Does Size and Site Matter in Therapeutic Decompressive Craniectomy? A Laboratory-Based Experimental Study.

BACKGROUND: Therapeutic decompressive craniectomy (TDC) controls increased intracranial pressure (ICP). Its role was controversial until its successful introduction to treat malignant middle cerebral artery ischemia. However, standardization of size and site of TDC remains controversial. This study was designed to evaluate whether size and site matter in TDC. METHODS: A replica skull of a patient with refractory increased ICP and successful TDC was used. ICP was increased using an intracranial balloon modified to monitor ICP and permit progressive incremental increases in ICP. When a desired increased ICP was reached, segments of TDC were removed sequentially to increase its size until the ICP normalized. We also measured the volume of air required to raise the ICP back to the increased ICP value. RESULTS: The most effective TDC size to lower increased ICP was 8.3 cm in diameter (P < 0.001). However, a 7.5-cm TDC was sufficient to control increased ICP of 25-30 mm Hg (P < 0.01). There was strong correlation between TDC size and potential volume created to accommodate brain swelling postoperatively (Pearson correlation coefficient = 0.95928). The location of TDC did not matter when size was ≤3.5 cm or ≥7.5 cm; location mattered when size was 4.5 cm or 5.5 cm, where anteriorly located flaps were more effective in lowering increased ICP and increasing cranial volume (P < 0.05). CONCLUSIONS: The size of a TDC is very important in reducing increased ICP. The size should be tailored to the level of increased ICP and the likelihood of further brain swelling postoperatively. A smaller TDC should be located more anteriorly to control increased ICP. Although location is not as important when increased ICP is >30 mm Hg and TDC size ≥8.3 cm is required.

Intraoperative Ultrasound-Guided Resection of Gliomas: A Meta-Analysis and Review of the Literature.

BACKGROUND: Image-guided surgery has become standard practice during surgical resection, using preoperative magnetic resonance imaging. Intraoperative ultrasound (IoUS) has attracted interest because of its perceived safety, portability, and real-time imaging. This report is a meta-analysis of intraoperative ultrasound in gliomas. METHODS: Critical literature review and meta-analyses, using the MEDLINE/PubMed service. The list of references in each article was double-checked for any missing references. We included all studies that reported the use of ultrasound to guide glioma-surgery. The meta-analyses were conducted according to statistical heterogeneity between the studies using Open MetaAnalyst Software. If there was no heterogeneity, fixed effects model was used for meta-analysis; otherwise, a random effect model was used. Statistical heterogeneity was explored by χ(2) and inconsistency (I(2)) statistics; an I(2) value of 50% or more represented substantial heterogeneity. RESULTS: A wide search yielded 19,109 studies that might be relevant, of which 4819 were ultrasound in neurosurgery; 756 studies used ultrasound in cranial surgery, of which 24 studies used intraoperative ultrasound to guide surgical resection and 74 studies used it to guide biopsy. Fifteen studies fulfilled our stringent inclusion criteria, giving a total of 739 patients. The estimated average gross total resection rate was 77%. Furthermore, the relationship between extent of surgical resection and study population was not linear. Gross total resection was more likely under IoUS when the lesion was solitary and subcortical, with no history of surgery or radiotherapy. IoUS image quality, sensitivity, specificity, and positive and negative predictive values deteriorated as surgical resection proceeded. CONCLUSION: IoUS-guided surgical resection of gliomas is a useful tool for guiding the resection and for improving the extent of resection. IoUS can be used in conjunction with other complementary technologies that can improve anatomic orientation during surgery. Real-time imaging, improved image quality, small probe sizes, repeatability, portability, and relatively low cost make IoUS a realistic, cost-effective tool that complements any existing tools in any neurosurgical operating environment.

ALA-induced fluorescence image guided surgery of meningiomas: A meta-analyses.

