Non-motor phenotypic subgroups in adult-onset idiopathic, isolated, focal cervical dystonia.

BACKGROUND: Non-motor symptoms are well established phenotypic components of adult-onset idiopathic, isolated, focal cervical dystonia (AOIFCD). However, improved understanding of their clinical heterogeneity is needed to better target therapeutic intervention. Here, we examine non-motor phenotypic features to identify possible AOIFCD subgroups. METHODS: Participants diagnosed with AOIFCD were recruited via specialist neurology clinics (dystonia wales: n = 114, dystonia coalition: n = 183). Non-motor assessment included psychiatric symptoms, pain, sleep disturbance, and quality of life, assessed using self-completed questionnaires or face-to-face assessment. Both cohorts were analyzed independently using Cluster, and Bayesian multiple mixed model phenotype analyses to investigate the relationship between non-motor symptoms and determine evidence of phenotypic subgroups. RESULTS: Independent cluster analysis of the two cohorts suggests two predominant phenotypic subgroups, one consisting of approximately a third of participants in both cohorts, experiencing increased levels of depression, anxiety, sleep impairment, and pain catastrophizing, as well as, decreased quality of life. The Bayesian approach reinforced this with the primary axis, which explained the majority of the variance, in each cohort being associated with psychiatric symptomology, and also sleep impairment and pain catastrophizing in the Dystonia Wales cohort. CONCLUSIONS: Non-motor symptoms accompanying AOIFCD parse into two predominant phenotypic sub-groups, with differences in psychiatric symptoms, pain catastrophizing, sleep quality, and quality of life. Improved understanding of these symptom groups will enable better targeted pathophysiological investigation and future therapeutic intervention.

Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson's disease.

BACKGROUND: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program. METHODS: PD patients (n = 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673). Safety and efficacy assessments were collected every 6 months. RESULTS: Mean total duration of exposure to levodopa-carbidopa intestinal gel was 4.1 years (range, 1.2 to 6.9 years). The overall discontinuation rate was 34% (average annual discontinuation rate, 10%). Although most patients (94%) reported an adverse event, the rate of adverse events decreased over time; 53% experienced a serious adverse event. Of patients in this extension study, 54% required jejunal tube replacement during the study, and 37% required percutaneous endoscopic gastrostomy tube replacement. Most patients were on levodopa monotherapy. Patients maintained reductions in "off" time and increases in mean "on" time without dyskinesia from initial levodopa-carbidopa intestinal gel infusion to he study end point (P < 0.001; n = 81). Activities of daily living and quality-of-life assessments demonstrated significant improvements that persisted through the study. CONCLUSIONS: This long-term study demonstrates sustained and clinically meaningful benefits from levodopa-carbidopa intestinal gel in advanced PD patients. Although adverse event rates decreased over time, vigilance is required for device-related complications and adverse events. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Effect of Levodopa-carbidopa Intestinal Gel on Non-motor Symptoms in Patients with Advanced Parkinson's Disease.

Background: Levodopa-carbidopa intestinal gel (LCIG; carbidopa-levodopa enteral suspension in the United States), delivered via percutaneous gastrojejunostomy (PEG-J) and titrated in the inpatient setting, is an established treatment option for advanced Parkinson's disease (PD) patients with motor fluctuations. However, long-term prospective data on the efficacy of LCIG on non-motor symptoms and the safety of outpatient titration are limited. Methods: In this 60-week, open-label phase 3b study, LCIG titration was initiated in an outpatient setting following PEG-J placement in PD patients. The efficacy of LCIG on motor and non-motor symptoms, quality of life, and safety was assessed. Results: Thirty-nine patients were enrolled in the study and 28 patients completed the treatment. A majority of patients (54%) completed outpatient titration within the first week of LCIG infusion. LCIG led to significant reductions from baseline in Non-Motor Symptom Scale (NMSS) total score (least squares mean ± SE = -17.6 ± 3.6, P < 0.001) and 6 of the NMSS domain scores (sleep/fatigue, attention/memory, gastrointestinal tract, urinary, sexual function, miscellaneous) at week 12. These reductions were maintained at week 60 with the exception of the urinary domain. "Off" time (-4.9 ± 0.5 hours/day, P < 0.001) and "On" time without troublesome dyskinesia (-4.3 ± 0.6 hours/day, P < 0.001) were improved at week 60. Adverse events (AEs) were reported in 37 (95%) patients. Conclusions: LCIG treatment led to reductions in non-motor symptom burden and motor fluctuations in advanced PD patients. The safety profile was consistent with previous studies that used inpatient titration and outpatient titration did not appear to pose additional risk.

Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial.

BACKGROUND: Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius-ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior-ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor. METHODS: We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS-either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3-4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four stimulation conditions: VIM on, VO on, both on, and both off (the order of testing was chosen by a computer-generated random sequence, assigned by independent members of the centre, and enacted by an unmasked DBS programming nurse). Each of four stimulation settings were tested over 4 consecutive days, with stimulation settings held constant for at least 12 h before testing. The primary outcome was change in mean total TRS score at the 6-month postoperative assessment with both leads activated, compared with the preoperative baseline mean TRS score. Analysis was by intention to treat. Safety was analysed in all patients who received the surgical implantation except in one patient who discontinued before the safety assessment. This trial is registered with ClinicalTrials.gov, number NCT00954421. FINDINGS: Between Jan 16, 2007, and Dec 17, 2013, we enrolled 12 patients who were randomly assigned either to 3 initial months of VIM-only or VO-only stimulation. One patient from the VO-only group developed an infection necessitating DBS explantation, and was excluded from the assessment of the primary outcome. Compared with the mean baseline TRS score of 57·0 (SD 10·2), the mean score at 6 months decreased to 40·1 (17·6), -29·6% reduction; t=-0·28, p=0·03. Three of 11 patients did not respond to surgical intervention. One patient died suddenly 2 years after surgery, but this was judged to be unrelated to DBS implantation. Serious adverse events included a superficial wound infection in one patient that resolved with antibiotic therapy, and transient altered mental status and late multiple sclerosis exacerbation in another patient. The most common non-serious adverse events were headache and fatigue. INTERPRETATION: Dual lead thalamic DBS might be a safe and effective option for improving severe, refractory multiple sclerosis tremor. Larger studies are necessary to show whether this technique is widely applicable, safe in the long-term, and effective in treating multiple sclerosis tremor or other severe tremor disorders. FUNDING: US National Institutes of Health, the Cathy Donnellan, Albert E Einstein, and Birdie W Einstein Fund, and the William Merz Professorship.

Occurrence of Dysphagia Following Botulinum Toxin Injection in Parkinsonism-related Cervical Dystonia: A Retrospective Study.

BACKGROUND: The aim was to compare the occurrence of post-injection dysphagia in parkinsonism-related cervical dystonia (PRCD) versus cervical dystonia (CD) of other etiologies (non-PRCD). A secondary objective was to explore potential clinical differences between PRCD and non-PRCD and their respective responses to botulinum toxin (BoNT). METHODS: A cross-sectional chart review was carried out of patients treated for CD with Onabotulinumtoxin A at the University of Florida. We collected demographic information, dose of BoNT injected, patient-reported presence of dysphagia as a side effect, patient-perceived duration of benefit and efficacy according to the Clinical Global Impression Scale (CGIS). RESULTS: Of the 144 patients included, 24 patients were diagnosed with PRCD and 120 were diagnosed as non-PRCD. Data analysis showed no significant differences in number of weeks of benefit from BoNT (PRCD 9.1±3.7 versus non-PRCD 9.4±3.7 weeks, p = 0.830), BoNT dosage (PRCD 235.0±95.6 versus non-PRCD 263.7±101.3 units, p = 0.181), median CGIS score (median = 2 or "much improved" for both groups, p = 0.88), or the presence of dysphagia after BoNT (PRCD 17% versus non-PRCD 19 %, p = 0.753, n = 132). In a subgroup analysis of the non-PRCD group, patients who experienced dysphagia were older than those who did not (63.9±8.9 years versus 58.1±14.4 years, p = 0.02). DISCUSSION: Despite an increased baseline risk of dysphagia in patients with PRCD, BoNT appears to be equally safe and equally beneficial in PRCD and non-PRCD patients.

