levetiracetam and Intracranial-Hemorrhages

We present a case of a 14-year-old, previously healthy female, admitted with acute coronavirus disease 2019 infection and new-onset seizures secondary to virus-associated necrotizing disseminated acute leukoencephalopathy. Her symptoms resolved completely with intravenous immunoglobulin and steroids. Pathophysiology and prognosis of neurologic manifestations of coronavirus disease 2019 remain unclear.

Topics: Adolescent; Anticonvulsants; COVID-19; COVID-19 Drug Treatment; Female; Humans; Immunoglobulins, Intravenous; Intracranial Hemorrhages; Leukoencephalopathies; Levetiracetam; Lorazepam; SARS-CoV-2; Seizures

We report the case of a 70-year-old diabetic woman who presented to the emergency department with multiple seizure episodes and coma, prompting the need for sedation and mechanical ventilation. She was transferred to our institution for neurosurgical evaluation as the initial CT scan identified hyperdense lesions in the left basal ganglia, interpreted as acute intracranial haemorrhage. On admission, laboratory tests were mostly normal except for blood glucose of 413 mg/dL. Medical records revealed a history of poorly controlled diabetes mellitus and non-adherence to therapy. After seizure control and lifting sedation, right-sided ataxia/involuntary movements were observed. Considering the patient's history and these findings, the CT scan was reviewed and the striatal region hyperdensities interpreted as lesions typical of non-ketotic hemichorea-hemiballismus. MRI was latter performed and confirmed the diagnosis, even though the unusual presentation. Levetiracetam initiation and glycaemic control optimisation led to great neurological improvement without seizure recurrence.

Topics: Aged; Anticonvulsants; Basal Ganglia; Blood Glucose; Coma; Diabetes Mellitus, Type 2; Diagnosis, Differential; Dyskinesias; Female; Humans; Hyperglycemia; Intracranial Hemorrhages; Levetiracetam; Magnetic Resonance Imaging; Medication Adherence; Seizures; Tomography, X-Ray Computed

Intracranial hemorrhage (ICH) is a devastating disease that induces hematoma formation with poor neuronal outcome. Levetiracetam (LEV) has been approval for epilepsy seizures. In a previous study, LEV exerted protective effects on cerebral ischemia models; however, the detail effects and the influence of LEV on ICH are still unknown. The aim of this study was to investigate whether oral administration of LEV (50 or 150 mg/kg) has protective effects on ICH injury using both in vivo and in vitro experiments. In in vivo experiments, we utilized ICH models induced by autologous blood (bICH) or collagenase (cICH) injection. Moreover, we established a neuronal injury model using SYSH5Y human neuroblastoma cell lines. In the bICH model, frequently oral administration of LEV attenuated both cerebral edema and neurological deficits. In addition, the expression levels of phosphorylation-extracellular signal‑related kinase (ERK) 1/2 and cleaved caspase-7 were increased after ICH, and LEV suppressed such alterations. In in vitro experiments, hematoma releasing factors, such as hemoglobin (Hb) and hemin, induced neuronal cell death, and LEV treatment attenuated neuronal injury in a dose-dependent manner. In the cICH model, neurological deficits induced by extensive hematoma formation were attenuated by LEV without affecting hematoma volume. Taken together, these findings suggested that LEV has protective effect on neurons after ICH injury. Therefore, LEV may not only be an efficacious therapeutic agent for seizures, but also for post-hemorrhagic stroke brain injury.

Topics: Animals; Anticonvulsants; Cerebral Hemorrhage; Disease Models, Animal; Humans; Intracranial Hemorrhages; Levetiracetam; Neuroprotective Agents

