Leslie A. Hamilton

Objectives: Status epilepticus (SE) is a severe neurological condition with significant morbidity and mortality. While guidelines offer recommendations for emergent therapy with benzodiazepines, there is limited guidance for medications for urgent control in SE. High-dose levetiracetam (LEV) (60 mg/kg) was introduced in the 2019 ESETT trial and has not been studied against the previous standard. Methods: This retrospective cohort evaluated patients admitted for SE. Patients were included if they received ≥1 dose of intravenous LEV ≥20 mg/kg from January 1, 2019, to January 14, 2022, and were 17 years of age or older. Traumatic injuries were excluded. Patients were divided into groups of LEV loading dose of P =0.0127]. After logistic regression analysis that included home ASM use, doses ≥40 mg/kg of LEV, and a total of ≥4 mg of lorazepam equivalents received, no difference was seen in ASM requirements. Patients who received <40 mg/kg were more likely to have a history of seizure and be on ASMs before admission. Conclusions: After logistic regression, the loading dose of LEV did not change the need for additional ASM to control seizures in SE. Further investigations evaluating the efficacy of 20 mg/kg compared with 60 mg/kg are needed; however, this study found no difference in seizure control between the groups.

Background: Acute ischemic stroke (AIS) accounts for 87% of all strokes and is associated with high morbidity and mortality. Stroke mimics, conditions that present with stroke‐like symptoms but are not AIS, represent an important proportion of stroke cases. Tenecteplase, an alteplase variant with higher fibrin affinity and a longer half‐life, has recently gained approval for the treatment of AIS. Limited evidence exists on the safety of tenecteplase in stroke mimics. Objective: The objective of this study was to determine the incidence of intracranial hemorrhage in patients with stroke‐like signs and symptoms who received tenecteplase with and without a confirmed diagnosis of AIS. Methods: This was a single‐center, retrospective cohort study conducted at a comprehensive stroke center. Patients who received tenecteplase for stroke‐like symptoms from June 2020 to December 2021 were included. Patients were grouped based on AIS diagnosis confirmed by neuroimaging or discharge diagnosis. The primary outcome was the incidence of intracranial hemorrhage, and secondary outcomes included incidence of symptomatic and asymptomatic intracranial hemorrhage, extracranial hemorrhage, hospital length of stay, angioedema development, and discharge disposition. Results: Of 250 patients, 174 were diagnosed with AIS and 76 with stroke mimics. Patients with AIS were older (69 years [SD: 13.8 years] vs. 62.3 years [SD: 16.1 years]; p = 0.0008), had higher hypertension prevalence (132 [75.9%] vs. 44 [57.9%]; p = 0.0042), and lower previous stroke prevalence (9 [5.2%] vs. 11 [14.5%]; p = 0.0126) compared with stroke‐mimic patients, respectively. Patients with AIS had shorter median tenecteplase door‐to‐needle times (38.5 min [IQR: 30 min, 53 min] vs. 46.5 min [IQR: 34.5 min, 64.5 min]; p = 0.0154) compared with stroke mimics. Intracranial hemorrhage occurred in 11.5% of patients with AIS and none in stroke mimics ( p = 0.0021). Symptomatic hemorrhage rates were similar between groups. Patients with AIS had longer median hospital stays (3 days [IQR: 2 days, 6 days] vs. 2 days [IQR: 2 days, 4 days]; p = 0.0018). Discharge dispositions and cases of angioedema were similar between groups. Conclusion: Tenecteplase appears safe for stroke mimics, with no disproportionate harm compared to patients with AIS. This study further supports the safety of tenecteplase in stroke mimics, aiding rapid treatment decisions in stroke‐like presentations.

Background: Hyperglycemia following an acute ischemic stroke has been linked to increased morbidity and mortality. Because of changes in a hospital‐wide sliding‐scale insulin protocol to incorporate half‐doses at midnight due to hypoglycemia risk, we aimed to evaluate the safety and efficacy of half‐dose sliding‐scale insulin at midnight compared with full doses in patients with acute ischemic stroke receiving enteral nutrition.Methods: This single‐center, retrospective cohort study involved 151 patients with acute ischemic stroke and receiving enteral nutrition in a neurocritical care unit between January 1, 2014, and December 31, 2021. The exposure of interest was half‐dose sliding‐scale insulin at midnight compared with full‐dose sliding‐scale insulin at midnight. The primary outcome was the incidence of hyperglycemia for a 48‐h period after stability while receiving enteral nutrition. Secondary outcomes were new infections, incidence of hypoglycemia, and incidence of delirium.Results: In the full‐dose group, 52 patients experienced hyperglycemia compared with 60 patients in the half‐dose group; however, after propensity matching for carbohydrate content in enteral nutrition and hemoglobin A1c, the results are not noninferior (risk difference, 3.9%; 95% CI, −21.2% to 13.3%; P = 0.1041). Delirium was significantly higher in the full‐dose group, whereas the half‐dose group had a higher rate of suspected bacterial infections.Conclusion: The study indicates that administering half‐dose sliding‐scale insulin at midnight in patients with acute ischemic stroke receiving enteral nutrition is not noninferior to full doses in controlling hyperglycemia. However, differences in delirium and infection rates suggest that glycemic changes may influence other outcomes.

