Unique pattern of neutrophil migration and function during tumor progression.

Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant, uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancer exhibited much more spontaneous migration than that of control neutrophils from tumor-free mice. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and increased production of ATP, relative to that of control neutrophils. Their enhanced spontaneous migration was mediated by autocrine ATP signaling through purinergic receptors. In ectopic tumor models and late stages of cancer, bone marrow neutrophils demonstrated potent immunosuppressive activity. However, these cells had metabolic and migratory activity indistinguishable from that of control neutrophils. A similar pattern of migration was observed for neutrophils and polymorphonuclear myeloid-derived suppressor cells from patients with cancer. These results elucidate the dynamic changes that neutrophils undergo in cancer and demonstrate the mechanism of neutrophils' contribution to early tumor dissemination.

RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells.

The ATR-CHK1 axis stabilizes stalled replication forks and prevents their collapse into DNA double-strand breaks (DSBs). Here, we show that fork collapse in Atr-deleted cells is mediated through the combined effects the sumo targeted E3-ubiquitin ligase RNF4 and activation of the AURKA-PLK1 pathway. As indicated previously, Atr-deleted cells exhibited a decreased ability to restart DNA replication following fork stalling in comparison with control cells. However, suppression of RNF4, AURKA, or PLK1 returned the reinitiation of replication in Atr-deleted cells to near wild-type levels. In RNF4-depleted cells, this rescue directly correlated with the persistence of sumoylation of chromatin-bound factors. Notably, RNF4 repression substantially suppressed the accumulation of DSBs in ATR-deficient cells, and this decrease in breaks was enhanced by concomitant inhibition of PLK1. DSBs resulting from ATR inhibition were also observed to be dependent on the endonuclease scaffold protein SLX4, suggesting that RNF4 and PLK1 either help activate the SLX4 complex or make DNA replication fork structures accessible for subsequent SLX4-dependent cleavage. Thus, replication fork collapse following ATR inhibition is a multistep process that disrupts replisome function and permits cleavage of the replication fork.

The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment.

Myeloid-derived suppressor cells (MDSC) are one of the major components of the tumor microenvironment. The main feature of these cells is their potent immune suppressive activity. MDSC are generated in the bone marrow and, in tumor-bearing hosts, migrate to peripheral lymphoid organs and the tumor to contribute to the formation of the tumor microenvironment. Recent findings have revealed differences in the function and fate of MDSC in the tumor and peripheral lymphoid organs. We review these findings here and, in this context, we discuss the current understanding as to the nature of these differences, the underlying mechanisms, and their potential impact on the regulation of tumor progression.

Invasive meningococcal disease in patients with complement deficiencies: a case series (2008-2017).

BACKGROUND: To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. METHODS: Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008-2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. RESULTS: A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. CONCLUSIONS: In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.

Defining the Anatomy of the Tendinous Intersections of the Rectus Abdominis Muscle and Their Clinical Implications in Functional Muscle Neurotization.

PURPOSE: Little is known about the definitive course of the tendinous intersections from anterior to posterior through the rectus abdominis (RA) muscle. The implications of a full thickness intersection may have effects on the ability to neurotize the RA. We hypothesized that these tendinous inscriptions would be fully adherent to the anterior rectus sheath, but there would be an incomplete penetrance into the posterior surface, thereby allowing for muscle fibers and neurovascular structures to run the entire course of the RA muscle. METHODS: Fifty-five cadaveric, hemiabdominal walls were evaluated. Measurements were taken of RA muscle thickness, depth of penetrance of the tendinous intersections, and intersection thickness. RESULTS: Of the 32 cadavers, 2 had 4 paired tendinous intersections and the remaining 30 cadavers had 3 paired tendinous intersections. Rectus abdominis muscle belly tended to be thicker at midbelly, between intersections than at the level of the corresponding intersection. A total of 168 tendinous intersections were assessed. Thirty (18%) of these inscriptions proved to be full thickness extending from anterior rectus sheath to posterior rectus sheath without any intervening muscle or neurovascular structures. Twenty-three (42%) of the 55 hemiabdomens assessed had at least one full-thickness tendinous intersection. CONCLUSIONS: The majority of RA muscles have 3 paired tendinous intersections. Most intersections are incomplete and only encompass the anterior rectus sheath. However, there may be a higher percentage of full-thickness intersections than previously appreciated and the clinical relevance behind these remains unclear.

A Novel Role for Programmed Cell Death Receptor Ligand-1 (PD-L1) in Sepsis-Induced Intestinal Dysfunction.

Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, co-inhibitory molecule, programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it isn't known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction. To address this, C57BL/6 or PD-L1 gene knockout mice were subjected to experimental sepsis and PD-L1 expression, intestinal permeability, tissue cytokine levels were assessed. Subsequently, septic or non-septic patient colonic samples (assigned by pathology report) were immunohistochemically stained for PD-L1 I a blinded fashion. Finally, human Caco2 cells were used for in vitro studies. The results demonstrated that PD-L1 was constitutively expressed and sepsis significantly up-regulates PD-L1 in IECs from C57BL/6 mice. Concurrently, we observed an increased PD-L1 expression in colon tissue samples from septic patients. PD-L1 gene deficiency reduced ileal permeability, tissue levels of IL-6, TNF-α and MCP-1, and prevented ileal tight junction protein loss compared to WT after sepsis. Comparatively, while Caco2 cell monolayers responded to inflammatory cytokine stimulation also with elevated PD-L1 expression, increased monolayer permeability and altering/decreasing monolayer tight junction protein morphology/expression; these changes were reversed by PD-L1 blocking antibody. Together these data indicate that ligation of ICE PD-L1 plays a novel role in mediating the pathophysiology of sepsis-induced intestinal barrier dysfunction.

Higher Tetanus Toxoid Immunity 2 Years After PsA-TT Introduction in Mali.

BACKGROUND: In 2010, mass vaccination with a then-new meningococcal A polysaccharide-tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction. METHODS: Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ≥0.1 IU/mL (indicating short-term protection) and ≥1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models. RESULTS: Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre-PsA-TT, significantly higher GMCs in all age-sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6-36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7-43.3; P < .0001) pre- and postvaccination. CONCLUSIONS: Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity.

Intramuscular and rectal therapies of acute seizures.

The intramuscular (IM) and rectal routes are alternative routes of delivery for antiepileptic drugs (AEDs) when the intravenous route is not practical or possible. For treatment of acute seizures, the AED used should have a short time to maximum concentration (Tmax). Some AEDs have preparations that may be given intramuscularly. These include the benzodiazepines (diazepam, lorazepam, and midazolam) and others (fosphenytoin, levetiracetam). Although phenytoin and valproate have parenteral preparations, these should not be given intramuscularly. A recent study of prehospital treatment of status epilepticus evaluated a midazolam (MDZ) autoinjector delivering IM drug compared to IV lorazepam (LZP). Seizures were absent on arrival to the emergency department in 73.4% of the IM MDZ compared to a 63.4% response in LZP-treated subjects (p < 0.001 for superiority). Almost all AEDs have been evaluated for rectal administration as solutions, gels, and suppositories. In a placebo-controlled study, diazepam (DZP) was administered at home by caregivers in doses that ranged from 0.2 to 0.5 mg/kg. Diazepam was superior to placebo in reduced seizure frequency in children (p < 0.001) and in adults (p = 0.02) and time to recurrent seizures after an initial treatment (p < 0.001). Thus, at this time, only MZD given intramuscularly and DZP given rectally appear to have the properties required for rapid enough absorption to be useful when intravenous routes are not possible. Some drugs cannot be administered rectally owing to factors such as poor absorption or poor solubility in aqueous solutions. The relative rectal bioavailability of gabapentin, oxcarbazepine, and phenytoin is so low that the current formulations are not considered to be suitable for administration by this route. When administered as a solution, diazepam is rapidly absorbed rectally, reaching the Tmax within 5-20 min in children. By contrast, rectal administration of lorazepam is relatively slow, with a Tmax of 1-2h. The dependence of gabapentin on an active transport system, and the much-reduced surface area of the rectum compared with the small intestine, may be responsible for its lack of absorption from the rectum. This article is part of a Special Issue entitled "Status Epilepticus".

