Tonic-clonic Convulsions Research Articles

Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats

Noda epileptic rat (NER) is a mutant rat, which spontaneously exhibits a tonic-clonic convulsion from 14 weeks of age. An intracellular recording study was performed to elucidate the abnormal excitability of NER hippocampal CA3 neurons. The recorded neurons were classified into two groups, group A and B neurons, according to the responses to a single stimulation of mossy fibers. In group A neurons, a stimulus elicited a long-lasting depolarization shift accompanying repetitive firings followed by after-hyperpolarization. In group B neurons, the same stimulus elicited a single spike without a long-lasting depolarization shift. Bath application of 1 mM Cd2+, a nonselective Ca2+ channel blocker, completely inhibited the abnormal excitation in group A neurons. We further examined the character of Ca2+ spikes in NER CA3 neurons. Ca2+ spikes were completely blocked by 10 μM Cd2+ in group A neurons, but not in either group B or control neurons, suggesting that Ca2+ channels in NER group A neurons have the hypersensitivity to Cd2+. Analysis using subtype specific blockers of Ca2+ channel raised the possible involvement of T-type Ca2+ channels. These results suggest that Ca2+ channel dysfunction is involved in the abnormal excitability of CA3 pyramidal neurons and pathogenesis of epilepsy in NER.

Study of the dynamics of anticonvulsant and anxiolytic action after oral administration of tin (II) chloride

This article is devoted to the study of anticonvulsant and anxiolytic activity of tin (II) chloride by oral administration. The anxiolytic effect was established in models of the Open Field and Black-and-White Camera tests; the anticonvulsant activity of SnCl (II) was evaluated in model of acute generalized seizures with the determination of pentylenetetrazole (PTZ) minimum effective doses inducing clonic-tonic convulsions and tonic extension in test animals. Statistical indicators were calculated using the Microsoft Excel software package using the arithmetic mean value (M) and the mean deviation mean value (m). The obtained data show that tin (II) chloride is a promising compound for the prevention of anxiety states, as well as disorders containing the convulsive component. Three hours after the start of the experiment, the minimum doses of pentylenetetrazole for inducing clonic-tonic convulsions and tonic extension, exceeded the control group data by an average of 75%. A decrease in motor activity by half compared with the control in the open field test during the 5 hours of the experiment indicates the sedative effect of tin (II) chloride. Tin (II) chloride is a promising compound for the relief of convulsive states and correction of depressive disorders. Thus, it is of interest to further study the spectrum of its pharmacological activity in order the use it in medicine.

Increased Antiseizure Effectiveness with Tiagabine Combined with Sodium Channel Antagonists in Mice Exposed to Hyperbaric Oxygen

Hyperbaric oxygen (HBO2) is acutely toxic to the central nervous system, culminating in EEG spikes and tonic-clonic convulsions. GABA enhancers and sodium channel antagonists improve seizure latencies in HBO2 when administered individually, while combining antiepileptic drugs from different functional classes can provide greater seizure latency. We examined the combined effectiveness of GABA enhancers (tiagabine and gabapentin) with sodium channel antagonists (carbamazepine and lamotrigine) in delaying HBO2-induced seizures. A series of experiments in C57BL/6 mice exposed to 100% oxygen at 5 atmospheres absolute (ATA) were performed. We predicted equally effective doses from individual drug-dose response curves, and the combinations of tiagabine + carbamazepine or lamotrigine were tested to determine the maximally effective combined doses to be used in subsequent experiments designed to identify the type of pharmacodynamic interaction for three fixed-ratio combinations (1:3, 1:1, and 3:1) using isobolographic analysis. For both combinations, the maximally effective combined doses increased seizure latency over controls > 5-fold and were determined to interact synergistically for fixed ratios 1:1 and 3:1, additive for 1:3. These results led us to explore whether the benefits of these drug combinations could be extended to the lungs, since a centrally mediated mechanism is believed to mediate hyperoxic-induced cardiogenic lung injury. Indeed, both combinations attenuated bronchoalveolar lavage protein content by ~ 50%. Combining tiagabine with carbamazepine or lamotrigine not only affords greater antiseizure protection in HBO2 but also allows for lower doses to be used, minimizing side effects, and attenuating acute lung injury.

