Therapeutic Hypothermia Compared with Normothermia in Adults with Traumatic Brain Injury; Functional Outcome, Mortality, and Adverse Effects: A Systematic Review and Meta-Analysis.

BACKGROUND: The main focus of traumatic brain injury (TBI) management is prevention of secondary injury. Therapeutic hypothermia (TH), the induction of a targeted low core body temperature, has been explored as a potential neuroprotectant in TBI. The aim of this article is to synthesize the available clinical data comparing the use of TH with the use of normothermia in TBI. METHODS: A systematic search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized clinical trials including one or more outcome of interest associated with TH use in TBI. Independent reviewers evaluated quality of the studies and extracted data on patients with TBI undergoing TH treatment compared with those undergoing normothermia treatment. Pooled estimates, confidence intervals (CIs), and risk ratios (RRs) or odds ratios were calculated for all outcomes. RESULTS: A total of 3,909 patients from 32 studies were eligible for analysis. Pooled analysis revealed a significant benefit of TH on mortality and functional outcome (RR 0.81, 95% CI 0.68-0.96, I2 = 41%; and RR 0.77; 95% CI 0.67-0.88, I2 = 68%, respectively). However, subgroup analysis based on risk of bias showed that only studies with a high risk of bias maintained this benefit. When divided by cooling method, reduced poor functional outcome was seen in the systemic surface cooling and cranial cooling groups (RR 0.68, 95% CI 0.59-0.79, I2 = 35%; and RR 0.44, 95% CI 0.29-0.67, I2 = 0%), and no difference was seen for the systemic intravenous or gastric cooling group. Reduced mortality was only seen in the systemic surface cooling group (RR 0.63, 95% CI 0.53-0.75, I2 = 0%,); however, this group had mostly high risk of bias studies. TH had an increased rate of pneumonia (RR 1.24, 95% CI 1.10-1.40, I2 = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09-2.44, I2 = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05-3.01, I2 = 21%). Once separated by low and high risk of bias, we saw no difference in these complications in the groups with low risk of bias. Overall quality of the evidence was moderate for mortality, functional outcome, and pneumonia and was low for coagulation abnormalities and cardiac arrhythmias. CONCLUSIONS: With the addition of several recent randomized clinical trials and a thorough quality assessment, we have provided an updated systematic review and meta-analysis that concludes that TH does not show any benefit over normothermia in terms of mortality and functional outcome.

Beta blockers in traumatic brain injury: a systematic review and meta-analysis.

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Beta blockers have shown promise in improving mortality and functional outcomes after TBI. The aim of this article is to synthesize the available clinical data on the use of beta blockers in acute TBI. Methods: A systematic search was conducted through MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for studies including one or more outcomes of interest associated with use of beta blockers in TBI. Independent reviewers evaluated the quality of the studies and extracted data on all patients receiving beta blockers during their hospital stay compared with placebo or non-intervention. Pooled estimates, CIs, and risk ratios (RRs) or ORs were calculated for all outcomes. Results: 13 244 patients from 17 studies were eligible for analysis. Pooled analysis demonstrated a significant mortality benefit of overall use of beta blocker (RR 0.8, 95% CI 0.68 to 0.94, I 2=75%). Subgroup analysis of patients with no preinjury use of beta blocker compared with patients on preinjury beta blockers showed no mortality difference (RR 0.99, 95% CI 0.7 to 1.39, I 2=84%). There was no difference in rate of good functional outcome at hospital discharge (OR 0.94, 95% CI 0.56 to 1.58, I 2=65%); however, there was a functional benefit at longer-term follow-up (OR 1.75, 95% CI 1.09 to 2.8, I 2=0%). Cardiopulmonary and infectious complications were more likely in patients who received beta blockers (RR 1.94, 95% CI 1.69 to 2.24, I 2=0%; RR 2.36, 95% CI 1.42 to 3.91, I 2=88%). Overall quality of the evidence was very low. Conclusions: Use of beta blockers is associated with decreased mortality at acute care discharge as well as improved functional outcome at long-term follow-up. Lack of high-quality evidence limits definitive recommendations for use of beta blockers in TBI; therefore, high-quality randomized trials are needed to further elucidate the utility of beta blockers in TBI. PROSPERO registration number: CRD42021279700.

