Deep Brain Stimulation For Pain Research Articles

Obituary. Tipu Zahed Aziz, 1956-2024

The extraordinary life of Tipu Aziz is described through anecdotes told to his former residents and fellows. A giant of functional neurosurgery, his primate experiments first demonstrated the subthalamic nucleus and pedunculopontine nucleus as targets for surgery for Parkinson's disease and he pioneered deep brain stimulation for pain including of the anterior cingulate cortex. Despite various career cul-de-sacs he climbed the ziggurat to the pinnacles of British neurosurgery and neuroscience. A pinball wizard of functional neurosurgery, he was mentored by a bygone Madmen era of gentlemen: chain-smoking, heavy-drinking workaholics whose nonchalant bravado, ‘can-do’ attitude, love of mischief, merriment and well-placed profanity he exemplified. Sometimes sharing a cigarette with a patient before surgery, we will not see his like again.

Directional recordings of somatosensory evoked potentials from the sensory thalamus in chronic poststroke pain patients

ObjectiveThe aim of this feasibility study was to investigate the properties of median nerve somatosensory evoked potential (SEPs) recorded from segmented Deep Brain Stimulation (DBS) leads in the sensory thalamus (VP) and how they relate to clinical and anatomical findings. MethodsWe analyzed four patients with central post-stroke pain and DBS electrodes placed in the VP. Median nerve SEPs were recorded with referential and bipolar montages. Electrode positions were correlated with thalamus anatomy and tractography-based medial lemniscus. Early postoperative clinical paresthesia mapping was performed by an independent pain nurse. Finally, we performed frequency and time–frequency analyses of the signals. ResultsWe observed differences of SEP amplitudes recorded along different directions in the VP. SEP amplitudes did not clearly correlate to both atlas-based anatomical position and fiber-tracking results of the medial lemniscus. However, the contacts of highest SEP amplitude correlated with the contacts of lowest effect-threshold to induce paraesthesia. ConclusionsSEP recordings from directional DBS leads offer additional information about the neurophysiological (re)organization of the sensory thalamus. SignificanceDirectional recordings of thalamic SEPs bear the potential to assist clinical decision-making in DBS for pain.

Deep Brain Stimulation for Pain in the Modern Era: A Systematic Review.

Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative. To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy. A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected. Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were periaqueductal/periventricular gray matter region, ventral posterior lateral/posterior medial thalamus, or both. Poststroke pain, phantom limb pain, and brachial plexus injury were the most common specific indications for DBS. Outcomes varied between studies and across chronic pain diagnoses. Two different groups of investigators targeting the affective sphere of pain have demonstrated improvements in quality of life measures without significant reductions in pain scores. DBS outcomes for chronic pain are heterogeneous thus far. Future studies may focus on specific pain diagnosis rather than multiple syndromes and consider randomized placebo-controlled designs. DBS targeting the affective sphere of pain seems promising and deserves further investigation.

Contemporary concepts of pain surgery.

Pain surgery is one of the historic foundations of neurological surgery. The authors present a review of contemporary concepts in surgical pain management, with reference to past successes and failures, what has been learned as a subspecialty over the past 50 years, as well as a vision for current and future practice. This subspecialty confronts problems of cancer pain, nociceptive pain, and neuropathic pain. For noncancer pain, ablative procedures such as dorsal root entry zone lesions and rhizolysis for trigeminal neuralgia (TN) should continue to be practiced. Other procedures, such as medial thalamotomy, have not been proven effective and require continued study. Dorsal rhizotomy, dorsal root ganglionectomy, and neurotomy should probably be abandoned. For cancer pain, cordotomy is an important and underutilized method for pain control. Intrathecal opiate administration via an implantable system remains an important option for cancer pain management. While there are encouraging results in small case series, cingulotomy, hypophysectomy, and mesencephalotomy deserve further detailed analysis. Electrical neuromodulation is a rapidly changing discipline, and new methods such as high-frequency spinal cord stimulation (SCS), burst SCS, and dorsal root ganglion stimulation may or may not prove to be more effective than conventional SCS. Despite a history of failure, deep brain stimulation for pain may yet prove to be an effective therapy for specific pain conditions. Peripheral nerve stimulation for conditions such as occipital neuralgia and trigeminal neuropathic pain remains an option, although the quality of outcomes data is a challenge to these applications. Based on the evidence, motor cortex stimulation should be abandoned. TN is a mainstay of the surgical treatment of pain, particularly as new evidence and insights into TN emerge. Pain surgery will continue to build on this heritage, and restorative procedures will likely find a role in the armamentarium. The challenge for the future will be to acquire higher-level evidence to support the practice of surgical pain management.

Deep brain stimulation for pain: distinguishing dorsolateral somesthetic and ventromedial affective targets.