Elevated Healthcare Burden Among Patients with Active Generalized Tonic-Clonic (GTC) Convulsions (P3.5-027)

Elevated Healthcare Burden Among Patients with Active Generalized Tonic-Clonic (GTC) Convulsions (P3.5-027)

Serotonin 2A and Sigma 1 Receptor Antagonists Synergize to Block the Acute Toxicity of Methamphetamine

Currently there are no Food and Drug Administration approved pharmacotherapies for methamphetamine (METH) overdose, thus identifying novel drug targets to prevent this devastating adverse event is a public‐health imperative. Previous research suggests that serotonin and sigma receptors may contribute to the adverse effects of METH.Determine whether antagonism of serotonin 2A (5‐HT2A) and sigma 1 (σ1) alone or in combination attenuates METH‐induced lethality, hyperthermia, convulsions, and seizures.Male, Swiss Webster mice received intraperitoneal injections of the selective 5‐HT2A receptor antagonist M100907 (1–10 mg/kg), the selective σ1 receptor antagonist BD 1047 (10–30 mg/kg), and a combination of M100907/BD 1047 (1:10 mg/kg) prior to treatment with METH (78 mg/kg ‐ LD67). Convulsions and lethality were assessed by observation, core body temperature was assessed by surgically implanted telemetric probes, and seizures were assessed by electroencephalography.M100907 and BD 1047 administered alone had no significant effect on METH‐induced lethality. However, combined antagonism of 5‐HT2A and σ1 receptors eliminated lethality in all mice tested (a reduction from LD67 to LD0). Similarly, only the combination of 5‐HT2A and σ1 receptor antagonism eliminated seizure activity. All three treatments decreased tonic‐clonic convulsions as measured on a modified Racine scale. None of the treatments decreased METH‐induced hyperthermia.This research suggests that reducing METH‐induced seizures may be critical for reducing METH‐induced lethality. These data support the continued investigation of the role of 5‐HT2A and σ1 receptors in METH overdose, including their potential to yield emergency reversal agents.Support or Funding InformationThese studies were supported by the National Institutes on Drug Abuse [NS100512] and by funding from the Mercer University College of Pharmacy (Murnane KS‐ Principal Investigator; Canal CE– Principal Investigator)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Food Poisoning by Ginkgo Seeds through Vitamin B6 Depletion

Overconsumption of Ginkgo biloba seeds induces food poisoning characterized by tonic-clonic convulsions and vomiting. The primary toxic component, 4'-O-methylpyridoxine (MPN), was purified from the seeds in 1985. This review includes the following aspects of ginkgo seed poisoning: 1) toxicity related to the content of MPN and MPN glucoside in G. biloba seeds; 2) the effect of MPN on vitamin B6 analogs, including an increase in pyridoxal and pyridoxic acid and decrease in pyridoxal-5'-phosphate plasma concentrations; 3) case reports of ginkgo seed poisoning in Asia, North America, and Europe, and their effective treatment via vitamin B6 administration. Considering the increase in the use of G. biloba seeds, it is essential to raise global awareness of their potential toxicity.

Deep tongue laceration following eclampsia, Cesarean section, repair and blood transfusion- A case report

Eclampsia still remains an issue of serious concern in Sub Saharan Africa. Preeclampsia is the precursor to eclampsia, in which hypertension and proteinuria are present, with or without oedema1-2. This is a case of Mrs SK, a 21year old Primigravida who was unsure of her last menstrual period, but she was said to be 9 months pregnant; she developed generalized tonic clonic convulsions with each episode lasting about 30 seconds. She sustained a V-shaped laceration affecting lower one third of the tongue with clots of blood on the affected area. A diagnosis of antepartum eclampsia was made. She was admitted into the eclamptic ward and resuscitated. Intravenous infusion and Magnesium sulphate were commenced using Zuspan Regimen. She had an emergency caesarean section and was delivered of a fresh still birth female baby who weighed 3.0kg. The lacerated tongue was repaired by maxillofacial surgeon and she was transfused with 2 pints of blood.Eclampsia is the leading cause of maternal mortality in developing countries. Recognizing the features of preeclampsia and instituting appropriate measures is mandatory in order to prevent the progression of the disease to eclampsia with its associated complications.

