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  • The sensory and motor representation of synchronized oscillations in the globus pallidus in patients with primary dystonia.

    12 December 2017

    In 15 patients with primary dystonia (six cervical and nine generalized dystonias) who were treated with bilateral chronic pallidal stimulation, we investigated the sensorimotor modulation of the oscillatory local field potentials (LFPs) recorded from the pallidal electrodes. We correlated these with the surface electromyograms in the affected muscles. The effects of involuntary, passive and voluntary movement and muscle-tendon vibration on frequency ranges of 0-3 Hz, theta (3-8 Hz), alpha (8-12 Hz), low (12-20 Hz) and high beta (20-30 Hz), and low (30-60 Hz) and high gamma (60-90 Hz) power were recorded and compared between cervical and generalized dystonia groups. Significant decreases in LFP synchronization at 8-20 Hz occurred during the sensory modulation produced by voluntary or passive movement or vibration. Voluntary movement also caused increased gamma band activity (30-90 Hz). Dystonic involuntary muscle spasms were specifically associated with increased theta, alpha and low beta (3-18 Hz). Furthermore, the increase in the frequency range of 3-20 Hz correlated with the strength of the muscle spasms and preceded them by approximately 320 ms. Differences in modulation of pallidal oscillation between cervical and generalized dystonias were also revealed. This study yields new insights into the pathophysiological mechanisms of primary dystonias and their treatment using pallidal deep brain stimulation.

  • Deep brain stimulation for pain relief: a meta-analysis.

    12 December 2017

    Deep brain stimulation (DBS) has been used to treat intractable pain for over 50 years. Variations in targets and surgical technique complicate the interpretation of many studies. To better understand its efficacy, we performed a meta-analysis of DBS for pain relief. MEDLINE (1966 to February 2003) and EMBASE (1980 to January 2003) databases were searched using key words deep brain stimulation, sensory thalamus, periventricular gray and pain. Inclusion criteria were based on patient characteristics and protocol clarity. Six studies (between 1977-1997) fitting the criteria were identified. Stimulation sites included the periventricular/periaqueductal grey matter (PVG/PAG), internal capsule (IC), and sensory thalamus (ST). The long-term pain alleviation rate was highest with DBS of the PVG/PAG (79%), or the PVG/PAG plus sensory thalamus/internal capsule (87%). Stimulation of the sensory thalamus alone was less effective (58% long-term success) (p < 0.05). DBS was more effective for nociceptive than deafferentation pain (63% vs 47% long-term success; p < 0.01). Long-term success was attained in over 80% of patients with intractable low back pain (failed back surgery) following successful trial stimulation. Trial stimulation was successful in approximately 50% of those with post-stroke pain, and 58% of patients permanently implanted achieved ongoing pain relief. Higher rates of success were seen with phantom limb pain and neuropathies. We conclude that DBS is frequently effective when used in well-selected patients. Neuroimaging and neuromodulation technology advances complicate the application of these results to modern practice. Ongoing investigations should shed further light on this complex clinical conundrum.

  • How safe is twistdrill craniostomy?

    12 December 2017

    The incidence of haemorrhagic complications of intracranial pressure monitoring (ICPM) has previously been reported. However, in these studies, the techniques employed to access the inside of the cranium varied. While 3-mm essentially blind 'twistdrill' craniostomies have been used, their role has been limited for fear of haemorrhagic sequelae. This has also restricted their use in clinical applications other than ICPM. We conducted a prospective observational study looking at haemorrhagic complications of the twistdrill in order to determine its safety and whether it has a role in other clinical settings. Over the period January 1994-February 2001, 941 patients had 1032 twistdrill procedures. There were 550 (58.4%) male patients and 391 (41.6%) female. The age range was 3 months to 93 years (median age 35 years). Only four procedures (0.38%) caused clinically significant bleeds attributable to the twistdrill --all of which were managed conservatively without requiring surgical evacuation. We conclude that twistdrill craniostomies are safe and that their use could be extended to other neurosurgical procedures and potentially to ICPM in non-neurosurgical centres.

  • The role of descending basal ganglia connections to the brain stem in parkinsonian akinesia.

    8 December 2017

    Akinesia is the most disabling symptom of Parkinson's disease. The neural mechanisms underlying it probably involve the descending projections of the basal ganglia to the brain stem as it improves after a pallidotomy or subthalamic nucleotomy but not after a thalamotomy. We describe the effects of lesioning the pedunculopontine nucleus in the normal primate in generating an akinetic syndrome. The possible clinical implications of this study are discussed.

