Sam Eljamel

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 patients 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.

Photodynamic applications in brain tumors: a comprehensive review of the literature.

INTRODUCTION GBM is the comment glioma. GBM-outcome had not changed much over two decades despite leaps in medical technology. Fewer than 25% survive 2 years. There is no jacket that fits all GBMs. This paper reviews the evidence for PDT in GBMs. RATIONALE Maximum safe resection is supported by level-II evidence. PDT-technology (PDTT) provides means to maximize safe resection. PDTT paints GBM red in contrast to brain because of selective uptake and retention of photosensitizers. Exposure to specific light wave produces cytotoxic singlet oxygen. PDT-APPLICATIONS: (1) Fluorescence image guided biopsy to sample high grade components of what looks like low grade glioma on MRI, 89% sensitive. (2) Fluorescence image guided surgery for maximum safe surgical resection is >84% sensitive, achieves complete resection in >65% and prolongs tumor free survival (1 observational and 2 RCT, p < 0.001). (3) Photodynamic treatment supported by several observational studies with combined total of >1000 patients and 3 RCT used PDT in GBMs. PDT was highly selective, safe, significantly improved good quality survival, and delayed tumor relapse (p < 0.001). SAFETY PDT had a very high safety track record, thromboembolism 2%, brain-oedema 1.3%, and skin photosensitivity complications 1-3%. CONCLUSION PDT in GBMs is safe, selective, and sensitive and leads to significant prolongation of good quality survival, delay in tumor relapse and significant reduction of further interventions. It would be impractical, impossible and probably unethical to randomize patients between PDT and placebo, in the same way it would be unethical to carry out a RCT to prove that the parachute saves lives.

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.

Cost-utility analysis of vagus nerve stimulators for adults with medically refractory epilepsy

INTRODUCTION The cost-utility of vagus nerve stimulator (VNS) devices for medically refractory epilepsy has yet to be estimated. METHODS Using a meta-analysis of randomised controlled trials of VNS, we estimate that six people require implantation in order for one person to experience a 50% reduction in seizure frequency. Costs averted from improved epilepsy control were ascertained from published literature. Values for health states were obtained from a series of 42 seizure clinic attenders using time trade-off techniques and the EQ-5D health status instrument. The cost per quality adjusted life year gained was estimated and the values obtained were tested in a sensitivity analysis. RESULTS Improved epilepsy control averted, on average, 745 pounds sterling health care costs per annum. People with epilepsy had great difficulty performing the time trade-off experiment, but those who managed to complete the task valued a 50% reduction in their own seizure frequency at 0.285 units. For a programme of six implants, the baseline model estimated the cost per quality adjusted life year gained at 28,849 pounds sterling. The most favourable estimate was equal to 4785 pounds sterling per quality adjusted life year gained, assuming that the number needed to treat was similar to published series in which one response was obtained for every three implants. The least favourable estimate was equal to 63,000 pounds sterling per quality adjusted life year gained, when EQ-5D utility values were used. The cost per quality adjusted life year gained was not sensitive to changes in length of stay, nor complication rates, but was significantly influenced by cost of device and device battery life expectancy. CONCLUSION There is not a strong economic argument against a programme of VNS implantation, although care should be taken to try and identify and treat those most likely to benefit.

Risk factors for developing oral 5-aminolevulenic 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.

Evaluation of a neurosurgical robotic system to make accurate burr holes

Neurosurgery has been driven forward by the latest breakthroughs in technology that combine science and engineering. Neurosurgical robotic systems are a good example of such a breakthrough that has several potential advantages over existing techniques. This study sought to evaluate the Pathfinder robotic system in order to establish whether it is capable of carrying out burr hole procedures in specific locations in human skull replicas, along predetermined trajectories and for precise depths.

The effects of PDT in primary malignant brain tumours could be improved by intraoperative radiotherapy

INTRODUCTION GBM has a poor survival despite surgery and chemoradiotherapy. Cytoreduction and PDT have postulated to afford better local GBM-control. However, the interaction of PDT with newer novel therapies had not been fully investigated. This study reviewed the impact of PDT in conjunction with intraoperative radiotherapy. METHODS Case note review of prospectively collected data of GBMs treated surgically by the senior author (SE). Patients received standard therapy (ST), ST+PDT or ST+PDT+IORT. ST involved maximum safe resection, PDT involved intracavity 100 J/cm² 630 nm laser and IORT involved intracavity 10-15 Gys using the PRS400®. Patients were followed up clinically and radiologically till death. RESULTS There were 73 patients included in this analysis (42 males). The average age was 59years. Thirty received PDT and 43 did not. The mean survival of PDT-patients was significantly longer than those had ST alone (62.9 weeks vs. 20.6 weeks) (p=0.001). Patients < 65 year of age survived longer than those ≥ 65 year (p=0.033). IORT on its own did not make a significant difference to survival (p=0.111). However the average survival for patients who received PDT+IORT was substantially higher than those who received PDT alone (79 weeks vs. 39.7 weeks). Using a Cox regression covariant analysis, demonstrated that PDT was the only therapy to make a statistically significant difference to survival (p=0.018). CONCLUSIONS PDT in high grade glioma was statistically significant therapeutic modality and its effects were further improved by IORT.

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

Abstract 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®.

Prediction of Implantable Pulse Generator Longevity in Deep Brain Stimulation: Limitations and Possible Solutions in Clinical Practice

Background: Deep brain stimulation (DBS) is used in the treatment of movement disorders, chronic pain and certain neuropsychiatric conditions. Its effect is achieved through local stimulation of specific targets of the brain. Electrical pulses are delivered at settings that can be tailored to provide optimum symptom control. DBS is powered by an implantable pulse generator (IPG). These IPGs do not have an indefinite lifespan and will eventually become depleted. Therefore, regular checks are carried out to monitor the IPG’s power status. Objective: To evaluate the utility of computer-based prediction of IPG longevity in patients with DBS devices by imputing the device’s settings. Patients: Eighty-two IPGs in 47 consecutive patients were studied comparing the actual longevity of the IPGs with their predicted longevity using a computer-based calculator. Results: Our study showed that the predicted longevities were too different from actual longevities to have a role in clinical practice. The time difference varied by more than 12 months in some cases, with a correlation coefficient of <0.68. There were multiple reasons for this. Conclusion: The longevities of IPGs could not be predicted accurately enough for the computer-based calculator to have a role in clinical practice or the proactive scheduling of IPG replacement. However, rechargeable IPGs may help avoid premature replacements and battery depletions.

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.