levetiracetam and Coma

Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital.. Children 24-83 months old with CM were enrolled in an eLVT dose-finding study starting with standard dose (40 mg/kg load, then 30 mg/kg Q12 hours) titrated upward until seizure freedom was attained in 75% of subjects. The RCT that followed randomized children to eLVT vs. phenobarbital for acute seizures and compared the groups on minutes with seizures based upon continuous electroencephalogram. Due to safety concerns, midway through the study children allocated to phenobarbital received the drug only if they continued to have seizures (either clinically or electrographically) after benzodiazepine treatment. Secondary outcomes were treatment failure requiring cross over, coma duration and neurologic sequelae at discharge. PK and safety assessments were also undertaken.. Among 30 comatose CM children, eLVT was rapidly absorbed and well-tolerated. eLVT clearance was lower in patients with higher admission serum creatinine (SCr), but overall PK parameters were similar to prior pediatric PK studies. Within 4 h of the first dose, 90% reached therapeutic levels (> 20 μg/mL) and all were above 6 μg/mL. 7/7 children achieved seizure freedom on the initial eLVT dose. Comparing 23 eLVT to 21 phenobarbital patients among whom 15/21 received phenobarbital, no differences were seen for minutes with seizure, seizure freedom, coma duration, neurologic sequelae or death, but eLVT was safer (p = 0.019). Phenobarbital was discontinued in 3/15 due to respiratory side effects.. Enteral LVT offers an affordable option for seizure control in pediatric CM and is safer than phenobarbital.. NCT01660672 . NCT01982812 .

Topics: Acute Disease; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Coma; Cross-Over Studies; Electroencephalography; Female; Humans; Levetiracetam; Malaria, Cerebral; Malawi; Male; Phenobarbital; Seizures; Time Factors

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

We tested the impact of antiepileptic drug (AED) administration on post-cardiac arrest epileptiform electroencephalographic (EEG) activity.. We studied an observational cohort of comatose subjects treated at a single academic medical center after cardiac arrest from September 2010 to January 2018. We aggregated the observed EEG patterns into 5 categories: suppressed; discontinuous background with superimposed epileptiform activity; discontinuous background without epileptiform features; continuous background with epileptiform activity; and continuous background without epileptiform activity. We calculated overall probabilities of transitions between EEG states in a multistate model, then used Aalen's additive regression to test if AEDs or hypothermia are associated with a change in these probabilities.. Overall, 828 subjects had EEG-monitoring for 42,840 h with a median of 40 [IQR 23-64] h per subject. Among patients with epileptiform findings on initial monitoring, 50% transitioned at least once to a non-epileptiform, non-suppressed state. By contrast, 19% with non-epileptiform initial activity transitioned to an epileptiform state at least once. Overall, 568 (78%) patients received at least one AED. Among patients with continuous EEG background activity, valproate, levetiracetam and lower body temperature were each associated with an increased probability of transition from epileptiform states to non-epileptiform states, where patients with discontinuous EEG background activity no agent linked to an increased probability of transitioning from epileptiform states.. After cardiac arrest, the impact of AEDs may depend on the presence of continuous cortical background activity. These data serve to inform experimental work to better define the opportunities to improve neurologic care post-cardiac arrest.

Topics: Anticonvulsants; Cohort Studies; Coma; Combined Modality Therapy; Electroencephalography; Female; Heart Arrest; Humans; Hypothermia, Induced; Hypoxia, Brain; Levetiracetam; Male; Middle Aged; Nervous System Diseases; Outcome and Process Assessment, Health Care; Resuscitation; Seizures; United States; Valproic Acid

