Brain Stimulation Bests Medical Therapy for PD

Major Finding: Measurement of quality of life with the PDQ-39 after 1 year improved significantly more in DBS patients than in medical therapy patients (−5.0 vs. −0.3).

Data Source: A randomized, open-label trial of 366 patients with Parkinson's disease.

Disclosures: Trial was funded by the U.K. Medical Research Council, Parkinson's U.K., and the U.K. Department of Health. Dr. Wheatley and most coauthors had no relevant disclosures. One coauthor received grants and fees from Medtronic for another similar study. Dr. Rodriguez-Oroz reported relationships with Medtronic and several companies that manufacture dopaminergic agents.

Parkinson's disease patients report better quality of life after 1 year of deep brain stimulation than with best medical therapy, according to the largest randomized trial of the two treatment options for patients with advanced disease.

In the PD SURG trial, deep brain stimulation (DBS) resulted in greater improvement in motor function scores and complications of therapy, as well as lower use of dopaminergic drugs, than did best medical therapy. However, both arms of the open-label study experienced a similar amount of cognitive decline, with significantly poorer function in verbal fluency and vocabulary in DBS patients.

The trial largely corroborates the results observed in two previous trials of DBS vs. best medical therapy that recorded follow-up out to 6 months (N. Engl. J. Med. 2006;355:896–908; JAMA 2009;301:63–73).

“Surgery is likely to remain an important treatment option for patients with PD, especially if the way in which deep brain stimulation exerts its therapeutic benefits is better understood, if its use can be optimised by better electrode placement and settings, and if patients who would have the greatest benefit can be better identified,” Dr. Keith Wheatley of the University of Birmingham (England) and his colleagues concluded (Lancet Neurol. 2010 April 29 [doi:10.1016/S1474-4422(10)70093-4

During 2000-2006, Dr. Wheatley and his associates randomized 366 patients evenly to either treatment group at 13 neurosurgical centers in the United Kingdom. The patients had a mean age of 59 years and were mostly men (about 70%) with a mean disease duration of 11.4 years. In each group, 45 patients were taking apomorphine at study entry; 145 total were taking it before the study.

Of 178 patients who underwent surgery, DBS targeted the subthalamic nucleus in 174 and the globus pallidus pars interna in 4. All but two of the surgeries were bilateral. A total of 12 patients in the best medical therapy arm underwent DBS surgery between baseline and 1 year but were analyzed in the medical therapy arm anyway.

Measurement of quality of life with the Parkinson's Disease Questionnaire (PDQ-39) after 1 year—the primary outcome—improved significantly more in DBS patients than in medical therapy patients (−5.0 vs. −0.3).

During “on” periods, the mean United Parkinson's Disease Rating Scale (UPDRS) total score after 1 year improved by a mean of 6.6 points in the surgery group and worsened by 1.6 points in the medical therapy group, which was a significant difference. In “off” time, UPDRS scores improved significantly more in DBS patients (−27.4) than in medical therapy patients (−0.9 points).

Cognitive status measured with the Dementia Rating Scale-II (DRS-II) declined by 0.4 points in each group after 1 year. Neuropsychological testing in a subset of patients revealed that verbal fluency and vocabulary had declined after 1 year significantly more in patients who had undergone surgery than in patients who took medication alone.

Treatment with DBS also resulted in a significantly lower mean levodopa equivalent dose after 1 year than did medical therapy alone (894 vs. 1,347 mg/day).

“The cost of surgery will be partly offset by the reduction in the amount of drug therapy required by patients who have had surgery. In particular, if apomorphine or continuous intestinal infusions of levodopa, with high recurrent costs, are the alternative drug treatment options, the cost-effectiveness equation might favor surgery … thus, it is important to identify patients who are or are not likely to benefit from surgery when the risks and costs are taken into account,” they wrote.

Overall, 36 surgery patients experienced 43 serious adverse events, including 16 infections. In the surgery group, 25 Parkinson's disease–related and drug-related serious adverse events occurred in 20 patients, compared with 14 events in 13 medical therapy patients. The two remaining serious adverse events in the group included one unsuccessful postoperative suicide and one death from hemorrhage during surgery.

The trial has a number of strengths that improved on previous trials, including a larger number of patients, a longer follow-up, and treatment with continuous infusions of apomorphine, Dr. Maria C. Rodriguez-Oroz wrote in an editorial (Lancet Neurol. 2010 April 29 [doi:10.1016/S1474-4422(10)70108-3

Dr. Rodriguez-Oroz of the Clinica Universidad de Navarra, Pamplona, Spain, added that some limitations of the trial raise questions about the results. For example, neither patients nor evaluators were masked to treatment. Evaluations of dyskinesia and “off” period time could have been done with a more reliable tool than the complications of therapy subsection of the UPDRS. Investigators made their own judgment about whether a patient was in the “on” state (without assessment of inter-rater reliability). The DRS-II might be inadequate to assess cognitive ability in Parkinson's. And the investigators did not record nonserious adverse events.