A Canadian National Survey of the Neurosurgical Management of Intracranial Abscesses.

OBJECTIVE: Intracerebral abscess is a life-threatening condition for which there are no current, widely accepted neurosurgical management guidelines. The purpose of this study was to investigate Canadian practice patterns for the medical and surgical management of primary, recurrent, and multiple intracerebral abscesses. METHODS: A self-administered, cross-sectional, electronic survey was distributed to active staff and resident members of the Canadian Neurosurgical Society and Canadian Neurosurgery Research Collaborative. Responses between subgroups were analyzed using the Chi-square test. RESULTS: In total, 101 respondents (57.7%) completed the survey. The majority (60.0%) were staff neurosurgeons working in an academic, adult care setting (80%). We identified a consensus that abscesses >2.5 cm in diameter should be considered for surgical intervention. The majority of respondents were in favor of excising an intracerebral abscess over performing aspiration if located superficially in non-eloquent cortex (60.4%), located in the posterior fossa (65.4%), or causing mass effect leading to herniation (75.3%). The majority of respondents were in favor of reoperation for recurrent abscesses if measuring greater than 2.5 cm, associated with progressive neurological deterioration, the index operation was an aspiration and did not include resection of the abscess capsule, and if the recurrence occurred despite prior surgery combined with maximal antibiotic therapy. There was no consensus on the use of topical intraoperative antibiotics. CONCLUSION: This survey demonstrated heterogeneity in the medical and surgical management of primary, recurrent, and multiple brain abscesses among Canadian neurosurgery attending staff and residents.

Anxiety and depression in patients with intracranial meningioma: a mixed methods analysis.

BACKGROUND: While diagnosis with a high-grade intracranial tumor is known to be associated with increased psychosocial burden, the burdens associated with meningioma are less well described. This study aimed to investigate the mental health burden in patients with meningiomas who have undergone surgical resection or serial observation, so as to identify and enhance awareness of gaps in care. METHODS: The Hospital Anxiety and Depression Scale (HADS) was administered to participants. Fisher's Exact tests were performed to evaluate frequency distributions and t-tests were applied to compare postoperative and non-surgical patients' HADS scores. Semi-structured interviews were completed on a subset of participants. Thematic analysis of interviews identified emerging themes. RESULTS: Thirty patients with intracranial meningiomas met inclusion criteria. The cohort's mean age was 56.01 years and 66.67% were women (n = 20). Fourteen underwent surgery; sixteen were treated conservatively with observation. The average time since diagnosis of the sample was 37.6 months. Prevalence of mild to severe symptoms of anxiety was 28.6% amongst surgical management patients and 50% for active surveillance patients (p = 0.325). The prevalence of mild to severe symptoms of depression was 7.14% amongst surgical management patients and 6.25% for active surveillance patients (p = 0.533). Emerging themes from eight interviews reveal the influence of resilience, uncertainty and time, social support, interactions with medical experts, and difficulties during recovery on mental health. CONCLUSION: The findings from the present study reveal that patients with meningiomas experience a significant mental health burden, illustrating the need for enhanced patient-centred care focusing on mental health.

Quality of life and satisfaction in surgical versus conservative treatment of nonsyndromic children with craniosynostosis.

