Randomized trial of pallidotomy versus medical therapy for Parkinson's disease

Abstract

Thirty-six patients with Parkinson's disease (PD) were randomized to either medical therapy (N ‫؍‬ 18) or unilateral GPi pallidotomy (N ‫؍‬ 18). The primary outcome variable was the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow-up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug-induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug-induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS ( p < 0.0001), "off" motor ( p < 0.0001) and complications of therapy subscores ( p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug-induced dyskinesias. Neurol 2003;53:558 -569 Over the past decade, there has been a marked resurgence of interest in surgery for Parkinson's disease (PD). Several factors have contributed to this: (1) the need for better therapies to treat the continued worsening of parkinsonian motor symptomatology and the development of drug-induced dyskinesias and motor fluctuations, (2) advances in our understanding of the physiological basis of parkinsonism and the rationale for surgery, 1,2,4 and (3) the report by Laitinen and colleagues of improvement in parkinsonian motor signs after pallidotomy. 3 Although there are now numerous reports on the benefits of pallidotomy for PD, 5-15 there has been only one randomized clinical trial comparing the effects of pallidotomy to best medical therapy. 16 In some of the previous studies, nontremulous 7 or predominately asymmetric 6 patients were selected, whereas in others nonstandardized methods of clinical evaluation were used. 10,12,13 Therefore, it is difficult to compare the results of pallidotomy across studies and to assess the effect of pallidotomy for patients regardless of symptom profile. AnnWe present here the results of a randomized, prospective clinical trial comparing the effectiveness of pallidotomy to best medical management in patients followed up for 6 months. In addition, we present data for the first 20 patients who have been followed up for 2 years. Patients and Methods Patient Recruitment and AssessmentPatients were recruited from the Movement Disorders Center at Emory and Grady Memorial Hospital Clinics. To limit patient attrition, we limited the geographical location for patient recruitment to a 500-mile radius from the City of Atlanta...

Unilateral subthalamic nucleus stimulation has a measurable ipsilateral effect on rigidity and bradykinesia in parkinson disease

“…Several reports demonstrate that bilateral STN DBS reduces rigidity as measured by clinical ratings in PD patients (Deuschl et (Vitek et al, 2003). However, these previous reports relied on clinical rigidity rating scales and did not employ objective, quantitative measures of rigidity.…”

“…Indeed, by recording from implanted STN DBS electrodes, the STN or nearby structures were shown to be active before self-paced movement in PD patients and such activity was induced by both ipsilateral and contralateral hand movement (Paradiso et al, 2003). This may also be the functional basis for the ipsilateral reduction of bradykinesia and rigidity by unilateral pallidotomy (Vitek et al, 2003). Takakusaki et al, 1996).…”

“…Interestingly, the effects of unilateral pallidotomy on ipsilateral bradykinesia in one study (Vitek et al, 2003) was significant at 24 months post-operatively when using a timed tasks (hand movement between two points) but was not significant when measured by UPDRS bradykinesia scores. This further supports our notion that kinematic measures are more sensitive than UPDRS scores for identification of subtle changes in motor behavior in PD, such as motor changes induced by unilateral DBS or ablative surgeries.…”

What Happened to Posteroventral Pallidotomy for Parkinson’s Disease and Dystonia?

“…38 Kishore et al 45 initially reported significant benefits at 6 months on all features of PD after unilateral pallidotomy, but by 24 months the only stable effects were on contralateral tremor and drug-induced dyskinesia. 46 In the RCT reported by Vitek et al, 33 the 34% decrease in the motor UPDRS score at 6 months waned to a 25% decrease at 24 months, similar to the 21% decrease found by the Toronto group at 24 months. 47 Whether these results signify a mitigation of the effects of expectation, truly waning clinical effects of pallidotomy, or advancing disease is not easy to assess.…”

“…[32][33][34][35][36] In a prospective single-blind (observer-blind) study without a control group, Lozano et al 34 found a 30% benefit from baseline 'off' period total motor (part 3) scores on the Unified Parkinson's Disease Rating Scale (UPDRS) after unilateral pallidotomy, with blinded videotape evaluations to control for observer bias, whereas Ondo et al 36 found only a 13.6% benefit (Table 1). Recently, two single-blind (observer-blind) RCTs 32,33 comparing unilateral pallidotomy to best medical therapy demonstrated 31% to 34% decrease in 'off' total motor UPDRS scores at 6 months, in contrast to 4% to 8% worsening in the control group.…”