Efficacy of Pain Intervention With Deep Brain Stimulation Neuromodulation

The EPIONE trial is a double blind randomised controlled crossover trial. Comparing DBS stimulation with "Pseudo-ON " stimulation in participants who have central post stroke pain refractory to best medical/non-medical therapy. All participants will have the device on (with different stimulation parameters depending on the phase) during the trial. Blinding refers to knowledge of stimulation parameters. Following the randomised crossover periods, stimulation is further honed (refined) for an additional period of 6 months, called the "optimisation" period. This may include making use of circadian and motion sensing features of the Picostim-DyNeuMo-2 device, for example to increase stimulation during sleep or movement as appropriate to the individual's symptoms.

Existing evidence for the efficacy of DBS for chronic post stroke pain:

Modern DBS efficacy trials often include a single- or double-blind design with a sham stimulation or crossover phase. Strict case ascertainment criteria are also typically used. Unlike these modern trials, most pain DBS trials are uncontrolled case series or case reports, with non-standardised recruitment criteria and considerable heterogeneity between cases, hence the need for trials of DBS for pain that meets current scientific standards.

A number of open-labelled studies have demonstrated moderate efficacy of DBS for chronic pain including CPSP. A meta-analysis published in 2005 described the results of 424 cases pooled from 6 studies. Sites of stimulation included the periaqueductal/periventricular grey (PAG/PVG), the sensory thalamus and the internal capsule (IC). The authors noted that techniques used to assess pain severity were too heterogeneous to compare between studies. The meta-analysis showed that trial stimulation was successful in 50% of patients with central pain (i.e. CPSP), and in the patients with successful trial stimulation who went on to implantation, 58% reported ongoing pain relief. Thus, according to this meta-analysis, the overall percentage of patients with CPSP who benefitted from DBS was 31%, but the proportion receiving benefit was much higher in those with a positive response to test stimulation (58%). This meta-analysis highlights the importance of being able to pre-select patients most likely to have successful trial stimulation, which the investigators hope to address in the present trial.

A subsequent trial reported the results of a series of 56 patients who received DBS for chronic pain, of whom 11 had central post-stroke pain. Only 2/11 had successful test stimulation, but the two who had DBS implanted reported ongoing pain relief. Another open label single centre trial reported early improvements in 69.6% of patients with chronic post-stroke pain who underwent DBS, and of patients who retained their DBS stimulators at 1 year, there was a significant improvement in pain VAS score (p < 0.001). A case series of 4 patients with intractable pharmacologically resistant hemi-body thalamic pain lasting for at least 2 years. Three of these patients had post-stroke pain. Post DBS assessments were at 3,6 and 12 months. Three patients achieved long-lasting pain relief of more than 40% at 3, 6 and 12 months.