levetiracetam and Subarachnoid-Hemorrhage

Seizures are important complications following a subarachnoid hemorrhage (SAH). The evidence for the use of antiepileptic drugs (AEDs) in treatment and prevention of those seizures is conflicting. The purpose of this review is to provide an up-to-date evidence summary of the incidence and outcomes of seizures following an SAH as well as the use of different AEDs post-SAH in order to evaluate the need for seizure prophylaxis, the choice of AEDs, and their dosing considerations in SAH patients. A literature search of PubMed, Medline, Embase, and the Cochrane Library was performed. A total of 37 studies were reviewed, mostly observational. Definitions of seizures in temporal relation to initial hemorrhage were variable. Similarly, the rates of seizures varied in the literature, ranging from 0 to 31%. Given the reported adverse outcomes associated with AED usage, seizure prophylaxis is not warranted. Levetiracetam appears to be better tolerated than phenytoin in SAH patients, though further research is needed. Higher initial dosing of levetiracetam might be required due to its enhanced clearance in SAH patients. In conclusion, there is a lack of quality evidence to definitively recommend the use of one AED over another. Further prospective research comparing the use of different AEDs in patients with an SAH is needed.

Topics: Anticonvulsants; Carbamazepine; Humans; Incidence; Levetiracetam; Phenytoin; Seizures; Subarachnoid Hemorrhage

Seizures may occur during or soon after rupture of an intracranial aneurysm. The use of antiepileptic drugs (AEDs) is a controversial issue. The overall conclusions from 2 recent studies in aneurysmal subarachnoid hemorrhage are that 1) many patients receive AEDs but should not; 2) long-term use is associated with worse outcome; and 3) short-term use is safer. Phenytoin may not be the first choice for seizure prophylaxis; newer AEDs such as levetiracetam might be more helpful in prevention and treatment of seizures.

Topics: Animals; Anticonvulsants; Electroencephalography; Head Injuries, Closed; Humans; Levetiracetam; Neurons; Neuroprotective Agents; Phenytoin; Piracetam; Seizures; Subarachnoid Hemorrhage; Treatment Outcome

Seizures occur in 10-20% of patients with subarachnoid hemorrhage (SAH), predominantly in the acute phase. However, anticonvulsant prophylaxis remains controversial, with studies suggesting a brief course may be adequate and longer exposure may be associated with worse outcomes. Nonetheless, in the absence of controlled trials to inform practice, patients continue to receive variable chemoprophylaxis. The objective of this study was to compare brief versus extended seizure prophylaxis after aneurysmal SAH.. We performed a prospective, single-center, randomized, open-label trial of a brief (3-day) course of levetiracetam (LEV) versus extended treatment (until hospital discharge). The primary outcome was in-hospital seizure. Secondary outcomes included drug discontinuation and functional outcome.. Eighty-four SAH patients had been randomized when the trial was terminated due to slow enrollment. In-hospital seizures occurred in three (9%) of 35 in the brief LEV group versus one (2%) of 49 in the extended group (p = 0.2). Ten (20%) of the extended group discontinued LEV prematurely, primarily due to sedation. Four of five seizures (including one pre-randomization) occurred in patients with early brain injury (EBI) on computed tomography (CT) scans (adjusted OR 12.5, 95% CI 1.2-122, p = 0.03). Good functional outcome (mRS 0-2) was more likely in the brief LEV group (83 vs. 61%, p = 0.04).. This study was underpowered to demonstrate superiority of extended LEV for seizure prophylaxis, although a trend to benefit was seen. Seizures primarily occurred in those with radiographic EBI, suggesting targeted prophylaxis may be preferable. Larger trials are required to evaluate optimal chemoprophylaxis in SAH, especially in light of worse outcomes in those receiving extended treatment.

