Epilepsy research
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Sudden unexplained/unexpected death in epilepsy (SUDEP), with an incidence of 0.35-9.3/1000 patient-years depending on the severity of epilepsy, remains a diagnostic and therapeutic challenge. Potential pathomechanisms comprise cardiac arrhythmia, due to myocardial ischemia, electrolyte disturbances, arrhythmogenic drugs, or transmission of the epileptic activity via the autonomic nervous system to the heart, and central or obstructive apnea. ⋯ Whereas cardiac dysfunction during seizures has been documented by electrocardiography, and cardiac abnormalities are found in up to 33% of SUDEP cases autoptically, investigations between seizures found only little cardiac abnormalities. More knowledge about the cardiovascular and pulmonary status of epileptic patients during, immediately after and between seizures is needed, which may contribute to better understand and possibly prevent SUDEP by measures like "cardioprotective" drugs, respiratory therapy or implantation of a cardioverter/defibrillator.
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Comparative Study
MAO(A) knockout mice are more susceptible to seizures but show reduced epileptogenesis.
The role of elevated neuroactive amine exposure during embryonic and early postnatal development on seizure threshold and epileptogenesis was examined using both electrical and pentylenetetrazol (PTZ) kindling in monoamine oxidase A knockout (MAO(A) KO) mice and their wildtype, parental strain (C3H). In the first experiment permanent bilateral electrodes were implanted in the amygdala of both C3H and MAO(A) KO mice. The mice had their afterdischarge threshold determined and then seizures were kindled daily for a total of 20 days. ⋯ We observed that the MAO(A) KO mice had shorter latencies to the onset of the first seizure, shorter total duration of seizures and fewer seizures per day. Overall the results of both experiments suggest that MAO(A) KO mice have an increased susceptibility to seizures, but are more resistant to epileptogenesis. We conclude that the high levels of neuroactive amines in the MAO(A) KO mice reorganize the brain to make the mice more susceptible to seizures but the remaining high levels of serotonin and norepinephrine likely inhibit epileptogenesis.
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Comparative Study
A comparison of three NMDA receptor antagonists in the treatment of prolonged status epilepticus.
Three different classes of NMDA receptor antagonists were compared for their effectiveness in terminating prolonged status epilepticus (SE), induced by continuous hippocampal stimulation. Animals were treated after 150 min of SE by intraperitoneal administration of increasing doses of 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), MK-801 (dizocilpine), ifenprodil, or saline. EEG recordings were used to determine seizure termination. ⋯ MK-801 (2.0 mg/kg) terminated SE in 6 of 10 animals within 60 min, CPP (15 mg/kg) terminated it in 1 of 9 animals; ifenprodil (30 mg/kg) did not terminate it in any of 9 animals treated. In the 300 min following administration, CPP (6/9) and MK-801 (6/10) were equally efficacious in terminating SE but ifenprodil (2/7) was less effective (P = 0.065, chi-square test). The results indicate that the non-competitive NMDA receptor antagonist MK-801 was superior to the competitive antagonist CPP and the pH-sensitive site antagonist ifenprodil, in terminating prolonged experimental SE.
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Comparative Study
Anticonvulsant effects of levetiracetam and levetiracetam-diazepam combinations in experimental status epilepticus.
Status epilepticus (SE) is a neurological emergency, with high mortality and high morbidity among survivors, and novel therapeutic agents are needed to improve this picture. We examined the effects of the antiepileptic drug levetiracetam (LEV) in an experimental model of self-sustaining status epilepticus (SSSE), induced in rats by electrical stimulation of the perforant path. LEV's unique spectrum of anticonvulsant activity, very high therapeutic index, and neuroprotective properties, make it a potentially interesting agent in the treatment of SE. ⋯ Treatment during the maintenance phase of SSSE diminished (at 200 mg/kg) or aborted seizures (in doses of 500 or 1000 mg/kg). Addition of LEV significantly enhanced the anticonvulsant effects of diazepam (DZP), even when both drugs where given in doses far below their therapeutic level. We conclude that LEV deserves further evaluation in the treatment of status epilepticus.
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Randomized Controlled Trial Meta Analysis Clinical Trial
Levetiracetam does not alter body weight: analysis of randomized, controlled clinical trials.
Increases in body weight gain are important, and clinically significant adverse effects of several antiepileptic drugs (AED) including valproate and gabapentin. Weight gain may contribute to medication non-compliance, discontinuation, and importantly, may have secondary medical implications as well. Levetiracetam (LEV) is indicated for adjunctive treatment of partial seizures. The objective of the present evaluation was to examine the effects of LEV treatment on body weight in adult patients. ⋯ We conclude that treatment with LEV at clinically relevant dosages is not associated with significant weight change. LEV would, therefore, appear to be a weight neutral AED.