Levetiracetam is an anti-epileptic drug commonly used in intensive care when seizure is suspected as a possible cause of coma. We propose to question the cofounding effect of Levetiracetam during the prognostication process in a case of anoxic coma. We report the story of a young woman presenting a comatose state following a hypoxic cardiac arrest. After a first EEG presenting an intermediate EEG pattern, a seizure suspicion led to prescribe Levetiracetam. The EEG showed then the appearance of burst suppression, which was compatible with a very severe pattern of post-anoxic coma. This aggravation was in fact related to an overdose of Levetiracetam (the only medication introduced recently) and was reversible after Levetiracetam cessation. The increased plasmatic dosages of Levetiracetam confirming this overdose could have been favoured by a moderate reduction of renal clearance, previously underestimated because of a low body-weight. This EEG dynamic was unexpected under Levetiracetam and could sign a functional instability after anoxia. Burst suppression is classically observed with high doses of anaesthetics, but is not expected after a minor anti-epileptic drug. This report proposes that Levetiracetam tolerance might not be straightforward after brain lesions and engages us to avoid confounding factors during the awakening prognostication, which is mainly based on the severity of the EEG. Hence, prognosis should not be decided on an isolated parameter, especially if the dynamic is atypical after a new prescription, even for well-known drugs. For any suspicion, the drug's dosage and replacement should be managed before any premature care's withdrawal.

Topics: Adult; Anticonvulsants; Coma; Drug Overdose; Electroencephalography; Female; Heart Arrest; Humans; Hypoxia; Levetiracetam; Piracetam

Pyrexia is a physiological response through which the immune system responds to infectious processes. Hyperpyrexia is known to be neurodegenerative leading to brain damage. Some of the neurotoxic effects of hyperpyrexia on the brain include seizures, decreased cognitive speed, mental status changes, coma, and even death. In the clinical management of hyperpyrexia, the goal is to treat the underlying cause of elevated temperature and prevent end organ damage.. This case illustrates a 39-year-old white American man referred from another medical facility where he had undergone an upper gastrointestinal tract diagnostic procedure which became complicated by blood aspiration and respiratory distress. During hospitalization, he developed a core body temperature of 41.6 °C (106.9 °F) leading to cognitive decline and coma with a Glasgow Coma Score of 3. Levetiracetam and amantadine were utilized effectively for preserving and restoring neurocognitive function. Prior studies have shown that glutamate levels can increase during an infectious process. Glutamate is an excitatory neurotransmitter that is utilized by the organum vasculosum laminae terminalis through the neuronal excitatory system and causes an increase in body temperature which can lead to hyperpyrexia. Similar to neurogenic fevers, hyperpyrexia can lead to neurological decline and irreversible cognitive dysfunction. Inhibition of the glutamate aids a decrease in excitatory states, and improves the brain's regulatory mechanism, including temperature control. To further improve cognitive function, dopamine levels were increased with a dopamine agonist.. We propose that a combination of levetiracetam and amantadine may provide neuroprotective and neurorestorative properties when administered during a period of hyperpyrexia accompanied by any form of mental status changes, particularly if there is a decline in Glasgow Coma Score.

Topics: Adult; Amantadine; Anticonvulsants; Brain; Brain Injuries; Cognition Disorders; Coma; Dopamine Agents; Drug Therapy, Combination; Glutamic Acid; Humans; Levetiracetam; Male; Malignant Hyperthermia; Piracetam; Tomography, X-Ray Computed

Posthypoxic coma is often associated with cortical and brainstem hyperexcitability. Five months following cardiopulmonary resuscitation after myocardial infarction and ventricular arrhythmia, a 47-year-old man presented with posthypoxic cerebral dysfunction, minimal responsiveness, severe spastic-dystonic tetraparesis, and stimulus-sensitive muscle spasms upon acoustic and sensory stimulation. Neurophysiological examination revealed increased long-loop reflexes in abductor pollicis brevis muscle following median nerve stimulation at the wrist, consistent with cortical hyperexcitability. Exaggerated startle responses provided evidence of concomitant brainstem disinhibition. Levetiracetam up to 3,000 mg per day suppressed transcortical long-loop reflexes in a dose-dependent manner without concomitant suppression of the H-reflex and only mild attenuation of the startle response. The present findings suggest a suppressive effect of levetiracetam on cortical neurons in the absence of a spinal effect on monosynaptic reflexes, and thus support the drug's efficacy in posthypoxic cortical hyperexcitability.

Topics: Coma; Evoked Potentials, Somatosensory; H-Reflex; Humans; Hypoxia, Brain; Levetiracetam; Male; Middle Aged; Nootropic Agents; Piracetam; Reflex, Startle; Somatosensory Cortex