Identification of clinically relevant patient endotypes in traumatic brain injury using latent class analysis.

Traumatic brain injury (TBI) is a complex condition where heterogeneity impedes the advancement of care. Understanding the diverse presentations of TBI is crucial for personalized medicine. Our study aimed to identify clinically relevant patient endotypes in TBI using latent class analysis based on comorbidity data. We used the Medical Information Mart for Intensive Care III database, which includes 2,629 adult TBI patients. We identified five stable endotypes characterized by specific comorbidity profiles: Heart Failure and Arrhythmia, Healthy, Renal Failure with Hypertension, Alcohol Abuse, and Hypertension. Each endotype had distinct clinical characteristics and outcomes: The Heart Failure and Arrhythmia endotype had lower survival rates than the Renal Failure with Hypertension despite featuring fewer comorbidities overall. Patients in the Hypertension endotype had higher rates of neurosurgical intervention but shorter stays in contrast to the Alcohol Abuse endotype which had lower rates of neurosurgical intervention but significantly longer hospital stays. Both endotypes had high overall survival rates comparable to the Healthy endotype. Logistic regression models showed that endotypes improved the predictability of survival compared to individual comorbidities alone. This study validates clinical endotypes as an approach to addressing heterogeneity in TBI and demonstrates the potential of this methodology in other complex conditions.

Economic Evaluations Comparing Deep Brain Stimulation to Best Medical Therapy for Movement Disorders: A Meta-Analysis.

BACKGROUND: Movement disorders (Parkinson's disease, essential tremor, primary dystonia) are a debilitating group of conditions that are progressive in nature. The mainstay of treatment is best medical therapy; however, a number of surgical therapies are available, including deep brain stimulation. Economic evaluations are an important aspect of evidence to inform decision makers regarding funding allocated to these therapies. OBJECTIVE: This systematic review and meta-analysis evaluated the cost effectiveness of including deep brain stimulation compared with best medical therapy for movement disorder indications in the adult population. METHODS: Ovid Medical Literature Analysis and Retrieval System Online, Embase, and Cochrane Central Register of Controlled Trials were queried. Only economic evaluations reporting incremental cost-effectiveness ratios for including deep brain stimulation versus best medical therapy for movement disorders were included. Studies were reviewed in duplicate for inclusion and data abstraction. Data were harmonized using the Consumer Price Index and Purchasing Power Parity to standardize values to 2022 US dollars. For inclusion in meta-analyses, studies were required to have sufficient data available to calculate an estimate of the incremental net benefit. Meta-analyses of pooled incremental net benefit based on the time horizon were performed. The study was registered at PROSPERO (CRD42022335436). RESULTS: There were 2190 studies reviewed, with 14 economic evaluations included following a title/abstract and full-text review. Only studies considering Parkinson's disease were available for the meta-analysis. Quality of the identified studies was low, with moderate transferability to the American Healthcare System, and certainty of evidence was low. However, studies with a longer time horizon (15 years to lifetime) were found to have significant positive incremental net benefit (indicating cost effectiveness) for including deep brain stimulation with a mean difference of US$40,504.81 (95% confidence interval 2422.42-78,587.19). CONCLUSIONS: Deep brain stimulation was cost effective for Parkinson's disease when considered over the course of the patient's remaining life after implantation. TRIAL REGISTRATION: Clinical Trial Registration: PROSPERO (CRD42022335436).

Intracranial hemorrhage in patients treated for SARS-CoV-2 with extracorporeal membrane oxygenation: A systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is routinely used in patients with severe respiratory failure and has been increasingly needed during the COVID-19 pandemic. In patients treated with ECMO, significant intracranial hemorrhage (ICH) risk exists due to circuit characteristics, anticoagulation, and disease characteristics. ICH risk may be substantially higher in COVID-19 patients than patients treated with ECMO for other indications. METHODS: We systematically reviewed current literature regarding ICH during ECMO treatment of COVID-19. We utilized Embase, MEDLINE, and Cochrane Library databases. Meta-analysis was performed for included comparative studies. Quality assessment was performed using MINORS criteria. RESULTS: A total of 54 studies with 4000 ECMO patients were included, all retrospective. Risk of bias was increased via MINORS score primarily due to retrospective designs. ICH was more likely in COVID-19 patients (RR 1.72, 95% CI 1.23, 2.42). Mortality among COVID patients on ECMO with ICH was 64.0%, compared with 41% in patients without ICH (RR1.9, 95% 1.44, 2.51). CONCLUSION: This study suggests increased hemorrhage rates in COVID-19 patients on ECMO compared to similar controls. Hemorrhage reduction strategies may include atypical anticoagulants, conservative anticoagulation strategies, or biotechnology advances in circuit design and surface coatings.

Systematic Review and Meta-Analysis of Randomized Controlled Trials for Scalp Block in Craniotomy.