Topics: Adult; Aged; Anticonvulsants; Female; Humans; Intracranial Aneurysm; Levetiracetam; Male; Middle Aged; Outcome Assessment, Health Care; Prospective Studies; Seizures; Subarachnoid Hemorrhage

To characterize the steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients requiring seizure prophylaxis after a neurologic injury and to determine which dosing regimens achieve serum concentrations within the recommended therapeutic range of 6-20 μg/ml. DESIGN. Prospective, open-label, steady-state pharmacokinetic study.. Neurocritical care unit in a tertiary care medical center. PATIENTS. Twelve adults (five men, seven women) admitted to the neurocritical care unit who required prophylactic anticonvulsant therapy after subarachnoid hemorrhage, subdural hematoma, or traumatic brain injury.. Patients received an intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours.. Serial blood samples were collected from all patients after a minimum of four doses of therapy. Serum levetiracetam concentrations were determined by ultraperformance liquid chromatography with tandem mass spectrometry detection, and pharmacokinetic data were analyzed by compartmental and noncompartmental methods. Monte Carlo simulations were performed for multiple levetiracetam dosing regimens to determine the probability of achieving a target trough concentration of 6 μg/ml or greater, 20 μg/ml or greater, and 6-20 μg/ml. The mean ± SD levetiracetam maximum serum concentration was 28.0 ± 8.0 μg/ml, minimum serum concentration 3.1 ± 1.8 μg/ml, half-life 5.2 ± 1.2 hours, systemic clearance 5.6 ± 1.8 L/hour, and volume of distribution at steady state 36.8 ± 6.3 L. Increasing the doses of levetiracetam increased the probability of achieving a target trough concentration of 6 μg/ml or greater but also increased the probability of achieving trough concentrations greater than 20 μg/ml. Levetiracetam doses of 1000 mg every 8 hours and 1500-2000 mg every 12 hours provided the highest probability of achieving a target trough concentration between 6 and 20 μg/ml.. Compared with previously published results in healthy volunteers and adults in status epilepticus, levetiracetam systemic clearance was faster and the terminal elimination half-life was shorter in neurocritical care patients. Higher doses or more frequent dosing may be needed to achieve target trough concentrations of 6-20 μg/ml.

Topics: Anticonvulsants; Brain Injuries; Critical Care; Female; Hematoma, Subdural; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Monte Carlo Method; Piracetam; Prospective Studies; Seizures; Subarachnoid Hemorrhage; Treatment Outcome

Anti-epileptic drugs are commonly used for seizure prophylaxis after neurological injury. We performed a study comparing intravenous (IV) levetiracetam (LEV) to IV phenytoin (PHT) for seizure prophylaxis after neurological injury.. In this prospective, single-center, randomized, single-blinded comparative trial of LEV versus PHT (2:1 ratio) in patients with severe traumatic brain injury (sTBI) or subarachnoid hemorrhage (NCT00618436) patients received IV load with either LEV or fosphenytoin followed by standard IV doses of LEV or PHT. Doses were adjusted to maintain therapeutic serum PHT concentrations or if patients had seizures. Continuous EEG (cEEG) monitoring was performed for the initial 72 h; outcome data were collected.. A total of 52 patients were randomized (LEV = 34; PHT = 18); 89% with sTBI. When controlling for baseline severity, LEV patients experienced better long-term outcomes than those on PHT; the Disability Rating Scale score was lower at 3 months (P = 0.042) and the Glasgow Outcomes Scale score was higher at 6 months (P = 0.039). There were no differences between groups in seizure occurrence during cEEG (LEV 5/34 vs. PHT 3/18; P = 1.0) or at 6 months (LEV 1/20 vs. PHT 0/14; P = 1.0), mortality (LEV 14/34 vs. PHT 4/18; P = 0.227). There were no differences in side effects between groups (all P > 0.15) except for a lower frequency of worsened neurological status (P = 0.024), and gastrointestinal problems (P = 0.043) in LEV-treated patients.. This study of LEV versus PHT for seizure prevention in the NSICU showed improved long-term outcomes of LEV-treated patients vis-à-vis PHT-treated patients. LEV appears to be an alternative to PHT for seizure prophylaxis in this setting.

