracture. In all cases securing the implantable pulse generator within the chest pocket resolved the issue. Twiddler's syndrome in the population of movement disorder patients treated with deep brain stimulation is an uncommon but important adverse event. It possesses a characteristic presentation and with appropriate diagnostic evaluation it is treatable and future occurrences are preventable.

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.

Distribution of motor impairment influences quality of life in Parkinson's disease.

We evaluated the relationship between upper extremity (UE) and lower extremity (LE) motor impairments in Parkinson's disease (PD) to overall disability and quality of life (QoL) measures. A total of 639 patients who were diagnosed with idiopathic PD were administered the Unified Parkinson's Disease Rating Scale (UPDRS), QoL, activities of daily living (ADL), and behavioral scales. Composite UE and LE scores from the motor section of the UPDRS were correlated with ADL, QoL, and behavioral measurement scores while controlling for disease duration. Patients with greater UE and LE motor impairments had lower QoL scores. However, LE impairments had a greater influence than UE impairments across all QoL measures.

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.

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.