Use of Arterial Spin-Labeling in Patients with Aneurysmal Sub-arachnoid hemorrhage.

Delayed cerebral ischemia (DCI) due to cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) has long been recognized as a major source of morbidity and mortality. Early detection of cerebral vasospasm and identification of patients who are likely to become symptomatic is crucial to guide aggressive medical and/or endovascular interventions. Magnetic resonance imaging using arterial spin-label (ASL) is a noninvasive mean for assessing cerebral blood flow and is based on direct magnetic labeling of arterial blood water protons. The diagnostic role of ASL in acute ischemic stroke, epilepsy, and neurodegenerative disorders has been explained in multiple studies but its ability to predict vasospasm in aSAH has not been published before. The purpose of this study is to highlight the diagnostic implications of different perfusion patterns of ASL in patients with aSAH which can be utilized to prevent DCI in such patients when other commonly used modalities are not available, contraindicated, or fail to detect vasospasm.

Examination of Racial Differences in a Posttraumatic Stress Disorder Group Therapy Program for Veterans.

Posttraumatic stress disorder (PTSD) is one of the most prevalent mental health diagnoses for veterans. Group therapy can be an effective and efficient means of treating PTSD, yet the literature exploring treatment outcomes for racial minorities is mixed and limited. The present study was an evaluation across racial groups of the PTSD Recovery Program, a manualized group therapy implemented at a Veterans Affairs hospital. Data were collected from male veterans (N = 450) who identified as non-Hispanic White or non-Hispanic African American and participated in a 10-week, combat-related, group therapy program between 2010 and 2014. Participants completed the Posttraumatic Stress Disorder Checklist-Military version (PCL-M) measure at pre-treatment and post-treatment. The Program led to a statistically significant reduction in PCL-M scores (Cohen's d = .64). Symptom reduction occurred regardless of race, with no racial differences in improvement. Racial and ethnic composition of groups was not related to outcomes. The Program was effective regardless of veteran group or provider. Results imply that the PTSD Recovery Program is an effective first-line option to treating non-Hispanic White and non-Hispanic African American veterans with PTSD. Future research should continue to explore the associations between group characteristics and treatment outcomes.

Seizure Prophylaxis in the Immediate Post-Hemorrhagic Period in Patients with Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Seizures are a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) and occur most commonly in the immediate posthemorrhagic period. Most commonly used antiepileptic drugs (AEDs) for seizure prophylaxis in aSAH include phenytoin and levetiracetam. There is no reliable data available on the safety and efficacy of restricting AED prophylaxis only till the aneurysm is secured. METHODS: We retrospectively chart reviewed patients admitted to our neurosciences intensive care unit (NICU) with aSAH during the past two years. Seizure incidence was studied in patients treated with phenytoin versus levetiracetam and in patients treated for 3-7 days vs. those where AED was discontinued immediately after aneurysm was secured. RESULTS: In 28 patients, AED prophylaxis was discontinued immediately after the aneurysm was secured, and in 21 patients, it was continued for 3-7 days. Of the 28 patients who received AED prophylaxis for less than or equal to two days, phenytoin was used in 20 patients and levetiracetam was used in eight patients. In patients receiving AED prophylaxis for 3-7 days, phenytoin was used in eight cases and levetiracetam was used in 13 cases. None of these patients had seizures reported during hospitalization or at three-month follow-up. CONCLUSION: Stopping the AED prophylaxis immediately after aneurysm coiling is not associated with increased risk of seizures. Seizures at presentation in patients with aSAH are not associated with development of epilepsy at three months. Both phenytoin and levetiracetam are well tolerated in patients with aSAH when limited to the immediate posthemorrhagic period.

Consecutive Endovascular Treatment of 20 Ruptured Very Small (<3 mm) Anterior Communicating Artery Aneurysms.

