Minimal Seizure Research Articles

Economic aspects of prolonged home video-EEG monitoring: a simulation study

IntroductionVideo EEG monitoring (VEM) is an important tool for characterizing clinical events suspected as seizures. It is also used for pre-surgical workups in patients with drug-resistant epilepsy (DRE). In-hospital VEM high cost, long admission waiting periods and some other inconveniences led to an interest in home VEM (HVEM). However, because antiseizure medications cannot be reduced at home, HVEM may require longer monitoring. While the economic aspect is one of the main motivations for HVEM, the cost of HVEM lasting several weeks has not been assessed.MethodsWe modeled the cost of HVEM for 8 weeks and compared it to the cost of 1-week in-hospital VEM. Additionally, we modeled the per-patient cost for a combination of HVEM and in-hospital VEM, considering that if in a proportion of patients HVEM fails to achieve its goal, they should undergo in-hospital VEM with drug reduction.ResultsThe average cost of HVEM up to 4–6 weeks of monitoring was lower than that for the 1-week in-hospital VEM. Combining the 3-week HVEM with 1-week in-hospital VEM (if needed) reduced the per-patient cost by 6.6–28.6% as compared to the situation when all the patients with DRE were referred to the in-hospital VEM.ConclusionsA prolonged intermittent HVEM can be cost-effective, especially if the minimal seizure frequency is about one seizure per week. The study findings support directing efforts into clinical trials and technology development.

Improved identification and differentiation from epileptiform activity of human hippocampal sharp wave ripples during NREM sleep.

In rodents, pyramidal cell firing patterns from waking may be replayed in nonrapid eye movement sleep (NREM) sleep during hippocampal sharp wave ripples (HC-SWR). In humans, HC-SWR have only been recorded with electrodes implanted to localize epileptogenicity. Here, we characterize human HC-SWR with rigorous rejection of epileptiform activity, requiring multiple oscillations and coordinated sharp waves. We demonstrated typical SWR in those rare HC recordings which lack interictal epileptiform spikes (IIS) and with no or minimal seizure involvement. These HC-SWR have a similar rate (~12 min-1 on average, variable across NREM stages and anterior/posterior HC) and apparent intra-HC topography (ripple maximum in putative stratum pyramidale, slow wave in radiatum) as rodents, though with lower frequency (~85 Hz compared to ~140 Hz in rodents). Similar SWR are found in HC with IIS, but no significant seizure involvement. These SWR were modulated by behavior, being largely absent (<2 min-1 ) except during NREM sleep in both Stage 2 (~9 min-1 ) and Stage 3 (~15 min-1 ), distinguishing them from IIS. This study quantifies the basic characteristics of a strictly selected sample of SWR recorded in relatively healthy human hippocampi.

Successful prevention of perinatal HIV transmission utilizing direct observation therapy in the setting of Acquired Immunodeficiency Syndrome (AIDS) and progressive multifocal leukoencephalopathy.

We report a case of a 22-year-old G1P0010 African-American female with poorly controlled perinatally acquired HIV/AIDS and recent diagnosis of progressive multifocal leukoencephalopathy (PML) by magnetic resonance imaging (MRI). She presented to a tertiary care facility for prenatal care and direct observation therapy after poor medication adherence during pregnancy. After multiple attempts at outpatient ART management, the patient was admitted at 35 weeks' gestation for direct observation therapy for both antiretroviral therapy and anti-seizure medication. Viral load at that time was 22,487 copies/mL and she was admitted and started on a salvage regimen which included: dolutegravir, tenofovir disoproxil fumarate/emtricitabine, darunavir, ritonavir, and trimethoprim/sulfamethoxazole for Pneumocystis jirovecii prophylaxis. The patient remained on direct observation therapy throughout her two-week hospital stay with final viral load of 1211 copies/mL, CD4 284/uL at time of delivery at 37 weeks' gestation, with minimal seizure activity. The infant received postnatal antiretroviral therapy including three doses of zidovudine and nevirapine with negative HIV PCR at birth, 2, 4, and 6 months postpartum and is currently HIV negative.