BACKGROUND: Though meningiomas are often benign and well circumscribed in nature, many are associated with recurrences and poor outcome because of their attachment to neurovascular nearby structures or invasion of adjacent venous sinuses or bone, forcing incomplete excision and deployment of further salvage therapy. Recently, ALA-FIGS has been reported as an aid to increase the chances of complete resection and minimizing collateral damage. METHODS: Critical review and meta-analyses of the literature published to date. All studies reporting ALA-FIGS in meningiomas were critically reviewed. Nineteen studies fulfilled the inclusion criteria with a total of 222 patients, of which 206 were included in the meta-analyses. RESULTS: ALA-FIGS was highly specific, and highly sensitive (95%, range 91.8-97.7%). There was no correlation between WHO grading (WHO grade I versus WHO grades II & III) and fluorescence (odds ratio 1.2, p>0.05). ALA-FIGS altered the surgical plan intraoperatively in 75% of high-grade and 19% of low-grade meningiomas, improving the extent of surgical excision. ALA-FIGS was also highly sensitive and specific in differentiating hypertrophy and tumor invasion of adjacent dura and bone. CONCLUSIONS: ALA-FIGS in meningiomas is very selective, highly sensitive, and improves the extent of surgical resection in meningiomas. Long-term outcome of these tumors in the future should be categorized into those with and without residual fluorescent tissue. A new surgical resection grading system based on ALA-FIGS is proposed.

Dual Orientation 16-MHz Single-Element Ultrasound Needle Transducers for Image-Guided Neurosurgical Intervention.

Image-guided surgery is today considered to be of significant importance in neurosurgical applications. However, one of its major shortcomings is its reliance on preoperative image data, which does not account for brain deformations and displacements that occur during surgery. In this work, we propose to tackle this issue through the incorporation of an ultrasound device within the type of biopsy needles commonly used as an interventional tool to provide immediate feedback to neurosurgeons during surgical procedures. To identify the most appropriate path to access a targeted tissue site, single-element transducers that look either forward or sideways have been designed and fabricated. Micromolded 1-3 piezocomposites were adopted as the active materials for feasibility tests and epoxy lenses have been applied to focus the ultrasound beam. Electrical impedance analysis, pulse-echo testing, and wire phantom scanning have been carried out, demonstrating the functionality of the needle transducers at [Formula: see text]. The capabilities of these transducers for intraoperative image guidance were demonstrated by imaging within soft-embalmed cadaveric human brain and fresh porcine brain.

Vagus Nerve Stimulation for Major Depressive Episodes.

Stimulation of the left vagus nerve is a novel antidepressive therapy that relies upon the vagal projections to the brain stem to modulate brain circuits involved in mood regulation. There is cumulative evidence from prospective and long-term studies that has demonstrated tolerability and effectiveness of vagus nerve stimulation (VNS) in major depressive episodes (MDE). VNS in MDE has the following advantages: symptomatic response (defined as at least a 50% improvement in MDE severity) occurs in at least 15-17% of patients after 10 weeks of VNS treatment and in at least 22-37% of patients after 12 months of VNS treatment, remissions are observed in at least 15-17% of patients after 12 months of treatment, there is a sustained response in 13-27% of patients during 12 months of VNS, and successful maintenance of the initial improvement is observed in a high percentage of patients (73-77% of patients who had meaningful or greater benefit after 3 months of treatment maintained at least meaningful benefit after 12 months of treatment). VNS is a well-tolerated treatment as indicated by the high continuation rates of VNS therapy in the D01 and D02 studies after 12 months of therapy (90-98%) and the low rate of adverse event-related study discontinuations through 12 months or more in these studies (3%). Adverse effects are characterized by the absence of systemic effects associated with drug therapy and are primarily limited to those related to stimulation of the vagus nerve; many of the common adverse effects only occurred when VNS was on with the ability to stop acute stimulation-related adverse effects immediately through the use of magnet deactivation of the VNS device. More importantly, there were no adverse cognitive and psychomotor effects observed with antidepressant drugs and electroconvulsive therapy, no overdose toxicity observed with antidepressant drugs, favorable findings in animal reproductive studies, and an ability to add VNS therapy to antidepressant drug therapy without producing drug-drug interactions. Finally, VNS has high treatment compliance because VNS therapy is programmed to work automatically without the need for action on the patient's part (no pills to swallow).

