Janet Romrell

Cognition and Mood in Parkinson's Disease in Subthalamic Nucleus versus Globus Pallidus Interna Deep Brain Stimulation: The COMPARE Trial

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.

Aspiration and swallowing in Parkinson disease and rehabilitation with EMST: A randomized trial

Objective: Dysphagia is the main cause of aspiration pneumonia and death in Parkinson disease (PD) with no established restorative behavioral treatment to date. Reduced swallow safety may be related to decreased elevation and excursion of the hyolaryngeal complex. Increased submental muscle force generation has been associated with expiratory muscle strength training (EMST) and subsequent increases in hyolaryngeal complex movement provide a strong rationale for its use as a dysphagia treatment. The current studys objective was to test the treatment outcome of a 4-week device-driven EMST program on swallow safety and define the physiologic mechanisms through measures of swallow timing and hyoid displacement. Methods: This was a randomized, blinded, sham-controlled EMST trial performed at an academic center. Sixty participants with PD completed EMST, 4 weeks, 5 days per week, for 20 minutes per day, using a calibrated or sham, handheld device. Measures of swallow function including judgments of swallow safety (penetration–aspiration [PA] scale scores), swallow timing, and hyoid movement were made from videofluoroscopic images. Results: No pretreatment group differences existed. The active treatment (EMST) group demonstrated improved swallow safety compared to the sham group as evidenced by improved PA scores. The EMST group demonstrated improvement of hyolaryngeal function during swallowing, findings not evident for the sham group. Conclusions: EMST may be a restorative treatment for dysphagia in those with PD. The mechanism may be explained by improved hyolaryngeal complex movement. Classification of evidence: This intervention study provides Class I evidence that swallow safety as defined by PA score improved post EMST.

Dual Electrode Thalamic Deep Brain Stimulation For The Treatment Of Posttraumatic And Multiple Sclerosis Tremor

OBJECTIVE: To report the results of ventralis intermedius nucleus/ventralis oralis posterior nucleus (VIM) plus ventralis oralis anterior (VOA)/ventralis oralis posterior (VOP) thalamic deep brain stimulation (DBS) for the treatment of posttraumatic and multiple sclerosis tremor. OBJECTIVE: The treatment of posttraumatic tremor and multiple sclerosis tremor, by either medication or surgery, has proven difficult. Lesions and DBS have had mixed and somewhat disappointing results. Previously, we reported the use of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border) as effective for the treatment of posttraumatic tremor in a single patient. In this study, we report the results of this technique on four patients. METHODS: Four patients with either posttraumatic tremor (n = 3) or multiple sclerosis tremor (n = 1) underwent placement of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border). Patients underwent preoperative testing and testing at a minimum of 6 months after implantation in four conditions: On VIM DBS/On VOA/VOP DBS; On VIM DBS/Off VOA VOP DBS (5 h DBS washout); Off VIM DBS/Off VOA/VOP DBS (12 h overnight washout); and Off VIM DBS/On VOA/VOP DBS (5 h DBS washout). RESULTS: Each of the patients showed improvements in all four conditions when compared with the baseline. All of the improvements were maintained with chronic DBS, without tremor rebound. An analysis was performed to determine whether each condition was associated with symptom reduction (percentage change). The percentage reduction was significant for each condition and measure, despite the small number of participants. For the total tremor rating scale score, the Off VIM/Off VOA/VOP condition yielded less symptom reduction than the On VIM condition or the On VOA/VOP condition. The On VIM and On VOA/VOP conditions did not differ significantly from each other in terms of contralateral upper extremity symptoms or total clinical score. Activation of both the VIM and VOA/VOP electrodes was associated with the greatest symptom reduction. CONCLUSION: Tremors, such as those examined in this study, that are refractory to medications and have a poor response to VIM DBS monotherapy, may respond favorably to VIM plus VOA/VOP DBS. Two electrodes may be better than one for the treatment of certain disorders; however, more study will be required to confirm this hypothesis.

Development and initial validation of a screening tool for Parkinson disease surgical candidates.

As there is currently no standardized assessment tool for evaluating Parkinson disease (PD) patients for deep brain stimulation (DBS), the authors developed the Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD). Part I of the study was a retrospective analysis of 174 patients presenting for a surgical screening. Part II was a multicenter study to assess the correlation of FLASQ-PD scores. The results of this study suggest that the FLASQ-PD may be a useful triage tool for screening PD patients for DBS surgery.

Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study.

Polysomnographic studies of Parkinsons disease (PD) patients with visual hallucinations (VH) usually reveal short, fragmented rapid eye movement (REM) sleep, with lower sleep efficiency and reduced total REM sleep. Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD. To confirm quetiapines efficacy in improving VH, and to determine whether the mechanism was due to its effect on REM sleep architecture, we performed a pilot, double-blind, placebo-controlled study. Sixteen PD patients experiencing VH were recruited. Eight patients were randomized to quetiapine and eight patients to placebo. Patients underwent pre- and post-treatment polysomnography. The Clinical Global Impression Scale (CGIS), Brief Psychiatric Rating Scale (BPRS), and Unified Parkinson Disease Rating Scale (UPDRS) motor subscale were obtained. There were no differences in baseline characteristics between the treatment arms except that the placebo group had more sleep in stage REM (74.7 min vs. 40.1 min; p < .001). Data were imputed for all patients who prematurely discontinued (four quetiapine and one placebo) in an intention-to-treat analysis. The average quetiapine dose was 58.3 mg/day. While there was no significant difference in the change in REM duration pre- vs. post-treatment in either arm, patients randomized to quetiapine improved on the CGIS (p = .03) and the hallucination item of the BPRS (p = .02). No difference was noted in the UPDRS motor scores. Despite the small sample, this is the first double-blind trial to show quetiapines efficacy over placebo in controlling VH in the PD population. However, normalization of sleep architecture was not supported as the mechanism.