Clinical and demographic characteristics related to onset site and spread of cervical dystonia.

BACKGROUND: Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort. METHODS: The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread. RESULTS: Site of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age. CONCLUSIONS: Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.

Clinical and genetic features of cervical dystonia in a large multicenter cohort.

OBJECTIVE: To characterize the clinical and genetic features of cervical dystonia (CD). METHODS: Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in GNAL, THAP1, and Exon 5 of TOR1A. RESULTS: The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in THAP1, TOR1A, and GNAL were identified in 8 participants (0.8%). Two individuals harbored novel missense SVs in Exon 5 of TOR1A. Synonymous and noncoding SVs in THAP1 and GNAL were identified in 4% of the cohort. CONCLUSIONS: Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in GNAL, THAP1, and TOR1A make small contributions to the pathogenesis of CD.

Bilateral Lower Sternocleidomastoid Botulinum Toxin Injections to Address Refractory Anterocollis.

Anterocollis is a type of cervical dystonia characterized by simultaneous and repetitive antagonist muscles contractions, resulting in abnormal neck flexion. It was described with a frequency of 6.8% from 399 patients with diagnosis of cervical dystonia and usually coexists with torticollis and/or laterocollis, as mixed cervical dystonia patterns. Botulinum toxin is usually a practical and effective treatment for cervical dystonia. The target muscles to inject in anterocollis are usually sternocleidomastoid and scalene muscles. There is also a case report suggesting longus collis involvement. Nevertheless, the dosage of the medication in anterocollis is limited by frequent side effects of dysphagia. We described 2 cases of refractory anterocollis. They did not benefit from conventional bilateral upper portion of sternocleidomastoid muscle injections with OnabotulinumtoxinA, but notably improved their symptoms and clinical global impression after switching to injections into bilateral lower portion of sternocleidomastoid muscles, without significant side effects.

Clinimetric testing of the comprehensive cervical dystonia rating scale.

INTRODUCTION: The aim of this study was to test the clinimetric properties of the Comprehensive Cervical Dystonia Rating Scale. This is a modular scale with modifications of the Toronto Western Spasmodic Torticollis Rating Scale (composed of three subscales assessing motor severity, disability, and pain) now referred to as the revised Toronto Western Spasmodic Torticollis Scale-2; a newly developed psychiatric screening instrument; and the Cervical Dystonia Impact Profile-58 as a quality of life measure. METHODS: Ten dystonia experts rated subjects with cervical dystonia using the comprehensive scale. Clinimetric techniques assessed each module of the scale for reliability, item correlation, and factor structure. RESULTS: There were 208 cervical dystonia patients (73% women; age, 59 ± 10 years; duration, 15 ± 12 years). Internal consistency of the motor severity subscale was acceptable (Cronbach's alpha = 0.57). Item to total correlations showed that elimination of items with low correlations (<0.20) increased alpha to 0.71. Internal consistency estimates for the subscales for disability and pain were 0.88 and 0.95, respectively. The psychiatric screening scale had a Cronbach's alpha of 0.84 and satisfactory item to total correlations. When the subscales of the Toronto Western Spasmodic Torticollis Scale-2 were combined with the psychiatric screening scale, Cronbach's alpha was 0.88, and construct validity assessment demonstrated four rational factors: motor; disability; pain; and psychiatric disorders. The Cervical Dystonia Impact Profile-58 had an alpha of 0.98 and its construction was validated through a confirmatory factor analysis. CONCLUSIONS: The modules of the Comprehensive Cervical Dystonia Rating Scale are internally consistent with a logical factor structure.

Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials.

BACKGROUND: Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy. METHODS: Safety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device-associated (n = 395) from non-procedure/device adverse events (n = 412). RESULTS: At the data cutoff, median exposure to levodopa-carbidopa intestinal gel was 911 days (range, 1-1980 days) with 963 total patient-years of exposure. Procedure/device adverse events occurred in 300 patients (76%), and serious adverse events occurred in 68 (17%); most frequently reported procedure/device adverse events and serious adverse events were complications of device insertion (41% and 8%, respectively) and abdominal pain (36% and 4%, respectively). Non-procedure/device adverse events occurred in 92% (379), with most frequently reported being insomnia (23%) and falls (23%); 42% (171) had non-procedure/device serious adverse events, with most frequently reported being pneumonia (5%) and PD symptoms (2%). Adverse events led to discontinuation in 17% (72), most frequently because of complication of device insertion (2.4%). There were 34 treatment-emergent deaths (8.3%) in the overlapping data sets, 2 of which (0.5%) were considered "possibly related" to the treatment system. CONCLUSION: In the largest collection of levodopa-carbidopa intestinal gel safety data from prospective clinical studies, procedure/device events were frequently reported and occasionally life threatening. Most non-procedure/device events were typical for levodopa treatment and an elderly population. These factors combined with high treatment efficacy led to a relatively low discontinuation rate in advanced PD patients.

Global attentional neglect of segmented lines in Parkinson's disease.

Global attention requires disengagement from focal elements of stimuli. Since people with Parkinson's disease (PD) may reveal impaired disengagement, this study attempted to learn if people with PD may be impaired at allocating global attention. Healthy adults and people with PD attempted to bisect lines of uniform thickness and lines composed of two segments of unequal thickness and length. When the longer line segment was to the right of the shorter segment, the group with PD demonstrated an increased deviation toward the longer segment, supporting the postulate that people with PD have an impaired ability to disengage focal attention and engage global spatial attention.

Rasagiline for the symptomatic treatment of fatigue in Parkinson's disease.

BACKGROUND: Fatigue affects 40% to 50% of all PD patients and is a leading cause of disability, with no clearly established or efficacious established treatments. METHODS: In this double-blinded, placebo-controlled, pilot trial, we investigated whether rasagiline improved fatigue among PD patients. Subjects were randomized to 1 mg daily of rasagiline or placebo for 12 weeks. The primary endpoint was a change in the Modified Fatigue Impact Scale from baseline to week 12. RESULTS: Thirty PD subjects (16 men), with Modified Fatigue Impact Scale baseline score of 67 ± 15, were randomized (16 to rasagiline vs. 14 to placebo). Significant improvement was noted in the mean Modified Fatigue Impact Scale score of the rasagiline group (12 points) as compared to placebo (8.5 points) from baseline to week 12 (P = 0.003). CONCLUSION: In this pilot study, rasagiline at a dose of 1 mg per day improved fatigue. Larger randomized studies are needed to confirm this finding.

Deep brain stimulation for tremor associated with underlying ataxia syndromes: a case series and discussion of issues.

BACKGROUND: Deep brain stimulation (DBS) has been utilized to treat various symptoms in patients suffering from movement disorders such as Parkinson's disease, dystonia, and essential tremor. Though ataxia syndromes have not been formally or frequently addressed with DBS, there are patients with ataxia and associated medication refractory tremor or dystonia who may potentially benefit from therapy. METHODS: A retrospective database review was performed, searching for cases of ataxia where tremor and/or dystonia were addressed by utilizing DBS at the University of Florida Center for Movement Disorders and Neurorestoration between 2008 and 2011. Five patients were found who had DBS implantation to address either medication refractory tremor or dystonia. The patient's underlying diagnoses included spinocerebellar ataxia type 2 (SCA2), fragile X associated tremor ataxia syndrome (FXTAS), a case of idiopathic ataxia (ataxia not otherwise specified [NOS]), spinocerebellar ataxia type 17 (SCA17), and a senataxin mutation (SETX). RESULTS: DBS improved medication refractory tremor in the SCA2 and the ataxia NOS patients. The outcome for the FXTAS patient was poor. DBS improved dystonia in the SCA17 and SETX patients, although dystonia did not improve in the lower extremities of the SCA17 patient. All patients reported a transient gait dysfunction postoperatively, and there were no reports of improvement in ataxia-related symptoms. DISCUSSION: DBS may be an option to treat tremor, inclusive of dystonic tremor in patients with underlying ataxia; however, gait and other symptoms may possibly be worsened.