Laser-induced autofluorescence spectroscopy: can it be of importance in detection of bladder lesions?

BACKGROUND: Non-muscle invasive bladder cancer can be missed during white light endoscopy in up to 50% of cases. We aimed to test whether or not we could find a difference between benign and cancerous tissue wavelengths using laser induced autofluorescence spectroscopy can increase cancer detection. MATERIALS AND METHODS: We analysed 67 tissue samples using spectral analysis. The WavSTAT (Spectra Science) optical biopsy device was used to record fluorescence spectra from biopsied tissue enabling calculation of an AUC for each spectrum, a measure of the mean spectral wavelength (λ¯ (nm)) and a dimensionless fluorescence ratio. Mann-Whitney test was used to compare the two groups. RESULTS: We found that 49.3% (33/67) of the tissue was benign, 44.8% (30/67) was CIS/cancerous tissue, and the remaining 4/67 samples were atypia (2) and dysplasia (2). The median AUC for the benign tissue was 19.53 (interquartile range [IQR]: 5.35-30.39) and that for CIS/cancerous tissue was 7.05 (IQR: 2.89-14.24) (P=0.002). The median wavelengths for the benign tissue and malignant tissue were 502.4nm (IQR: 500.3-504.3nm) and 505.2nm (IQR: 502.1-513.2nm), respectively (P=0.003). The median fluorescence ratio was 0.080 (IQR: 0.070-0.088) for benign tissue and 0.096 (IQR: 0.079-0.221) for CIS/cancerous tissue (P=0.002). CONCLUSIONS: We found statistical differences between the median AUC calculations and median wavelengths for the benign and cancerous tissue. We also found a statistical difference between the fluorescence ratios between the two tissue types. There seems to be a role for optical spectroscopy in verifying bladder lesions.

A multicentre, prospective, randomized, controlled study to evaluate the use of a fibrin sealant as an adjunct to sutured dural repair.

BACKGROUND: Obtaining intra-operative watertight closure of the dura is considered important in reducing post-operative cerebrospinal fluid (CSF) leak. The purpose of this study was to evaluate a fibrin sealant as an adjunct to sutured dural repair to obtain intra-operative watertight closure in cranial neurosurgery. METHODS: This randomized, controlled multicenter study compared a fibrin sealant (EVICEL® Fibrin Sealant [Human]) to sutured dural closure (Control). Subjects underwent supratentorial or posterior fossa procedures. Following primary dural repair by sutures, the closure was evaluated for intra-operative CSF leak by moderately increasing the intracranial pressure. If present, subjects were randomized to EVICEL® or additional sutures (2:1 ratio), stratified by surgical approach. Following treatment, subjects were successful if no CSF leaks were present during provocative challenge. Safety was assessed to 30 days post-surgery, including incidence of CSF leakage. RESULTS: One hundred and thirty-nine subjects were randomized: 89 to EVICEL® and 50 to Control. Intra-operative watertight closure was achieved in 92.1% EVICEL®-treated subjects versus 38.0% controls; a treatment difference of 54.1% (p < 0.001). The treatment differences in the supratentorial and posterior fossa strata were 49.1% and 75.7%, respectively (p < 0.001). The incidence of adverse events was similar between treatment groups. No deaths or unexpected serious adverse drug reactions were reported. CSF leakage within 30 days post-operatively was 2.2% and 2.0% in EVICEL® and control groups, respectively. In addition, 2 cases of CSF rhinorrhoea were observed in the EVICEL® group. Although not associated with the suture line where EVICEL® was applied, when combined with the other CSF leaks, the observed leak rate in the EVICEL® group was 4.5%. CONCLUSIONS: These results indicate that EVICEL® is effective as an adjunct to dural sutures to provide watertight closure of the dura mater in cranial surgery. The study confirmed the safety profile of EVICEL®.

