Neuromodulation for central post-stroke pain: mechanism, safety and outcome

Approximately 8% of stroke patients develop central post stroke pain (CPSP). CPSP is a specific type of neuropathic pain, resulting directly from an ischaemic or haemorrhagic brain injury along the pain circuitry. CPSP is usually severe and chronic, and has a profound impact on quality of life, sometimes even leading to suicidality. Although there is level 1 evidence for several neuropathic analgesics, the numbers needed to treat are high, side effects common and pain reduction typically only moderate. Consequently, the majority of CPSP patients is considered pharmacorefractory. As early as the 1950s, neurosurgical pioneers experimented with electrical brain stimulation for different types of neuropathic pain, including CPSP. For this purpose, electrodes were implanted in deep brain structures, usually in the ventral caudal (Vc) nucleus of the thalamus (deep brain stimulation; DBS) or, more recently, on the surface of the brain at the level of the primary motor area (motor cortex stimulation; MCS). Based on a very limited number of small case series, the success rate (i.e. the proportion of patients who report a pain intensity reduction of ≥50% with stimulation vs. preoperatively) for both Vc-DBS and MCS for CPSP is currently estimated at 2/3 in the first months postoperatively, dropping to 1/3 at 1 year postoperatively, with stable numbers in the long run. In Belgium, both MCS and DBS for chronic neuropathic pain were reimbursed until 2018, when reimbursement was ceased due to a lack of available scientific evidence. Between 1990 and 2018, approximately 40 patients underwent DBS or MCS for CPSP in UZ Leuven, with a success ratio of approximately 50% >1 year postoperatively. A major difficulty in counselling these patients remains the unpredictability of the outcome. For MCS, non-invasive repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) has a high positive predictive value and fair negative predictive value, but for DBS, there is currently no known useful outcome predictor. Lately, both in Leuven and internationally, there has been a renewed interest in DBS and MCS for CPSP, partially due to increasing numbers of stroke and related CPSP patients, and also due to a lack of efficacious alternatives. The objective of this research project is to establish the subjective (mainly patient-reported pain and quality of life) and objective (changes in pain threshold) outcome and safety profile of 3 neuromodulation techniques (M1-rTMS, Vc-DBS and MCS) in patients with pharmaco-refractory CPSP, as well as to establish the biological basis for this effect (through functional imaging and brain recordings).