Dose Dependent Efficacy of Lacosamide in Protection of Pentylenetetrazol Induced Seizure in Rats

Epilepsy is a common and frequently devastated disorder affecting 0.5 to 1% of the population with annual incidence rate of approximately 30 to 50 per 1, 00,000 per year. Lacosamide is a novel anti-epileptic drug, recently been licensed for adjunctive therapy of partial or secondary generalized seizures. Objective: To evaluate dose dependent efficacy of lacosamide in protection of Pentylenetetrazol (PTZ) induced seizures in rats. Method: The study was conducted in albino rats of either sex, weighing between 100-150 gm. The animals were grouped into 6 groups, each compromised of 8 animals. Group I was treated with requisite volume of normal saline, group II received pentylenetetrazol (80mg/kg, i.p). Animals in group III, IV,V and VI were pretreated with graded doses of lacosamide (3,10,30& 50mg/kg i.p),thirty minutes later, the lacosamide pretreated groups were treated with pentylenetetrazol (80mg/kg/i.p). Results: It was found that animals in control group were normal, while the animals with PTZ treatment showed convulsions followed by mortality. However in group III 38%, group IV 60%, group V 88% & group VI 100% protection was observed with lacosamide against PTZ induced seizures. Conclusion: So, in our study we observed that in the doses of 30 and 50mg/kg, ip, lacosamide increased the seizure threshold and showed protection against the minimal seizure.

Pharmacotherapy of Epilepsy: Focus on Levetiracetam

Levetiracetam is a second-generation antiepileptic drug which first came to the United States market in 1999. It has a mechanism of action that is not well elucidated. However, it is a very favorable antiepileptic drug due to its reliable pharmacokinetics, minimal drug interactions, seizure efficacy and good tolerability. It is an agent that has established efficacy as an adjunct therapy agent for partial and refractory seizures. As a monotherapy agent, levetiracetam also appears to be an attractive agent with observed efficacy and tolerability. Since levetiracetam has recently become available intravenously, it is also being reviewed as an agent for acute status epilepticus. In pediatrics, levetiracetam is widely used with efficacy seen in small clinical trials for a variety of seizure types. Levetiracetam is well tolerated: the most common adverse effect being somnolence and behavioral effects. Overall, levetiracetam is a notable antiepileptic drug that has added significantly to the current antiepileptic armamentarium.

Safety of Imipenem/Cilastatin in Neurocritical Care Patients

Infection in the intensive care unit (ICU) empirically requires broad-spectrum antibiotics. Imipenem/cilastatin, often reserved for more serious hospital-acquired infections, is thought to be associated with a higher risk of seizures than other penicillins and carbapenems. We sought to evaluate the safety of imipenem/cilastatin in the treatment of infections, including meningitis, in neurocritical care patients. Pertinent literature was identified through MEDLINE (1966-2007) using search terms imipenem, seizure, carbapenem, and meropenem. A review of the literature is presented. Carbapenem antibiotics remain active against most Gram-positive and Gram-negative organisms, and are often used in critically ill patients. Drug-induced seizures are a rare but serious adverse effect, with carbapenems being one of the most common classes of antibiotics associated with seizures. Seizure rates in patients treated with imipenem/cilastatin and meropenem are similar. One small pediatric study of 21 patients showed a high incidence of seizures and is often cited as the reason imipenem should not be used in meningitis. However, many studies noting seizures with both meropenem and imipenem/cilastatin attribute this to patients with lower body weight, elderly, or those with impaired renal function. When dosed appropriately, imipenem/cilastatin may be used to treat serious infections in critically ill patients with central nervous system (CNS) disorders or injury with minimal seizure risk. Imipenem/cilastatin safety data is lacking for meningitis and cautious use is warranted.

Kinetics of drug action in disease states. XXXIII: Disparate effects of pentylenetetrazol in rats as a function of renal disease model and pharmacologic endpoint.

The purpose of this investigation was to determine if the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (PTZ) are altered in renal dysfunction. Female rats subjected to bilateral ureteral ligation (with sham-operated controls) or injected with uranyl nitrate (with saline injected controls) were infused intravenously with PTZ until the onset of either a minimal (myoclonic jerk) or maximal (tonic hindlimb extension) seizure. Neither chemically nor surgically induced renal dysfunction caused a change in the concentrations of PTZ in CSF, serum, or brain at onset of minimal seizures. When PTZ was infused to onset of maximal seizures, the rats with chemically induced renal dysfunction required higher concentrations, whereas the ureter-ligated rats convulsed at lower concentrations of PTZ than did the corresponding control animals. Thus, the effects of experimental renal dysfunction on the convulsant action of PTZ are dependent on both the disease model and the endpoint used for the pharmacodynamic measurement. Apparently, renal dysfunction did not affect the PTZ-induced seizure threshold, but inhibited the spread of seizures. The increased sensitivity of ureter-ligated rats may be due to their pronounced retention of water, since water loading is known to increase seizure susceptibility.