BACKGROUND: Small aneurysms located at the anterior communicating artery carry significant procedural challenges due to a complex anatomy. Recent advances in endovascular technologies have expanded the use of coil embolization for small aneurysm treatment. However, limited reports describe their safety and efficacy profiles in very small anterior communicating artery aneurysms. OBJECTIVE: We sought to review and report the immediate and long-term clinical as well as radiographic outcomes of consecutive patients with ruptured very small anterior communicating artery aneurysms treated with current endovascular coil embolization techniques. METHODS: A prospectively maintained single-institution neuroendovascular database was accessed to identify consecutive cases of very small (<3 mm) ruptured anterior communicating artery aneurysms treated endovascularly between 2006 and 2013. RESULTS: A total of 20 patients with ruptured very small (<3 mm) anterior communicating artery aneurysms were consecutively treated with coil embolization. The average maximum diameter was 2.66 ± 0.41 mm. Complete aneurysm occlusion was achieved for 17 (85%) aneurysms and near-complete aneurysm occlusion for 3 (15%) aneurysms. Intraoperative perforation was seen in 2 (10%) patients without any clinical worsening or need for an external ventricular drain. A thromboembolic event occurred in 1 (5 %) patient without clinical worsening or radiologic infarct. Median clinical follow-up was 12 (±14.1) months and median imaging follow-up was 12 (±18.4) months. CONCLUSION: This report describes the largest series of consecutive endovascular treatments of ruptured very small anterior communicating artery aneurysms. These findings suggest that coil embolization of very small aneurysms in this location can be performed with acceptable rates of complications and recanalization.

Stenting and angioplasty for idiopathic intracranial hypertension: a case series with clinical, angiographic, ophthalmological, complication, and pressure reporting.

BACKGROUND: Previous studies have demonstrated that cerebral dural sinus stenosis (DSS) may be a potential patho-physiological cause of idiopathic intracranial hypertension (IIH). Endovascular therapy for DSS is emerging as a potential alternative to treat IIH. Here, we present the results of our case series. METHOD: We prospectively collected angiographic and manometric data on patients that underwent angioplasty/stenting for IIH. All patients had failed maximal medical therapy (MMT) and had confirmed sinus stenosis. Demographic, clinical and radiological presentation, and outcomes were collected retrospectively. RESULTS: A total of 18 patients underwent 25 procedures. Demographics revealed a mean age of 30 (range 15-59), 83% (15/18) were female, 72% (13/18) were white, and mean body mass index of 36 (range 23-59.2). All patients presented with classic IIH. Symptom improvement or resolution was reported in 94% (17/18) of patients. All patients had resolution and/or stabilization/improvement of their papilledema. Headaches related to increased pressure improved in 56% (10/18). Re-stenosis and retreatment occurred in 33% (6/18). No procedural related complications were reported. CONCLUSION: Dural sinus angioplasty and stenting is relatively safe, feasible, and clinically efficacious for patients with symptomatic sinus stenosis who have failed standard therapy. The long-term durability of patency and clinical improvement remains unknown.

Middle cerebral artery aneurysm endovascular and surgical therapies: comprehensive literature review and local experience.

The middle cerebral artery is a common location for cerebral aneurysms and is associated with a lower risk of rupture than aneurysms located in the anterior or posterior communicating arteries. No evidence supports the superiority of clipping over coiling to treat middle cerebral artery aneurysm (MCAA) or vice versa. The feasibility of treating the MCAA with endovascular therapy as the first choice of treatment in cohorts of nonselected aneurysms exceeds 90%. A randomized clinical trial comparing the 2 approaches in nonselected cases with long-term follow-up will shed light on which patients may benefit from one approach over another.

Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial.

BACKGROUND: Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14·7%) of 224 patients in the stenting group and 13 (5·8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial. METHODS: We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70-99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00576693. FINDINGS: During a median follow-up of 32·4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0·0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7·1% at year 1 (95% CI 0·2 to 13·8%; p=0·0428), 6·5% at year 2 (-0·5 to 13·5%; p=0·07) and 9·0% at year 3 (1·5 to 16·5%; p=0·0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group: any stroke (59 [26%] of 224 patients vs 42 [19%] of 227 patients; p=0·0468) and major haemorrhage (29 [13%]of 224 patients vs 10 [4%] of 227 patients; p=0·0009). INTERPRETATION: The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis. FUNDING: National Institute of Neurological Disorders and Stroke (NINDS) and others.

