New findings published in Neurology, the medical journal of the American Academy of Neurology (AAN), have confirmed the long-term effectiveness of deep brain stimulation of the subthalamic nucleus (STN-DBS) in treating Parkinson’s disease—with a “significant improvement” in motor complications and a stable reduction of dopaminergic drugs being observed more than 15 years after surgery. The study’s researchers state that this is, to the best of their knowledge, “the longest and largest follow-up described in patients with DBS”.
Speaking to NeuroNews, the study’s lead author Elena Moro (professor of Neurology, Movement Disorders Unit, Grenoble Alpes University Hospital Center, Grenoble, France) said: “We recognise that, in the very long term, it can be difficult to predict the improvement in QoL [quality of life] after DBS. However, considering that these people with Parkinson’s disease undertaking DBS have been living with the condition for at least 10 years, for them to not have a decreased quality of life after a total of 25 years of Parkinson’s is quite an achievement from my point of view.”
In their report, Moro et al write that—in people with advanced Parkinson’s disease—STN-DBS is a well-recognised and effective treatment in both short- and long-term follow-up. Despite this, the few available data regarding motor response from STN-DBS after more than 10 years focus on small populations, and do not allow solid conclusions about the treatment’s effects “in the very long term” to be drawn. This lack of direct evidence on its sustained benefits means it is challenging to decide whether to replace the stimulator device at the end of its lifespan, they add.
The researchers therefore embarked on a study to evaluate the effects of STN-DBS beyond 15 years after surgery—mainly focusing on changes in Parkinson’s disease-related motor complications. For this, data on motor complications, QoL, activities of daily living, Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores, dopaminergic treatment, stimulation parameters, and side-effects of STN-DBS, were retrospectively retrieved from all consecutive Parkinson’s patients operated on with bilateral STN-DBS at the Grenoble Alpes University Hospital from 1993 to 2004, and then compared before surgery, and at one year and beyond 15 years after surgery.
Some 51 patients, with a median follow-up time of 16 years (range=15–24 years; mean=17.06±2.18 years), were ultimately recruited, and STN-DBS was found to be effective in improving motor fluctuations and dyskinesia in 39 of these patients (76%). Compared to baseline, the time spent with dyskinesia (item 32 of UPDRS) was reduced by 75%, and the time spent in the “off state” (item 39 of UPDRS) diminished by 58.7%. In addition, dopaminergic drugs were reduced by 50.6% at long-term follow-up. Parkinson’s Disease QoL (PDQL) total scores improved by 13.8%, and the emotional function and social function domains in the patient cohort also improved by 13.6% and 29.9%, respectively.
“Few and mostly manageable” device-related adverse events, including lead reimplantation due to intracranial infections, lead malfunctions, or lead suboptimal placement, were observed during long-term follow-up, the authors write. On these adverse events, Moro stated: “Device-related side-effects are obviously expected in any study. Compared to the available literature, we did not find any unexpected issues. However, over the past 30 years, DBS technology has made several advances, and I expect to have fewer adverse events in the future with the new devices.”
She added that, in advanced Parkinson’s, medications used to treat the disease often induce side-effects like dyskinesia, motor and non-motor fluctuations, impulse control disorders, and psychosis, but that this study demonstrates the benefits STN-DBS holds as “the only therapy” capable of minimising these side-effects through the reduction of dopaminergic drugs.
Overall, this retrospective, single-centre study showed that STN-DBS is effective in improving motor complications in the very long-term follow-up of people with advanced Parkinson’s disease. Short-term QoL improvements and medication reductions were also sustained in the longer term—despite the inevitable progression of levodopa-resistant motor and non-motor symptoms in the late stages of the disease—providing Class IV evidence that, for people with Parkinson’s, STN-DBS remains effective in treating motor complications at least 15 years after surgery. “This information about the long-term outcomes after DBS surgery can be useful to patients, caregivers and treating physicians when counselling about surgery,” the authors also state.
“So far, the clinical evidence that both STN and pallidal DBS are effective in advanced Parkinson’s disease is very strong,” Moro added. “No other invasive treatments or new neuromodulation techniques can be compared in terms of the number of people treated, number of published studies, and follow-up. However, even for DBS, very long-term data at more than 10 years after surgery are lacking, and—although retrospective—this study reports on the oldest cohort in the world with STN-DBS. Within 30 years, patients belonging to this cohort show that DBS significantly impacted their life. While Parkinson’s disease did progress, surgery reduced their disease disability to a great extent for more than 15 years. To date, no other invasive treatment has shown these results.”
In their report, Moro et al allude to several limitations of their study, including the high percentage of patients (40.6%) lost at long-term follow-up creating a risk of bias—as “those patients on whom longer term follow-up is available are likely to be the ones who are doing well”. The lack of motor symptom evaluation in the off-medication condition at long-term follow-up, missing evaluations of activities of daily living in the off-medication condition, a lack of data on non-motor symptoms at long-term follow-up, and a lack of long-term follow-up data for some patients, are also cited as potential limitations.
On the subject of future research directions in this space, Moro added: “Ideally, one would compare a control group with a surgical group in the long term. However, these studies are very difficult, since it has been demonstrated already that DBS is superior to the best medical treatment, and it would therefore not be ethical to deny DBS to people who want to have it. Because of this, observational long-term cohorts are important to add further knowledge about long-term DBS effects. Our study also did not focus on several non-motor aspects of Parkinson’s disease. Further study might investigate these important areas.”