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Purpose Uncertainty in medical decision making is a well-described phenomenon, and numerous scholars have acknowledged and illustrated the process of training medical students to grapple with this aspect of medical practice. While clinical uncertainty has been defined previously, medical trainees face additional forms of uncertainty beyond the clinical setting that have not, as yet, been investigated empirically. One area in which uncertainty can manifest outside of the clinical setting is during professional development. Medical students face substantial stress and ambiguity throughout their training, with the residency application period representing a culmination of these pressures. Here, the authors examined medical students' experiences during the residency application period and used these findings to define training for professional uncertainty. Method In 2018-2019, 6 focus groups of fourth-year medical students were conducted exploring students' experiences during the residency application period, including but not limited to Step 2 Clinical Knowledge, away rotations, and securing letters of recommendation. The authors then used constructivist, phenomenological methods to analyze participant responses. Results Students frequently discussed challenges they faced during the residency application period. From these conversations, 2 themes were identified: (1) professional uncertainty related to career-based advice, which resulted from mixed messaging and inadequate information and (2) professional uncertainty related to competing responsibilities, which students experienced when determining how to allocate a limited amount of time to multiple conflicting forces. Conclusions These results were used to define a novel concept-training for professional uncertainty. By navigating the residency application process, students learned to face various facets of professional uncertainty that they will continue to face throughout their careers. Since uncertainty can have many negative effects, including declining performance and burnout, defining professional uncertainty and training students to grapple with it is necessary to maximize their success throughout their careers.

BACKGROUND: Cannabinoid Hyperemesis Syndrome (CHS) is a form of cyclic vomiting syndrome characterized by episodic vomiting occurring every few weeks or months and is associated with prolonged and frequent use of high-dose cannabis. CHS in the pediatric population has been increasingly reported over the last decade and can lead to life-threatening complications such as pneumomediastinum, which warrant careful consideration for surgical intervention. CASE PRESENTATION: A 17-year-old female with no significant past medical history presented to the emergency department with abdominal pain, nausea, and vomiting for 24 hours. She had four episodes of green-yellow emesis followed by dry heaves. She also complained of chest and back pain, worse with deep inspiration. Upon further history, the patient reported a similar episode of abdominal pain and repetitive vomiting six months prior to the current episode. She smoked cannabis at least once daily and has done so for the past two years. Chest X-ray revealed a subtle abnormal lucency along the anteroposterior window and anterior mediastinum, consistent with a small amount of pneumomediastinum without any other acute intrathoracic abnormalities. Follow-up chest computed tomography with contrast showed multiple foci of air within the anterior and posterior mediastinum tracking up to the thoracic inlet. There was no evidence of contrast extravasation; however, small esophageal perforation could not be excluded. Given uncomplicated pneumomediastinum without frank contrast extravasation, the patient was treated medically with piperacillin-tazobactam, metronidazole, and micafungin for microbial prophylaxis; hydromorphone for pain control; as well as with pantoprazole, ondansetron, and promethazine. Nutrition was provided via total parenteral nutrition. The patient was intensely monitored for signs of occult esophageal perforation, but none were detected. She was advanced to a soft diet on hospital day eight, solid food diet on day nine, at which point antibiotics were discontinued, and the patient was subsequently discharged. CONCLUSION: CHS in an increasingly common disorder encountered in the pediatric setting due to rising prevalence of cannabis use. The management of CHS and potentially life-threatening complications such as pneumomediastinum should be given careful consideration. Pneumomediastinum can be a harbinger of more sinister pathology such as esophageal perforation, which may warrant urgent surgical intervention.