Age related increased threshold for electroshock seizure in BDF1 mice

The thresholds for inducing the minimal and maximal electroshock seizures were examined in relation to age in BDF1 mice of both sexes. The 50 percent effective intensities for the maximal electroshock seizure (tonic hindlimb extensor component) were lowest in the youngest age groups (6-month-old) for both male (10.68 mA) and female (9.18 mA) animals. The threshold increased with age and became significantly higher at 24 months (14.00 mA, 12.70 mA for male and female mice respectively). There was also a further increase in threshold at 30 months for both sexes. Similarly, the threshold for inducing the minimal seizure also increased with age but the differences in mean threshold levels between the youngest and oldest groups were much smaller in comparison to the maximal seizure. It was concluded that the threshold for inducing electroshock seizures significantly increases with age in mice of both sexes.

Brain Seizure Threshold of Prenatally Nicotine-Treated Offspring

DOI: http://dx.doi.org/10.5915/17-1-12718 The trimester of pregnancy through which nicotine may influence the postnatal development, has not been previously reported. Hence, 3 different doses of nicotine equivalent to 10 cigarettes (900 ug/kg). 20 cigarettes (1800 ug/kg) or 30 cigarettes (2700 ug/kg) were given daily subcutaneously (S.C.) during each trimester into 3 groups of pregnant mice. Their offspring were subjected to minimal electroshock seizure threshold (MEST) test. During the second trimester, the drug reduced the MEST of the offspring when they were I month old. However. during the third trimester, nicotine reduced their MEST when they were I and 2 months old. Thus, pregnant mothers are not recommended to be exposed to nicotine during the late stages of pregnancy.

The anticonvulsant effects of propranolol and β-adrenergic blockade

The anticonvulsant activity of racemic and (+)-propranolol was studied in rats. Neither drug changed the current to produce a minimal seizure in 50% of animals. Both drugs were effective in the maximal electroshock seizure test, the (+) isomer being more potent than the racemic form. Since the (+) isomer is practically devoid of beta-adrenergic blocking activity, the anticonvulsant effects of propranolol do not result from beta-adrenergic blockade.

Effects of intraventricularly administered monoamines on seizure susceptibility and body temperature in rats

Rats injected through permanent intraventricular cannulas with 8 μg of norepinephrine, 32 μg of dopamine or 8 μg of serotonin were tested 5 min later by the measurement of the electroshock seizure threshold and the duration of various components of tonic-clonic seizures induced electrically or with flurothyl. Each of the monoamines decreased the threshold for the minimal seizure and increased the duration of the tonic extension and postictal depression phases of maximal electroshock convulsions. The findings with flurothyl were less consistent among the monoamines, but decreased latencies for the myoclonic jerk and generalized convulsions and prolonged recovery from the seizure were observed. With the doses used all the monoamines produced hypothermia. In animals supplied with sufficient external heat to prevent hypothermia, the decreased electroshock seizure threshold was returned to normal. These findings indicate that the seizure-facilitating effects of intraventricularly administered monoamines are attributable to decreased body temperature.

Studies on the effects of histaminergic agents on seizure susceptibility in mice.

The influence of pharmacological modifications of the functional activity of the central histaminergic system was studied on the susceptibility of mice to pentylenetetrazol-induced minimal (clonic) and maximal (tonic) seizures. Enhancement in the functional activity of the system by central administration of histamine or 4-methylhistamine of peripheral L-histidine loading failed to modify the risk of seizures. By contrast, reduction in histaminergic function was found to alter seizure susceptibility. Brocresine, an inhibitor of histamine synthesis, decreased and increased the risk of pentylenetetrazol-induced minimal and maximal seizures, respectively. Many, but not all, classical anti-histamines (H1 antagonist) and metiamide (H2 antagonist) and metiamide (H2 antagonist) increased minimal seizure susceptibility after periheral and intraventricular administration, respectively.

Effects of Δ8- and Δ9-Tetrahydrocannabinol on experimentally induced seizures

Effects of Δ 8- and Δ 9-tetrahydrocannabinol ( Δ 8- and Δ 9-THC) on three experimentally induced seizure models, i.e., audiogenic seizure (AS) test, maximal electroshock seizure (MES) test and pentylenetetrazol (PTZ)-induced seizure test were determined in the audiogenic rat. Both tetrahydrocannabinols possess a dose-related anticonvulsant effect against AS, MES and PTZ-induced maximal seizure. Although anticonvulsant potencies do not significantly differ, Δ 8THC is three times more neurotoxic than Δ 9THC. In addition, both THC's are without effect on minimal seizure and lethality induced by PTZ. Furthermore, the low protective indexes (TD50/ED50) determined in this study suggest that Δ 8 and Δ 9 THC may have poor therapeutic potentials as antiepileptic drugs.