Safety and predictors of aneurysm retreatment for remnant intracranial aneurysm after initial endovascular embolization.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) is a rare but devastating form of stroke. Endovascular therapy has been criticized for its higher rate of recanalization and retreatment. The safety and predictors of retreatment are unknown. We report the clinical outcomes, imaging outcomes and predictors for aneurysm retreatment after initial endovascular embolization. METHOD: We identified patients who underwent endovascular retreatment from July 2005 through November 2011. Aneurysm and patient data were collected. Periprocedural complications were reported as intraoperative perforation (IOP) or thromboembolic event (TEE). Aneurysm and patient characteristics were compared between aneurysms requiring retreatment and those not requiring retreatment to evaluate aneurysm retreatment predictors. RESULTS: A total of 111/871 (13%) aneurysms underwent retreatment. Two (0.2%) were retreated for recurrent acute SAH, 82 (74%) aneurysms were located in the anterior circulation, 47 (42%) required stent and 5 (5%) required balloon assist during retreatment. There were a total of 5 (5%) IOP and 6 (5%) TEE from which 2 (2%) and 1 (1%) were symptomatic, respectively. Overall symptomatic events rate were 2.7%. Patients were followed up for an average of 15±14 months. Seven (0.8%) aneurysms required a second retreatment without any recurrent SAH. Multivariable analysis revealed an OR for aneurysms requiring retreatment of 2.965 for aneurysms presenting as aneurysmal SAH, 1.791 for aneurysms in the posterior circulation and 1.053 for aneurysms with large dome size. CONCLUSIONS: Aneurysm retreatment is a safe option without a significant increase in morbidity or mortality. SAH, posterior circulation aneurysms and larger aneurysm dome size are predictors of aneurysms requiring retreatment.

Complications of endovascular therapy for acute ischemic stroke and proposed management approach.

Over the past decade, endovascular therapy has emerged as a promising therapeutic approach for select patients with acute ischemic stroke. However, the morbidity, mortality, and complication rates in intra-arterial recanalization trials are higher than in the National Institute of Neurological Disorders and Stroke trial of IV tissue plasminogen activator. This review discusses common complications associated with endovascular therapy for acute ischemic stroke, avoidance of complications, and management of some of the common complications.

Multimodal endovascular therapy of traumatic and spontaneous carotid cavernous fistula using coils, n-BCA, Onyx and stent graft.

BACKGROUND AND PURPOSE: Carotid cavernous fistula (CCF) can be classified as either direct or indirect according to the arterial feeder source. The current standard treatment for CCF is endovascular embolization. In this case series, 21 CCF (direct and indirect) embolization procedures were treated with multimodal endovascular therapy to explore safety, technique and clinical efficacy. METHOD AND PATIENTS: The neurointerventional database was reviewed for all cases of CCF. Demographic information, indications for the procedure, presenting symptoms, endovascular therapy types, complications and procedure angiographic and clinical efficacy were collected. RESULTS: 21 CCF embolization procedures were performed using multimodal therapy on 15 patients (eight females and seven males) with a mean age of 56.4±22.4 years (15-90 years), with 60% traumatic CCF and 40% spontaneous CCF presenting mainly with typical visual symptoms. 10 patients were treated in one session, four patients underwent two sessions and one required three sessions of endovascular therapy. Complete fistula occlusion was achieved in 10/15 patients (73.3%) in one session and in 14/15 (93.3%) patients after two or more sessions. One patient's symptoms (case No 15) improved dramatically after the second session despite incomplete obliteration of the CCF. No periprocedural complications were reported. Long term follow-up showed one recurrence of the CCF with a mean follow-up time of 201±17.2 months (range 1-56 months). Patient No 6 was lost to follow-up. CONCLUSION: Multimodal endovascular embolization of CCF appears to be safe with a high success rate of complete obliteration. This case series demonstrates complete occlusion in 73.3% of the patients after one session and in 93.3% after the second session.

Endovascular embolization of head and neck tumors.

Endovascular tumor embolization as adjunctive therapy for head and neck cancers is evolving and has become an important part of the tools available for their treatment. Careful study of tumor vascular anatomy and adhering to general principles of intra-arterial therapy can prove this approach to be effective and safe. Various embolic materials are available and can be suited for a given tumor and its vascular supply. This article aims to summarize current methods and agents used in endovascular head and neck tumor embolization and discuss important angiographic and treatment characteristics of selected common head and neck tumors.

Stent-assisted parent artery occlusion of giant cerebrovascular aneurysms to avoid mass effect.

BACKGROUND: Endovascular treatment of giant cerebrovascular aneurysms (GCA) may be challenging due to risk of worsening mass effect, thromboembolism, rupture, and recurrence. The purpose of this study was to provide a preliminary evaluation of GCA therapy using stent-assisted coil parent artery occlusion (PAO) to reduce the likelihood of mass effect, aneurysm recurrence, and vessel recanalization. MATERIALS AND METHODS: Five patients with GCAs were treated by PAO by deploying detachable coils within a Neuroform-3 stent across the aneurysm neck. Patients were monitored clinically to note any changes after treatment. Magnetic resonance angiography was performed 3 to 12 months after stent placement, and incomplete PAO and aneurysm recurrence were noted. RESULTS: Stent-assisted PAO was technically successful in all GCAs with no residual aneurysm filling and without any coil herniation into the aneurysm sac. None of the patients had recanalization of the vessel or GCA or clinical worsening over a follow-up period of 3-17 months. Symptomatic mass effect improved in 2 and resolved in 2 patients. CONCLUSION: Based on our preliminary experience, stent-assisted PAO in GCAs is technically feasible and may be a valid option in patients who tolerate balloon test occlusion to minimize the likelihood of increased mass effect from coil embolization.

Pediatric cerebral angiography: analysis of utilization and findings.

Pediatric neuroendovascular procedures are being performed with increasing frequency, for various indications. Reported here is the experience of interventionally trained neurologists performing pediatric cerebral diagnostic angiography between August 1, 2005, and April 30, 2008, at a single tertiary institution. Data regarding patient demographics, diagnostic indication and angiographic diagnosis, procedural complications, and procedural specifications were recorded to assess practice patterns and to track procedural morbidity. In all, 42 patients had 46 procedures during the study period. Mean age was 9.97 years (standard deviation S.D. = 5.39; range, 0.3-18 years); 22/42 were male (52%). Known or suspected vascular malformation was the diagnostic indication for 20 patients; of these, 12 had an arteriovenous malformation, 5 had venous abnormalities, and 3 exhibited no angiographic vascular malformations. In 13 total procedures there was no angiographic pathology. General anesthesia was used in 29/46 procedures (63%). A total of 190 cerebral arteries were individually selected, with a mean number of vessels catheterized of 4.1 (S.D. = 1.7) per procedure. No procedural thromboembolic complications, iatrogenic arterial dissection, or neurologic or vascular access site complications occurred. In conclusion, pediatric cerebral angiography seems to be generally safe, although there should be a strong diagnostic indication, given the inherent procedural risk.

Interventional acute ischemic stroke therapy with intracranial self-expanding stent.