Objectives: Intractable headaches are a common occurrence in patients experiencing an aneurysmal subarachnoid hemorrhage (aSAH). Utilization of multimodal pain management regimens has become the standard of care for the treatment of acute and chronic pain. The primary objective of this study was to evaluate the use of a new multimodal pain regimen for headache in patients who have experienced aSAH. Methods: This was an Institutional Review Board approved study evaluating the use of a multimodal pain regimen for treatment of headache pain in 104 patients who experienced aSAH in a neuro intensive care unit. Patients diagnosed with aSAH from January 2017 to December 2019, which was prior to the implementation of the multimodal pain regimen, were compared to aSAH patients from March 2020 through 2022, who were treated with the multimodal pain regimen. The primary endpoint was morphine milligram equivalent usage during the first 5 days of admission before and after the implementation of the multimodal pain regimen. The secondary endpoints were pain scores during the first 5 days of admission. Results: As compared to those who did not receive the aSAH headache pathway (n = 39, premultimodal regimen), those who did receive the pathway (n = 65, multimodal regimen) received significantly more morphine milligram equivalents over the first 5 days of admission (30.0 [0, 97.5] vs 82.5 [15, 135]); P = 0.0053. There was no difference in the median average pain score. Conclusions: The MM pain pathway did not reduce the total morphine equivalents utilized for the treatment of aSAH-associated headache.

Objectives: To investigate the safety of administering low-dose aspirin (81 mg) 18 hours after intravenous thrombolytic therapy. Methods: This is a retrospective cohort investigation. Individuals received either alteplase or tenecteplase for acute ischemic stroke followed by aspirin 81 mg (after follow-up imaging). An institutional change moved follow-up post-thrombolytic CT scans to 18 hours, and qualifying patients were grouped based on whether they received aspirin ≤24 hours or >24 hours. Chart reviews were conducted to assess the primary outcome of new or worsening intracranial hemorrhage, as well as secondary outcomes of change in stroke scale scores at discharge and 3 months, lengths of stay, favorable outcomes at 3 months, hospital readmission, and mortality. Results: Out of 350 patients screened, 130 qualified for inclusion—50 of whom received aspirin ≤24 hours (mean 21.1 hours, SD±6.2), and 80 who received aspirin >24 hours (mean 34 hours, SD±8.2). Only 1 new intracranial bleed occurred following aspirin administration in the >24-hour group. No statistically significant differences were observed in any of the secondary outcomes, although there was higher mortality (3/50 vs. 2/80, P=0.372) and shorter hospital length of stay (median difference −1.0 day, P=0.0336) in the <24 hours group. Conclusions: Low-dose aspirin administration sooner than 24 hours following thrombolytic therapy did not increase bleeding events. Sooner aspirin administration after ischemic stroke can potentially enhance the prevention of secondary embolization and did not demonstrate worse clinical outcomes; however, further randomized controlled trials are needed.

Background: Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). Objective: The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC. Methods: This was a retrospective cohort study conducted at an academic medical center designated as a comprehensive stroke center. Consecutive patients admitted for ICH who reported use of apixaban or rivaroxaban prior to admission were considered for inclusion in the study. Patients were treated with 25 to 50 units/kg of aPCC. Intracerebral hemorrhage volume was measured before administration of aPCC and then again within 36 hours of aPCC administration. Results: A total of 40 patients were included in the final analysis. Overall, the cohort was predominantly male (24 [60%]), white (27 [67.5%]), and the mean age was 75.3 ± 10.5 years. Most patients reported taking apixaban prior to admission (31 [77.5%]) and a large proportion were also taking aspirin (13 [32.5%]). The mean change in ICH volume was 1.12 ± 6.03 mL ( P = 0.2475). Conclusions and Relevance: There was a nonsignificant change in mean ICH volume and no reported cases of thromboembolism. Due to the relatively high proportion of patients with significant hematoma expansion, more studies are needed on which patient population would best benefit from treatment with aPCC.

Background and Purpose: The purpose of this study was to assess the incidence of seizures in patients with spontaneous intracerebral hemorrhage (ICH) who received prophylactic levetiracetam. Methods: This was a retrospective cohort study evaluating the use of levetiracetam in patients without a history of seizures who experienced a spontaneous intracerebral hemorrhage. Patients were excluded if they were younger than 18 years of age, had a documented history of a seizure disorder, or had an antiseizure drug documented on their home medication list. Patients were based on their exposure to levetiracetam. The primary outcome was incidence of seizure during hospital admission. Secondary outcomes included occurrence of adverse events, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Results: Of the 229 patients included in the final analysis, 21 were in the levetiracetam group (LEV) and 208 were in the no levetiracetam group (no LEV). No statistical difference in seizure incidence was observed when comparing the LEV and no LEV groups (1 [4.8%] LEV vs 3 [1.4%] no LEV; P = .32). There was also no statistical difference in the median ICU LOS (2 days [1 day, 5 days] LEV vs 2 days [1 day, 3 days] no LEV; P = .27), median hospital LOS (6 days [2 days, 8 days] LEV vs 6 days [3 days, 9 days] no LEV; P = .27), or adverse events. Conclusions: This study does not support the use of levetiracetam prophylaxis in patients who have experienced an ICH.

Background: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH.Methods: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling.Results: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41–3.67, p‐value = 0.001, OR 2.76, 95% CI 1.37–5.55, p‐value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57–5.06, p‐value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48–12.74, p‐value p‐value <0.0001, respectively).Conclusions: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.