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Cerebral vasospasm remains a significant source of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Dantrolene has shown promise in several animal studies in the treatment of cerebral vasospasm. The present study seeks to critically review the evidence of its use in human subjects, aiming to 1) describe the forms and dosages used, 2) describe its safety profile, and 3) describe its effectiveness in treating cerebral vasospasm.A systematic review of intra-arterial dantrolene use in cerebral vasospasm was performed. A total of 86 articles were identified across all databases, 6 of which were ultimately included in the present study. Primary outcomes included a description of the form and dosage of dantrolene prescribed, the incidence of adverse effects after dantrolene use, and its efficacy for the treatment of cerebral vasospasm.Study designs included 2 randomized controlled trials (33.3%), 2 case series (33.3%), and 2 case reports (33.3%). Both the intra-arterial and intravenous administration of dantrolene has been performed with varying dose regimens. Although there exists limited clinical information regarding side effects, a case of liver toxicity was reported. All existing studies reported benefit in vasospasm measured either by transcranial Doppler or digital subtraction angiography. The level of evidence was low, consisting largely of retrospective studies that had a high likelihood of bias.Dantrolene is a promising new therapeutic agent in the treatment of cerebral vasospasm. Although existing reports of its use are encouraging, high-quality prospective randomized trials are necessary for recommendations pertaining to dose, route, indications, and efficacy.

Objective: To assess whether diabetes alone or in association with Apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s Disease (AD) diagnosis. Methods: A retrospective cohort study of 33,456 participants from the National Alzheimer’s Coordinating Center database. Results: Participants with one or two APOE ε4 alleles had 2.71 (CI:2.55–2.88) and 9.37 (CI:8.14–10.78) times higher odds of AD diagnosis, respectively, relative to those with zero ε4 alleles. In contrast, diabetic participants showed 1.07 (CI:0.96–1.18) times higher odds of AD relative to nondiabetics. Diabetes did not exacerbate the odds of AD in APOE ε4 carriers. APOE ε4 carriage was correlated with declines in long-term memory and verbal fluency, which were strongly correlated with conversion to AD. However, diabetes was correlated with working memory decline, which had a relatively weak correlation with AD. Conclusions: Unlike APOE ε4, there was little evidence that diabetes was a risk factor for AD.

BackgroundDual antiplatelet therapy (DAP) is necessary to prevent thromboembolic events during carotid stenting, stent-assisted coil embolization, and implant of flow diverters (FD). However, DAP in the acute phase may be challenging. An intravenous alternative, cangrelor, has rapid onset, short plasma half-life, and more reliable antiplatelet action for acute interventions. The study objective was to evaluate feasibility and safety of IV cangrelor during acute neuroendovascular surgery procedures.MethodsWe performed a retrospective analysis of our database of patients treated with stent-assisted coil embolization, FD placement for aneurysmal subarachnoid hemorrhage (aSAH), or stenting for acute internal carotid artery (ICA) occlusion where IV cangrelor was used. Morbidity, mortality, incidence of thromboembolic events, hemorrhages, and 90-day outcomes were reported.ResultsTen patients were found in our database from June 2018 through January 2019. Four patients had aSAH, four had middle cerebral artery strokes with tandem lesions, one had an ICA occlusion, and one had a vertebral artery aneurysm. One of the ten patients experienced a thrombotic event. One patient developed new post-procedural bleeding and two had worsening intracranial hemorrhage. Five patients were discharged home in stable condition, two to acute rehabilitation, one to a nursing facility, and two others expired (likely the result of the severe and evolving strokes). Of the eight who were discharged, six (75%) had a good 90-day functional outcome (modified Rankin Scale 0–2).ConclusionAcute administration of IV cangrelor with or without oral ticagrelor is a feasible antiplatelet treatment option for acute neuroendovascular procedures.

IV alteplase is a primary treatment for acute ischemic stroke (AIS) at a weight-based dose (WBD) of 0.9 mg/kg and maximum dose (MD) of 90 mg. There are conflicting data regarding outcomes for those weighing ≥100 kg. There is also a paucity of data in Hispanics. The prevalence of adult obesity in the US has progressively increased; hence, the percentage of patients receiving the maximum dose also is expected to rise. We examined differences between patients treated with WBD vs. MD.A retrospective review of our center's Get With The Guidelines-Stroke database was performed for IV alteplase cases between October 2013-February 2017. Selection criteria included age ≥18 years, IV alteplase administration, and a recorded measured weight. Patients were dichotomized into WBD group weighing100 kg and MD group weighing ≥100 kg. Categorical variables were analyzed using Chi square tests and continuous variables were analyzed using independent samples t-tests. Multivariable logistic regression analysis was performed to determine whether MD in combination with other variables was associated with poor outcomes.There were 328 patients included in the study, 38 (11.6%) received MD. Proportions of younger, male, and non-Hispanic were higher in the MD group. There were no statistically significant differences for initial NIHSS, discharge modified Rankin Scale (mRS), 90-day mRS, symptomatic intracerebral hemorrhage (sICH), or systemic hemorrhage between groups.One in ten patients thrombolysed for the treatment of AIS received MD. In a predominantly Hispanic population, those who received MD and WBD had similar rates of sICH, discharge disposition, and functional outcome (mRS) at discharge and at 90 days. Limitations include small sample size and attrition for the 90-day mRS.

Alzheimer’s disease (AD) is a neurodegenerative disease that disproportionately impacts memory and the hippocampus. However, it is unclear how AD pathology influences the activity of surviving neurons in the hippocampus to contribute to the memory symptoms in AD. One well-understood connection between spatial memory and neuronal activity in healthy brains is the activity of place cells, neurons in the hippocampus that fire preferentially in a specific location of a given environment (the place field of the place cell). In the present study, place cells were recorded from the hippocampus in a recently-developed rat model of AD (Tg-F344 AD) at an age (12–20 months) at which the AD rats showed marked spatial memory deficits. Place cells in the CA2 and CA3 pyramidal regions of the hippocampus in AD rats showed sharply reduced spatial fidelity relative to wild-type (WT) rats. In contrast, spiking activity of place cells recorded in region CA1 in AD rats showed good spatial fidelity that was similar to CA1 place cells in WT rats. Oral administration of the M(1) muscarinic acetylcholine receptor agonist VU0364572 impacted place cell firing rates in CA1 and CA2/3 hippocampal regions but did not improve the spatial fidelity of CA2/3 hippocampal place cells in AD rats. The results indicated that, to the extent the spatial memory impairment in AD rats was attributable to hippocampal dysfunction, the memory impairment was more attributable to dysfunction in hippocampal regions CA2 and CA3 rather than CA1.