BACKGROUND AND PURPOSE: Rapid and safe recanalization of occluded intracranial arteries in acute ischemic stroke (AIS) is challenging. Newly available self-expanding intracranial atherosclerotic stents (SEIS), which can be deployed rapidly and safely, make acute stenting an option for treating AIS. We present the feasibility of this technique. METHODS: A retrospective analysis evaluated procedural protocols and clinical response to treatment in patients with AIS treated with SEIS. Descriptive statistics are presented with initial and follow-up National Institutes of Health Stroke Scale and modified Rankin Score. RESULTS: Nine patients with AIS underwent acute SEIS placement. There was successful deployment of the Neuroform (n=4) and Wingspan (n=4/5) stents in the M1/M2 (n=5) and M3 (n=1) middle cerebral artery segments, intracranial internal carotid artery (one of 2), and intracranial vertebrobasilar junction (one). Mean time of SEIS deployment from AIS onset was 5.1 hours. Complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 3) and partial/complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 2 or 3) recanalization occurred in 67% and 89%, respectively. One intracranial hemorrhage (11%) and one acute in-stent thrombosis (successfully treated with abciximab and balloon angioplasty) occurred. Stroke-related mortality occurred in 3 of 9 (33%) patients and survivors had modified Rankin Score < or = 2. Follow-up angiography (mean, 8 months; range, 2 to 14 months) in 4 of 9 patients showed no stent restenosis. CONCLUSIONS: This preliminary experience with SEIS in refractory AIS demonstrated the technical feasibility and high rate of recanalization with acute stenting. Long-term safety and strategies to limit in-stent thrombosis and optimize periprocedural management are crucial before initiating future randomized efficacy studies with SEIS in AIS refractory to standard therapy.

Takotsubo cardiomyopathy associated with seizures.

BACKGROUND: Takotsubo syndrome is a reversible neuromyocardial failure that has been thought to be related to an acute catecholamine toxicity of the myocardium brought upon by a stressful event. The neurocritical care unit population is particularly vulnerable for this condition given the acute presentation of neurological emergencies, which most often can be catastrophic. We present a case series of this syndrome and a review of the literature. METHOD: Our recent experience with three cases that were prospectively identified with the diagnosis of Takotsubo syndrome is reported with clinical presentation, evaluation, and management approach. Review of the literature is presented in the discussion. RESULTS: We present three episodes of Takotsubo neuromyocardial syndrome in two patients that were admitted to our neurointensive care unit that presented with seizures and had typical clinical presentation, echocardiographic and cardiac catheterization findings. All the episodes were treated with vasoactive medications, ventilatory support, afterload and preload reduction, and treatment of the underlying condition. There was complete reversal of their symptoms and findings in each episode. CONCLUSIONS: Patients with critical neurological illnesses such as large ischemic or hemorrhagic stroke, status epilepticus, recurrent seizure activities as in our study may be at a higher risk for Takotsubo neuromyocardial syndrome.

Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway.

Recent evidence demonstrates that apolipoprotein E (apoE) influences the central nervous system (CNS) response to both acute and chronic injury. To address the mechanisms by which apoE influences neurological disease, we examined differential gene expression in the brains of apoE transgenic mice after closed head injury. Apart from confirming the knockout of apoE, the largest differential gene expression occurred for the interleukin-9 receptor (IL-9R), which was > 100-fold up-regulated in apoE-deficient versus wild-type mice. We observed a similar pattern of posttraumatic IL-9R up-regulation in APOE4 targeted replacement mice as compared with their APOE3 counterparts. This difference in gene expression was associated with increased neuronal protein expression of IL-9R in E4 animals compared with E3 as demonstrated by immunohistochemistry. The consequence of IL-9R binding in mast cells is the induction of proliferation and differentiation. This indirectly favors degranulation and release of histamine and inflammatory mediators, which have previously been demonstrated to exacerbate secondary neuronal injury. We found that apoE-deficient animals had increased levels of systemic histamine after injury and that pre-treatment with antihistamines improved functional outcomes in apoE-deficient but not wild-type animals after head injury. These results suggest that apoE modifies secondary neuronal injury caused by histamine release and are consistent with previous observations that apoE affects the CNS inflammatory response in an isoform-specific manner.

Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury.

