Spinal cord untethering and midline myelotomy for delayed, symptomatic post-traumatic syringomyelia due to retained ballistic fragments: case report.

INTRODUCTION: Post-traumatic syringomyelia is an uncommon complication after traumatic spinal cord injury. This case study details our decision-making and surgical approach for a patient with symptomatic post-traumatic syringomyelia after sustaining a gunshot wound. CASE PRESENTATION: A 24-year-old man with past medical history of distant American Spinal Injury Association Impairment Grade B spinal cord injury due to ballistic injury developed delayed post-traumatic syringomyelia, resulting in unilateral sensory loss and left upper extremity weakness. CT and MR imaging revealed a syrinx spanning his cervical and thoracic spine causing significant spinal cord compression. To relieve achieve decompression and restore CSF flow dynamics, we performed a bony extradural decompression, bullet fragment extraction, spinal cord untethering, and midline myelotomy. Postoperatively, the patient demonstrated clinical and radiographical improvement. DISCUSSION: Post-traumatic syringomyelia is potentially morbid sequalae of spinal cord injuries. Suspicion for post-traumatic syringomyelia should be maintained in patients with delayed, progressive neurologic deficits. In this setting, surgical intervention may require extradural and intradural procedures to mitigate neural compression along the dilated central canal by the syrinx.

Reexamining the Role of Postoperative ICU Admission for Patients Undergoing Elective Craniotomy: A Systematic Review.

OBJECTIVES: The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy. DATA SOURCES: A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021. STUDY SELECTION: Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care. DATA EXTRACTION: Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies-of Interventions tool, respectively. DATA SYNTHESIS: In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation. CONCLUSIONS: Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy.

Synthesizing Molecular and Immune Characteristics to Move Beyond WHO Grade in Meningiomas: A Focused Review.

No portion of this manuscript has previously been presented. Meningiomas, the most common primary intracranial tumors, are histologically categorized by the World Health Organization (WHO) grading system. While higher WHO grade is generally associated with poor clinical outcomes, a significant subset of grade I tumors recur or progress, indicating a need for more reliable models of meningioma behavior. Several groups have developed risk scores based on molecular or immunologic characteristics. These classification schemes show promise, with several models preliminarily demonstrating similar or superior accuracy to WHO grading. Improved understanding of immune system recognition and targeting of meningioma subtypes is necessary to advance the predictive power, as well as develop new therapies. Here, we characterize meningioma molecular drivers, predictive of recurrence and progression, and describe specific aspects of the immune response to meningiomas while highlighting critical questions and ongoing research. Relevant manuscripts of interest were identified using a systematic approach and synthesized into this focused review. Finally, we summarize the ongoing and completed clinical trials for immunotherapy in meningiomas and offer perspective on future directions.

Case Series in the Utility of Invasive Blood Pressure Monitoring in Microvascular Decompression.

BACKGROUND: The utility of arterial lines in microvascular decompression (MVD) is not well described. OBJECTIVE: To examine the safety and costs of arterial lines compared with noninvasive blood pressure (NIBP) monitoring in MVDs. METHODS: We retrospectively reviewed patients undergoing MVD from 2012 to 2020. Patients were grouped by procedure date from 2012 to 2014 and 2015 to 2020, reflecting our institution's decreasing trend in arterial line placement around 2014 to 2015. Patient features, intraoperative characteristics, and postoperative complications were collected for all cases. Statistical differences were evaluated using chi-squared analyses and t-tests. RESULTS: Eight hundred fifty-eight patients underwent MVDs, with 204 between 2012 and 2014 and 654 between 2015 and 2020. Over time, the frequency of arterial line placement decreased from 64.2% to 30.1%, P < .001. Arterial lines involved 11 additional minutes of preincision time, P < .001. Patients with arterial lines required both increased doses and costs of vasoactive medications intraoperatively. Patients receiving arterial lines demonstrated no significant differences in complications compared with patients with NIBP monitoring. On average, patients with arterial lines incurred $802 increased costs per case compared with NIBP monitoring. CONCLUSION: NIBP monitoring in MVDs provides neurologically and hemodynamically safe outcomes compared with invasive blood pressure monitoring. For patients without significant cardiopulmonary risk factors, NIBP monitoring may be a cost-effective alternative in MVDs.

Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis.

IMPORTANCE: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis. OBJECTIVE: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults. DATA SOURCES: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses. STUDY SELECTION: Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist ≥3 months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms. MAIN OUTCOME(S) AND MEASURE(S): The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6 months) and long-term (>6 months) follow-up. RESULTS: Of 1458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%-50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%-34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced frequency of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission. CONCLUSIONS AND RELEVANCE: Fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.

Neurological Complications in COVID-19 Patients With ECMO Support: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with Coronavirus disease 2019 (COVID-19)-related acute respiratory disease (ARDS) increasingly receive extracorporeal membrane oxygenation (ECMO) support. While ECMO has been shown to increase risk of stroke, few studies have examined this association in COVID-19 patients. OBJECTIVE: We conducted a systematic review to characterise neurological events during ECMO support in COVID-19 patients. DESIGN: Systematic review of cohort and large case series of COVID-19 patients who received ECMO support. DATA SOURCES: Studies retrieved from PubMed, EMBASE, Cochrane, Cochrane COVID-19 Study Register, Web of Science, Scopus, Clinicaltrials.gov, and medRχiv from inception to November 11, 2020. ELIGIBILITY CRITERIA: Inclusion criteria were a) Adult population (>18 year old); b) Positive PCR test for SARS-CoV-2 with active COVID-19 disease; c) ECMO therapy due to COVID-19 ARDS; and d) Neurological events and outcome described while on ECMO support. We excluded articles when no details of neurologic events were available. RESULTS: 1,322 patients from 12 case series and retrospective cohort studies were included in our study. The median age was 49.2, and 75% (n=985) of the patients were male. Diabetes mellitus and dyslipidaemia were the most common comorbidities (24% and 20%, respectively). Most (95%, n=1,241) patients were on venovenous ECMO with a median P:F ratio at the time of ECMO cannulation of 69.1. The prevalence of intracranial haemorrhage (ICH), ischaemic stroke, and hypoxic ischaemic brain injury (HIBI) was 5.9% (n=78), 1.1% (n=15), and 0.3% (n=4), respectively. The overall mortality of the 1,296 ECMO patients in the 10 studies that reported death was 36% (n=477), and the mortality of the subset of patients who had a neurological event was 92%. CONCLUSIONS: Neurological injury is a concern for COVID-19 patients who receive ECMO. Further research is required to explore how neuromonitoring protocols can inform tailored anticoagulation management and improve survival in COVID-19 patients with ECMO support.

Management of syringomyelia associated with tuberculous meningitis: A case report and systematic review of the literature.

Determinants of tuberculosis (TB) syringomyelia, its management options and outcomes are still under investigation. The aim of this study is to present a case of TB syringomyelia with markedly improved symptoms status-post surgery and to understand the clinical characteristics and outcomes of 33 TB syringomyelia cases reported in the literature. Specifically, we examined the differences between patients who were managed medically and those who underwent surgical intervention. Inclusion criteria for the cases were (1) syringomyelia caused by TB infection rather than co-occurrence of these conditions, (2) management protocol described, and (3) post-treatment outcome described. The median age was 30 years (interquartile range (IQR): 23-40) with 55% males. The median time between TB onset to syringomyelia diagnosis was 2 years. Nineteen patients were surgically treated, 11 were medically treated, and 3 received no treatment. Twenty-one patients showed improvement in at least one prior symptom, but no patient experienced a full recovery. Those that underwent surgical intervention were more likely to have TB meningitis (95% vs. 64%, p < 0.05) upon initial TB presentation and have a greater interval between TB onset and syringomyelia presentation (median of 2.6 vs. 0.33 years, ns). A greater proportion of the surgically managed patients experienced improvement in any symptom (74% vs. 45%, ns). Future case-controlled studies with larger sample sizes are required to validate and further understand the outcomes of surgically-managed TB syringomyelia.

Preclinical efficacy of ribavirin in SHH and group 3 medulloblastoma.

OBJECTIVE: Medulloblastoma, the most common pediatric brain malignancy, has Sonic Hedgehog (SHH) and group 3 (Myc driven) subtypes that are associated with the activity of eukaryotic initiation factor 4E (eIF4E), a critical mediator of translation, and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and master regulator of transcription. Recent drug repurposing efforts in multiple solid and hematologic malignancies have demonstrated that eIF4E and EZH2 are both pharmacologically inhibited by the FDA-approved antiviral drug ribavirin. Given the molecular overlap between medulloblastoma biology and known ribavirin activity, the authors investigated the preclinical efficacy of repurposing ribavirin as a targeted therapeutic in cell and animal models of medulloblastoma. METHODS: Multiple in vitro assays were performed using human ONS-76 (a primitive SHH model) and D425 (an aggressive group 3 model) cells. The impacts of ribavirin on cellular growth, death, migration, and invasion were quantified using proliferation and Cell Counting Kit-8 (CCK-8) assays, flow cytometry with annexin V (AnnV) staining, scratch wound assays, and Matrigel invasion chambers, respectively. Survival following daily ribavirin treatment (100 mg/kg) was assessed in vivo in immunodeficient mice intracranially implanted with D425 cells. RESULTS: Compared to controls, ribavirin treatment led to a significant reduction in medulloblastoma cell growth (ONS-76 proliferation assay, p = 0.0001; D425 CCK-8 assay, p < 0.0001) and a significant increase in cell death (flow cytometry for AnnV, ONS-76, p = 0.0010; D425, p = 0.0284). In ONS-76 cells, compared to controls, ribavirin significantly decreased cell migration and invasion (Matrigel invasion chamber assay, p = 0.0012). In vivo, ribavirin significantly extended survival in an aggressive group 3 medulloblastoma mouse model compared to vehicle-treated controls (p = 0.0004). CONCLUSIONS: The authors demonstrate that ribavirin, a clinically used drug known to inhibit eIF4E and EZH2, has significant antitumor effects in multiple preclinical models of medulloblastoma, including an aggressive group 3 animal model. Ribavirin may represent a promising targeted therapeutic in medulloblastoma.

Clinically Silent Brain Injury and Perioperative Neurological Events in Patients With Left Ventricular Assist Device: A Brain Autopsy Study.

Current studies underestimate the prevalence of brain injury in patients with left ventricular assist devices (LVADs), as CT scans are not sensitive in detecting cerebral ischemia. Using postmortem neuropathological evaluation, we sought to characterize the types and risk factors of brain injury in LVAD patients. We reviewed 24 LVAD patients who underwent brain autopsy with gross and microscopic examinations from 1993 through 2019 at a single tertiary center. Patients who expired less than 7 days after implantation or who underwent explantation more than 7 days before death were excluded. Our study demonstrated that all LVAD nonsurvivors developed brain injury. The most common brain injury was hemorrhage (71%), followed by infarct (42%) and hypoxic ischemic brain injury (HIBI) (33%), and 10 patients (42%) presented with more than 1 brain injury. Cerebral microbleeds (CMBs) and intracranial hemorrhage were present in 33% and 42%, respectively. In those with intracranial hemorrhage, subarachnoid hemorrhage (25%) and intracerebral hemorrhage (25%) were more common than subdural hematoma (4%). Intracranial hemorrhage was associated with driveline infection (P = 0.047), and HIBI was associated with prior history of chronic obstructive pulmonary disease (P = 0.037). Fourteen (60%) had clinically silent brain injury with 65% of hemorrhages and 70% of infarcts being silent. However, the impact of silent brain injury on neurologic outcome and mortality remains unclear. Standardized neurologic monitoring and surveillance are recommended to better detect these clinically silent brain injury.