levetiracetam and Hypoxia

Among the most common autonomic signs visible in preterm neonates, apnea can represent the first sign of several neurologic and non-neurologic disorders, and seizure is a relatively infrequent cause. Herein authors present a case of neonatal autonomic apnea, discussing the polygraphic video-EEG features of this pathological entity and the differential diagnosis with central apnea and autonomic apnea.. A female preterm Caucasian infant (29 + 4 weeks' gestational age (GA)), first twin of a twin pregnancy, at birth was intubated and surfactant administration was performed. She was ventilated via invasive ventilation for three days, with subsequent weaning with non-invasive ventilation for other two days, when she stopped requiring any ventilator support. After one week the ventilation weaning, the child presented episodes of cyanosis associated with sudden oxygen desaturation, skin pallor, apnea, and bradycardia. Therefore, the child underwent a continuous video-eeg recording with polygraphic study. The exam showed the presence of apneic episodes with an abrupt and clear start, associated with oxygen desaturation at 70%, with minimal thoracic effort at onset, and then evolving into central apnea. Central apnea lasted about 16 s and presented clear start- and end-points. These episodes were also associated with suppression of the EEG trace in frequency and amplitude, and after about 10 s of central apnea an abrupt decrease of the child's heart rate (more than 50% variation, from 160 bpm to 65 bpm) was recorded. In the suspect of epileptic apneas of autonomic origin, a therapy with oral Levetiracetam, at a starting dose of 10 mg/Kg/day, then increased up to 40 mg/Kg/day, was initiated, and after about 48 h the first administration of the anticonvulsant therapy, no new episodes of cyanosis or electrical apneas were recorded.. Herein the authors suggest to consider the diagnosis of autonomic seizures in those neonates with apneic events associated with EEG suppression. Considering that apnea events are not only present in preterm infants but also in term neonates, it is mandatory to diagnose in this context neonatal seizures for a correct diagnosis and a proper therapeutic choice.

Topics: Anticonvulsants; Apnea; Autonomic Nervous System Diseases; Bradycardia; Cyanosis; Diagnosis, Differential; Diseases in Twins; Electroencephalography; Female; Gestational Age; Humans; Hypoxia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Levetiracetam; Seizures; Sleep Apnea, Central; Video Recording

Topics: Administration, Intravenous; Anticonvulsants; Electroencephalography; Humans; Hypoxia; Levetiracetam; Male; Medication Adherence; Pulmonary Edema; Radiography, Thoracic; Seizures; Status Epilepticus; Treatment Outcome; Young Adult

Perinatal hypoxia can lead to multiple chronic neurological deficits, e.g., mental retardation, behavioral abnormalities, and epilepsy. Levetiracetam (LEV), 2S-(2-oxo-1-pyrrolidiny1) butanamide, is an anticonvulsant drug with proven efficiency in treating patients with focal and generalized seizures. Rats were underwent hypoxia and seizures at the age of 10-12 postnatal days (pd). The ambient level and depolarization-induced exocytotic release of [

Topics: Aging; Animals; Animals, Newborn; Exocytosis; gamma-Aminobutyric Acid; Hippocampus; Hypoxia; Levetiracetam; Male; Nerve Endings; Rats, Wistar

Acute ischemic stroke (AIS) in pediatric populations accounts for more than half of pediatric strokes and is associated with significant morbidity and mortality. Pediatric AIS can present with nonspecific symptoms or symptoms that mimic alternate pathology.. A 4-month-old female presented to the emergency department for fever, decreased oral intake, and "limp" appearance after antibiotic administration. She was febrile, tachypneic, and hypoxic. Her skin was mottled with 3-s capillary refill, her anterior fontanelle was tense, and she had mute Babinski reflex bilaterally but was moving all extremities. The patient was hyponatremic, thrombocytopenic, and tested positive for influenza A. A computed tomography scan of the brain revealed an acute infarction involving the right frontal, parietal, temporal, and occipital lobes in addition to hyperdensities concerning for thrombosed cortical veins. The patient was transferred for specialty evaluation and was discharged 2 weeks later on levetiracetam. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pediatric AIS can present with nonspecific symptoms that mimic alternate pathology. A high level of suspicion is needed so as not to miss the diagnosis of pediatric AIS in the emergency department. A thorough neurologic assessment is warranted, and subtle abnormalities should be investigated further.