Topics: Adult; Anticonvulsants; Brain Injuries; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Phenytoin; Piracetam; Prospective Studies; Seizures; Single-Blind Method; Subarachnoid Hemorrhage

Neuroelectric disruptions such as seizures and cortical spreading depolarization may contribute to the development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, effects of antiepileptic drug prophylaxis on outcomes remain controversial in SAH. The authors investigated if prophylactic administration of new-generation antiepileptic drugs levetiracetam and perampanel was beneficial against delayed neurovascular events after SAH. This was a retrospective single-center cohort study of 121 consecutive SAH patients including 56 patients of admission World Federation of Neurological Surgeons grades IV - V who underwent aneurysmal obliteration within 72 h post-SAH from 2013 to 2021. Prophylactic antiepileptic drugs differed depending on the study terms: none (2013 - 2015), levetiracetam for patients at high risks of seizures (2016 - 2019), and perampanel for all patients (2020 - 2021). The 3rd term had the lowest occurrence of delayed cerebral microinfarction on diffusion-weighted magnetic resonance imaging, which was related to less development of DCI. Other outcome measures were similar among the 3 terms including incidences of angiographic vasospasm, computed tomography-detectable delayed cerebral infarction, seizures, and 3-month good outcomes (modified Rankin Scale 0 - 2). The present study suggests that prophylactic administration of levetiracetam and perampanel was not associated with worse outcomes and that perampanel may have the potential to reduce DCI by preventing microcirculatory disturbances after SAH. Further studies are warranted to investigate anti-DCI effects of a selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist perampanel in SAH patients in a large-scale prospective study.

Topics: Anticonvulsants; Brain Ischemia; Cerebral Infarction; Cohort Studies; Humans; Levetiracetam; Microcirculation; Prospective Studies; Retrospective Studies; Seizures; Subarachnoid Hemorrhage

Levetiracetam is used for seizure prophylaxis in patients presenting with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). We aim to characterize the optimal levetiracetam dosage for seizure prophylaxis.. This retrospective cohort study included adult patients at an academic tertiary hospital presenting with SAH or TBI who received levetiracetam at a total daily dose (TDD) equivalent to or greater than 1000 mg. The primary outcome was combined seizure incidence, including clinical and subclinical seizures.. We identified 139 patients (49.6% male, mean age 53 years) for inclusion. For patients receiving a 1000-mg TDD, the administration was 500 mg twice daily. For patients receiving >1000-mg TDD, 77/78 patients received 1000 mg twice daily and one patient received 750 mg twice daily. Patients receiving 1000-mg TDD had a higher seizure incidence than those receiving >1000-mg TDD (p = 0.01), despite no difference in examined confounders, including history of alcoholism (p = 0.49), benzodiazepine use (p = 0.28), or propofol use (p = 0.17). No difference in adverse effects was observed (anemia, p = 0.44; leukopenia, p = 0.60; thrombocytopenia, p = 0.86).. Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing >1000-mg TDD.

Topics: Adult; Anticonvulsants; Brain Injuries, Traumatic; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Seizures; Subarachnoid Hemorrhage

Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5-12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration.

Topics: Adult; Australia; Humans; Levetiracetam; Seizures; Subarachnoid Hemorrhage; Treatment Outcome

Topics: Aged; Hemosiderosis; Humans; Intensive Care Units; Levetiracetam; Magnetic Resonance Angiography; Male; Subarachnoid Hemorrhage; Tomography, X-Ray Computed

Convexity subarachnoid haemorrhage (cSAH) is a rare type of spontaneous, non-traumatic, and nonaneurysmal SAH characterised by blood collections in one or more cortical sulci in the convexity of the brain; the aetiology varies. We report a clinical case series of 3 patients with cSAH associated with probable cerebral amyloid angiopathy (CAA) who presented with focal sensory seizures and responded well to corticosteroid treatment.. Case 1 was a 67-year-old man reporting right-sided paroxysmal sensory episodes with Jacksonian progression, cheiro-oral symptoms, and motor dysphasia. Case 2 was a 79-year-old man reporting left-sided paroxysmal episodes with cheiro-oral signs and dysarthria. Case 3 was a 71-year-old woman also reporting recurrent left cheiro-oral signs and dysarthria. None of the patients had headache or clinical dementia. Aneurysms were ruled out using MR angiography.. Brain CT scan detected an isolated hyperintensity in a sulcus of the frontal convexity; brain gradient echo T2-weighted MRI sequences showed meningeal haemosiderosis and microbleeds. However, no atrophy was identified in medial temporal lobes including the hippocampal formation. All patients had low levels of beta-amyloid in CSF, low values on the Hulstaert index and high levels of phosphorylated tau protein. Patients were initially treated with prednisone and levetiracetam, but symptoms recurred in 2 patients after prednisone was discontinued.. We present a series of 3 patients with cSAH associated with CAA, characterised by a stereotypical syndrome responding well to corticoid treatment; there were no cases of headache or clinical dementia.