BACKGROUND: Scalp block is regional anesthetic injection along nerves innervating the cranium. Scalp blocks for craniotomy may decrease postoperative pain and opioid consumption. Benefits may extend beyond the anesthetic period. OBJECTIVE: To analyze evidence for scalp block on postoperative pain and opioid use. METHODS: This systematic review and meta-analysis, Prospective Register of Systematic Reviews registration (CRD42022308048), included Ovid Medical Literature Analysis and Retrieval System Online, Embase, and Cochrane Central Register of Controlled Trials inception through February 9, 2022. Only randomized controlled trials were included. We excluded studies not reporting either main outcome. Duplicate reviewers performed study selection, risk of bias assessment, data extraction, and evidence certainty Grading of Recommendations Assessment, Development, and Evaluation appraisal. Main outcomes were postoperative pain by visual analog scale within 72 hours and opioid consumption as morphine milligram equivalent (MME) within 48 hours. RESULTS: Screening filtered 955 studies to 23 trials containing 1532 patients. Risk of bias was overall low. Scalp block reduced postoperative pain at 2 through 72 hours, visual analog scale mean differences of 0.79 to 1.40. Opioid requirements were reduced at 24 hours by 16.52 MME and 48 hours by 15.63 MME. CONCLUSION: Scalp block reduces postoperative pain at 2 through 48 hours and may reduce pain at 72 hours. Scalp block likely reduces opioid consumption within 24 hours and may reduce opioid consumption to 48 hours. The clinical utility of these differences should be interpreted within the context of modest absolute reductions, overall care optimization, and patient populations. This is the first level 1A evidence to evaluate scalp block efficacy in craniotomy.

Subarachnoid Hemorrhage, Delayed Cerebral Ischemia, and Milrinone Use in Canada.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data. The objective of this study was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI. METHODS: We performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. A 19-question electronic survey (Survey Monkey) was developed and validated by the CNRC following a DCI-related literature review (PubMed, Embase). The survey was distributed to members of the Canadian Neurosurgical Society and to Canadian members of the Neurocritical Care Society. Responses were analyzed using quantitative and qualitative methods. RESULTS: The response rate was 129/340 (38%). Agreement among respondents was limited to the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for the prevention of DCI. Several inconsistencies were identified. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients who felt to require IV milrinone, IA vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI. CONCLUSION: DCI is an important clinical entity for which no homogeneity and standardization exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the definition, identification, and treatment of DCI.

Work-up and Management of Asymptomatic Extracranial Traumatic Vertebral Artery Injury.

BACKGROUND: Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1-2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains. METHODS: A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics. RESULTS: One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3-6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1-3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3-6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1-3 months. CONCLUSION: This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.

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.

Retrospective Review of the Clinical Outcomes of Surgically Managed Patients with Intracranial Abscesses: A Single-Center Review.

OBJECTIVE: This study analyzed patient, radiologic, and clinical factors associated with operative brain abscesses and patients' functional outcomes. METHODS: A retrospective analysis was conducted of neurosurgical cases of brain abscesses from 2009 to 2019 at a Canadian center. Functional outcome was recorded as Modified Rankin Scale score and Extended Glasgow Outcome Scale score. Multivariate analysis was conducted to identify relevant prognostic factors. RESULTS: We identified 139 patients managed surgically for brain abscesses. Resection alone was performed in 64% of patients, whereas 26.6% underwent aspiration alone. Most were adults (93.2%) and male (68.3%). Immunocompromise risk factors included diabetes (24.5%), cancer (23.7%), and immunosuppressive therapy (11.5%). Likely sources were postoperative (17.3%), systemic spread (16.5%), and poor dentition (12.9%). Microorganisms cultured from abscess samples were mixed growth (28%), Streptococcus anginosus (24.5%), and Staphylococcus aureus (7.9%). Disposition was home (42.4%) or repatriation to a home hospital (50.4%). By Extended Glasgow Outcome Scale, 25.2% had an unfavorable outcome including a mortality of 11.5%. Factors on multivariate analysis associated with poor outcome included diabetes (odds ratio, 2.8; 95% confidence interval [CI], 1.2-5.0) and ventricular rupture (odds ratio, 5.0; 95% CI, 1.7-13.5; hazard ratio, 12; 95% CI, 3.9-37.0). Supratentorial superficial eloquently located abscess was also associated with poor outcome (hazard ratio, 5.5; 95% CI, 1.8-16.7). Outcomes were similar with surgical excision and aspiration. CONCLUSIONS: Ventricular rupture and diabetes are significant risk factors for poor outcomes in intraparenchymal brain abscesses. No clear difference in outcomes was found between surgical excision or aspiration in our retrospective cohort.

Pediatric craniocerebral gunshot injuries: A National Trauma Database study.