Topics: Female; Fever; Humans; Hypoxia; Infant; Influenza, Human; Levetiracetam; Nootropic Agents; Stroke; Tachycardia; Tomography, X-Ray Computed

Animal models are valuable tools for screening novel therapies for patients who suffer from epilepsy. However, a wide array of models are necessary to cover the diversity of human epilepsies. In humans, neonatal hypoxia (or hypoxia-ischemia) is one of the most common causes of epilepsy early in life. Hypoxia-induced seizures (HS) during the neonatal period can also lead to spontaneous seizures in adulthood. This phenomenon, i.e., early-life hypoxia leading to adult epilepsy - is also seen in experimental models, including rats. However, it is not known which anti-seizure medications are most effective at managing adult epilepsy resulting from neonatal HS. Here, we examined the efficacy of three anti-seizure medications against spontaneous seizures in adult rats with a history of neonatal HS: (1) phenobarbital (PHB), the oldest epilepsy medicine still in use today; (2) levetiracetam (LEV); and (3) tiagabine (TGB). Both LEV and TGB are relatively new anticonvulsant drugs that are ineffective in traditional seizure models, but strikingly effective in other models. We found that PHB and LEV decreased seizures in adult rats with a history of HS, whereas TGB exacerbated seizures. These divergent drug effects indicate that the HS model may be useful for differentiating the clinical efficacy of putative epilepsy therapies.

Topics: Animals; Animals, Newborn; Anticonvulsants; Brain; Disease Models, Animal; Hypoxia; Levetiracetam; Male; Phenobarbital; Prohibitins; Rats, Long-Evans; Seizures; Tiagabine

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

Perinatal asphyxia to the developing brain remains a major cause of morbidity. Hypothermia is currently the only established neuroprotective treatment available for term born infants with hypoxic-ischemic encephalopathy, saving one in seven to eight infants from developing severe neurological deficits. Therefore, additional treatments with clinically applicable drugs are indispensable. This study investigates a potential additive neuroprotective effect of levetiracetam combined with hypothermia after hypoxia-induced brain injury in neonatal mice. 9-day-old C57BL/6-mice (P9) were subjected either to acute hypoxia or room-air. After 90min of systemic hypoxia (6% O2), pups were randomized into six groups: 1) vehicle, 2) low-dose levetiracetam (LEV), 3) high-dose LEV, 4) hypothermia (HT), 5) HT combined with low-dose LEV and 6) HT combined with high-dose LEV. Pro-apoptotic factors, neuronal structures, and myelination were analysed by histology and on protein level at appropriate time points. On P28 to P37 long-term outcome was assessed by neurobehavioral testing. Hypothermia confers acute and long-term neuroprotection by reducing apoptosis and preservation of myelinating oligodendrocytes and neurons in a model of acute hypoxia in the neonatal mouse brain. Low-dose LEV caused no adverse effects after neonatal hypoxic brain damage treated with hypothermia whereas administration of high-dose LEV alone or in combination with hypothermia increased neuronal apoptosis after hypoxic brain injury. LEV in low- dosage had no additive neuroprotective effect following acute hypoxic brain injury.

Topics: Animals; Animals, Newborn; Anticonvulsants; Anxiety; Apoptosis; Behavior, Animal; Brain; Brain Injuries; Dose-Response Relationship, Drug; Female; Hypothermia, Induced; Hypoxia; Levetiracetam; Male; Mice; Mice, Inbred C57BL; Neurons; Neuroprotective Agents; Oligodendroglia; Piracetam; Recognition, Psychology; Rotarod Performance Test

Postanoxic myoclonus is a rare manifestation after an anoxic event, with fewer than 150 cases reported in the literature. The condition is characterized by myoclonic jerks, which are worse on action than at rest, and postural lapses, ataxia, and dysarthria. The disability caused by postanoxic myoclonus can be profound, and treatment in the rehabilitation setting is exceptionally challenging. We present 2 patients who suffered from postanoxic myoclonus after an anoxic event, both of whom were successfully treated with a combination of levetiracetam, valproic acid, and clonazepam. These cases act as a framework for discussing the management of postanoxic myoclonus in the clinical setting.

Topics: Aged; Anticonvulsants; Clonazepam; Drug Therapy, Combination; Humans; Hypoxia; Levetiracetam; Male; Middle Aged; Myoclonus; Piracetam; Valproic Acid