The treatment of traumatic brain injury (TBI) remains limited, and aside from surgical hematoma evacuation, clinical management is largely supportive and directed toward management of cerebral edema and intracranial hypertension. Secondary neuronal injury caused by ischemia and the development of cerebral edema may occur in the subacute phase, with intracranial pressures often peaking in the first several days following injury. Because inflammation contributes significantly to the pathophysiology of cerebral ischemia and endothelial dysfunction underlies the development of cerebral edema, therapeutic strategies that target the post-traumatic inflammatory cascade and reduce endothelial dysfunction hold enormous potential to improve clinical outcomes after TBI. Statins inhibit inflammation by suppressing inflammatory cytokine release, and by interfering with multiple steps of leukocyte recruitment and migration into the CNS. In this study, we demonstrate that treatment with atorvastatin and simvastatin markedly reduced functional neurological deficits after traumatic brain injury in mice. These effects were accompanied by histological reduction in degenerating hippocampal neurons and suppression of inflammatory cytokine mRNA expression in brain parenchyma. Furthermore, statin treatment improved cerebral hemodynamics following head injury. Thus, the administration of statins may represent a viable therapeutic strategy in the acute treatment of closed head injury.

Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: A multivariate analysis of an institutional experience.

OBJECT: Impairment of endothelial nitric oxide synthase (eNOS), endothelium-dependent relaxation, and cerebrovascular autoregulation all occur in vasospastic cerebral arteries following subarachnoid hemorrhage (SAH). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, both improve endothelial function and increase eNOS messenger RNA, protein, and enzymatic activity threefold. Increasing experimental evidence in animal models of SAH suggests that statins may ameliorate cerebral vasospasm. The authors hypothesized that patients chronically treated with statins would have a decreased risk of symptomatic vasospasm after SAH. METHODS: The authors retrospectively reviewed the charts of 115 patients with SAH who were consecutively admitted to the Neuroscience Intensive Care Unit of Duke University between 1998 and 2001. The independent association of statin therapy to symptomatic vasospasm was assessed using multivariate logistic regression analysis. Fifteen patients (13%) admitted with SAH were receiving statin therapy for at least 1 month before admission. Forty-nine patients (43%) experienced symptomatic vasospasm a mean of 5.8 +/- 3 days after onset of SAH. Current statin therapy on admission (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01-0.77) was independently associated with an 11-fold reduction in the risk of symptomatic vasospasm. Fisher Grade 3 SAH (OR 2.82, 95% CI 1.50-5.71) and rupture of anterior cerebral or internal carotid artery aneurysm (OR 3.77, 95% CI 1.29-10.91) were independently associated with an increased risk of symptomatic vasospasm. CONCLUSIONS: In this retrospective case series, patients who received statin therapy for at least 1 month demonstrated an 11-fold decrease in the risk of developing symptomatic vasospasm after SAH.

Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage.

OBJECTIVES: Prophylactic treatment with antiepileptic drugs is common practice following subarachnoid hemorrhage (SAH) and traumatic brain injury. However, commonly used antiepileptic drugs have multiple drug interactions, require frequent monitoring of serum levels, and are associated with adverse effects that may prompt discontinuation. In the current study, we test the hypothesis that levetiracetam, an anticonvulsant with favorable interaction and adverse event profiles, is neuroprotective in clinically relevant models of SAH and closed head injury (CHI). METHODS: A single intravenous dose of vehicle, low-dose (18 mg/kg), or high-dose (54 mg/kg) levetiracetam was administered intravenously followed CHI. Functional assessments were performed on a daily basis, and histological assessments performed at 24 hours. In a separate series of experiments, mice were randomized to receive intravenous administration of vehicle, low-dose, or high-dose levetiracetam every 12 hours for 3 days following SAH. Functional endpoints were assessed daily, followed by measurement of MCA luminal diameter on day 3. RESULTS: A single dose of levetiracetam improved functional and histological outcomes after CHI. This effect appeared specific for levetiracetam and was not associated with fosphenytoin treatment. Treatment with levetiracetam also improved functional outcomes and reduced vasospasm following SAH. CONCLUSION: Levetiracetam is neuroprotective in clinically relevant animal models of SAH and CHI. Levetiracetam may be a therapeutic alternative to phenytoin following acute brain injury in the clinical setting when seizure prophylaxis is indicated.