BACKGROUND Levetiracetam is an antiepileptic drug frequently used in critically ill patients. Levetiracetam is primarily eliminated as a parent compound via glomerular filtration and requires dose adjustment in renal insufficiency, but the literature on patients receiving continuous veno-venous hemofiltration (CVVH) is scant. CASE REPORT We report the levetiracetam pharmacokinetic profile of a patient being treated with levetiracetam 1000 mg intravenously every 12 h who required continuous veno-venous hemofiltration (CVVH). The patient underwent CVVH utilizing a high-flux polyethersulfone membrane filter. The blood flow rate was 250 ml/min, and the predilution replacement therapy fluid flow rate was 2000 ml/h. After achieving presumed steady-state on levetiracetam 1000 mg q12h, serial plasma samples (pre- and post-filter) and effluent samples were drawn at 2, 4, 6, 8, and 10 h. Levetiracetam concentrations were determined utilizing LC-MS/MS. The levetiracetam maximum concentration (Cmax), minimum concentration (Cmin), half-life, area under the concentration-time curve (AUC0-12), clearance (CL), and volume of distribution (Vd) were 30.7 µg/ml, 16.1 µg/ml, 12.9 h, 272 mg·hr/L, 3.68 L/h, and 0.73 L/kg, respectively. The sieving coefficient was 1.03±0.08. CVVH represented 61.3% of the total levetiracetam clearance. The patient was maintained on CVVH for 24 consecutive days and then transitioned to intermittent hemodialysis and remained seizure-free. CONCLUSIONS CVVH is highly effective in removing levetiracetam from circulating plasma. Due to the effective removal, standard doses of levetiracetam are required to maintain adequate plasma concentrations. Dose reductions utilizing HD or estimated creatinine clearance recommendations will likely lead to subtherapeutic levels, especially if higher CVVH flow rates are used.

Topics: Aged; Anticonvulsants; Hemofiltration; Humans; Intracranial Hemorrhages; Levetiracetam; Male; Piracetam; Seizures

Seizure prophylaxis is used in a variety of conditions, including supratentorial intracranial hemorrhage (ICH). In adults, studies have demonstrated phenytoin as the drug of choice for seizure prophylaxis; in children, levetiracetam is often provided due to its favorable side effect profile and pharmacokinetics. This study evaluated the difference in efficacy between these treatment options.. This retrospective review included 126 patients between 1 month and 17 years of age with acute supratentorial ICH; all received seizure prophylaxis. Demographic data and outcome assessments were compared.. Seizure prophylaxis was provided with (fos)phenytoin in 40 children, levetiracetam in 61 children, and both drugs in 25 patients. Baseline characteristics of the treatment groups were similar, except that more patients treated with (fos)phenytoin had seizures on presentation. Patients treated solely with (fos)phenytoin had a higher probability of early seizures (within 7 days of ICH) compared with those treated only with LVT, controlling for relevant variables including seizures on presentation (OR 24.6, p = 0.002). Patients treated with (fos)phenytoin were more likely to need additional antiepileptic drugs for seizure control (p = 0.005). There was no significant difference in the incidence of late seizures (> 7 days after ICH) (p = 0.265). Adverse events necessitating a change in therapy were uncommon.. Levetiracetam is a reasonable alternative to (fos)phenytoin for prophylaxis of early posthemorrhagic seizures. Levetiracetam and (fos)phenytoin are well tolerated in children. Prospective studies are needed to determine superiority, optimal dosing, and impact on long-term outcomes.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Incidence; Infant; Intracranial Hemorrhages; Levetiracetam; Male; Phenytoin; Piracetam; Primary Prevention; Retrospective Studies; Seizures; Treatment Outcome

To date, common therapy in patients with intracranial hemorrhage (ICH) includes prophylaxis of seizure using antiepileptic drugs, commonly phenytoin. Phenytoin therapy is associated with a high incidence of cognitive disturbance. Levetiracetam is known to cause less cognitive disruption and may be a suitable alternative for seizure prophylaxis. Cognitive outcomes in ICH patients receiving seizure prophylaxis with levetiracetam or phenytoin are compared.. A retrospective chart review was conducted with 269 patients who received prophylactic levetiracetam or phenytoin between August 2005 and May 2008. A total of 85 reviewed patients met inclusion criteria (phenytoin n = 25, levetiracetam n = 60).. Statistically significant results included higher Glasgow Coma Scores (GCS) at dismissal (median, 14 vs. 11, P = 0.023), lower seizure incidence (0.0 vs. 8%, P = 0.03) for patients receiving levetiracetam than those treated with phenytoin and patients being discharged home (21.7% vs. 16%, P = 0.03). Observed trends included greater cognitive function retention rate (56.7% vs. 36%, P = 0.08).. Despite similarities in hemorrhage type and severity at onset, patients receiving levetiracetam had better cognition at discharge and fewer seizures than patients receiving phenytoin. These data suggest that levetiracetam is more effective than phenytoin for seizure prophylaxis without suppression of cognitive abilities in patients with ICH.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Cognition Disorders; Female; Humans; Intracranial Hemorrhages; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Seizures; Young Adult