The "brittle response" to Parkinson's disease medications: characterization and response to deep brain stimulation.

OBJECTIVE: Formulate a definition and describe the clinical characteristics of PD patients with a "brittle response" (BR) to medications versus a "non-brittle response" (NBR), and characterize the use of DBS for this population. METHODS: An UF IRB approved protocol used a retrospective chart review of 400 consecutive PD patients presenting to the UF Center for Movement Disorders and Neurorestoration. Patient records were anonymized and de-identified prior to analysis. SPSS statistics were used to analyze data. RESULTS: Of 345 included patients, 19 (5.5%) met criteria for BR PD. The BR group was comprised of 58% females, compared to 29% in the NBR group (P = .008). The former had a mean age of 63.4 compared to 68.1 in the latter. BR patients had lower mean weight (63.5 vs. 79.6, P = <.001), longer mean disease duration (12.6 vs. 8.9 years, P = .003), and had been on LD for more years compared to NBR patients (9.8 vs. 5.9, P = .001). UPDRS motor scores were higher (40.4 vs. 30.0, P = .001) in BR patients. No differences were observed regarding the Schwab and England scale, PDQ-39, and BDI-II. Sixty-three percent of the BR group had undergone DBS surgery compared to 18% (P = .001). Dyskinesias were more common, severe, and more often painful (P = <.001) in the BR group. There was an overall positive benefit from DBS. CONCLUSION: BR PD occurred more commonly in female patients with a low body weight. Patients with longer disease duration and longer duration of LD therapy were also at risk. The BR group responded well to DBS.

An eight-year clinic experience with clozapine use in a Parkinson's disease clinic setting.

BACKGROUND: To examine our eight year clinic-based experience in a Parkinson's disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD). METHODS: The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy. RESULTS: There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45-87 years (mean 68.3±10.15), disease duration of 17-240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = -0.36, p<0.01) and H&Y score (r = -0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05). CONCLUSIONS: This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting.

Rescue GPi-DBS for a Stroke-associated Hemiballism in a Patient with STN-DBS.

BACKGROUND: Hemiballism/hemichorea commonly occurs as a result of a lesion in the subthalamic region. CASE REPORT: A 38-year-old male with Parkinson's disease developed intractable hemiballism in his left extremities due to a small lesion that was located adjacent to the right deep brain stimulation (DBS) lead, 10 months after bilateral subthalamic nucleus (STN)-DBS placement. He underwent a right globus pallidus internus (GPi)-DBS lead implantation. GPi-DBS satisfactorily addressed his hemiballism. DISCUSSION: This case offered a unique look at basal ganglia physiology in human hemiballism. GPi-DBS is a reasonable therapeutic option for the treatment of medication refractory hemiballism in the setting of Parkinson's disease.

Driving errors in Parkinson's disease: moving closer to predicting on-road outcomes.

