Erlick A.C. Pereira

Deep brain stimulation: indications and evidence.

Deep brain stimulation is a minimally invasive targeted neurosurgical intervention that enables structures deep in the brain to be stimulated electrically by an implanted pacemaker. It has become the treatment of choice for Parkinson’s disease, refractory to, or complicated by, drug therapy. Its efficacy has been demonstrated robustly by randomized, controlled clinical trials, with multiple novel brain targets having been discovered in the last 20 years. Multifarious clinical indications for deep brain stimulation now exist, including dystonia and tremor in movement disorders; depression, obsessive–compulsive disorder and Tourette’s syndrome in psychiatry; epilepsy, cluster headache and chronic pain, including pain from stroke, amputation, trigeminal neuralgia and multiple sclerosis. Current research augurs for novel indications, including hypertension and orthostatic hypotension. The development, principles, indications and effectiveness of the technique are reviewed here. While deep brain stimulation is a standard and widely accepted treatment for Parkinson’s disease after 20 years of experience, in chronic pain it remains restricted to a handful of experienced, specialist centers willing to publish outcomes despite its use for over 50 years. Reasons are reviewed and novel approaches to appraising clinical evidence in functional neurosurgery are suggested.

Deep brain stimulation of the pedunculopontine nucleus in Parkinson's disease. Preliminary experience at Oxford.

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinsons disease and related disorders. Here, we summarize our non-human primate and neuroimaging research of relevance to our surgical targeting of the PPN. We also describe our clinical experience of PPN DBS with greatest motor improvements achieved by stimulation at low frequencies.

British surgeons' experiences of mandatory online workplace-based assessment

Summary Objectives An online workplace-based assessment tool, the Intercollegiate Surgical Curriculum Programme (ISCP), has become mandatory for all British surgical trainees appointed since August 2007. A compulsory £125 annual trainee fee has also been introduced to fund its running costs. The study sought to evaluate user satisfaction with the ISCP. Design and setting A total of 539 users across all surgical specialties (including 122 surgeons acting as assessors) were surveyed in late 2008 by online questionnaire regarding their experiences with the ISCP. Results Sixty-seven percent had used the tool for at least one year. It was rated above average by only 6% for its registration process and only 11% for recording meetings and objectives. Forty-nine percent described its online assessments as poor or very poor, only 9% considering them good or very good. Seventy-nine percent rated the websites user friendliness as average or worse, as did 72% its peer-assessment tool and 61% its logbook of procedures. Seventy-six percent of respondents had carried out paper assessments due to difficulties using the website. Six percent stated that the ISCP had impacted negatively on their training opportunities, 41% reporting a negative impact overall upon their training; only 6% reported a positive impact. Ninety-four percent did not consider the trainee fee good value, only 2% believing it should be paid by the trainee. Conclusions The performance of the ISCP leaves large numbers of British surgeons unsatisfied. Its assessments lack appropriate evidence of validity and its introduction has been problematic. With reducing training hours, the increased online bureaucratic burden exacerbates low morale of trainees and trainers, adversely impacting potentially upon both competency and productivity.

Abnormal thalamocortical dynamics may be altered by deep brain stimulation: Using magnetoencephalography to study phantom limb pain

Deep brain stimulation (DBS) is used to alleviate chronic pain. Using magnetoencephalography (MEG) to study the mechanisms of DBS for pain is difficult because of the artefact caused by the stimulator. We were able to record activity over the occipital lobe of a patient using DBS for phantom limb pain during presentation of a visual stimulus. This demonstrates that MEG can be used to study patients undergoing DBS provided control stimuli are used to check the reliability of the data. We then asked the patient to rate his pain during and off DBS. Correlations were found between these ratings and power in theta (6-9) and beta bands (12-30). Further, there was a tendency for frequencies under 25 Hz to correlate with each other after a period off stimulation compared with immediately after DBS. The results are interpreted as reflecting abnormal thalamocortical dynamics, previously implicated in painful syndromes.

Regional Cerebral Perfusion Differences between Periventricular Grey, Thalamic and Dual Target Deep Brain Stimulation for Chronic Neuropathic Pain

Regional cerebral blood flow changes were evaluated in different subcortical brain targets following deep brain stimulation (DBS) for chronic pain. Three patients with intractable neuropathic pain were assessed; one had stimulating electrodes in the ventroposterolateral thalamic nucleus (VPL), one in the periventricular grey (PVG) area, and one had electrodes in both targets. Pain relief was achieved in all patients. Cerebral perfusion was measured by single-photon emission computed tomography to determine the effects of DBS. Comparison was made between individual scans using subtraction analysis. DBS consistently increased perfusion in the posterior subcortical region between VPL and PVG, regardless of the site of stimulation. Furthermore, thalamic and dual target DBS increased thalamic perfusion, yet PVG DBS decreased perfusion in the PVG-containing midbrain region and thalamus. Dual target stimulation decreased anterior cingulate and insular cortex perfusion. The study demonstrates regional differences in cerebral perfusion between three accepted and efficacious targets for analgesic DBS.