Evaluation of Thiel cadaveric model for MRI-guided stereotactic procedures in neurosurgery.

BACKGROUND: Magnetic resonance imaging (MRI)-guided deep brain stimulation (DBS) and high frequency focused ultrasound (FUS) is an emerging modality to treat several neurological disorders of the brain. Developing reliable models to train and assess future neurosurgeons is paramount to ensure safety and adequate training of neurosurgeons of the future. METHODS: We evaluated the use of Thiel cadaveric model to practice MRI-guided DBS implantation and high frequency MRI-guided FUS in the human brain. We performed three training sessions for DBS and five sonications using high frequency MRI-guided FUS in five consecutive cadavers to assess the suitability of this model to use in training for stereotactic functional procedures. RESULTS: We found the brains of these cadavers preserved in an excellent anatomical condition up to 15 months after embalmment and they were excellent model to use, MRI-guided DBS implantation and FUS produced the desired lesions accurately and precisely in these cadaveric brains. CONCLUSION: Thiel cadavers provided a very good model to perform these procedures and a potential model to train and assess neurosurgeons of the future.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children. METHODS: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence. RESULTS: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

Photodynamic diagnostic ureterorenoscopy with orally administered 5-aminolaevulinic acid as photosensitiser: how I do it.

OBJECTIVE: To explain our use of photodynamic diagnostic ureterorenoscopy, we provide a detailed description of the choice of photosensitiser, equipment needed, a safety profile, and pointers on our technique. TECHNIQUE: Patients are given oral 5-aminolaevulinic acid (5-ALA) as a photosensitiser 3-4 h pre-operatively, and by using a Xenon blue light source, an eyepiece which blocks light below 450 nm which is fitted onto the ureterorenoscope, we are able to conduct a thorough photodiagnosis of the upper urinary tract. CONCLUSION: Our technique of photodynamic diagnostic ureterorenoscopy has shown that the sensitivity, specificity and detection rates of upper urinary tract lesions can be significantly increased with the use of oral 5-ALA. Therefore, we provide a detailed explanation of the use of oral 5-ALA photosensitiser, indications and contraindications of the technique in addition to equipment used and potential complications of the procedures.

Protoporphyrin-IX fluorescence guided surgical resection in high-grade gliomas: The potential impact of human colour perception.

INTRODUCTION: Protoporphyrin-IX (Pp-IX) fluorescence had been used frequently in recent years to guide microsurgical resection of high-grade gliomas (HGG), particularly following the publication of a randomized controlled trial demonstrating its advantages. However, Pp-IX fluorescence is dependent upon the surgeons' eyes' perception of red fluorescent colour. This study was designed to evaluate human eye fluorescence perception and establish a fluorescence scale. MATERIALS AND METHODS: 20 of 108 pre-recorded images from intraoperative fluorescence of HGG were used to construct an 8-panel visual analogue fluorescence scale. The scale was validated by testing 56 participants with normal colour vision and three red-green colour-blind participants. For intra-rater agreement ten participants were tested twice and for inter-observer reliability the whole cohort were tested. RESULTS: The intra- and inter-observer reliability of the scale in normal colour vision participants was excellent. The scale was less reliable in the violet-blue panels of the scale. Colour-blind participants were not able to distinguish between red fluorescence and blue-violet colours. CONCLUSION: The 8-panel fluorescence scale is valid in differentiating red, pink and blue colours in a fluorescence surgical field among participants with normal colour perception and potentially useful to standardize fluorescence-guided surgery. However, colourblind surgeons should not use fluorescence-guided surgery.

Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders.

