Long-Term Results of Deep Brain Stimulation of the Anterior Cingulate Cortex for Neuropathic Pain.

BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a recent technique that has shown some promising short-term results in patients with chronic refractory neuropathic pain. Three years after the first case series, we assessed its efficacy on a larger cohort, with longer follow-up. METHODS: Twenty-four patients (19 males; average age, 49.1 years) with neuropathic pain underwent bilateral ACC DBS. Patient-reported outcome measures were collected before and after surgery, using the Numerical Rating Scale (NRS), Short-Form 36 quality of life (SF-36), McGill Pain Questionnaire (MPQ), and EuroQol 5-domain quality of life (EQ-5D) questionnaire. RESULTS: Twenty-two patients after a trial week were fully internalized and 12 had a mean follow-up of 38.9 months. Six months after surgery the mean NRS score decreased from 8.0 to 4.27 (P = 0.004). There was a significant improvement in the MPQ (mean, -36%; P = 0.021) and EQ-5D score significantly decreased (mean, -21%; P = 0.036). The physical functioning domain of SF-36 was significantly improved (mean, +54.2%; P = 0.01). Furthermore, in 83% of these patients, at 6 months, NRS score was improved by 60% (P < 0.001) and MPQ decreased by 47% (P < 0.01). After 1 year, NRS score decreased by 43% (P < 0.01), EQ-5D was significantly reduced (mean, -30.8; P = 0.05) and significant improvements were also observed for different domains of the SF-36. At longer follow-ups, efficacy was sustained up to 42 months in some patients, with an NRS score as low as 3. CONCLUSIONS: Follow-up results confirm that ACC DBS alleviates chronic neuropathic pain refractory to pharmacotherapy and improves quality of life in many patients.

Post-Traumatic Tremor and Thalamic Deep Brain Stimulation: Evidence for Use of Diffusion Tensor Imaging.

BACKGROUND: Deep brain stimulation (DBS) is a well-established treatment to reduce tremor, notably in Parkinson disease. DBS may also be effective in post-traumatic tremor, one of the most common movement disorders caused by head injury. However, the cohorts of patients often have multiple lesions that may impact the outcome depending on which fiber tracts are affected. CASE DESCRIPTION: A 20-year-old man presented after road traffic accident with severe closed head injury and polytrauma. Computed tomography scan showed left frontal and basal ganglia hemorrhagic contusions and intraventricular hemorrhage. A disabling tremor evolved in step with motor recovery. Despite high-intensity signals in the intended thalamic target, a visual analysis of the preoperative diffusion tensor imaging revealed preservation of connectivity of the intended target, ventralis oralis posterior thalamic nucleus (VOP). This was confirmed by the postoperative tractography study presented here. DBS of the VOP/zona incerta was performed. Six months postimplant, marked improvement of action (postural, kinetic, and intention) tremor was achieved. CONCLUSIONS: We demonstrated a strong connectivity between the VOP and the superior frontal gyrus containing the premotor cortex and other central brain areas responsible for movement control. In spite of an existing lesion in the target, the preservation of these tracts may be relevant to the improvement of the patient's symptoms by DBS.

Tractography Study of Deep Brain Stimulation of the Anterior Cingulate Cortex in Chronic Pain: Key to Improve the Targeting.

BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a new treatment for alleviating intractable neuropathic pain. However, it fails to help some patients. The large size of the ACC and the intersubject variability make it difficult to determine the optimal site to position DBS electrodes. The aim of this work was therefore to compare the ACC connectivity of patients with successful versus unsuccessful DBS outcomes to help guide future electrode placement. METHODS: Diffusion magnetic resonance imaging (dMRI) and probabilistic tractography were performed preoperatively in 8 chronic pain patients (age 53.4 ± 6.1 years, 2 females) with ACC DBS, of whom 6 had successful (SO) and 2 unsuccessful outcomes (UOs) during a period of trialing. RESULTS: The number of patients was too small to demonstrate any statistically significant differences. Nevertheless, we observed differences between patients with successful and unsuccessful outcomes in the fiber tract projections emanating from the volume of activated tissue around the electrodes. A strong connectivity to the precuneus area seems to predict unsuccessful outcomes in our patients (UO: 160n/SO: 27n), with (n), the number of streamlines per nonzero voxel. On the other hand, connectivity to the thalamus and brainstem through the medial forebrain bundle (MFB) was only observed in SO patients. CONCLUSIONS: These findings could help improve presurgical planning by optimizing electrode placement, to selectively target the tracts that help to relieve patients' pain and to avoid those leading to unwanted effects.