  • Movement-related synchronization of gamma activity is lateralized in patients with dystonia.

    12 December 2017

    There is evidence for synchronization at frequencies both under 30 Hz and over 60-80 Hz in the so-called gamma frequency band in patients with Parkinson's disease (PD). Gamma activity increases after dopaminergic therapy and during voluntary movement, suggesting that it might be physiological and relate to motor processing in the basal ganglia (BG). We recorded local field potential (LFP) activity during a choice reaction time task in 11 patients with dystonia undergoing implantation of the internal globus pallidus for therapeutic stimulation. The spectral content of the LFP was averaged with respect to movement onset over 6-11 Hz, 18-25 Hz and 60-80 Hz, separately for responses ipsilateral and contralateral to movement. There was a perimovement increase in 60-80 Hz activity in the LFP, but only contralateral to movement. In contrast, low-frequency LFP activity decreased symmetrically during movement. This occurred earlier in the 18-25 Hz band than in the 6-11 Hz band, and was followed by a postmovement increase in oscillatory activity in the 18-25 Hz band that was contralateral to movement. The presence of a lateralized movement-related increase in gamma activity in the BG of patients with dystonia, similar to that recorded in patients with treated PD, suggests that this may be a residual feature of normal BG function. Moreover, the results provide further support for functional distinctions between BG oscillatory activities of different frequency.

  • Parkinson's disease and primate research: past, present, and future.

    12 December 2017

    Scientific research involving non-human primates has contributed towards many advances in medicine and surgery. This review discusses its role in the progress made towards our understanding of Parkinson's disease and its treatment. Established medical treatments like dopamine agonists continue to need primate models to assess their efficacy, safety, and mechanism of action. The recently developed treatment of deep brain stimulation of the subthalamic nucleus required validation in primates before entering the clinic. Controversies surrounding future treatments such as gene therapy show the need for properly evaluated preclinical research using appropriate animal models before progression to clinical trials. Research on primates has played--and continues to play--a crucial part in deepening our understanding of Parkinson's disease, improving current therapies, and developing new treatments that are both safe and effective. In animal research, the "three Rs" of humane technique--reduction, refinement, and replacement--should be adhered to.

  • Surgical insights into Parkinson's disease.

    13 December 2017

    Surgery for Parkinson's disease was popularized in the mid-twentieth century before the advent of effective medical therapies. Early lesioning treatments contributed to our understanding of the functional anatomy of Parkinson's disease. Observations of the limitations and long-term complications of established pharmacological therapies for Parkinson's disease, together with major contributions from animal research to elucidate the roles of the basal ganglia in movement disorders, inspired a recent renaissance in neurosurgical interventions for Parkinson's disease including deep brain stimulation; this continues to yield much neurophysiological information. The development of potentially restorative treatment modalities, such as gene therapy, neural transplantation and nanotechnology, hold much promise for surgery, both therapeutically and in revealing further insights into Parkinson's disease pathophysiology.

  • Deep brain stimulation for phantom limb pain.

    12 December 2017

    Phantom limb pain is an often severe and debilitating phenomenon that has been reported in up to 85% of amputees. Its pathophysiology is poorly understood. Peripheral and spinal mechanisms are thought to play a role in pain modulation in affected individuals; however central mechanisms are also likely to be of importance. The neuromatrix theory postulates a genetically determined representation of body image, which is modified by sensory input to create a neurosignature. Persistence of the neurosignature may be responsible for painless phantom limb sensations, whereas phantom limb pain may be due to abnormal reorganisation within the neuromatrix. This study assessed the clinical outcome of deep brain stimulation of the periventricular grey matter and somatosensory thalamus for the relief of chronic neuropathic pain associated with phantom limb in three patients. These patients were assessed preoperatively and at 3 month intervals postoperatively. Self-rated visual analogue scale pain scores assessed pain intensity, and the McGill Pain Questionnaire assessed the quality of the pain. Quality of life was assessed using the EUROQOL EQ-5D scale. Periventricular gray stimulation alone was optimal in two patients, whilst a combination of periventricular gray and thalamic stimulation produced the greatest degree of relief in one patient. At follow-up (mean 13.3 months) the intensity of pain was reduced by 62% (range 55-70%). In all three patients, the burning component of the pain was completely alleviated. Opiate intake was reduced in the two patients requiring morphine sulphate pre-operatively. Quality of life measures indicated a statistically significant improvement. This data supports the role for deep brain stimulation in patients with phantom limb pain. The medical literature relating to the epidemiology, pathogenesis, and treatment of this clinical entity is reviewed in detail.