Validation of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults with epilepsy.

OBJECTIVE: This study aimed to assess the accuracy and operating characteristics of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults with epilepsy. METHODS: Tertiary epilepsy center patients served as the study population, with 237 agreeing to structured interview using the Mini-International Neuropsychiatric Interview (MINI), a "gold standard" instrument developed for rapid diagnosis of neuropsychiatric disorders, including major depressive disorder (MDD); 172 also completed the PHQ-9, and 127 completed both the PHQ-9 and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) within two days of the MINI. Sensitivity, specificity, positive and negative predictive values, and areas under the ROC curves for each instrument were determined. Cut-points of 10 for the PHQ-9 and 15 for the NDDI-E were used, and ratings at or above the cut-points were considered screen-positive. The PHQ-9 was divided into cognitive/affective (PHQ-9/CA) and somatic (PHQ-9/S) subscales to determine comparative depression screening accuracy. RESULTS: The calculated areas under the ROC curves for the PHQ-9 (n=172) and the PHQ-9/CA and PHQ-9/S subscales were 0.914, 0.924, and 0.846, respectively, with the PHQ-9 more accurate than the PHQ-9/S (p=0.002) but not different from the PHQ-9/CA (p=0.378). At cut-points of 10 and 15, respectively, the PHQ-9 had higher sensitivity (0.92 vs 0.87) but lower specificity (0.74 vs 0.89) compared with the NDDI-E. The areas under the ROC curves of the PHQ-9 and the NDDI-E showed similar accuracy (n=127; 0.930 vs 0.934; p=0.864). SIGNIFICANCE: The PHQ-9 is an efficient and nonproprietary depression screening instrument with excellent accuracy validated for use in adult patients with epilepsy as well as multiple other medical populations.

Responsive neurostimulation as a treatment for super-refractory focal status epilepticus: a systematic review and case series.

OBJECTIVE: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters. METHODS: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel. RESULTS: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint. CONCLUSIONS: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

The discovery of BMS-457, a potent and selective CCR1 antagonist.

A series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis.

Bedside Flexible Cystoscopy-Guided Ureteric Stent Insertion for Early Control of Sepsis.

Sepsis is a life-threatening condition that needs the clinician to act quickly and swiftly in order to provide the best medical outcome for the patient. Sepsis can lead to multi-organ dysfunction, which is not only a risk to life but also utilizes multiple resources within the healthcare services. The management of any infection is reliant on two major factors: antimicrobial therapy and source control. We present two cases where source control, in the form of a ureteric stent insertion, was performed at bedside via the use of flexible cystoscopy to provide source control in the management of a septic patient.

EEG Correlates of Spikes in Intracranial Pressure Caused by Transient Ventriculoperitoneal Shunt Malfunction.

SUMMARY: A 30-year-old man with recurrent headaches and seizure-like activity and a 26-year-old woman with worsening headaches were admitted to the hospital. Both had ventriculoperitoneal shunts and history of several shunt revisions for congenital hydrocephalus. The ventricle size visualized on computed tomography scans was unremarkable, and shunt series were negative in both cases. Both patients began to present with brief periods of unresponsiveness, and video electroencephalography at that time showed periods of diffuse delta slowing. Lumbar punctures revealed increased opening pressures. Despite normal imaging and shunt series, both patients ultimately had increased intracranial pressure caused by shunt malfunction. This series demonstrates the difficulty of diagnosing potential transient increases in intracranial pressure based on standard-of-care diagnostics/examination and the potentially critical role for EEG in the identification of shunt malfunction.

Diagnosis and management of elevated intracranial pressure in the emergency department.