Chapter 6 - Monitoring for seizures in the intensive care unit

Acute symptomatic seizures have been known to occur in critically ill patients for many years. It was not until the widespread use of continuous EEG (cEEG) in the critically ill did we appreciate the incidence of electrographic seizures and status epilepticus in the ICU (Newey and Kinzy, 2018). Many of the seizures that occur are without any apparent clinical signs at the time of the recording. The patients often have convulsive seizures at onset then over the next few hours they lose the ability to have a generalized tonic clonic convulsion. They may then have subtle clinical signs (ictal nystagmus, facial twitching, etc.) or lose any apparent motor response. The end result is that many of the patients lose any clinical signs for their seizures by the time they are in the ICU and their seizures are termed "nonconvulsive." The recognition of seizures in the ICU is important for the effects the seizures have on outcome, particularly in morbidity and mortality and the risk of developing epilepsy after the acute symptomatic event. The use of cEEG in the ICU population has not only highlighted the high incidence of seizure activity but has also been used to assess overall cerebral function with applications in ischemia monitoring and prognostication, and to assess the degree of encephalopathy. This chapter will illustrate the core principles of cEEG monitoring in the critical care population including the incidence of seizures, determining who is at highest risk for seizures, how long patients should be monitored and ICU EEG seizure.

Sudden seizure during cesarean section

Rationale:A first seizure can range from a fleeting subjective experience or a twitch (myoclonic jerk) through to a tonic-clonic convulsion. A first seizure occurred in a parturient during cesarean section is very rare. We describe the case of a parturient who suffered seizure when the fetus was delivered.Patient concerns:Our patient is a 31-year-old parturient with a first seizure during cesarean section.Diagnoses:Seizure.Interventions:The patient received supportive therapy to maintain oxygen supply and propofol was administered to terminate seizure during cesarean section.Outcomes:after therapy, the patient regained full consciousness and normal spontaneous respiration. She had no recall of the seizure attack. The post-operative recovery was uneventful.Lessons:Symptoms during seizure are very important to diagnose. It will be both harmful to mother and the fetus, when the pregnant woman suffers seizure during pregnancy or cesarean delivery. In this situation, supportive therapy need to be immediately initiate and propofol may be the most suitable drug to terminate seizure during cesarean delivery.

Disease Profile of Seizure in Children

This study was done in the Departmen tof Paediatrics, Rajshahi Medical College Hospital, Rajshahi to final out the disease profile of children Hospitalised with seizure presentation. From 01/01/14 to 31/12/14 period a total of 12,560 children in the age group 6 months to 12 years were admitted in the Paediatric department. Among these 656 (5.2%) children were admitted due to convulsion. 62.8% were male and 37.2% female, 53% febrile and 47% a febrile, 59% were less than 5 years. Generalized tonic clonic convulsion (GTC) was the most common seizure type (72.8%). Febrile convulsion, seizure disorder, meningitis and encephalitis were common causes of convulsion.TAJ 2012; 25: 35-37

186. Seizure-induced cognitive impairment in a rat model of preeclampsia: Effects of multiple seizures and anti-seizure treatments

