Bilateral high frequency subthalamic stimulation in Parkinson's disease: long-term neurological follow-up

High frequency stimulation of the subthalamic nucleus (STN) is gaining recognition as a new symptomatic treatment for Parkinson's disease (PD). The first available long-term observations show the stability of the efficacy of this procedure in time.

Quadripolar leads were implanted bilaterally under stereotactic conditions in the STN of patients with advanced PD. High frequency stimulation was applied for 24 hours a day. Following implant, antiparkinsonian medication was reduced as much as possible and stimulation was gradually increased. The patients were evaluated in the practically defined "off" condition and in the "on" condition using the unified PD rating scale (UPDRS) and the Schwab & England scale. Neuropsychological testing was performed before and after the implant. Thirty-three patients were followed up for at least 3 months and 13 among them until 36 months.

The patients had a mean age of 56.8+/-7.1 years and a mean disease duration of 13.8+/-5.5 years; they were followed-up for an average of 25.7+/-13.5 months. At the time of the last available visit, the stimulation amplitude was 2.47+/-0.40 V (the total energy delivered averaged 1.57+/-0.8 microW). The levodopa-equivalent daily dose was reduced by 56.2% (p<0.001). Parkinsonian features were improved in all patients, the greatest changes were seen for tremor, gait, bradykinesia and postural stability, then rigidity and limb akinesia. Compared with the pre-implant conditions, the UPDRS motor score in the "off" condition was improved by 51.6% at the time of the last visit (p<0.001), the UPDRS activities of daily living score was improved by 68.5% (p<0.001), the Schwab & England scale was improved by 196.8% (p<0.001). The neuropsychological data did not show significant changes. Night sleep improved in all patients, due to increased mobility at night. In almost all patients insomnia was resolved. All patients gained weight after surgery with an increase of 11.1% (p<0.001) compared to their pre-implant weight. The most common permanent side effects consisted in hypophonia and dysarthria, transient side effects were increased sexuality and mania, the most common side effects related to stimulation were ballic or choreic dyskinesias. The most common adverse event related to the surgical procedure was transient psychosis; unexplained switching-off of the stimulator was the most common device-related effect.

This study extends our recently published 3-years FU series. It confirms again that symptomatic efficacy of STN stimulation is retained during the 2(nd) and 3(rd) years following the implant, without any obvious decay of efficacy or need for increase of energy delivered. Improvement of dyskinesias also persists and the procedure is well tolerated. Side effects and adverse events are sometimes severe, but can be managed in most cases. The improvement of daily living activities outweighs by far the motor benefit, indicating that the use of this procedure significantly improves the patients' lifestyle.