BACKGROUND: For patients with psychiatric illnesses remaining refractory to 'standard' 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 'established' 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-up 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.

Comparison of intraoperative fluorescence and MRI image guided neuronavigation in malignant brain tumours, a prospective controlled study.

INTRODUCTION: MBT carry poor prognosis and more than 80% of MBT recur locally within 2 cm of the resection margin because of inadequate surgical removal. A number of techniques have been implemented in recent years to improve surgical removal of MBT with variable success. We examined two methods commonly used to resect MBT to establish which one offered the best chances of gross total removal; MRI guided technology and ALA-induced fluorescence. PATIENTS AND METHODS: Twenty consecutive patients diagnosed with MBT were included in this study. They were given 20mg ALA per kg body weight 3h before anaesthesia orally mixed in water. Surgery was planned using preoperative enhanced MPR age images. Surgery was executed using the Stealth Station image guidance system and ALA-induced fluorescence microsurgical techniques. During surgery the intensity of fluorescence was graded into red, pink or blue. The intensity of fluorescence was also measured using pulsed 405 nm laser and a compact spectrometer using a touch probe directly placed on the tissue. The extent of tumour invasion was assessed intraoperatively using standard white light, blue light and spectroscopic measurements. Postoperative enhanced MRI was used to assess the extent of resection and the volume of residual tumour was measured. RESULTS: There were six newly diagnosed GBM, eight recurrent GBM, one oligodendroglioma (ODG) and five metastases (MET). On enhanced MRI, the mean diameter of new GBM, recurrent GBM, ODG and MET was 2.3 cm, 2.3 cm, 1.5 cm, and 2.3 cm respectively. Under the blue light, the mean diameter of new GBM, recurrent GBM, ODG and MET was 2.9 cm, 3 cm, 1.5 cm and 2.3 cm respectively. The results of quantitative measurements of fluorescence ratios revealed that red fluorescence corresponded to 5.9-11.6 (solid tumour on histology), and pink fluorescence measured 0.8-1.9 (infiltrating edge of tumour on histology). When we compared the maximum tumour diameter of GBM we found on average it was 10mm wider on spectroscopy compared to standard white light microscopy and 6mm wider than what the enhanced MRI demonstrated. CONCLUSIONS: Fluorescence technology revealed that GBMs are wider than the enhanced MRI had demonstrated, while MET enhanced MRI was similar in size to fluorescence. Furthermore, solid tumour can be identified intraoperatively and can be measured using fluorescence and spectroscopy techniques and it can be removed safely. Infiltrating tumour can also be identified intraoperatively using this technology and can be removed in non-eloquent areas to maximise surgical resection.

Risk factors for developing oral 5-aminolevulinic acid-induced side effects in patients undergoing fluorescence guided resection.

Oral 5 aminolevulinic acid (5-ALA) is used to assist surgical resection of malignant tumours in the brain and other locations. Hypotension and alteration of liver functions have been reported as potential adverse effects. This study was designed to assess the incidence and contributing factors that cause 5-ALA induced side effects in a cohort of 90 patients. Hypotension occurred in 11% of patients irrespective of 5-ALA dose. The only contributing factor was the presence of cardiovascular disease and antihypertensive drug therapy with an odd ratio of 17.7. Liver function were disturbed in 2% in patients who received 20mg or less/kg body weight compared to 4% in those who received a dose of >20mg/kg 5-ALA. The liver dysfunction was minor and was not clinically significant. We concluded that 5-ALA induced side effects were minimal and hypotension more likely to occur in patients receiving antihypertensive drug therapy.

Herpes simplex encephalitis following microvascular decompression for trigeminal neuralgia.