Pereira, Erlick A. C. DM, FRCS*,‡; Boccard, Sandra G. PhD*; Aziz, Tipu Z. MD, FRCS, FMedSci*,‡ Author Information

Long-term Outcomes of Deep Brain Stimulation for Neuropathic Pain

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. To prospectively assess long-term efficacy of DBS for chronic neuropathic pain in a single-center case series. 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). 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. 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.

Long term effect of thalamic deep brain stimulation for pain due to brachial plexus injury

Long term effect of thalamic deep brain stimulation for pain due to brachial plexus injury

The Benefit of Subthalamic Deep Brain Stimulation for Pain in Parkinson Disease

Pain is a well-recognized feature of Parkinson disease (PD), which is primarily a motor disorder. In a previous study, we showed that subthalamic deep brain stimulation (STN DBS) improves pain as well as motor symptoms 3 months after surgery in PD patients. To determine whether there is a long-term beneficial effect of STN DBS on pain in PD. We studied 21 patients with PD who underwent STN DBS. Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr staging. Pain was evaluated by asking patients about the quality and severity of pain in each body part. Evaluations were performed at baseline and at 3 and 24 months after surgery. At baseline, 18 of the 21 patients (86%) experienced pain. After surgery, most of the pain reported at baseline had improved or disappeared at 3 months and improved further at 24 months. The benefit of STN DBS for pain evaluated at 24 months was comparable to that with medication at baseline. At 24 months, 9 patients (43%) reported new pain that was not present at baseline. Most of the new pain was musculoskeletal in quality. Despite the development of new pain, the mean pain score at follow-up was lower than at baseline. STN DBS improves pain in PD, and this beneficial effect persists, being observed after a prolonged follow-up of 24 months. In addition, in many of the PD patients new, mainly musculoskeletal pain developed on longer follow-up.

Deep brain stimulation of the periaqueductal gray for treatment of nociceptive pain: tryptophan loading and the serotonergic circuit of pain

Background: Pain and pain-related diseases pose a major treatment challenge. Current medical treatments frequently provide inadequate pain control to patients, or cause dependence and other unwanted side-effects. Despite initial failures of open-label trials to show efficacy in the use of deep brain stimulation (DBS) for pain, several groups have reported utility of this modality on carefully selected patients. There are several characterized pain pathways in operation in the human brain. A common theme to the pathways thus far identified is their dependence on the neurotransmitter serotonin for modulation of pain. Deep brain stimulation for pain may well activate one of the serotonin-dependent pathways to stimulate relief. Greater experience, and improvements in both technology and patient selection, has paved the way for the potential use of electrical stimulation of subcortical structures to manage intractable and nociceptive pain syndromes and also for the mechanistic study of the pathways involved in the symptomatic relief of pain caused by stimulation. Methods: We preoperatively loaded four patients with 4 grams of L-tryptophan, and implanted DBS electrodes in the periaqueductal gray (PAG). Results: Upon loading the patients with 4 grams of L-tryptophan two weeks preoperatively and the continual use of tryptophan at doses greater than 2.5 grams, we note a significant improvement in the pain symptoms of all of our patients implanted at the PAG. Upon decrease in L-tryptophan dose below 2.5 grams, every patient experienced return of their pain symptoms despite PAG stimulation. The average length of followup is 9.75 months with a range of three to 14. Conclusions: Tryptophan loading of the patient prior to PAG electrode placement, and the continued use of tryptophan postoperatively correlates with better outcomes and more significant pain reduction. Tryptophan probably increases serotonin levels and results in activation of anti-nociceptive pain pathways at the PAG.

Deep brain stimulation for chronic pain: results of two multicenter trials and a structured review.

A U.S. Food and Drug Administration ruling required clinical trials to evaluate the safety and efficacy of deep brain stimulation devices, thereby limiting treatment to the investigational setting. As an investigator in two clinical trials of deep brain stimulation, I sought to determine why pain remained an unapproved indication despite regulatory approval of the same device for tremor. The results of two multicenter trials of deep brain stimulation for pain were analyzed, and the pertinent literature was reviewed using published guidelines for the evaluation of clinical trial reports. The first-generation Model 3380 lead trial enrolled 196 patients; the current Model 3387 trial enrolled 50 patients. Prospectively defined criteria for success included at least half of patients reporting >/=50% pain relief at 1 year. Manufacture of the Model 3380 lead was discontinued, and the 3387 trial closed early because of slow enrollment, high attrition, and low efficacy. When results were analyzed according to the study plan, neither trial was successful. Consequently, deep brain stimulation has not been approved for pain control by the U.S. Food and Drug Administration. Deep brain stimulation has not been shown to produce effective long-term pain relief. Future studies of motor cortex stimulation and similar therapies will require appropriate control groups and accepted methods of data collection and analysis to support claims that predictable and reliable analgesic effects are produced in humans.