BACKGROUND: We aimed to determine the outcomes and prognostic factors in pediatric craniocerebral gunshot injury (CGI) patients. Pediatric patients may have significantly different physiology, neuroplasticity, and clinical outcomes in CGI than adults. There is limited literature on this topic, mainly case reports and small case series. METHODS: We queried the National Trauma Data Bank for all pediatric CGI between 2014 and 2017. Patients were identified using International Classification of Diseases, Ninth Revision, codes. Demographic, emergency department, and clinical data were analyzed. Subgroup analysis was attempted for groups with Glasgow Coma Scale (GCS) scores of 9 to 15 and ages 0 to 8 years. RESULTS: In a 3-year period, there were 209 pediatric patients (aged 0-18 years) presenting to American hospitals with signs of life. The overall mortality rate was 53.11%. A linear relationship was demonstrated showing a mortality rate of 79% by initial GCS in GCS score of 3, 56% in GCS scores of 4 to 8, 22% in GCS scores of 9 to 12, and 5% in GCS scores of 13 to 15. The youngest patients, aged 0 to 8 years, had dramatically better initial GCS and subsequently lower mortality rates. Regression analysis showed mortality benefit in the total population for intracranial pressure monitoring (odds ratio, 0.267) and craniotomy (odds ratio, 0.232). CONCLUSION: This study uses the National Trauma Data Bank to quantify the prevalence of pediatric intracranial gunshot wounds, with the goal to determine risk factors for prognosis in this patient population. Significant effects on mortality for invasive interventions including intracranial pressure monitoring and craniotomy for all patients suggest low threshold for use of these procedures if there is any clinical concern. The presence of a 79% mortality rate in patients with GCS score of 3 on presentation suggests that as long as there is not a declared neurologic death, intracranial pressure monitoring and treatment measures including craniotomy should be considered by the consulting clinician. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Craniocerebral gunshot injury bullet migration to the cardiac right ventricle.

BACKGROUND: Missile embolism is the process of slow velocity projectiles penetrating into vascular spaces followed by arterial, venous, or paradoxical embolism of the fragments. This is a rare complication in craniocerebral gunshot injuries (CGI), with only five other cases previously published demonstrating pulmonary or arterial emboli from these injuries. There is a high rate of mortality from these injuries. CASE DESCRIPTION: A patient presented with a CGI from an occipital trajectory, causing penetrating fragments into the venous sinus system. The weapon was a Glock Model 17M 9 mm with a hollow-point bullet, fired close range. Initial chest X-ray demonstrated only atelectasis. After stabilization, 18 min from the initial chest X-ray, subsequent computed tomography (CT) imaging demonstrated extensive intracranial injuries and fragmentation of the bullet with the expected devastating intracranial injuries. Unexpectedly, chest CT revealed metallic fragments in the right cardiac ventricle which was redemonstrated on follow-up chest X-ray. Unfortunately, his extensive intracranial injuries and poor clinical status were nonsurvivable, and thus the family elected to discontinue supportive measures. CONCLUSION: This case demonstrates radiographic imaging of a metallic intravascular fragment from CGI through presumed transvenous mechanisms. The imaging provides a consistent timeline demonstrating migration can occur in the acute phase. This study additionally supports the presumed mechanism for pulmonary of migration through the right heart. Fragment embolization should be considered in cases of acute deterioration in this patient population.

Outcomes of civilian pediatric craniocerebral gunshot wounds: A systematic review.

BACKGROUND: Pediatric craniocerebral gunshot injuries (CGIs) occur both in the context of accidental and intentional trauma. The incidence and physiology of pediatric CGIs merit reexamination of prognostic factors and treatment priorities. This study characterizes the current understanding of mortality and prognostic factors in this patient population. METHODS: A systematic search was conducted. Selection criteria included all studies published since 2000, which described civilian isolated CGIs in pediatric patients. Data were analyzed qualitatively and quantitatively to identify factors prognostic for the primary outcome of mortality. Secondary outcomes included functional outcome status, requirement for surgery, and injury complications. Study quality was assessed with the Newcastle-Ottawa Scale. This study was registered with PROSPERO (CRD42019134231). RESULTS: Initial search revealed 349 unique studies. Forty underwent full text screening, and eight studies were included in the final synthesis. The overall mortality rate was 44.8%. Most CGIs occurred in older teenagers. Aggressive surgical treatment was recommended by one author, while remaining studies emphasized clinical judgment. Reported prognostic factors include initial Glasgow Coma Scale, pupil reactivity, involvement of multiple lobes or deep nuclei, and bihemispheric injuries. Reported complications from CGIs included seizure, meningitis, abscess, cerebrospinal fluid leak, bullet migration, focal neurological deficits, endocrine abnormalities, cognitive deficits, and neuropsychological deficits. The Glasgow Outcome Scale was the predominant measure of function and demonstrated a moderate recovery in 17.4% and a good recovery in 27.3% of patients. CONCLUSION: This systematic review analyzed the existing evidence for prognostic factors in the context of pediatric CGIs. Significant long-term clinical improvement is possible with interventions including urgent surgical therapy. Fixed bilateral pupils and low initial Glasgow Coma Scale correlate with mortality but do not predict all patient outcomes. Patients younger than 15 years are underreported and may have differences in outcome. The literature on pediatric CGIs is limited and requires further characterization. LEVEL OF EVIDENCE: Systematic Review, level IV.