The authors present the first reported case of herpes simplex encephalitis (HSE) precipitated by trigeminal nerve microvascular decompression (MVD). The presentation of this specific case together with the pathogenesis and management of HSE are discussed, with a relevant literature review. This 29-year-old woman with treatment-resistant trigeminal neuralgia underwent a successful elective MVD of the right trigeminal nerve. She was discharged but was readmitted 1 week postoperatively with clinical signs and symptoms of meningitis. A CSF sample was obtained through lumbar puncture before she was treated initially with ceftriaxone. The polymerase chain reaction test of CSF was later positive for herpes simplex virus Type 1, at which point the patient was switched to a 2-week course of intravenous acyclovir before being discharged. Although this disease is rare, to avoid a delay in antiviral treatment the authors suggest that HSE should be considered in any patient presenting with a meningoencephalitic picture following MVD.

Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme.

OBJECT: Glioblastoma multiforme (GBM) is the most common astrocytic brain tumor and carries a dire prognosis. Despite current therapeutic options--surgery, radiotherapy, and chemotherapy--survival varies from 11.3 to 14.6 months. A group of drugs known as histone deacetylase inhibitors (HDIs) has demonstrated a potentially beneficial role in cancer treatment, particularly in combination with other therapies. A drug that exhibits potential as an HDI is sodium valproate (VPA), which is frequently used to treat seizures in patients with cerebral neoplasms. The present study was undertaken to investigate the role of VPA as an antitumor agent in the management of patients with GBM. METHODS: A review was conducted in terms of how HDIs work, the use of antiepileptic drugs (AEDs), and the effects of AEDs on survival in a local cohort of patients diagnosed with GBM. The local cohort of patients was determined by reviewing the electronic histopathology and AED informatics systems. A meta-analysis of papers on the use of AEDs in GBM was also performed. RESULTS: The local cohort consisted of 236 patients with GBM, 210 of whom had complete data available for analysis, a median age of 62 years, and 1-year survival of 26%. Patients treated with AEDs had a significantly longer survival than those who were not (Mantel-Cox log-rank test 19.617, p < 0.001). Those treated with VPA had significantly longer survival than those who did not receive an AED (Mantel-Cox log-rank test 17.506, p < 0.001), and patients treated with VPA had a significantly longer survival than those who had received other AEDs (Mantel-Cox log-rank test 5.303, p < 0.02). CONCLUSIONS: Authors of this study demonstrated evidence supporting the theory that VPA may benefit patients with GBM in terms of survival.

Strategies for the return of behavioral surgery.

BACKGROUND: Behavioral surgery (BS) is resurging because of unmet clinical need, advances in basic sciences, neuroimaging, neurostimulation, and stereotaxy. However, there is a danger that BS will fall unless acceptable strategies are adopted by BS providers. METHODS: A critical review of conditions leading to rise of psychosurgery (PS) and concerns resulting in its fall was conducted to learn lessons and safeguard BS of the future. RESULTS: PS rose and spread in 1960 like wildfire without adequate preclinical and clinical studies. Hundreds of patients had PS without adequate preoperative diagnosis or assessment, proper consent, and non-objective reporting of outcome. Furthermore, there was public opposition against PS because of its potential abuse to control violent behavior and dissidents. Advances in neurostimulation, neuroimaging, and stereotaxy, and emergence of treatment-resistant mental disorders led to increased interest in BS. Several recent studies have shown BS to be safe and effective. However, concerns related to strength of evidence, safety, efficacy, consent, and objectivity of studies have been raised. Unless clinical and regulatory governance structures are adopted in each jurisdiction, BS will face the same fate as that of PS in the past. CONCLUSION: THE FUTURE OF BS AS A SAFE AND EFFECTIVE THERAPY IS DEPENDENT UPON ADOPTING CLEAR MORAL ETHICAL AND GOVERNANCE STANDARDS ON THE FOLLOWING LINES: Patients must have failed adequate therapies; must be assessed by psychiatrist-led multidisciplinary teams; patients' abilities to give consent and diagnosis must be verified by independent authorities designated for this purpose by the state; and the independent authority must also decide whether the teams were adequately trained to perform BS.