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.

NEURAL SIGNATURES IN PATIENTS WITH NEUROPATHIC PAIN

The mechanisms by which neural signals are encoded to produce conscious sensations remain a central question in neuroscience. Invasive recordings from human brain structures in vivo give us the opportunity to study neural correlates of these sensations. Pain is a sensation fundamental to survival and its subjective nature in the clinical setting makes it difficult to quantify. It remains without direct objective neuronal correlates. Here we describe an 8–14 Hz, spindle-shaped neural signal present in both the sensory thalamus and periaqueductal gray area (PAG) in humans that directly correlates to the subjective reporting of pain intensity. Local field potentials (LFPs) recorded by deep brain macroelectrodes reveal the ensemble activity of neuronal groups in particular brain regions.1 The oscillatory amplitude of such ensembles is proportionate to the degree of synchrony with which they oscillate.2 Properties of oscillations including their synchrony, frequency, and corresponding power spectra vary both between brain structures and dynamically, depending upon the activity performed.3 ### Methods. Twelve patients (11 male, 1 female) underwent deep brain stimulation for treatment of chronic neuropathic pain. Etiology was as follows; poststroke pain (4), phantom limb pain (3), facial pain of various causes (4), and brachial plexus injury (1). Nuclei targeted were periaqueductal gray (PAG) alone in 3 patients, ventroposterolateral/medial nucleus of the thalamus (VPL/VPM) in 6 patients, and both in 3 patients. This was decided upon based on clinical grounds (in general, sensory thalamus was avoided if the patient had had a thalamic stroke). Three patients …

Refractory epilepsy and deep brain stimulation

Up to one-third of all patients with epilepsy have epilepsy refractory to medical therapy. Surgical options include temporal lobectomy, focal neocortical resection, stereotactic lesioning and neurostimulation. Neurostimulatory options comprise vagal nerve stimulation, trigeminal nerve stimulation and deep brain stimulation (DBS). DBS enables structures in the brain to be stimulated electrically by an implanted pacemaker after a minimally invasive neurosurgical procedure and has become the therapy of choice for Parkinsons disease refractory to or complicated by drug therapy. Here we review DBS for epilepsy, a powerful emerging treatment in the surgical armamentarium for drug refractory epilepsy, with a focus on extratemporal epilepsy.

Pre-operative DTI and probabilisitic tractography in four patients with deep brain stimulation for chronic pain.

This study aimed to examine, using diffusion tensor imaging (DTI), differences in electrode placement in four patients undergoing deep brain stimulation for chronic neuropathic pain of varying aetiology. A pre-operative DTI was obtained for each patient, who was then implanted with deep brain stimulation electrodes in the periventricular/periaqueductal grey area with good pain relief. Using seeds from the postoperative MRI scan, probabilistic tractography was performed from the pre-operative DTI.

Deep brain stimulation for pain

Deep brain stimulation (DBS) is a neurosurgical intervention whose efficacy, safety, and utility have been shown in the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, many prospective case series have been reported, but few have published findings from patients treated during the past decade using current standards of neuroimaging and stimulator technology. We summarize the history, science, selection, assessment, surgery, and personal clinical experience of DBS of the ventral posterior thalamus, periventricular/periaqueductal gray matter, and, latterly, the rostral anterior cingulate cortex (Cg24) in 100 patients treated now at two centers (John Radcliffe Hospital, Oxford, UK, and Hospital de São João, Porto, Portugal) over 12 years. Several experienced centers continue DBS for chronic pain with success in selected patients, in particular those with pain after amputation, brachial plexus injury, stroke, and cephalalgias including anesthesia dolorosa. Other successes include pain after multiple sclerosis and spine injury. Somatotopic coverage during awake surgery is important in our technique, with cingulate DBS considered for whole-body pain or after unsuccessful DBS of other targets. Findings discussed from neuroimaging modalities, invasive neurophysiological insights from local field potential recording, and autonomic assessments may translate into improved patient selection and enhanced efficacy, encouraging larger clinical trials.