Major Finding: Measurement of quality of life with the PDQ-39 after 1 year improved significantly more in DBS patients than in medical therapy patients (−5.0 vs. −0.3).

Data Source: A randomized, open-label trial of 366 patients with Parkinson's disease.

Disclosures: Trial was funded by the U.K. Medical Research Council, Parkinson's U.K., and the U.K. Department of Health. Dr. Wheatley and most coauthors had no relevant disclosures. One coauthor received grants and fees from Medtronic for another similar study. Dr. Rodriguez-Oroz reported relationships with Medtronic and several companies that manufacture dopaminergic agents.

Parkinson's disease patients report better quality of life after 1 year of deep brain stimulation than with best medical therapy, according to the largest randomized trial of the two treatment options for patients with advanced disease.

In the PD SURG trial, deep brain stimulation (DBS) resulted in greater improvement in motor function scores and complications of therapy, as well as lower use of dopaminergic drugs, than did best medical therapy. However, both arms of the open-label study experienced a similar amount of cognitive decline, with significantly poorer function in verbal fluency and vocabulary in DBS patients.

The trial largely corroborates the results observed in two previous trials of DBS vs. best medical therapy that recorded follow-up out to 6 months (N. Engl. J. Med. 2006;355:896–908; JAMA 2009;301:63–73).

“Surgery is likely to remain an important treatment option for patients with PD, especially if the way in which deep brain stimulation exerts its therapeutic benefits is better understood, if its use can be optimised by better electrode placement and settings, and if patients who would have the greatest benefit can be better identified,” Dr. Keith Wheatley of the University of Birmingham (England) and his colleagues concluded (Lancet Neurol. 2010 April 29 [doi:10.1016/S1474-4422(10)70093-4

During 2000-2006, Dr. Wheatley and his associates randomized 366 patients evenly to either treatment group at 13 neurosurgical centers in the United Kingdom. The patients had a mean age of 59 years and were mostly men (about 70%) with a mean disease duration of 11.4 years. In each group, 45 patients were taking apomorphine at study entry; 145 total were taking it before the study.

Of 178 patients who underwent surgery, DBS targeted the subthalamic nucleus in 174 and the globus pallidus pars interna in 4. All but two of the surgeries were bilateral. A total of 12 patients in the best medical therapy arm underwent DBS surgery between baseline and 1 year but were analyzed in the medical therapy arm anyway.

Measurement of quality of life with the Parkinson's Disease Questionnaire (PDQ-39) after 1 year—the primary outcome—improved significantly more in DBS patients than in medical therapy patients (−5.0 vs. −0.3).

During “on” periods, the mean United Parkinson's Disease Rating Scale (UPDRS) total score after 1 year improved by a mean of 6.6 points in the surgery group and worsened by 1.6 points in the medical therapy group, which was a significant difference. In “off” time, UPDRS scores improved significantly more in DBS patients (−27.4) than in medical therapy patients (−0.9 points).

Cognitive status measured with the Dementia Rating Scale-II (DRS-II) declined by 0.4 points in each group after 1 year. Neuropsychological testing in a subset of patients revealed that verbal fluency and vocabulary had declined after 1 year significantly more in patients who had undergone surgery than in patients who took medication alone.

Treatment with DBS also resulted in a significantly lower mean levodopa equivalent dose after 1 year than did medical therapy alone (894 vs. 1,347 mg/day).

“The cost of surgery will be partly offset by the reduction in the amount of drug therapy required by patients who have had surgery. In particular, if apomorphine or continuous intestinal infusions of levodopa, with high recurrent costs, are the alternative drug treatment options, the cost-effectiveness equation might favor surgery … thus, it is important to identify patients who are or are not likely to benefit from surgery when the risks and costs are taken into account,” they wrote.

Overall, 36 surgery patients experienced 43 serious adverse events, including 16 infections. In the surgery group, 25 Parkinson's disease–related and drug-related serious adverse events occurred in 20 patients, compared with 14 events in 13 medical therapy patients. The two remaining serious adverse events in the group included one unsuccessful postoperative suicide and one death from hemorrhage during surgery.

The trial has a number of strengths that improved on previous trials, including a larger number of patients, a longer follow-up, and treatment with continuous infusions of apomorphine, Dr. Maria C. Rodriguez-Oroz wrote in an editorial (Lancet Neurol. 2010 April 29 [doi:10.1016/S1474-4422(10)70108-3

Dr. Rodriguez-Oroz of the Clinica Universidad de Navarra, Pamplona, Spain, added that some limitations of the trial raise questions about the results. For example, neither patients nor evaluators were masked to treatment. Evaluations of dyskinesia and “off” period time could have been done with a more reliable tool than the complications of therapy subsection of the UPDRS. Investigators made their own judgment about whether a patient was in the “on” state (without assessment of inter-rater reliability). The DRS-II might be inadequate to assess cognitive ability in Parkinson's. And the investigators did not record nonserious adverse events.