BACKGROUND: Elevated intracranial pressure is a devastating complication of catastrophic brain injury. Intracranial hypertension is commonly seen in neurologic injury secondary to traumatic brain injuries. Uncontrolled pressures can lead to permanent neurologic damage, but acute medical management is often overlooked when pursuing surgical management options that may not always be indicated. DISCUSSION: Traumatic brain injury is the leading cause of death in patients with severe neurologic injury. Diagnosing elevated intracranial pressures is imperative in initiating prompt treatment to reduce secondary central nervous system injury, morbidity, and mortality. Although the initial injury to the brain is typically irreversible, intracranial pressure control can assist in salvaging the remaining brain tissue from additional damage. We will discuss the initial medical and surgical management of traumatic brain injury to prevent further neurologic deterioration and reduce mortality. CONCLUSION: Recent literature has reported several methods to detect elevated intracranial pressure easily and studies describing multiple treatment modalities. These investigations suggest that early detection and timely treatment of intracranial hypertension are beneficial in reducing mortality.

Work, Parenting, and Well-being: An International Survey of Neurologists During the COVID-19 Pandemic.

Background and Objectives: COVID-19 reframed the relationship between work and home and, in general, made both more difficult-especially for parents. We hypothesized that, among neurologists, the effects of the pandemic on productivity and on well-being would be greater on those with children than on those without children and that the effects would be greater on women with children than on men with children. Methods: We conducted an international electronic survey launched by the Practice Current section of the American Academy of Neurology. The survey included questions on demographics (self-identified gender, number of children and elderly dependents, childcare support, and country and state when applicable), workflow changes because of COVID-19, impacted domains, and productivity and well-being using the Likert scale. Counts are presented as descriptive statistics. Statistical analysis was performed using Mann-Whitney U and Kruskal-Wallis tests. Results: We collected 243 fully completed surveys from providers in all continents with high representation of the United States (76%), providers who identified as women (71.6%), and neurologists with children (91%) among respondents. A majority worked remotely (28% fully, 43% mix). Neurologists reported decreased academic productivity (72%), work benefits (65%), and time for writing (48%). These findings were more prominent in respondents with children and among women practicing outside of the United States. Increased pressure from productivity expectations and lack of time for family were reported by 47% and 41% of respondents, respectively. Discussion: The disruption from the COVID-19 pandemic affected academic productivity and decreased the well-being of neurologists in general and of neurologists with children more drastically. This could potentially hinder the promotion and retention of junior neurologists who were juggling life and work during the pandemic outbreak and its recurrent surges.

Intersectionality and COVID-19: Academic Medicine Faculty's Lived Experiences of Well-Being, Workload, and Productivity During the Pandemic.

Purpose: The aim of this study was to utilize an intersectional framework to examine academic faculty's lived experiences during COVID-19. Specifically, we set out to: (1) describe the multiple intersectional identities (e.g., gender, race/ethnicity, rank, caregiver status, disability status) represented by the faculty, (2) examine potential disparities in well-being, workload, and productivity linked to these intersectional factors, and (3) identify qualitative themes endorsed by faculty as they relate to lived experiences during COVID-19. Methods: This was a cross-sectional mixed-methods research study. The Center for Women in Medicine and Science (CWIMS) at the University of Minnesota developed and implemented a survey between February-June of 2021 in response to national reports of disparities in the impacts of COVID-19 on faculty with lived experiences from multiple intersections. Results: There were 291 full-time faculty who participated in the study. Quantitative findings indicated that faculty with multiple intersectional identities (e.g., woman+assistant professor+caregiver+underrepresented in medicine) reported greater depression symptoms, work/family conflict, and stress in contrast to faculty with fewer intersectional identities. Furthermore, faculty with more intersectional identities reported higher clinical workloads and service responsibilities and lower productivity with regard to research article submissions, publications, and grant submissions in contrast to faculty with fewer intersectional identities. Qualitative findings supported quantitative findings and broadened understanding of potential underlying reasons. Conclusions: Findings confirm anecdotal evidence that faculty with lived experiences from multiple intersections may be disproportionately experiencing negative outcomes from the pandemic. These findings can inform decisions about how to address these disparities moving into the next several years with regard to promotion and tenure, burnout and well-being, and faculty retention in academic medical settings. Given these findings, it is also important to intentionally plan responses for future public health crises to prevent continued disparities for faculty with multiple intersectional identities.

