BACKGROUND Awake craniotomy (AC) is performed for the resection of brain tumours in close proximity to areas of eloquent brain function to maximize reduction of tumour mass and minimize neurological injury. This study compares the efficacy and safety of dexmedetomidine vs propofol-remifentanil-based conscious sedation, during AC for supratentorial tumour resection. METHODS Prospective, randomized, controlled trial including 50 adult patients undergoing AC who were randomly assigned to a dexmedetomidine (DEX group, n=25) or propofol-remifentanil group (P-R group, n=25). The primary outcome was the ability to perform intraoperative brain mapping assessed on a numeric rating scale (NRS). Secondary outcome was the efficacy of sedation measured by the modified Observer's Assessment of Alertness/Sedation (OAA/S) scale. Other outcome measures including haemodynamic and respiratory variables, pain, sedation and anxiety scores, adverse events, and patient satisfaction were also compared. RESULTS There were no differences between DEX and P-R groups regarding the ability to perform intraoperative brain mapping [mean NRS score (95% CI): 10.0 (9.9-10.0) vs 9.7 (9.5-10.0), P=0.13] and level of sedation during mapping [mean OAA/S score (95% CI): 4.1 (3.5-4.7) vs 4.3 (3.9-4.7), P=0.51], respectively. Respiratory adverse events were more frequent in the P-R group (20 vs 0%, P=0.021). Heart rate was significantly lower in the DEX group across time (P<0.001); however, the need for treatment of bradycardia was not different between groups. CONCLUSIONS Quality of intraoperative brain mapping and efficacy of sedation with dexmedetomidine were similar to propofol-remifentanil during AC for supratentorial tumour resection. Dexmedetomidine was associated with fewer respiratory adverse events. CLINICAL TRIAL REGISTRATION NCT01545297.

L’acide folique (vitamine B9) est une vitamine hydrosoluble du groupe B. On le trouve dans les aliments sous forme de folate et dans les supplements sous forme d’acide folique, dont la biodisponibilite est plus importante. Le folate joue un role essentiel dans la synthese et la reparation de l’ADN, ainsi que dans la croissance et la division cellulaires. Il contribue egalement a la methylation de l’ADN et est donc important pour la regulation epigenomique.

Periconceptional folic acid significantly reduces the risk of neural tube defects. It is difficult to achieve optimal levels of folate by diet alone, even with fortification of flour, especially because flour consumption in Canada is slightly decreasing. Intermittent concerns have been raised concerning possible deleterious effects of folate supplementation, including the masking of symptoms of vitamin B-12 deficiency and an association with cancer, especially colorectal cancer. Both concerns have been disproved. The Canadian Paediatric Society endorses the following steps to enhance folate intake in women of child-bearing age: encouraging the consumption of folate-rich foods such as leafy vegetables, increasing the level of folate food fortification, taking a supplement containing folate and B-12, and providing free folate supplementation to disadvantaged women of child-bearing age. These recommendations are consistent with those of the Society of Obstetricians and Gynaecologists of Canada.

PURPOSE AND METHODS Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent. RESULTS AND CONCLUSION Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. The application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children.

The authors review the cases of 60 children (aged 5 months to 18 years) with thalamic tumors who were seen at The Hospital for Sick Children between 1951 and 1983. The diagnosis of thalamic tumor was based on neuroradiological studies; 33 children were first seen in the pre-computerized tomography (CT) era and 27 since the advent of CT scanning. Histological diagnosis was obtained in 37 patients at the time of operation. A further four tumors were verified histologically at autopsy. Thirty-six patients required cerebrospinal fluid shunt placement. Sixteen patients had no surgery on their tumor, three underwent needle biopsy, 20 underwent open biopsy, and 21 had partial resection. Forty-four patients were irradiated. All 20 patients with malignant tumors died, with a mean survival time of 1.1 years. Of 19 patients with benign tumors, 11 died, with a mean survival time of 5.3 years, and eight are still alive after a mean period of 7.2 years since diagnosis. Based on this series, the authors recommend open biopsy of thalamic tumors (and resection if deemed safe), followed by radiation in selected cases.

The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation.