Nonmotor Symptoms in PD after Deep Brain Stimulation of the Subthalamic Nucleus

Abstract & Commentary

By Panida Piboolnurak, MD, Assistant Professor, Department of Neurology and Neuroscience, Weill Medical College, Cornell University. Dr. Piboolnurak reports no financial relationship relevant to this field of study.

Synopsis: It is well accepted that subthalamic nucleus deep brain stimulation is effective in improving motor function in Parkinson's disease. However, the effect of DBS (deep brain stimulation) on non-motor symptoms still needs to be further studied.

Source: Zibetti M, Torre E, Cinquepalmi A, et al. Motor and nonmotor symptom follow-up in parkinsonian patients after deep brain stimulation of the subthalamic nucleus. Eur Neurol 2007;58:218-223.

Although motor symptoms constitute the cardinal features of Parkinson's disease (PD), non-motor symptoms, including neuropsychiatric conditions (depression, anxiety, psychosis, and cognitive impairment), autonomic disorders (orthostatic hypotension, urinary dysfunction, and gastrointestinal disturbance), sleep disorders, and sensory symptoms (pain and dysesthesias) also contribute greatly to disability and quality of life. Many studies have provided compelling evidence of long-term benefit of subthalamic nucleus deep brain stimulation (STN DBS) on motor symptoms. However, the influence of STN DBS on non-motor symptoms is less well established.

In this study, the authors investigated the impact of STN DBS on motor and non-motor symptoms in 36 PD patients (14 women and 22 men) at 12 and 24 months after DBS surgery. Mean age at surgery was 61.2 ± 6.2 years. Mean disease duration was 16.7 ± 4.4 years. Unified Parkinson's Disease Rating Scale (UPDRS) was used as an assessment tool. Data concerning constipation and urological dysfunction were collected from clinical charts in the form of nominal data (presence or absence). Daily PD medication requirement data were collected in the form of levodopa equivalent dosage.

Comparing between preoperative off-medication and postoperative off-medication/on-stimulation condition, UPDRS III (objective motor scores) improved 52% and 55% at 12 and 24 months after surgery, respectively. Total UPDRS II score (motor and non-motor items of activity of daily living) improved 60% and 59% at 12 and 24 months, respectively. Off-duration was reduced by 92% and 98% at 12 and 24 months. Levodopa equivalent daily dosage was reduced by 60% and 59% at 12 and 24 months, comparing to the preoperative dosage. Postoperative total UPDRS I score and subscores (intellectual impairment, thought disorder, depression, and motivation) were not different compared to preoperative scores. However, when analyzing each patient individually, 3 patients developed moderate memory loss at 24 months, 3 patients developed benign hallucinations, 6 patients developed depression, and 6 patients developed motivation impairment.

Preoperatively, UPDRS II non-motor subscores for salivation, swallowing, and sensory complaints were improved by medications. Postoperatively, these scores also were improved by the combination of medication and stimulation comparable to preoperative medication effect, while PD medication dosage was markedly reduced. In addition, sleep-related problems and constipation improved after surgery. However, falling unrelated to freezing, nausea, symptomatic orthostatic hypotension, and urological dysfunction were unchanged.

The authors concluded that STN DBS improved motor symptoms and some non-motor symptoms such as salivation, swallowing, sensory complaints, sleep problems, and constipation. The improvement in those non-motor symptoms was explained by the improvement in bradykinesia, relatively constant motor control, and dopaminergic medication reduction. The authors also pointed out that this study had some weak points, including a small number of patients, low prevalence of some non-motor symptoms, and limitation of UPDRS in capturing the extent of non-motor features.

Commentary

Although non-motor symptoms of Parkinson's disease are less visible than motor symptoms, they can be very disruptive for the patients and are more difficult to treat. Moreover, PD medications frequently can worsen or induce those symptoms. This study provided the evidence that STN DBS can improve motor symptoms and some of non-motor symptoms, including: saliva drooling, swallowing difficulty, sensory symptoms related to parkinsonism, sleep-related problems, and constipation. However, some non-motor symptoms may not be purely non-motor. For instance, saliva drooling is more likely due to a reduction in saliva swallowing. Difficulty in swallowing can be due to malfunction of voluntary pharyngeal muscles and/or involuntary smooth muscles of pharynx and esophagus. Possible causes of a fall include postural instability, freezing, and orthostatic hypotension. Moreover, sleep disturbances can result from both motor and non-motor symptoms as well as from medication side effect. As the authors pointed out, further study using a more specific assessment tool for non-motor symptoms, with a larger number of patients, will be able to give a better answer whether STN DBS can improve non-motor symptoms.