An Easy Solution for Difficult Urethral Catheter: Three-Way Urethral Catheter Insertion Using a Guidewire Technique.

Urethral catheter insertion is a skill taught to all medical students but often not practised for a multitude of reasons. The difficult catheter can be a clinical nightmare for the junior doctor, especially on call, and can lead to significant mortality and morbidity with suboptimal repeated attempts. The incorporation of a soft-tipped hydrophilic guidewire technique for the insertion of a two-way urethral catheter has been described in the literature and has the potential to reduce the morbidity and mortality of patients by making the insertion of a catheter less traumatic. Here, we propose and describe the insertion of a three-way urethral catheter, performed using the technique employed for the insertion of a two-way urinary catheter via the use of a hydrophilic guidewire, with similar outcomes. A hydrophilic soft-tipped guidewire to insert a three-way urethral catheter can be used in the wards, in the emergency department, and in a theatre setting. The district hospital in which this method was employed demonstrated a 100% success rate in the insertion of a urethral catheter (N = 15), with 26% of cases (four patients out of 15) having a three-way urethral catheter inserted using the soft-tipped hydrophilic guidewire method. Follow-ups of these patients showed that there were no complications or adverse effects experienced by the patients. The use of a soft-tipped guidewire approach to insert a difficult urethral catheter can reduce the financial burden on the healthcare system by eliminating costs due to harm/trauma caused by repeated unsuccessful urethral catheter attempts or those attempts that have been performed suboptimally and have led to potential patient harm. The use of a hydrophilic guidewire-assisted technique to insert a three-way urinary catheter is a safe and easy option for those who have had repeated unsuccessful attempts. The hydrophilic guidewire approach has the potential to reduce morbidity and mortality associated with urethral catheterisation and improve patient safety.

Subcutaneous delivery of FGF21 mRNA therapy reverses obesity, insulin resistance, and hepatic steatosis in diet-induced obese mice.

Fibroblast growth factor 21 (FGF21) is a promising therapeutic agent for treatment of type 2 diabetes (T2D) and non-alcoholic steatohepatitis (NASH). We show that therapeutic levels of FGF21 were achieved following subcutaneous (s.c.) administration of mRNA encoding human FGF21 proteins. The efficacy of mRNA was assessed following 2-weeks repeated s.c. dosing in diet-induced obese (DIO), mice which resulted in marked decreases in body weight, plasma insulin levels, and hepatic steatosis. Pharmacokinetic/pharmacodynamic (PK/PD) modelling of several studies in both lean and DIO mice showed that mRNA encoding human proteins provided improved therapeutic coverage over recombinant dosed proteins in vivo. This study is the first example of s.c. mRNA therapy showing pre-clinical efficacy in a disease-relevant model, thus, showing the potential for this modality in the treatment of chronic diseases, including T2D and NASH.

Subarachnoid hemorrhage in the emergency department.

BACKGROUND: Subarachnoid hemorrhage accounts for more than 30,000 cases of stroke annually in North America and encompasses a 4.4% mortality rate. Since a vast number of subarachnoid hemorrhage cases present in a younger population and can range from benign to severe, an accurate diagnosis is imperative to avoid premature morbidity and mortality. Here, we present a straightforward approach to evaluating, risk stratifying, and managing subarachnoid hemorrhages in the emergency department for the emergency medicine physician. DISCUSSION: The diversities of symptom presentation should be considered before proceeding with diagnostic modalities for subarachnoid hemorrhage. Once a subarachnoid hemorrhage is suspected, a computed tomography of the head with the assistance of the Ottawa subarachnoid hemorrhage rule should be utilized as an initial diagnostic measure. If further investigation is needed, a CT angiography of the head or a lumbar puncture can be considered keeping risks and limitations in mind. Initiating timely treatment is essential following diagnosis to help mitigate future complications. Risk tools can be used to assess the complications for which the patient is at greatest. CONCLUSION: Subarachnoid hemorrhages are frequently misdiagnosed; therefore, we believe it is imperative to address the diagnosis and initiation of early management in the emergency medicine department to minimize poor outcomes in the future.