Sleep in epilepsy is best studied in longitudinal preclinical animal models, where state changes can have significant effects on epileptic activities. Voluminous data makes it very difficult to mark sleep stages manually. This demands an automated way to detect sleep and wake states. We developed an approach to characterize sleep-wake states in continuous video-electroencephalography (EEG) recordings in animals. We compared brute force approach based on frequency band-power based thresholding with machine learning algorithms to detect sleep in 600 hours of EEG data from 4 epileptic and 2 control animals. We found that conventional delta and theta band-powers were prominent in sleep; however, this was not sufficient to detect sleep algorithmically. We therefore extracted a set of novel frequency bands to robustly differentiate individual sleep states by using brute-force algorithm and machine learning models, among which k-nearest neighbors (KNN) was the best predictor of sleep with 94% accuracy. We subsequently characterized sleep patterns in animals with chronically induced epileptic spiking in the neocortex from tetanus toxin injections using brute-force algorithm. We found that epileptic spiking animals (without seizures) sleep more frequently, with significantly longer sleep segments and overall daily sleep time, as compared to control animals. This automated algorithm could help expedite sleep studies and help us understand the relationship between sleep and patients with epilepsy.

Problem Medical schools have implemented various ways to engage students in improving medical curricula. These systems, however, usually focus on the preclerkship curriculum, perhaps because medical students move through this phase of medical education synchronously, making it easier to collect student input. In contrast, clerkship and postclerkship curricula often lack similar levels of student engagement in program evaluation. Approach To increase communication among students, faculty, and administration during the clinical years of medical education, the Student Curricular Board (SCB) at the University of Illinois College of Medicine's Chicago campus (UICOM-Chicago) developed a student-driven feedback model in 2016 that aimed to parallel the system previously implemented in the preclerkship years. Interested fourth-year students were selected by their peers to represent individual core clerkships, and they communicated regularly with clerkship directors about concerns from current clerkship students. Third-year students applied and were selected to represent their cohort of peers moving through clerkship tracks. Proposed changes and improvements were tracked via novel, student-driven SOAP-Education (SOAP-Ed) progress notes written throughout the academic year. Outcomes In response to a program evaluation survey conducted after implementation of this pilot, third-year students said they felt that their feedback was taken seriously by faculty and administration. Furthermore, student feedback led to meaningful changes in core clerkship curricula and in the system used to gather clerkship feedback. Clerkship directors expressed appreciation for this partnership, and students said they gained valuable leadership experience and knowledge of curricular development. Next steps Current SCB members and curricular leadership plan to assess student and faculty perceptions of this system and its efficacy and to work toward expansion to all UICOM campuses. Lessons learned from this student-driven model of feedback in third-year core clerkships will likely add to the conversation on how to better engage medical students as active stakeholders in their own education.

In 2014, the Association of American Medical Colleges recruited 10 institutions across the United States to pilot the 13 Core Entrustable Professional Activities for Entering Residency (Core EPAs). The goal was to establish a competency-based framework to prepare graduating medical students for the transition to residency. Within the Core EPAs pilot, medical students play an influential role in the development and implementation of EPA-related curricula. Student engagement was a priority for the Core EPAs institutions given students' roles as the end users of the curriculum, thus they may offer valuable insight into its design and implementation. Here, the authors provide the perspective of medical students who serve as leaders in the Core EPAs pilot at their respective institutions. They describe student leadership models across the pilot institutions as well as 6 key challenges to implementation of the Core EPAs: (1) How and when should the Core EPAs be introduced? (2) Who is responsible for driving the assessment process? (3) What feedback mechanisms are required? (4) What systems are required for advising, mentoring, or coaching students? (5) Should EPA performance contribute to students' grades? and (6) Should entrustment decisions be tied to graduation requirements? Using a polarity management framework to address each challenge, the authors describe inherent tensions, approaches used by the Core EPAs pilot institutions, and student-centered recommendations for resolving each tension. By sharing the experiences and perspectives of students engaged in the Core EPAs pilot, the authors hope to inform implementation of EPA-oriented assessment practices and feedback across institutions in the United States.

One area in which medical students can add significant value is medical education, and involving them as key stakeholders in their education can have a profound impact on students and the institutions that serve them. However, detailed descriptions of the structure, implementation and quality of programs facilitating student engagement are lacking. We describe the structure of a novel student engagement program at the University of Illinois College of Medicine-Chicago (UICOM-Chicago) known as the Student Curricular Board (SCB). We surveyed 563 medical students across all levels of training at our institution in order to examine the impact of this program, including its strengths and potential areas of improvement. The SCB serves as a highly structured and collaborative student group that has far-reaching involvement from course-level program evaluation to longitudinal curriculum design. Medical students overwhelmingly valued opportunities to be involved in their curriculum. Students with the greatest exposure to the SCB were more aware of specific program initiatives and expressed increased interest in academic medicine as a career. By highlighting this innovative student engagement program, we aim to share best practices for a highly structured, value-added approach to medical student engagement in medical education that is applicable to other medical schools and student leaders.

Stroke is a leading cause of death and disability worldwide. Inflammation and microvascular dysfunction have been associated with brain injury and long-term disability after both ischemic and hemorrhagic stroke. Recent studies have suggested a potential role of extracellular vesicles (EVs) as a link underlying these pathogenic processes. EVs are cell-derived particles enveloped by a lipid bilayer, containing proteins, lipids, and nucleic acids. From a functional standpoint, EVs can facilitate intercellular communication, including across the blood-brain barrier (BBB). Recent advances in EV research have shown a preferential release of EVs from specific cell types in the context of stroke, some of which were associated with increased neuroinflammation, microvascular dysfunction, and neuronal cytotoxicity while others offered a degree of neuroprotection. However, one historic challenge in the studies of EVs in stroke is the lack of consistent definitions and methods to analyze EVs, only recently updated in the MISEV2018 guidelines. Given limitations and complexity in the treatment of stroke, particularly delivery of therapeutics across the BBB, increasing attention has been paid towards manipulating EVs as one vehicle that can permit targeted therapeutic delivery to the central nervous system. These discoveries point towards a future where a better understanding of EVs will advance our knowledge of stroke-associated mechanisms of cerebral and systemic injury and contribute to the development of novel treatments. Here, we review the role that EVs play in ischemic and hemorrhagic stroke.

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for 5% of strokes but results in significant morbidity and mortality. In addition to systemic inflammation, up to half of patients develop cardiac injury; however, the relationship between systemic inflammation and cardiac injury after aSAH is unknown. We investigated changes in leukocyte counts in relation to cardiac dysfunction MATERIALS AND METHODS: We reviewed the records of consecutive patients with SAH at our large academic medical referral center. The inclusion criteria were aSAH and available cardiac troponin I (cTnI) levels within 48 h of admission. The primary outcome was cardiac injury, defined as cTnI ≥0.04 ng/mL (lab reference range 0.01-0.03 ng/mL). We compared baseline characteristics, including serum leukocyte counts and performed univariable and multivariable logistic regression analysis to determine whether changes in leukocyte subpopulations predict cardiac injury.Of 288 SAH patients, 250 met inclusion criteria. Of these, 116 (46.4%) had elevated cTnI. In univariable analysis, total leukocyte count (p 0.001), absolute neutrophil count (ANC, p 0.001), and absolute monocyte count (p = 0.013), were associated with elevated cTnI. in multivariable analysis, total leukocyte count (OR=1.079, p = 0.037) and ANC (OR=1.081, p = 0.044) remained predictors of elevated cTnI. Adjusted ANC distinguishes between aSAH patients with normal and elevated TnI (area under the curve=0.766, p 0.001) with specificity of 89.2%.Elevated total leukocytes and ANC are independently associated with cardiac injury in aSAH. Systemic inflammatory responses after aSAH may play a role in cardiac dysfunction, warranting additional studies to further characterize how cardiac inflammation after aSAH drives subsequent morbidity and mortality.

BACKGROUND Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm. METHODS We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm. RESULTS A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P

Aneurysmal subarachnoid hemorrhage has a high mortality rate and, for those who survive this devastating injury, can lead to lifelong impairment. Clinical trials have demonstrated that cerebral vasospasm of larger extraparenchymal vessels is not the sole contributor to neurological outcome. Recently, the focus of intense investigation has turned to mechanisms of early brain injury that may play a larger role in outcome, including neuroinflammation and microvascular dysfunction. Extravasated blood after aneurysm rupture results in a robust inflammatory response characterized by activation of microglia, upregulation of cellular adhesion molecules, recruitment of peripheral immune cells, as well as impaired neurovascular coupling, disruption of the blood-brain barrier, and imbalances in endogenous vasodilators and vasoconstrictors. Each of these phenomena is either directly or indirectly associated with neuronal death and brain injury. Here, we review recent studies investigating these various mechanisms in experimental models of subarachnoid hemorrhage with special emphasis on neuroinflammation and its effect on microvascular dysfunction. We discuss the various therapeutic targets that have risen from these mechanistic studies and suggest the utility of a multi-targeted approach to preventing delayed injury and improving outcome after subarachnoid hemorrhage.

Introduction: Up to 50% of subarachnoid hemorrhage (SAH) patients develop cardiac injury. The relationship between early systemic inflammation and cardiac injury after SAH is unknown. Here we examined changes in blood leukocyte counts and their relationship to cardiac dysfunction. Methods: We reviewed the medical records of 288 SAH patients admitted to our Comprehensive Stroke Center. Patients were dichotomized based on elevated (≥0.04ng/mL) or normal (70%) from echocardiogram data. We performed univariate and multivariate logistic regression to establish the relationship between blood leukocyte counts and cardiac injury. Results: Of 288 SAH patients, 241 had TnI levels performed at the time of admission and 119 (49.4%) of these had elevated TnI on admission. Patients with elevated TnI were significantly older, had higher grade SAH, abnormal EF, and were more likely to have hypertension and dyslipidemia. 10 (4.1%) had low EF while 58 (24.1%) had high EF on admission echocardiogram. In univariate analysis, total leukocyte count (p Conclusions: Blood total leukocyte count is an independent predictor of cardiac injury in SAH patients. This highlights the role of inflammation in mediating cardiac dysfunction after brain hemorrhage, and raises questions regarding the potential of anti-inflammatory therapy for cardioprotection in SAH.

Objective: Studies in subarachnoid hemorrhage (SAH) animal models are limited to early timepoints, after which the brain is extracted to confirm hemorrhage. For long-term studies, blood is resorbed by the time of euthanasia and thus alternative methods of confirming SAH are necessary. Here, we used in vivo MRI to determine the presence, extent, and location of blood in the endovascular perforation rat model of SAH. Methods: Animals were divided into two groups - SAH and sham controls (no perforation). Rats were imaged at 24 hours in a 9.4T MRI scanner. T2-weighted imaging (T2WI) was used to quantify and localize the volume and extension of blood. T2WI was performed with a fast spin echo sequence with TR/TE = 5000/60 ms, FOV = 40x40 mm 2 , 0.75 mm slice thickness, and no interslice gap. SAH was identified as hypointense signal at the skull base, a normally hyperintense region due to cerebrospinal fluid in the basal cisterns. Regions of interest were identified and segmented manually. Pixels were converted to areas, and the total hypointense volume (V hypo ) was computed by summing all areas. V hypo was normalized to total brain volume (TBV) for each animal. Ability to detect blood via MRI was compared to the gold standard of direct visualization of blood after brain extraction using receiver operating characteristic (ROC) curves. The location of blood was plotted along a standardized antero-posterior axis. 3D reconstructions were developed in 3D Slicer to visualize the spatial distribution of hemorrhage. Results: V hypo values were 1.6±1.4 mm 3 sham (n = 8) and 7.5±3.9 mm 3 for SAH (n = 10) [p=0.0003]. This difference persisted when V hypo was normalized to TBV (p=0.0005). There was no difference in the TBV between groups (p=0.1493). V hypo distinguished between SAH and sham animals (p=0.001, area under curve = 0.963). A cutoff of V hypo = 4.63 mm 3 corresponded to 100% specificity and 80% sensitivity for confirming SAH. The spatial distribution of bleeding varied along the antero-posterior axis within the subarachnoid space. Conclusions: We developed an in vivo MRI method for the quantification of SAH blood volume and location in rats. This will be used for future long-term studies to confirm and grade severity of SAH.

Introduction Epilepsy is a debilitating neurological condition characterized by spontaneous seizures as well as significant comorbid behavioral abnormalities. In addition to seizures, epileptic patients exhibit interictal spikes far more frequently than seizures, often, but not always observed in the same brain areas. The exact relationship between spiking and seizures as well as their respective effects on behavior are not well understood. In fact, spiking without overt seizures is seen in various psychiatric conditions including attention-deficit hyperactivity disorder. Methods In order to study the effects of spiking and seizures on behavior in an epileptic animal model, we used long-term video-electroencephalography recordings at six cortical recording sites together with behavioral activity monitoring. Animals received unilateral injections of tetanus toxin into either the somatosensory or motor cortex. Results Somatosensory cortex-injected animals developed progressive spiking ipsilateral to the injection site, while those receiving the injection into the motor cortex developed mostly contralateral spiking and spontaneous seizures. Animals with spiking but no seizures displayed a hyperactive phenotype, while animals with both spiking and seizures displayed a hypoactive phenotype. Not all spikes were equivalent as spike location strongly correlated with distinct locomotor behaviors including ambulatory distance, vertical movements, and rotatory movement. Conclusions Together, our results demonstrate relationships between brain region-specific spiking, seizures, and behaviors in rodents that could translate into a better understanding for patients with epileptic behavioral comorbidities and other neuropsychiatric disorders.

BACKGROUND/OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating neurological injury, further complicated by few available methods to objectively predict outcomes. With the recent shift in focus to neuroinflammation as a potential cause of adverse outcomes following SAH, we investigated the inflammasome-derived enzyme, caspase-1, as a potential biomarker for poor functional outcome. METHODS: SAH patients were recruited from a regional stroke referral center. Cerebrospinal fluid (CSF) samples from 18 SAH subjects were collected via an external ventricular drain and obtained as close as possible to admission (within 72 hours). For control subjects, we collected CSF from 9 patients undergoing lumbar puncture with normal CSF. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4–5) and poor outcomes (GOS of 1–3). RESULTS: CSF analysis demonstrated a nearly seven-fold increase in caspase-1 activity in SAH patients compared to controls (p

Introduction: The role of neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) and its relationship to outcome is the subject of many ongoing studies. The proteolytic enzyme, caspase-1, activated by the inflammasome complex, is known to contribute to numerous downstream pro-inflammatory effects. In this study, we investigated caspase-1 activity in the cerebrospinal fluid (CSF) of SAH patients and its association to outcome. Methods: SAH patients were recruited from a regional stroke referral center. CSF samples from 18 SAH subjects were collected via an external ventricular drain and obtained within 72 hours of the onset of symptoms. For control subjects, we collected the CSF from 9 patients undergoing lumbar puncture with normal CSF and normal brain MRI. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). The levels of caspase-1 activity in various groups were analyzed using Mann-Whitney and Pearson correlation tests. Caspase-1 activity was also adjusted by initial severity of bleed using analysis of covariance (ANCOVA). Results: Caspase-1 levels from SAH patients were significantly higher than that measured from the control group (mean 1.06x10-2 vs 1.90x10-3 counts per second (CPS)/μl*min), p = 0.0002). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Caspase-1 activity was significantly higher in the poor outcome group (mean 1.54x10-2 vs 1.60x10-3 CPS/μl*min), p = 0.0012). Additionally, caspase-1 activity had a statistically significant correlation with GOS score (r = -0.60; p = 0.0100). When adjusted for initial severity of bleed, the difference in caspase-1 activity in good vs. poor outcome remained significant (adjusted mean 7.10x10-3 vs. 2.54x10-2 CPS/μl*min, p=0.004). Conclusions: The inflammasome-dependent protein caspase-1 is elevated in CSF early after SAH and higher in those with poor functional outcome. Inflammasome activity therefore may serve as a novel biomarker to predict outcome shortly after aneurysm rupture.

