Subthalamic nucleus deep brain stimulation doesn’t appear to change the course of Parkinson’s disease when it is performed on patients with long-standing disease.
In the longest follow-up cohort study to date, Dr. Aristide Merola and his colleagues tracked patients who underwent the procedure at about age 60 years. They all showed similar declines in cognition, gait stability, and continence – marks of the disease’s later stage, according to their study, which was published in the July issue of Brain.
However, the study should not be construed as a negation of DBS’s potential therapeutic value, wrote Dr. Merola of the University of Turin (Italy) and his coauthors. Instead, they suggested that one can "speculate whether the subthalamic nucleus DBS surgical procedure should be proposed earlier, considering that Parkinson’s disease progression might not follow a linear course, and it is possible that age might influence the development of non-motor features more than disease duration" (Brain 2011;134:2074-84).
The study comprised 19 patients who underwent subthalamic nucleus DBS after a mean disease duration of 22 years. The investigators compared the baseline results of clinical and neuropsychological testing to those at 1 year, 3 years, and 5 years. For 14 patients who underwent testing after more than 7 years post surgery, the mean follow-up duration was 8 years.
The cohort consisted of 9 men and 10 women. The patients had developed disease symptoms relatively early in life (at a mean of 39 years). Their mean age at the intervention was 61 years.
The patients were evaluated with the UPDRS (Unified Parkinson\'s Disease Rating Scale) at baseline, which was before the DBS. After the procedure, the scale was administered at each follow-up point in four disease states: stimulation on/medication off, stimulation off/medication off, stimulation off/medication on, and stimulation on/medication on.
The authors noted that they paid "particular attention to the main axial, non-motor, and psychiatric symptoms," assessing subjects for falls, postural instability, non-levodopa responsive gait freezing, urinary incontinence, dysphagia, and speech difficulty. They used pharmacologic treatment as a measure of other symptoms, including constipation, postural hypotension, depression, and hallucinations.
Freedom from those symptoms is a prerequisite for DBS surgery; therefore at baseline, none of the patients showed evidence of them.
Long-Term DBS Treatment Evaluations
Follow-up considered not only the years out from surgery, but also the years of disease duration. The long-term follow-up evaluations showed a similar pattern of symptom progression in all patients, regardless of the disease state in which they were measured. However, the combination of stimulation on/medication on was consistently more effective at controlling symptoms than were the other states.
"The majority of patients progressively developed falls (64%), postural instability (100%), non-levodopa responsive freezing of gait (64%), dysphagia (86%), urinary incontinence (57%), severe postural hypotension (36%) and dementia (43%) during the course of follow-up," the authors wrote. "On the other hand, neuropsychological data showed a gradual decline in the performance of all the main cognitive domains, in agreement with previous findings" that showed a fivefold prevalence of dementia in patients with Parkinson’s disease, compared with the general population.
Complications of levodopa therapy significantly improved initially after DBS. But this improvement gradually decreased over the follow-up time. The same pattern occurred in activities of daily living. The mean levodopa equivalent daily dose decreased in the first year after surgery (from a mean of 890 mg to 336 mg). Over the entire follow-up, the dose continued to increase, but only rose to a mean of 435 mg/day after more than 7 years.
When the investigators examined the progression of falls, postural instability, and gait freezing, a similar pattern emerged. There was a slight increase from 1 to 3 years, and then a sharper increase at 5 years. After more than 7 years – with 14 patients still being followed – 9 of them had postural instability, all had gait freezing, and 9 had fallen.
"The initial positive effects of subthalamic nucleus DBS on balance and postural stability ... in the first years from surgery seem to be mostly related to the improvement of rigidity and bradykinesia, rather than to a specific effect on balance and gait," the authors noted.
At baseline, only one patient showed moderate dysphagia. During the follow-up period, the incidence of dysphagia increased, as did speech difficulties. After more than 7 years, 12 had dysphagia, 3 required a percutaneous gastrostomy, and 9 had speech disturbance.
Constipation and postural hypotension, as measured by the need for drug intervention, remained low for 3 years after surgery. For those who reached a follow-up observation longer than 7 years, half required a catheter or diaper.