Useful Field of View as a Reliable Screening Measure of Driving Performance in People With Parkinson's Disease: Results of a Pilot Study

Purpose: To determine the correlations of the Useful Field of View (UFOV), compared to other clinical tests of Parkinsons disease (PD); vision; and cognition with measures of on-road driving assessments and to quantify the UFOVs ability to indicate passing/failing an on-road test in people with PD. Methods: Nineteen randomly selected people with idiopathic PD, mean age = 74.8 (6.1), 14 (73.7%) men, 18 (94.7%) Caucasians, were age-matched to 104 controls without PD. The controls had a mean age of 75.4 (6.4), 59 (56.7%) men, 96 (92.3%) Caucasians. Both groups were referred for a driving evaluation after institutional review board approval. Results: Compared to neuropsychological and clinical tests of vision and cognition, the UFOV showed the strongest correlations (r > .75, p < 0.05) with measures of failing a standardized road test and number of driving errors. Among PD patients, the UFOV Risk Index score of 3 (range 1–5) was established as the optimal cutoff value for passing the on-road test, with sensitivity 87 percent and specificity 82 percent, AUC = 92 percent (SE 0.61, p = .002). Similarly, the UFOV 2 (divided attention) optimum cutoff value is 223 ms (range 16–500 ms), sensitivity 87.5 percent, specificity 81.8 percent, AUC = 91 percent (SE 0.73, p = .003). The UFOV 3 (selected attention) optimal cutoff value is 273 ms (range 16–500 ms), sensitivity 75 percent, specificity 72.7 percent, AUC = 87 percent (SE 0.81, p = .007). Conclusion: In this pilot study among PD patients, the UFOV may be a superior screening measure (compared to other measures of disease, cognition, and vision) for predicting on-road driving performance but its rigor must be verified in a larger sample of people with PD.

Rationale for current therapies in Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disorder that affects an estimated 1 million people in the US and tens of millions worldwide. Medication therapy has made significant advances and improvements especially over the last 10 years. A number of new treatments and new strategies have emerged and the quality of life for the average sufferer has improved. This review will describe the rationale and strategies for current medical therapies in PD, with special emphasis on the use of antipsychotic agents. Levodopa remains the most efficacious medication for the management of PD. Long-term use of levodopa, however, is associated with the development of motor fluctuations including dyskinesia. Trials with dopamine agonists have demonstrated a delay in the onset of dyskinesia with the use of this therapy. There is also active, ongoing investigation to determine whether a neuroprotective effect may be present with agonist therapy. Anticholinergics have been successfully used to treat tremor as well as sialorrhoea and urinary urgency. Catechol-O-methyltransferase inhibitors increase ‘on time’, decrease ‘off time,’ and improve motor scores. Continuous stimulation of dopamine receptors may decrease the fluctations observed with pulsatile delivery of anti-Parkinsonian medications, but this will require more study. Monoamine oxidase-B inhibitors, specifically selegiline, may provide symptomatic improvement; the question as to whether a neuroprotective benefit is present remains unanswered. Amantadine has demonstrated both symptomatic benefit and dyskinesia benefit in some patients. Selective dopamine blockers such as clozaril and quetiapine, have been shown to be effective in the treatment of psychosis. This class of medications is particularly useful as an adjunctive to levodopa and dopamine agonists. Doses of dopaminergic drugs can be escalated to treat Parkinsonian symptoms, whereas selective dopamine blockers can be added to block psychosis. Old management strategies required a reduction in dopaminergic therapy and therefore worsened Parkinsonian symptoms. Even though there have been great advances in the medical options for symptomatic management of PD, there are still many unmet needs for this patient population.

Clinical cases where lesion therapy was chosen over deep brain stimulation.

Deep brain stimulation (DBS) surgery has become the gold standard for treatment of select refractory cases of Parkinson disease and essential tremor. Despite the usefulness of DBS surgery in many cases, there remain situations where lesion therapy (subthalamotomy, pallidotomy or thalamotomy) may provide a reasonable alternative to DBS. We reviewed the University of Florida Institutional Review Board-approved database for movement disorders surgery and identified 286 DBS leads placed in 189 patients as well as 4 additional patients who had lesion therapy. In these 4 cases we reviewed the clinical presentations that resulted in a multidisciplinary team opting for lesion therapy over DBS. Lesion therapy represents a viable alternative and has several important advantages, including a decreased need for access to specialists and clinical follow-up, improved affordability, and a lower infection risk.

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 Parkinsons 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.

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 Parkinsons disease. Direct dyskinesia suppression (dDS) was defined as improvement in dyskinesia subscore of the unified Parkinsons 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.