Introduction: Cognitive impairment is common after aneurysmal subarachnoid hemorrhage (aSAH), however differences between low and high grade aSAH is less well defined. In this study we investigated the contribution of aSAH-associated early brain injury (EBI) to neurocognitive decline. Methods: We retrospectively studied aSAH patients admitted to a tertiary referral center (group 1). EBI was defined as mild, moderate, or severe based on baseline Hunt and Hess score (1-2 vs. 3 vs. 4-5, respectively). Cognition was assessed by the Montreal Cognitive Assessment (MoCA) administered by blinded personnel prior to hospital discharge. Sociodemographic characteristics and pertinent complications, including use of ventricular diversion, vasospasm, delayed neurologic deterioration, and cerebral infarct were recorded. Ischemic stroke (group 2) and non-neurological patients (group 3) served as controls. MoCA scores were compared using ANCOVA adjusting for baseline differences. Results: Groups 1, 2, and 3 included 84, 43, and 25 patients, respectively. There was no difference in sex but there was a difference in age (52.2±12.2, 60.5±14.9, 52.2±7.0 years, p=0.008). MoCA scores (mean±SD) for groups 1, 2, and 3 were 20.0±5.2, 20.0±5.4, and 23.6±5.0. These differences were statistically different after adjustment for age and level of education (p=0.001). In pairwise analysis, MoCA scores for aSAH patients were similar to ischemic stroke but lower than for non-neurologic patients. Among aSAH patients, the rate of mild, moderate, and severe EBI were 71%, 21%, and 8% (MoCA scores 20.7±5.3, 18.2±4.9 and 18.3±4.2, respectively). No significant differences in MoCA scores were noted based on EBI severity. Also, the scores of aSAH patient with mild EBI were comparable to ischemic stroke but lower than for non-neurological controls. Conclusion: Cognitive decline is commonly seen in aSAH survivors irrespective of the EBI severity. The cognitive decline observed in mild EBI patients highlights an underappreciated degree of cognitive decline in individuals who are otherwise expected to have good outcomes. Cognitive screening in low-grade aSAH patients is warranted.

Introduction: Neuroinflammation is common after subarachnoid hemorrhage (SAH). The complement protein C1q is a well-known inflammatory mediator that has emerged as a key player in neuroimmune synaptic alterations. In this study, we sought to evaluate changes in cerebrospinal fluid (CSF) C1q after SAH and its association with outcome and symptomatic vasospasm (sVS). Methods: Subjects with SAH were recruited from a regional referral center. Cases were eligible to participate if they had nontraumatic aneurysmal SAH and an external ventricular drain. Samples were obtained within 72 hours of symptom onset. Control subjects were those undergoing lumbar puncture with normal CSF and normal brain MRI. C1q levels were determined using commercially available ELISA, normalized by total CSF protein, and divided into tertiles. SAH subjects were prospectively followed through hospitalization and categorized into those with good outcome (Glasgow Outcome Scale, GOS, of 5) or poor outcome (GOS of 2-4). Patients were also further categorized into those with and without sVS, defined by the presence of arterial narrowing on angiography and neurological deterioration. The rates of patients with poor outcome and sVS in each C1q tertile were compared. Results: We analyzed the CSF of 29 SAH and 11 control patients. Mean age of SAH patients was higher than controls (53.2 vs. 42.0, p=0.03) while there were no sex differences across groups. Levels of C1q were elevated in SAH patients compared to controls (p=0.02). Within the SAH group, 7 (24%) were defined as good outcome while 22 (76%) were defined as poor outcome. Mean C1q levels were comparable between these two groups (p=0.61). Symptomatic vasospasm occurred in 18 (62%) SAH patients - 16 (89%) with poor outcome and 2 (11%) with good outcome. Patients with sVS had decreased levels of C1q compared to those without (p=0.03). The rate of poor outcome per tertile of C1q was 100%, 60%, and 70%, while the rate of sVS per tertile was 88%, 70%, and 40% of patients. Conclusions: The complement protein C1q is elevated in CSF of SAH patients and may contribute to early neuroinflammation. C1q levels also appear to be lower in patients who experience sVS, suggesting that elevated C1q may have a protective role in early SAH.