OBJECTIVE: Craniosynostosis represents the second most common reason for referral to pediatric neurosurgery. However, the quality of life and neurodevelopmental impact of leaving this physical disorder uncorrected is poorly understood. METHODS: This multicenter cross-sectional study identified previously managed nonsyndromic infants (< 24 months of age) with single-suture craniosynostosis at both pediatric neurosurgical centers in Alberta, Canada. The primary variable of interest was the allocated treatment (surgical vs conservative). The primary outcome was the Pediatric Quality of Life Inventory (PedsQL), a validated measure of quality of life examining physical, emotional, social, and school functioning. Treatment decision satisfaction and the reasons for selected management were quantified and collected directly from caregivers. RESULTS: One hundred fourteen children met the inclusion criteria: 78% underwent surgery and 22% had conservative treatment. The most common suture affected was sagittal (54%), followed by metopic (33%), coronal (10%), and lambdoid (3%). Caregivers most commonly opted for surgery because of severe appearance (80%). Seventy-six percent and 72% of the caregivers of children with conservative management did so due to concerns of surgical risks and mild appearance, respectively. There was a statistically significant relationship between both the parents' (p < 0.001) and the surgeon's (p = 0.001) impression of a severe head shape and surgical management. Parental satisfaction with their child's appearance as well as satisfaction with their treatment decision did not differ between management types. Regarding quality of life, on univariate analysis, the conservative group had a statistically higher physical summary score (p = 0.01), psychosocial summary score (p = 0.004), and mean total scale score (p = 0.003) compared to the surgical group. However, after adjusting for severity and age at consult, no significant independent associations between management type and any of the PedsQL summary scores were found. CONCLUSIONS: Alberta families have a high number of children with craniosynostosis treated with conservative management. Conservatively managed infants were largely minimally affected patients, particularly those with metopic synostosis. The study found no independent association between management type (surgery vs conservative) and quality of life when adjusted for important patient factors.

Late recurrence of choroid plexus carcinoma.

BACKGROUND: Choroid plexus carcinomas (CPC) are rare malignant brain tumours arising from the choroid plexus epithelium. CPC are most common in the paediatric population, particularly those under 2 years of age. Common presentations include headache, diplopia and signs of increased intracranial pressure such as nausea and vomiting. Infants may present with increased head circumference, bulging fontanelles, splayed cranial sutures and/or neurological delay. Diagnosis is made via radiological and histological analysis. MANAGEMENT AND PROGNOSIS: Gross total resection (GTR) is the preferred treatment and infers the best survival rate, but despite this, prognosis remains poor. The utility of chemotherapy and/or radiation in CPC management remains controversial, and an optimal treatment regimen has not been identified. Even with GTR, recurrence is common and usually occurs within months after resection. Delayed recurrence is exquisitely rare and has been reported very few times to date. CASE PRESENTATION: Here, we present a rare case of delayed CPC recurrence 10 years after initial presentation. A 2-month-old male was diagnosed with CPC and received GTR, chemotherapy and stem cell transplant. The patient presented with a recurrent CPC 10 years after the initial diagnosis. CONCLUSIONS: This case demonstrates the importance of long-term surveillance and raises questions regarding the natural history, recurrence patterns and factors contributing to long-term relapse in CPC. Further research should be targeted at identifying patient factors contributing to increased risk of late recurrence and whether adjuvant treatments play any role in decreasing this.

Pharmacological characterization of a high-affinity p-tyramine transporter in rat brain synaptosomes.

p-Tyramine is an archetypal member of the endogenous family of monoamines known as trace amines, and is one of the endogenous agonists for trace amine-associated receptor (TAAR)1. While much work has focused on the function of TAAR1, very little is known about the regulation of the endogenous agonists. We have previously reported that p-tyramine readily crosses lipid bilayers and that its release from synaptosomes is non-exocytotic. Such release, however, showed characteristics of modification by one or more transporters. Here we provide the first characterization of such a transporter. Using frontal cortical and striatal synaptosomes we show that p-tyramine passage across synaptosome membranes is not modified by selective inhibition of either the dopamine, noradrenaline or 5-HT transporters. In contrast, inhibition of uptake-2 transporters significantly slowed p-tyramine re-uptake. Using inhibitors of varying selectivity, we identify Organic Cation Transporter 2 (OCT2; SLC22A2) as mediating high affinity uptake of p-tyramine at physiologically relevant concentrations. Further, we confirm the presence of OCT2 protein in synaptosomes. These results provide the first identification of a high affinity neuronal transporter for p-tyramine, and also confirm the recently described localization of OCT2 in pre-synaptic terminals.