Effect of subthalamic nucleus or globus pallidus interna stimulation on oculomotor function in patients with Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) of either the globus pallidus interna (GPi) or subthalamic nucleus (STN) is similarly effective for treating somatomotor manifestations of Parkinson's disease (PD), but differences in how stimulation of each target affects oculomotor function are poorly understood. OBJECTIVE: We sought to determine if stimulation of the STN, but not the GPi, affects oculomotor function in PD patients. METHODS: Nineteen PD patients with DBS implants (8 bilateral GPi, 9 bilateral STN and 2 unilateral STN) were studied. Testing was performed with stimulation on, then off. Somatomotor function was tested using the Unified Parkinson's Disease Rating Scale (UPDRS) motor exam. For oculomotor testing, patients performed pro- and antisaccade tasks while monitored with an infrared eye tracker. Saccadic latency, saccadic intrusions, and square-wave jerks (SWJs) were measured for each trial. RESULTS: As expected, UPDRS motor scores improved with both GPi and STN stimulation. With GPi stimulation, there was no significant difference in oculomotor function with stimulation on or off. However, with STN stimulation on, there was a significant increase in the mean number of SWJs/s, as well as a significant decrease in latency for both pro- and antisaccade tasks. CONCLUSION: Stimulation of either GPi or STN had similar effects on somatomotor function, but only STN stimulation significantly altered oculomotor function.

Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson's disease.

Inflammation is a pathological hallmark of Parkinson's disease (PD). Chronic pro-inflammatory responses contribute to the loss of neurons in the neurodegenerative process. The present study was undertaken to define the peripheral innate and adaptive immune contributions to inflammation in patients with PD. Immunophenotyping revealed a shift of peripheral myeloid and lymphoid cells towards a pro-inflammatory phenotype. Regulatory T cells (Tregs) were reduced in number, and their suppression of T responder proliferation decreased. The PD Tregs did not suppress activated pro-inflammatory myeloid cells. Ex vivo expansion of Tregs from patients with PD restored and enhanced their suppressive functions while expanded Tregs displayed increased expression of foxp3, il2ra (CD25), nt5e (CD73), il10, il13, ctla4, pdcd1 (PD1), and gzmb. Collectively, these findings documented a shift towards a pro-inflammatory peripheral immune response in patients with PD; the loss of Treg suppressive functions may contribute significantly to this response, supporting PD as a disorder with extensive systemic pro-inflammatory responses. The restoration and enhancement of Treg suppressive functions following ex vivo expansion may provide a potential cell therapeutic approach for patients with PD.

Five-year follow-up of unilateral posteroventral pallidotomy in Parkinson's disease.

BACKGROUND: Neurocognitive outcome research of individuals with Parkinson's disease after unilateral pallidotomy is inconsistent. Although some studies reported few cognitive changes, other investigations have more consistently shown both transient and long-term cognitive decline postoperatively. METHODS: We report the long-term motor and neurocognitive outcome 5 years post surgery for 18 patients with Parkinson's disease (12 men and 6 woman; all right-handed) who underwent right or left unilateral posteroventral pallidotomy. RESULTS: Pallidotomy patients revealed long-term motor benefits from the surgery in their "off" state and control of dopa-induced dyskinesias in their "on" state, which is consistent with previous research. We found mild declines in oral and visuomotor information processing speed, verbal recognition memory, and mental status 5 years after surgery, which differs from previous literature regarding the long-term neurocognitive outcome after pallidotomy. Differences between the right and left pallidotomy patients for both motor and cognitive skills were not found. CONCLUSION: Although deep brain stimulation is presently the treatment of choice, pallidotomy continues to be performed around the world. Consequently, although unilateral pallidotomy should be considered a treatment option for patients with Parkinson's disease who suffer from severe unilateral disabling motor symptoms or dyskinesias, the long-term neurocognitive outcome should also be considered in treatment decisions.

Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.

BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING: Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS: Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. INTERVENTION: Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. MAIN OUTCOME MEASURES: Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. RESULTS: Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. CONCLUSIONS: Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.

Assessment of appropriate medication administration for hospitalized patients with Parkinson's disease.

BACKGROUND: For Parkinson's disease (PD) patients, adherence to a regular PD medication schedule is important in achieving optimal symptom control. There are few published studies quantifying PD medication administrations in hospitalized PD patients. METHODS: Hospitalization records for 100 veterans with idiopathic PD and admitted to our center were reviewed to determine the on time rate and contraindicated medication doses. A barcode based computerized medication administration system within the electronic medical record provided information of the exact time the medication was given to a patient. RESULTS: Eighty-nine idiopathic PD patients met study inclusion criteria. Among them, 87 were on levodopa monotherapy or in combination with other PD medications. Two patients were on dopamine agonists only. A total of 3873 doses of PD medications were prescribed during hospitalization. Among 675 incorrect medication administrations, 322 doses were omitted, 300 doses late by ≥ 30 min, and 53 doses given early by ≥ 30 min. Contraindicated medications were prescribed for 19 patients. The correct administration percentage was lower during the first 2 days post-admission compared to subsequent days (mean 74.6% vs. 82.8%) and higher for patients who had neurological consultations (mean 85.5% vs. 76.5%). Correct administration rates were better for patient-based medication schedules (85.6%) than with hospital-based schedules (77.5%), but did not achieve statistical significance. CONCLUSION: Adherence to regular PD medication dosing schedules during hospitalization is problematic, but improves with specialist consultation. Staff involved in the admission process for PD patients should work to safeguard against disruption of the prescribed home dosing schedule.