BACKGROUND: Cognitive impairment is common after aneurysmal subarachnoid hemorrhage (SAH). However, compared to predictors of functional outcome, meaningful predictors of cognitive impairment are lacking. OBJECTIVE: Our goal was to assess which factors during hospitalization can predict severe cognitive impairment in SAH patients, especially those who might otherwise be expected to have good functional outcomes. We hypothesized that the degree of early brain injury (EBI), vasospasm, and delayed neurological deterioration (DND) would predict worse cognitive outcomes. METHODS: We retrospectively reviewed SAH patient records from 2013–2019 to collect baseline information, clinical markers of EBI (Fisher, Hunt-Hess, and Glasgow Coma scores), vasospasm, and DND. Cognitive outcome was assessed by Montreal Cognitive Assessment (MoCA) and functional outcomes by modified Rankin Scale (mRS) at hospital discharge. SAH patients were compared to non-neurologic hospitalized controls. Among SAH patients, logistic regression analysis was used to identify predictors of severe cognitive impairment defined as a MoCA score

Introduction: Subarachnoid hemorrhage (SAH) accounts for up to 5% of strokes each year and has a mortality around 40%. Early brain injury (EBI) develops within the first 72 hours of the SAH and involves neuroinflammation, activation of platelets and clotting factors, blood-brain barrier dysfunction, and neuronal loss. These changes set the stage for the development of further delayed brain injury and long-term impairments such as the development of seizures which is common after SAH. In this study we investigate the association of EBI and epileptogenesis. Methods: Using the endovascular perforation (EVP) model of SAH in rats, our lab has performed histological studies of EBI for markers including Iba-1 (inflammation), fibrinogen (microthrombosis), EBA (vascular integrity), and Flurojade B (FJB, neuronal degeneration). We coupled the EVP model with the implantation of subdural electrodes for long-term video electroencephalography (EEG) to characterize the development of interictal spikes and seizures following SAH. The EEG activity was continuously monitored for 4 months post-SAH. Results: Results of our study show a two- to three-fold increase in immunoreactivity of Iba-1, fibrinogen, EBA, and FJB following SAH compared to sham controls. EEG analysis demonstrated the presence of frequent interictal spikes during the first week post-SAH that often cluster and are periodic. By 3-4 weeks after SAH, clinical and subclinical seizures are observed that then increase in frequency and duration over time. Conclusions: This is the first study using long-term EEG monitoring to investigate the occurrence of seizures in the animal model of SAH. EBI after SAH is multifactorial and likely drives long-term deficits such as the development of a chronic epileptic condition. Neuroinflammation is a potential driver of epileptogenesis post-SAH. The use of immunomodulatory drugs in the late development of seizures in SAH may warrant further investigation.

Delayed cerebral ischemia (DCI) is common after subarachnoid hemorrhage (SAH) and represents a significant cause of poor functional outcome. DCI was mainly thought to be caused by cerebral vasospasm; however, recent clinical trials have been unable to confirm this hypothesis. Studies in humans and animal models have since supported the notion of a multifactorial pathophysiology of DCI. This review summarizes some of the main mechanisms under investigation including cerebral vascular dysregulation, microthrombosis, cortical spreading depolarizations, and neuroinflammation. Recent guidelines have differentiated between DCI and angiographic vasospasm and have highlighted roles of the microvasculature, coagulation and fibrinolytic systems, cortical spreading depressions, and the contribution of the immune system to DCI. Many therapeutic interventions are underway in both preclinical and clinical studies to target these novel mechanisms as well as studies connecting these mechanisms to one another. Clinical trials to date have been largely unsuccessful at preventing or treating DCI after SAH. The only successful pharmacologic intervention is the calcium channel antagonist, nimodipine. Recent studies have provided evidence that cerebral vasospasm is not the sole contributor to DCI and that additional mechanisms may play equal if not more important roles.