Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation

Abstract

The response to levodopa changes over time in Parkinson's disease, probably due to alterations in the dopaminergic system, progression of the disease and pulsatile oral intake of the drug. Bilateral high-frequency stimulation of the subthalamic nucleus (STN) allows a large reduction or the complete cessation of levodopa intake in patients with advanced Parkinson's disease. We studied variation in the motor short-duration response (SDR) during a levodopa challenge in bilaterally STN-stimulated patients. Twenty-eight consecutive patients with a mean duration of Parkinson's disease of 16.6 +/- 6.0 years at the time of surgery were enrolled. Fourteen patients were evaluated both before STN stimulation and 3 months after surgery (group 1) whereas the other 14 patients were assessed before implantation and after a mean of 3 years of STN stimulation (group 2). After drug withdrawal for one night, the hand-tapping test (TT) was carried out every 15 min, together with evaluation of dyskinesias using a modified Goetz scale. The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was assessed every 30 min. In operated patients, STN stimulation was stopped 15 min before starting the clinical evaluations. A suprathreshold oral levodopa dose was given after one motor evaluation and two TTs. The clinical evaluation was carried out until the TT score returned to the baseline. In group 1, six patients continued without levodopa after surgery and the other eight received a daily mean dose of 337 mg; in group 2, seven patients continued without levodopa and the other seven received a daily mean dose of 386 mg. The main change in the levodopa SDR was a significant reduction in levodopa-induced dyskinesias in both groups. In those patients of group 1 who did not receive levodopa after surgery, the motor UPDRS magnitude decreased and the 'on' UPDRS motor score worsened. In group 2, the results were similar, but in the patients who continued to receive levodopa after surgery the TT magnitude increased. On the whole, chronic bilateral STN stimulation tended to decrease the magnitude of the levodopa SDR without changing the duration and latency of the response. These results suggest that continuous STN stimulation induces long-term plastic changes of the dopaminergic system, with slow and partial desensitization. In addition, the persistence of levodopa intake after surgery might hinder this beneficial process.

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

“…However, comparing the MED-ON/STIM-ON scores with the preoperative MED-ON, a significant improvement was observed only at 1 year; at 11 years, all symptoms except rigidity significantly worsened. A reduced magnitude of the response to levodopa was noticed also for symptoms usually considered drug-responsive, and this could have different explanations: during the follow-up patients were taking a levodopa amount smaller than in the preoperative, and this could affect the response to levodopa challenge [14]; chronic STN-DBS could affect the magnitude of levodopa response, probably due to long-term plastic changes of the dopaminergic system [15]; the quality of levodopa responsiveness deteriorates over time.…”

Disentangling the Role of Cortico-Basal Ganglia Loops in Top–Down and Bottom–Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease

“…However, it should be noted that, in this condition, none of the patients showed an intensity of tremor, bradykinesia, and rigidity of the right hand that might compromise performance in the various tasks. It should also be considered that med-off and med-off/stimoff represent typical conditions for testing PD patients in both experimental and clinical contexts (Alberts et al, 2008;Funkiewiez et al, 2006;Schupbach et al, 2005;Moro, Esselink, Benabid, & Pollak, 2002).…”

Increased Gamma Oscillatory Activity in the Subthalamic Nucleus During Tremor in Parkinson's Disease Patients

“…The group consisted of two women and seven men, who at the time of operation had a mean age of 59.5 yr (range: 55-67) and a mean duration of PD of 10.7 Ϯ 3.7 (mean Ϯ SD) years. All patients were assessed preoperatively using the Unified Parkinson's Disease Rating Scale (UPDRS) (Fahn et al 1987) before and after an acute levodopa challenge (Moro et al 2002). During surgery, the patients were awake and off dopaminergic medications for Ն12 h from the last oral dose of antiparkinsonian medications.…”