Topics: Aged; Anticonvulsants; Brain; Cerebral Amyloid Angiopathy; Dexamethasone; Female; Glucocorticoids; Hemosiderosis; Humans; Levetiracetam; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Piracetam; Prednisone; Subarachnoid Hemorrhage; Tomography, X-Ray Computed

Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. Our objective was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Brain Ischemia; Female; Follow-Up Studies; Hematoma; Humans; Incidence; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures; Severity of Illness Index; Subarachnoid Hemorrhage; Time Factors; Treatment Outcome; Young Adult

Continuous electroencephalography (cEEG) is increasingly used to detect both clinical and subclinical seizures in patients with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). We assess whether EEG findings predict outcomes in TBI/SAH patients enrolled in a levetiracetam (LEV) vs. fosphenytoin (fos-PHT) seizure prevention trial (NCT00618436). This prospective, single-blinded, comparative trial randomized 52 patients with TBI or SAH to receive prophylactic LEV or fos-PHT. Continuous video EEG monitoring was conducted for the initial 72 h of medication administration. The association between EEG findings (degree of generalized and focal slowing, presence and frequency of epileptiform discharges and seizures) and outcomes (Glasgow Outcomes Scale-Extended (GOS-E) and Disability Rating Scale (DRS)) at discharge, 3 and 6 months was assessed using a generalized linear model. Severity of generalized slowing tended to be associated with outcomes in both treatment groups (discharge DRS, p=0.042; discharge GOS-E, p=0.026; 3 month DRS, p=0.051). The presence of focal slowing, the presence and frequency of epileptiform discharges and the presence of seizures were not predictive of outcome in either treatment group (all p>0.15). While it has been shown that LEV is associated with better outcome than fos-PHT when used as seizure prophylaxis in brain injury, aside from severity of generalized slowing, electrographic findings of focal slowing, epileptiform discharges, and seizures were not themselves associated with outcomes in patients with TBI or SAH enrolled in a randomized clinical trial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Injuries; Disability Evaluation; Electroencephalography; Female; Glasgow Outcome Scale; Humans; Levetiracetam; Linear Models; Male; Middle Aged; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures; Statistics, Nonparametric; Subarachnoid Hemorrhage; Young Adult

Topics: Anticonvulsants; Female; Humans; Levetiracetam; Middle Aged; Piracetam; Recurrence; Seizures; Subarachnoid Hemorrhage; Time Factors

Topics: Anticonvulsants; Epilepsy; Humans; Incidence; Levetiracetam; Phenytoin; Piracetam; Subarachnoid Hemorrhage

The optimal regimen for seizure prophylaxis after subarachnoid hemorrhage (SAH) remains uncertain. Based on data suggesting that a short course may be adequate, coupled with an association between phenytoin exposure and poor cognitive outcome, our institution modified their seizure prophylaxis protocol for patients with SAH from an extended course of phenytoin to 3 days of levetiracetam. This study sought to compare the incidence of seizures before and after this change to evaluate whether a short course of levetiracetam would be as effective in preventing in-hospital seizures.. This study analyzed 442 consecutive patients admitted with SAH between January 2003 and January 2008, including 297 patients treated before the protocol change (PHT group) and 145 treated afterward (LEV group). Occurrence of all seizures was extracted from a prospectively collected intensive care unit database and further review of medical records. In-hospital seizures were divided into early (occurring on or before day 3, all patients on prophylaxis) and those occurring late (after day 3, LEV group off prophylaxis).. In-hospital seizures occurred in 3.4% of the PHT group and 8.3% of the LEV group (P = 0.03). Although the rate of early seizures was not different (1.4% PHT vs. 2.8% LEV, P = 0.45), there was a higher rate of late seizures (2% PHT vs. 5.5% LEV, P = 0.05).. The use of short-duration levetiracetam for seizure prophylaxis after SAH was associated with a higher rate of in-hospital seizures than an extended course of phenytoin, mainly related to an increase in late seizures, when the levetiracetam had been discontinued. This suggests that a longer duration of prophylaxis may be required to minimize seizures in patients with SAH, although confirmatory studies are required.