Age-related medical conditions such as Parkinson's disease (PD) compromise driver fitness. Results from studies are unclear on the specific driving errors that underlie passing or failing an on-road assessment. In this study, we determined the between-group differences and quantified the on-road driving errors that predicted pass or fail on-road outcomes in 101 drivers with PD (mean age = 69.38 ± 7.43) and 138 healthy control (HC) drivers (mean age = 71.76 ± 5.08). Participants with PD had minor differences in demographics and driving habits and history but made more and different driving errors than HC participants. Drivers with PD failed the on-road test to a greater extent than HC drivers (41% vs. 9%), χ²(1) = 35.54, HC N = 138, PD N = 99, p < .001. The driving errors predicting on-road pass or fail outcomes (95% confidence interval, Nagelkerke R² =.771) were made in visual scanning, signaling, vehicle positioning, speeding (mainly underspeeding, t(61) = 7.004, p < .001, and total errors. Although it is difficult to predict on-road outcomes, this study provides a foundation for doing so.

Testosterone level and the effect of levodopa and agonists in early Parkinson disease: results from the INSPECT cohort.

BACKGROUND: To determine if testosterone levels are influenced by dopaminergic therapy in Parkinson disease (PD) patients. Testosterone level has been reported to be low in patients with PD and other neurodegenerative diseases. In this study, we sought to determine whether dopaminergic therapy (i.e. levodopa and dopamine agonist) influenced testosterone levels. We used a cohort of consecutive male patients from the INSPECT trial--a multi-center, prospective, study that primarily investigated the effects of short-term treatment with pramipexole or levodopa on [(123)I] B-CIT SPECT imaging in early PD. METHODS: Testosterone levels were drawn on consenting male subjects with early PD who enrolled in the INSPECT trial at three study visits (baseline, 12 weeks post-treatment, and 8-12 weeks post-washout). Subjects were randomized to: no treatment, pramipexole (up to 3 mg) or levodopa (up to 600 mg). Testosterone levels were obtained twice (prior to 10 AM) and averaged for each of three study visits. RESULTS: Thirty two male patients participated in this sub-study and there were no significant differences in disease characteristics in the 3 groups at baseline. Twenty-nine patients completed the follow-up visits and were suitable for analysis. There were statistically significant differences in the change in free testosterone level, increased in both the levodopa group and pramipexole group but decreased in the untreated group at 12-weeks post-treatment. There were no significant differences in the changes of UPDRS total or motor scores, although there was a strong trend toward improvement in motor scores. The testosterone level persisted in its increase only in the pramipexole group at the end of the washout period. CONCLUSION: These preliminary data support the premise that dopaminergic medications do not reduce testosterone levels in early PD patients.

Comparable Botulinum Toxin Outcomes between Primary and Secondary Blepharospasm: A Retrospective Analysis.

BACKGROUND: Blepharospasm is a focal cranial dystonia, which could be idiopathic in origin or secondary to an underlying disorder that commonly impairs quality of life. Botulinum toxin (BoNT) injections have become the treatment of choice; however, a less favorable response to BoNT is expected in secondary blepharospasm. No studies have been conducted comparing outcomes between blepharospasm cohorts. We therefore aim to compare BoNT outcomes in primary and secondary blepharospasm subjects. METHODS: A retrospective review of 64 blepharospasm subjects receiving BoNT therapy was conducted. Demographics, BoNT treatment schedules, duration of BoNT therapy, and side effects were recorded. Outcome measures were duration of benefit, peak-dose benefit recorded with the Clinical Global Impressions Scale (CGIS), and related side effects. RESULTS: No difference was found between the two cohorts regarding duration of benefit from treatment (primary 9.47 weeks vs. secondary 9.63 weeks, p = 0.88). Perceived peak-dose benefit was more commonly reported as "very much improved" in secondary patients, but this was not significant (p = 0.13). Higher BoNT dosages were required in both groups over time, with a mean increase of 20.5% in primary and 26.5% in secondary blepharospasm. Ptosis (8%) and diplopia (6%) were the most common reported side effects. Mean follow-up in years was similar between groups, 3.6 years for primary vs. 2.4 years for secondary blepharospasm (p = 0.17). DISCUSSION: BoNT injections were effective with comparable benefits seen in both primary and secondary blepharospasm populations. Clinicians should be aware of the similar benefit from BoNT reported in secondary blepharospasm patients. The average duration of benefit in this cohort was comparable with previous reports.