Deep brain stimulation for chronic pain.

Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome.

Deep brain stimulation of the anterior cingulate cortex: targeting the affective component of chronic pain.

Deep brain stimulation (DBS) has shown promise for relieving nociceptive and neuropathic symptoms of refractory chronic pain. We assessed the efficacy of a new target for the affective component of pain, the anterior cingulate cortex (ACC). A 49-year-old man with neuropathic pain underwent bilateral ACC DBS. Patient-reported outcome measures were collected before and 2 years after surgery using a Visual Analogue Scale, Short-Form 36 quality of life survey, McGill pain questionnaire, EuroQol-5D questionnaires (EQ-5D; Health State) and neuropsychological assessments. The patient improved with DBS. Two years after surgery, the Visual Analogue Scale decreased from 6.7 to 3.0, McGill pain questionnaire improved by 42% and EQ-5D Health State increased by 150%. Stimulating the ACC at 130 Hz, 330 µs and 3 V facilitated neuropathic pain relief. The DBS remained efficacious during the 2-year follow-up period. Affective ACC DBS can relieve chronic neuropathic pain refractory to pharmacotherapy and restore quality of life.

Targeting the affective component of chronic pain: a case series of deep brain stimulation of the anterior cingulate cortex.

BACKGROUND: Deep brain stimulation (DBS) has shown considerable promise for relieving nociceptive and neuropathic symptoms of refractory chronic pain. Nevertheless, for some patients, standard DBS for pain remains poorly efficacious. Pain is a multidimensional experience with an affective component: the unpleasantness. The anterior cingulate cortex (ACC) is a structure involved in this affective component, and targeting it may relieve patients' pain. OBJECTIVE: To describe the first case series of ACC DBS to relieve the affective component of chronic neuropathic pain. METHODS: Sixteen patients (13 male and 3 female patients) with neuropathic pain underwent bilateral ACC DBS. The mean age at surgery was 48.7 years (range, 33-63 years). Patient-reported outcome measures were collected before and after surgery using a Visual Analog Scale, SF-36 quality of life survey, McGill Pain Questionnaire, and EQ-5D (EQ-5D and EQ-5D Health State) questionnaires. RESULTS: Fifteen patients (93.3%) transitioned from externalized to fully internalized systems. Eleven patients had data to be analyzed with a mean follow-up of 13.2 months. Post-surgery, the Visual Analog Scale score dropped below 4 for 5 of the patients, with 1 patient free of pain. Highly significant improvement on the EQ-5D was observed (mean, +20.3%; range, +0%-+83%; P = .008). Moreover, statistically significant improvements were observed for the physical functioning and bodily pain domains of the SF-36 quality-of-life survey: mean, +64.7% (range, -8.9%-+276%; P = .015) and mean +39.0% (range, -33.8%-+159%; P = .050), respectively. CONCLUSION: Affective ACC DBS can relieve chronic neuropathic pain refractory to pharmacotherapy and restore quality of life.

Long-term outcomes of deep brain stimulation for neuropathic pain.

BACKGROUND: Deep brain stimulation (DBS) to treat neuropathic pain refractory to pharmacotherapy has reported variable outcomes and has gained United Kingdom but not USA regulatory approval. OBJECTIVE: To prospectively assess long-term efficacy of DBS for chronic neuropathic pain in a single-center case series. METHODS: Patient reported outcome measures were collated before and after surgery, using a visual analog score, short-form 36-question quality-of-life survey, McGill pain questionnaire, and EuroQol-5D questionnaires (EQ-5D and health state). RESULTS: One hundred ninety-seven patients were referred over 12 years, of whom 85 received DBS for various etiologies: 9 amputees, 7 brachial plexus injuries, 31 after stroke, 13 with spinal pathology, 15 with head and face pain, and 10 miscellaneous. Mean age at surgery was 52 years, and mean follow-up was 19.6 months. Contralateral DBS targeted the periventricular gray area (n = 33), the ventral posterior nuclei of the thalamus (n = 15), or both targets (n = 37). Almost 70% (69.4%) of patients retained implants 6 months after surgery. Thirty-nine of 59 (66%) of those implanted gained benefit and efficacy varied by etiology, improving outcomes in 89% after amputation and 70% after stroke. In this cohort, >30% improvements sustained in visual analog score, McGill pain questionnaire, short-form 36-question quality-of-life survey, and EuroQol-5D questionnaire were observed in 15 patients with >42 months of follow-up, with several outcome measures improving from those assessed at 1 year. CONCLUSION: DBS for pain has long-term efficacy for select etiologies. Clinical trials retaining patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.