Hypoxic-ischemic encephalopathy (HIE) resulting from perinatal asphyxia often leads to severe neurologic impairment or even death. There is a need to advance therapy for infants with HIE, for example to combine hypothermia with pharmacological treatment strategies. Levetiracetam (LEV) is approved for clinical administration to infants older than 4 weeks of age and is also used off-label in neonates. Furthermore, LEV was shown to be neuroprotective in adult animal models of brain injury.. The aim of this study was to evaluate the neuroprotective potential of LEV in vitro using primary hippocampal neurons, and in vivo using an established model of neonatal hypoxic-ischemic brain injury.. LEV treatment per se did not induce neurotoxicity in the developing rodent brain. Following oxygen glucose deprivation, we observed some, although not a significant, increase in cell death after LEV treatment. In vivo, LEV was administered under normothermic and hypothermic conditions following hypoxic-ischemic brain damage. LEV administration significantly increased brain injury under normothermic conditions. Compared to the normothermia-treated group, in the hypothermia group LEV administration did not increase hypoxic-ischemic brain injury.. This study demonstrates that LEV treatment increases neonatal hypoxic-ischemic brain injury. Administration of LEV in the acute phase of the injury might interfere with the balanced activation and inactivation of excitatory and inhibitory receptors in the developing brain. The neurotoxic effect of LEV in the injured newborn brain might further suggest an agonistic effect of LEV on the GABAergic system. Hypothermia treatment attenuates glutamate release following hypoxic-ischemic brain injury and might therefore limit the potentially deleterious effects of LEV. As a consequence, our findings do not necessarily rule out a potentially beneficial effect, but argue for cautious use of LEV in newborn infants with pre-existing brain injury.

Topics: Animals; Apoptosis Inducing Factor; Caspase 3; Cell Count; Cell Death; Cells, Cultured; Cerebral Cortex; Disease Models, Animal; Dose-Response Relationship, Drug; Embryo, Mammalian; Gene Expression Regulation; Glucose; Hippocampus; Hypothermia, Induced; Hypoxia; Hypoxia-Ischemia, Brain; Levetiracetam; Mice; Neurons; Neuroprotective Agents; Piracetam

Chronic post-anoxic myoclonus, also known as Lance-Adams syndrome, may develop following hypoxic brain injury, and is resistant to pharmacological therapy.. The patient we presented developed post-anoxic action myoclonus with severe, completely incapacitating myoclonic jerks. Myoclonus did not respond to the treatment with commonly used agents, i.e. valproate and clonazepam alone or in combination. Improvement of the action myoclonus was observed only after adding levetiracetam.. Although Lance-Adams syndrome may not be fully curable at this point, levetiracetam appears to be a promising agent that can significantly improve functional level and overall quality of life of patients with this disorder.

Topics: Accidents, Traffic; Anticonvulsants; Electroencephalography; Fracture Fixation, Internal; Humans; Hypoxia; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Myoclonus; Piracetam; Zygoma

A 67-year-old woman abruptly developed acute pulmonary oedema, severe bradycardia and then cardiac arrest while in hospital 6 days after an elective hernia repair. She was resuscitated, intubated and transferred to the intensive care unit. Within 24 hours, she began to display repetitive, generalised myoclonic jerks that failed to respond to therapy with conventional anticonvulsants; an electroencephalogram confirmed myoclonic status. After administration of levetiracetam was begun on Day 3, myoclonic jerks reduced, and there was gradual clinical improvement. By Day 6 after the arrest, the patient was alert and oriented (Glasgow Coma Score, 15/15). Although she died on Day 11 after massive haemoptysis and cardiac arrest, this patient demonstrates the possibility of reasonable neurological recovery despite early onset of myoclonic status.

Topics: Aged; Anticonvulsants; Critical Care; Female; Heart Arrest; Humans; Hypoxia; Levetiracetam; Myoclonus; Piracetam; Prognosis

Hypoxia-inducible transcription factor-1 (HIF-1) is critically involved in adaptive endogenous mechanisms to hypoxic brain injury by transcriptional activation of specific target genes that restore oxygen supply. Exogenously, neuroprotective properties of levetiracetam (LEV) have been suggested in experimental cerebral ischemia and epilepsy. We aimed to elucidate 1) effects of acute hypoxic distress on HIF-1 and vasoactive target genes, and 2) effects of LEV on HIF-1-regulated mechanisms in the brain at early developmental stages. To this end, we studied the impact of hypoxia in the presence or absence of LEV on the O2-dependent HIF-1alpha subunit as well as on VEGF and iNOS in the developing brain of normoxic and hypoxic mice. C57BL/6 mice (P0, P7) were treated with saline or LEV (i.p.; 50 mg/kg) 1 h before exposure to either normoxia (21% O2; N) or hypoxia (8% O2 of 6 h; H) without reoxygenation. HIF-1alpha was analyzed by Western blot and immunohistochemistry and mRNA levels were quantified by TaqMan RT-PCR. Hypoxia led to prominent accumulation of cerebral HIF-1alpha protein in cortical neurons and glial cells and significant up-regulation of VEGF mRNA at P0 (N, 0.018+/-0.002, vs. H, 0.031+/-0.003, n=6; p<0.05) and P7 (N, 0.096+/-0.032, vs. H, 0.873+/-0.069, n=7; p<0.001). Interestingly, we detected a significant decrease of iNOS mRNA levels in hypoxic brains. LEV treatment did not alter HIF-1alpha accumulation either in normoxic or hypoxic brains (P0, P7). Moreover, significant changes of VEGF and NOS mRNA levels did not occur with the exception that hypoxia-induced decreased iNOS levels were not observed in P0 brains. We conclude that acute systemic hypoxia differentially affects expression of HIF-1-regulated vasoactive factors in the newborn mouse brain. Of clinical importance, LEV treatment did not alter crucial HIF-1-regulated neuroprotective mechanisms.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Brain; Disease Models, Animal; Gene Expression Regulation, Developmental; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Levetiracetam; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Nitric Oxide Synthase Type II; Nootropic Agents; Piracetam; Vascular Endothelial Growth Factor A