Major Finding: Measurement of quality of life with the PDQ-39 after 1 year improved significantly more in DBS patients than in medical therapy patients (−5.0 vs. −0.3).

Data Source: A randomized, open-label trial of 366 patients with Parkinson's disease.

Disclosures: Trial was funded by the U.K. Medical Research Council, Parkinson's U.K., and the U.K. Department of Health. Dr. Wheatley and most coauthors had no relevant disclosures. One coauthor received grants and fees from Medtronic for another similar study. Dr. Rodriguez-Oroz reported relationships with Medtronic and several companies that manufacture dopaminergic agents.

Parkinson's disease patients report better quality of life after 1 year of deep brain stimulation than with best medical therapy, according to the largest randomized trial of the two treatment options for patients with advanced disease.

In the PD SURG trial, deep brain stimulation (DBS) resulted in greater improvement in motor function scores and complications of therapy, as well as lower use of dopaminergic drugs, than did best medical therapy. However, both arms of the open-label study experienced a similar amount of cognitive decline, with significantly poorer function in verbal fluency and vocabulary in DBS patients.

The trial largely corroborates the results observed in two previous trials of DBS vs. best medical therapy that recorded follow-up out to 6 months (N. Engl. J. Med. 2006;355:896–908; JAMA 2009;301:63–73).

“Surgery is likely to remain an important treatment option for patients with PD, especially if the way in which deep brain stimulation exerts its therapeutic benefits is better understood, if its use can be optimised by better electrode placement and settings, and if patients who would have the greatest benefit can be better identified,” Dr. Keith Wheatley of the University of Birmingham (England) and his colleagues concluded (Lancet Neurol. 2010 April 29 [doi:10.1016/S1474-4422(10)70093-4

During 2000-2006, Dr. Wheatley and his associates randomized 366 patients evenly to either treatment group at 13 neurosurgical centers in the United Kingdom. The patients had a mean age of 59 years and were mostly men (about 70%) with a mean disease duration of 11.4 years. In each group, 45 patients were taking apomorphine at study entry; 145 total were taking it before the study.

Of 178 patients who underwent surgery, DBS targeted the subthalamic nucleus in 174 and the globus pallidus pars interna in 4. All but two of the surgeries were bilateral. A total of 12 patients in the best medical therapy arm underwent DBS surgery between baseline and 1 year but were analyzed in the medical therapy arm anyway.

Measurement of quality of life with the Parkinson's Disease Questionnaire (PDQ-39) after 1 year—the primary outcome—improved significantly more in DBS patients than in medical therapy patients (−5.0 vs. −0.3).

During “on” periods, the mean United Parkinson's Disease Rating Scale (UPDRS) total score after 1 year improved by a mean of 6.6 points in the surgery group and worsened by 1.6 points in the medical therapy group, which was a significant difference. In “off” time, UPDRS scores improved significantly more in DBS patients (−27.4) than in medical therapy patients (−0.9 points).

Cognitive status measured with the Dementia Rating Scale-II (DRS-II) declined by 0.4 points in each group after 1 year. Neuropsychological testing in a subset of patients revealed that verbal fluency and vocabulary had declined after 1 year significantly more in patients who had undergone surgery than in patients who took medication alone.

Treatment with DBS also resulted in a significantly lower mean levodopa equivalent dose after 1 year than did medical therapy alone (894 vs. 1,347 mg/day).

“The cost of surgery will be partly offset by the reduction in the amount of drug therapy required by patients who have had surgery. In particular, if apomorphine or continuous intestinal infusions of levodopa, with high recurrent costs, are the alternative drug treatment options, the cost-effectiveness equation might favor surgery … thus, it is important to identify patients who are or are not likely to benefit from surgery when the risks and costs are taken into account,” they wrote.

Overall, 36 surgery patients experienced 43 serious adverse events, including 16 infections. In the surgery group, 25 Parkinson's disease–related and drug-related serious adverse events occurred in 20 patients, compared with 14 events in 13 medical therapy patients. The two remaining serious adverse events in the group included one unsuccessful postoperative suicide and one death from hemorrhage during surgery.

The trial has a number of strengths that improved on previous trials, including a larger number of patients, a longer follow-up, and treatment with continuous infusions of apomorphine, Dr. Maria C. Rodriguez-Oroz wrote in an editorial (Lancet Neurol. 2010 April 29 [doi:10.1016/S1474-4422(10)70108-3

Dr. Rodriguez-Oroz of the Clinica Universidad de Navarra, Pamplona, Spain, added that some limitations of the trial raise questions about the results. For example, neither patients nor evaluators were masked to treatment. Evaluations of dyskinesia and “off” period time could have been done with a more reliable tool than the complications of therapy subsection of the UPDRS. Investigators made their own judgment about whether a patient was in the “on” state (without assessment of inter-rater reliability). The DRS-II might be inadequate to assess cognitive ability in Parkinson's. And the investigators did not record nonserious adverse events.