The effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intractable Parkinson's disease (PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug-induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3-month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined "on/off" Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1-year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.

These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.

NCT00056563 and NCT01076452.

Ablative and chronic stimulation procedures targeting the internal pallidum (GPi) and the subthalamic nucleus (STN) have led to major advancements in the treatment of Parkinson's disease and other movement disorders. Although these procedures have evolved to primarily target the posterior ventrolateral sensorimotor portion of GPi and to less selectively target STN, centrally, the ideal targets within these structures remain to be fully established. In this study, we sought to identify the optimal targeting sites in GPi and STN for reversal of parkinsonian signs through a series of reversible injections of the GABA A agonist muscimol in these nuclei in parkinsonian primates.Akinesia and bradykinesia were strongly ameliorated by discrete inactivation within the centromedial extent of the sensorimotor territory in GPi and the lateral portion of the sensorimotor territory in STN. This suggests that akinesia and bradykinesia might, in fact, originate from abnormalities in the same, or at least overlapping, motor circuits in the parkinsonian state. Inactivation of areas outside of the motor territories did not improve parkinsonism but induced circling and behavioral abnormalities. The segregation of basal ganglia-thalamocortical circuits appears to be therefore maintained, at least to a large extent, in the parkinsonian state.These results underscore that inactivation of discrete regions in the central territory of GPi and the lateral portion of STN are sufficient to ameliorate parkinsonian motor signs and that extension of lesions into nonmotor territories may be deleterious. Surgical outcomes might therefore be optimized by placing more discrete lesions and by restricting the extent of chronic stimulation.

Patients: One hundred twelve patients with PD, including 18 de novo untreated patients, and 60 age-matched controls. Intervention: Modern, precise eye tracking technology was used to assess oculomotor parameters. Oculomotor function was compared between groups during fixation and while tracking a randomly displaced target on a PC monitor. Main Outcome Measures: Fixation stability and saccadic parameters. Results: All patients with PD and 2 of 60 control subjects showed oscillatory fixation instability (ocular tremor), with an average fundamental frequency of 5.7 Hz and average magnitude of 0.27°. Saccadic parameters and occurrences of square wave jerks did not differ between subjects with PD and controls. The amplitude and frequency of fixation instability did not correlate with disease duration, clinical Unified Parkinson's Disease Rating Scale scores, or dopa-equivalent dosing. No differences in oculomotor parameters were found between medicated and unmedicated patients with PD. Conclusions: All patients with PD exhibited persistent ocular tremor that prevented stability during fixation. The pervasiveness and specificity of this feature suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing PD.

To assess the long‐term outcome following unilateral pallidotomy for advanced Parkinson's disease, we performed nonblinded Core Assessment Program for Intracerebral Transplantations protocol assessments in 10 of the original 15 patients in our pilot study for 4 years following surgery. Although Unified Parkinson's Disease Rating Scale motor examination scores returned to baseline levels at 3 and 4 years, most patients continued to show sustained improvements in contralateral tremor, akinesia, and drug‐induced dyskinesias. Contralateral tremor was absent at 4 years in all seven patients with preoperative tremor. Contralateral “off” arm movement times (averaged for three tasks) decreased by 37% at 1 year and by 30% at 4 years. Contralateral dyskinesia scores improved by 82% at 1 year and by 64% at 4 years. In contrast, after reaching speeds equal to the contralateral side at 1 year, ipsilateral “off” movement times increased by 13% over baseline levels at 4 years. Although most gait and postural stability measures showed modest initial improvement followed by a return to baseline values, “on” stand–walk–sit task performance declined significantly at 4 years. Despite the restriction of our surgeries to one side and the expected natural progression of Parkinson's disease, the results of patient self‐assessments suggest that 4 years after unilateral pallidotomy, most patients continue to experience a quality of life above preoperative levels.

No abstract

Abstract-This study examined the frequency and degree of caregiver burden in persons with parkinsonism, a group of disorders with four primary symptoms that include tremor, rigidity, postural instability, and bradykinesia. We assessed associations between perceived caregiver burden and physical, cognitive, and functional impairments using well-established tools for persons with parkinsonism. The 49 individuals with parkinsonism ranged in age from 61 to 87 (mean = 75), while their caregivers (N = 49) ranged in age from 48 to 83 (mean = 70). The caregivers were predominantly either wives (82%) or daughters (6%), with other family members, friends, and/or neighbors (12%) making up the rest. The caregivers reported a relatively high ability for coping (mean scores = 4.6/6). Caregiver burden was significantly negatively associated with activities of daily living and motoric difficulties as measured on the Unified Parkinson's Disease Rating Scale (UPDRS). Likewise, caregiver burden was negatively associated with caregiver self-reported sleep and coping ability. Results did not demonstrate an association on the UPDRS among mentation, behavior, and mood. We found a significant negative correlation for mentation between the Folstein Mini-Mental Status Examination and caregiver burden measures; however, we did not find this association with the Dementia Rating Scale-2. Patient's self-reported pain and caregiver burden were not associated.