In the present study, we evaluated the anti-seizure and anti-myoclonic activity of levetiracetam and brivaracetam in an established rat model of cardiac arrest-induced post-hypoxic myoclonus. We found that brivaracetam (0.3 mg/kg, the minimal effective dose) was more potent than levetiracetam (3 mg/kg, the minimal effective dose) against post-hypoxic seizures. The anti-seizure activity of both compounds occurred 30 min following intraperitoneal (i.p.) administration and was maintained over the entire 150 min post-dose observation period. Both brivaracetam and levetiracetam significantly reduced auditory stimulated post-hypoxic myoclonus from a dose 0.3 mg/kg. At that dose, the anti-myoclonic activity of brivaracetam was already maximal whereas it continued to increase in a dose-relation manner with levetiracetam, suggesting that brivaracetam is a more potent agent. The onset and the duration of anti-myoclonic activity of both compounds were similar. These findings demonstrate that brivaracetam possesses more potent anti-seizure and anti-myoclonic activity than levetiracetam in an established rat model of cardiac arrest-induced post-hypoxic myoclonus.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsies, Myoclonic; Heart Arrest; Hypoxia; Levetiracetam; Piracetam; Pyrrolidinones; Rats; Rats, Sprague-Dawley; Seizures

Some anticonvulsants show neuroprotective effects, and may be of use in reducing neuronal death resulting from stroke or traumatic brain injury. Here I report that a broad range of anticonvulsants protect cells in hippocampal slice cultures from death induced by oxygen/glucose deprivation (OGD). Hippocampal slice cultures were submitted to 1 h OGD and the resulting cell death was quantified 24 h later using a novel automated fluorescent scanning method. The classical anticonvulsants phenobarbital, phenytoin, ethosuximide, chlordiazepoxide and midazolam all significantly and dose-dependently reduced cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 microM. In conclusion, several classical and newer anticonvulsants have neuroprotective properties in an in vitro model that simulates cerebral ischemia.

Topics: Acetates; Amines; Animals; Anticonvulsants; Carbamates; Carbamazepine; Cell Death; Cells, Cultured; Chlordiazepoxide; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Ethosuximide; Felbamate; Gabapentin; gamma-Aminobutyric Acid; Glucose; Hippocampus; Hypoxia; Ischemia; Lamotrigine; Levetiracetam; Midazolam; Neurons; Neuroprotective Agents; Nipecotic Acids; Oxcarbazepine; Phenobarbital; Phenylcarbamates; Phenylenediamines; Phenytoin; Piracetam; Propylene Glycols; Rats; Rats, Wistar; Tiagabine; Triazines; Valproic Acid

Topics: 5-Hydroxytryptophan; Anticonvulsants; Clonazepam; Humans; Hypoxia; Levetiracetam; Myoclonus; Neuroprotective Agents; Piracetam

Etiracetam, a nonanaleptic drug related to the nootropic substance piracetam, was found to facilitate memory retrieval in rats in several experimental situations, when injected 30 min prior to retention testing. The drug was active when memory deficits were induced by electroconvulsive shock, undertraining, or by a long training-to-test interval. The behavioral paradigms included a one-trial inhibitory avoidance task and a complex multitrial, spatially discriminated approach task. The clinical interest of drugs which facilitate retrieval processes is also discussed.

Topics: Animals; Avoidance Learning; Electroshock; Food; Food Deprivation; Handling, Psychological; Hypoxia; Levetiracetam; Male; Memory; Piracetam; Prejudice; Pyrrolidinones; Rats; Time Factors