| 1. |
- Nuttin, Bart, et al.
(författare)
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Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group. - 0022-3050 .- 1468-330X. ; 85:9, s. 1003-1008
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Tidskriftsartikel (refereegranskat)abstract
- Background For patients with psychiatric illnesses remaining refractory to 'tandard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered 'stablished' in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-p evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.
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| 2. |
- Schechtmann, Gastón
(författare)
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Drug-enhanced spinal cord stimulation for neuropathic pain : studies on neurochemical mechanisms and clinical applications
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spinal cord stimulation (SCS) is an effective surgical treatment for neuropathic pain refractory to pharmacological therapy. For many patients suffering from this type of chronic pain, SCS is in fact the ultimate treatment option. However, 30 to 40 percent of well selected patients fail to obtain useful pain relief with SCS, and in some patients an initial good analgesic effect diminishes over time. Therefore, the need to improve the efficacy of SCS in these patients, prompted us to perform experimental research in order to advance the comprehension of the underlying mechanisms of SCS and further, to apply this knowledge clinically in order to develop new therapeutic strategies. When SCS is applied to the dorsal columns, multiple neuronal networks may be activated and several neurotransmitters are released in the spinal dorsal horn. This neuronal response to SCS may be regarded as equivalent to in situ drug delivery to the spinal cord in physiological amounts. The present thesis provides evidence that the analgesic effect of SCS partially relies on the activation of the cholinergic system because stimulation applied in rats with nerve injury produces a release of acetylcholine (ACh) in the dorsal horn. This effect occurred only in rats that in preceding experiments have been found to respond to SCS. It was also demonstrated that the SCS effect on signs of neuropathy was mediated via the activation of muscarinic, particularly M4, receptors. Intrathecal clonidine, a partial α2 receptor agonist, has proven to be an effective drug for both neuropathic and nociceptive pain. It is known that its analgesic action is in part related to an augmented spinal release of ACh, binding mainly to M4 receptors. In this thesis it was demonstrated that in nerve injured rats, concurrent administration of clonidine and SCS may potentiate the suppressive effect of SCS on mechanical hypersensitivity. In a previous experimental study, it was shown that the administration of subeffective doses of a GABAB receptor agonist, baclofen, may enhance the effect of SCS. It is now demonstrated that also two anticonvulsants, gabapentin and pregabalin, in low and by themselves ineffective doses, may potentiate the suppressive effect of SCS on signs of neuropathy in rats. On the basis of these experimental studies, a double-blind, placebo-controlled clinical trial was performed, demonstrating that clonidine and baclofen in low intrathecal doses may enhance the analgesic effect of SCS in neuropathic pain, improving also quality of life. A long-term follow-up of a group of patients with combined SCS and baclofen treatment revealed that they still enjoyed good pain relief. The present studies contribute to the understanding of the mode of action of SCS and it provides a new therapeutic option to enhance the pain relieving effect of SCS by concomitant administration of low doses of intrathecal drugs for patients who obtain insufficient analgesia by SCS alone. This thesis also represents an attempt to translate knowledge from experiments performed in animals to clinical application.
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| 3. |
- Wu, Hemmings, et al.
(författare)
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Deep brain stimulation for refractory obsessive-compulsive disorder (OCD) : emerging or established therapy?
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26, s. 60-65
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Tidskriftsartikel (refereegranskat)abstract
- A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.
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