Topics: Adult; Aged; Anticonvulsants; Databases, Factual; Delayed-Action Preparations; Disease-Free Survival; Epilepsy; Female; Humans; Incidence; Inpatients; Intensive Care Units; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Subarachnoid Hemorrhage

Both valproic acid and levetiracetam are anti-epileptic drugs, often used either alone or in combination. The present study compares valproate (VPA) with levetiracetam (LEV) as an intravenous (i.v.) anticonvulsant treatment in intensive care patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of seizures.. A prospective, single-center patient registry of 35 intensive care unit (ICU) patients with onset seizure and/or high risk of seizures underwent an anticonvulsive, first-line single treatment regimen either with VPA or LEV. Plasma concentrations (pc), interactions between drugs in the ICU context, adverse effects and seizure occurrences were observed and recorded.. A significant decrease in the pc in patients treated with LEV was observed after changing from intravenous (160±51μmol/l) to enteral liquid application (113±58μmol/l), corresponding to a 70.3% bioavailability for enteral liquid applications. The pc in VPA patients decreased significantly, from (491±138μmol/l) to (141±50μmol/l), after adding meropenem to the therapy (p<0.05). Three epileptic seizures occurred during anticonvulsive therapy in the LEV group, and two in the VPA group, including one non-convulsive status epilepticus (NCSE).. Though this finding needs further verification, the enteral liquid application of levetiracetam seems to be associated with lower bioavailability than the common oral application of levetiracetam. The use of the antibiotic drug meropenem together with valproic acid leads to lower pc levels in patients treated with of valproic acid. For clinical practice, this indicates the need to monitor the levels of valproic acid in combination with meropenem.

Topics: Administration, Oral; Aged; Aneurysm, Ruptured; Anti-Bacterial Agents; Anticonvulsants; Biological Availability; Brain Ischemia; Critical Care; Drug Interactions; Enteral Nutrition; Epilepsy; Female; Humans; Intensive Care Units; Levetiracetam; Male; Meropenem; Middle Aged; Piracetam; Prospective Studies; Seizures; Subarachnoid Hemorrhage; Thienamycins; Valproic Acid

To determine the utility and tolerability of levetiracetam (LEV) compared to phenytoin (PHT) in preventing clinical seizures in patients with subarachnoid hemorrhage (SAH).. Utility and tolerability of PHT and LEV in patients with SAH were determined by the occurrence of breakthrough clinical seizures or adverse events necessitating a change of medication. Comparisons were performed with Chi-square tests.. All 176 patients were initially treated with PHT. No breakthrough clinical seizures occurred. In 70 (39.8%) patients, PHT was replaced with LEV due to adverse events including elevation of transaminases, thrombocytopenia, unexplained fever, rash, gastrointestinal disturbance, and worsening mental status. After switching to LEV, all adverse effects resolved except gastrointestinal disturbance and worsening mental status in 4 patients. Adverse events occurred more often in patients taking PHT.. In patients with SAH, LEV appears to have superior tolerability compared to PHT.

Topics: Adult; Aged; Anticonvulsants; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Subarachnoid Hemorrhage; Treatment Outcome

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).. 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.. 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.. 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.

Topics: Animals; Disease Models, Animal; Drug Administration Schedule; Head Injuries, Closed; Injections, Intravenous; Levetiracetam; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Piracetam; Random Allocation; Subarachnoid Hemorrhage; Time Factors; Vasospasm, Intracranial