By Harini Sarva, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College; Assistant Attending Neurologist, New York Presbyterian Hospital

Dr. Sarva reports no financial relationships relevant to this field of study.

SYNOPSIS: This trial of deep brain stimulation of the ventral striatum/anterior limb of the internal capsule improved several measures of the affective sphere of pain in those suffering from post-stroke pain, despite no significant improvement seen in the pain disability index.

SOURCE: Lempka SF, Malone DA Jr, Hu B, et al. Randomized clinical trial of deep brain stimulation for poststroke pain. Ann Neurol 2017;81:653-663.

This six-month, double-blind, randomized, placebo-controlled, crossover study followed by an 18-month open-label extension assessed the effects of stimulation of the ventral striatum/anterior limb of the internal capsule (VS/ALIC) in the treatment of post-stroke pain. The primary endpoint was at least a 50% reduction in the pain disability index (PDI) and the secondary endpoints included > 50% improvement in the PDI in 50% of patients at two-year follow up; affirmative response to the prospect of repeating this treatment if the same outcome was possible; and > 50% improvement in the visual analogue scale in 50% of patients at two-year follow up. Inclusion criteria were hemi-body pain and anesthesia dolorosa due to contralateral thalamic or somatosensory pathway lesion, at least six months of medically refractory pain, a PDI score of at least 30 at the time of enrollment, pain severity of > 5 on a 0 to 10 scale, and failure to respond to at least one oral narcotic, one antiepileptic, or one antidepressant. Exclusion criteria were severe psychiatric or cognitive comorbidities and contraindications to DBS. After assessing 69 patients, 10 were included, but eventually nine were randomized as follows: four to the DBS “off” group and five to the DBS “on” group for three months with subsequent crossing over of each group. Five of the nine patients continued the open-label extension for 18 months. Various neuropsychiatric tests were performed at one, two, and three months during the randomization phase. The average age of the patients was 51.3 years, mean time since stroke 4.7 years, and the mean pain intensity was 8.5 out of 10 on a 0 to 10 scale. The randomization phase did not reveal significant differences in the PDI, but those receiving active stimulation had significant improvements in the Beck Depression Inventory, McGill Affective Pain Rating Scale, Montgomery–Asberg Depression Rating Scale, and the McGill Present Pain Scale. At the end of the open label extension, about one-third of total participants continued to report a positive response on these affective scales. The participants were able to predict correctly whether they were being stimulated during the randomization phase at a significantly higher rate than chance. Lastly, when asked if they would have the procedure again despite the same results, five of nine responded positively. Serious adverse events, such as wound dehiscence and infection, resolved.

COMMENTARY

Post-stroke pain significantly affects quality of life and is very challenging to treat. Standard treatments with narcotics, antidepressants, antiepileptics, physical therapy, and botulinum toxin are limited either by side effects or limited effect. Since chronic pain is more than just physical, somatic pain that involves both affective and cognitive components, a multimodal approach is necessary to improve symptoms and reduce disability. VS/ALIC neuromodulation has been shown to improve symptoms of anxiety, treatment-resistant depression, and obsessive-compulsive disorder. Focusing on the affective aspects of chronic pain may improve sense of wellbeing and reduce anxiety related to worsening the chronic pain by performing daily activities. Despite the improvements in affective measures, no PDI change was appreciated. Yet, five of nine patients would have the procedure again. Thus, despite the lack of improvement in disability from pain, mood improvements did show preliminary benefits in these patients. This study, though promising and adding to our understanding of chronic pain, has several limitations. The first limitation is the small sample size, followed by the relatively short follow-up, despite the 18-month extension. As we know from the literature of DBS for movement disorders, it may take longer than 18 months to demonstrate benefit, particularly in patients with longer standing disease. This is particularly true in dystonia patients with severe postures that respond after six months or longer of stimulation and continue to improve over time. The anatomical differences in stroke patients also may contribute to challenges in accurately implanting and subsequently programming these patients, which can lead to unwanted side effects from spread of stimulation to adjacent structures. Also, it still is unclear what the ideal stimulation parameters are in these affective disorders, and further DBS studies are necessary to determine them. Finally, as cognition is affected in stroke, the long-term effects of neuromodulation of the VS/ALIC on cognition would need to be assessed. The movement disorders literature regarding the effects of DBS on cognition is not consistent enough to draw conclusions.