Acute and chronic effects of d- and 1-amphetamine on seizure susceptibility in mice

The effects of d- and 1-amphetamine were studied on different patterns of seizure activity in male mice, e.g., pentylenetetrazol-induced minimal (clonic) and maximal (tonic) seizures and low-frequency electroshock seizure threshold (1.f. EST). Acute administration of d- and 1-amphetamine increased susceptibility to minimal and 1.f. EST. Whereas 1-amphetamine increased maximal seizure susceptibility, the d-isomer decreased susceptibility to this seizure pattern. Daily injections of the amphetamine isomers for 7 consecutive days produced tolerance to all these changes in seizure threshold. d-Amphetamine was approximately twice as active as 1-amphetamine in altering seizure threshold. These studies are in agreement with the concept that amphetamine-enhanced pentylenetetrazol-induced seizures are mediated by dopamine. Chronic administration of saline for 7 days reduced susceptibility to maximal seizures and 1.f. EST 35 and 72%, respectively, but had little effect on minimal seizure threshold.

CNS excitability changes during altitude acclimatization and deacclimatization in rats

Electroshock convulsions in rats at sea level and at natural and simulated high altitudes demonstrated a central nervous system (CNS) excitation during acclimatization and depression during deacclimatization. Excitation, shown by decreased minimal seizure threshold and by increased duration of tonic extension during maximal seizures, was evident after 1 or 2 days exposure to 12,500 ft and after 2 hr to 20,000 ft. Changes in maximal seizures disappeared after 2 months at 12,500 ft, but seizure thresholds were significantly lower than in sea level controls even after 8 months. Recovery from maximal seizures remained prolonged and variable at altitude. During deacclimatization after 8 months at 12,500 ft or 6 days at 20,000 ft, CNS depression was shown by absence or shorter duration of tonic extension during maximal seizures and by a rapid rise in seizure thresholds. Increased excitability at altitude is probably due to hypoxia and hyperventilation-induced hypocapnia. The depression during deacclimatization is similar to that produced by hypercapnia and hyperoxia and suggests that CNS sensitivity to CO2 and O2 becomes altered during acclimatization.

Strain differences in seizure responses and brain cholinesterase activity in rats.

SummaryMarked strain differences in minimal electroshock seizure threshold, maximal electroshock seizure pattern, and duration of post-seizure depression were found in adult males and females of 6 strains of rats. Seizure thresholds in one group averaged only 65% of thresholds in another group. Duration of tonic extension during maximal seizures and duration of post-seizure depression showed 10- to 16-fold variations among strains tested. Females in general showed greater convulsive susceptibility than males of the same strain, probably because of the excitatory action of estradiol. In males, differences in seizures were compared with values for brain acetylcholine (ACh) concentrations and cholinesterase (ChE) activities reported previously for these strains. In each of the 3 pairs of strains, selectively bred from 3 foundation stocks, the strain with the lower seizure threshold had the higher ChE. On the other hand, intensity of seizures and postseizure depression could not be related to brain ACh or ChE.

Gonad-brain relationship: effects of castration and testosterone on electroshock convulsions in male rats.

The effects of castration and testosterone on brain excitability were investigated in male rats by measuring the minimal electroshock seizure threshold and the maximal electroshock seizure pattern. The principal results were: (a) Castration. Postpuberally castrated rats demonstrated less excitability than intact controls, as shown by changes in the maximal seizure pattern. However, excitability, measured by seizure thresholds, appeared slightly increased when castration was performed prepuberally. (b) Testosterone. The daily administration of high doses of testosterone to castrated rats increased the seizure threshold, whereas low and moderate doses had no effect. This decrease in excitability was further evidenced by an anticonvulsant effect on the maximal seizure pattern at 74 days of age after 2 weeks of testosterone injections. On the other hand, continued administration of the androgen reversed the anticonvulsant pattern to a convulsant one at 95 and 109 days of age, even though seizure thresholds we...

Anticonvulsant properties of l-glutamine and l-asparagine in mice and rats.

SummaryTwo amides, l-glutamine and l-asparagine, were tested for anti-convulsant activity in mice after acute administration by a battery of 6 anticonvulsant assay procedures and after chronic administration by 3 tests. In addition, both agents were tested in mice for ability to prevent methionine sulfoximine-induced seizures and in rats for ability to elevate the minimal electroshock seizure threshold lowered by food restriction. The results indicate that both these agents are virtually devoid of anticonvulsant activity as measured by a number of diverse laboratory screening procedures.