Introduction Eclamptic seizures include tonic-clonic convulsions that can be recurrent and cause acute memory deficits and cognitive impairment. While a brief seizure may cause minimal injury, recurrent seizures can impair memory and cognition. In addition, whether preeclampsia (PE) increases the susceptibility to seizure-induced cognitive impairment, or if anti-seizure treatments are protective remains unclear. Objective/Hypothesis We tested the hypothesis that multiple seizures would cause greater memory impairment than a single seizure in PE versus normal pregnancy, and compared the protective effects of magnesium sulfate ( MgSO 4 ) and diazepam (Dz) on seizure-induced cognitive dysfunction. Methods Pregnant (d19-20) Sprague Dawley rats were normal (Preg) or with PE (induced by a high cholesterol diet gestational d7-20). The chemoconvulsant pentylenetetrazol (PTZ; i.p.) was used to compare the effect of one versus multiple tonic–clonic seizures on cognition. Rats either received one PTZ injection (60 mg/kg; n = 6/group), multiple PTZ injections (5–40 mg/kg; n = 13/group), or vehicle (CTL; n = 7/group). Rats having seizure(s) received MgSO 4 (270 mg/kg i.p.) or Dz (10 mg/kg i.p.) 20 min after PTZ. Short-term memory was tested 24 h post-seizures using a novel object recognition task, and recognition index calculated: (novel object time)/(total object time). Data are mean ± SEM and comparisons made using a Student’s t-test. Results Preg and PE rats that had multiple seizures had decreased recognition indices compared to CTL (0.49 ± 0.04 vs. 0.69 ± 0.06, p 0.05 and 0.46 ± 0.07 vs. 0.70 ± 0.05, p 0.05) that was unaffected by MgSO 4 or Dz in PE rats (0.49 ± 0.12 and 0.42 ± 0.08, respectively) and Preg rats (0.46 ± 0.08 and 0.51 ± 0.04, respectively). A single seizure did not affect short-term memory in either group. Discussion Cognitive function was significantly impaired after multiple seizures in both Preg and PE rats; however, a single seizure did not affect memory function. Neither MgSO 4 nor Dz treatment improved cognition after multiple seizures, highlighting the importance of prevention of eclampsia and seizure cessation to maternal cognitive health.

Case of acute enteroviral meningoencephalitis occurring concurrent with cytomegalovirus infection

Background: Outbreak of EV-71 was recorded in Rostov-on-Don, Russia in 2013. 165 children and 4 adults were suffered. Mild or moderate forms were observed in almost all cases. Very severe course of disease occurred in one adult. Methods & Materials: A retrospective analysis of medical record of severe enteroviral meningoencephalitis in 25-year-old woman was performed Results: The patient had morbid obesity (Grade III). She fell ill at the same time with 3-year old son. Mild form of EV-71 was diagnosed in child. In his mother a conclusion about enterovirus EV-71 as the causative agent of meningoencephalitis was made based on clinical and epidemiological data. The patient was hospitalized with tonic-clonic convulsions, headaches, repeated vomiting, fever (38 °C). Elements maculopapular rash were observed on palms and feet. In CSF cytosis was 640/3 (36% lymphocytes), glucose of 2.3 mmol/l. Enterovirus RNA in CSF was negative. Anti-EV IgM and IgG in blood were negative, but anti-CMV IgM and IgG were detected. MRI revealed signs of cerebral edema, with displacement of midline structures (2-7 mm). The patient's condition was very severe and for 4 weeks she was on ventilator. The fever persisted for 2 days. Immune status was: CD3+ - 74%, CD3 + CD4+ 44%, CD3+ CD8+ - 30%, CD16+ 11%, CD19+ - 13%, IgA - less than 0,66 g/l, IgM - 6.8 g/l, IgG - 7.8 g/l, CIC -206 UE, CD25+ a- 5.5%, HLA-DR+ 15%, CD95+ - 5.3%, anti -DNA 0.65 IU/ml. Repeated MRI after a week revealed negative dynamics with the appearance of inflammatory foci in CNS. Additionally, cardiomyopathy and left-side lower lobe pneumonia were diagnosed. The patient received intensive supportive therapy. Only after one month positive dynamics was detected. Full recovery was observed after one year. Conclusion: The peculiarity of this case was the combination of enteroviral meningoencephalitis with reactivation of CMV. This can be attributed to the severe immunosuppression metabolic syndrome characterized by violation of the immunoregulatory index and the processes of intercellular cooperation and the lack of switching synthesis IgM to IgG. These changes in the immune status were the most likely a cause of severe illness.

Risk factors of preeclampsia and eclampsia in Sanglah General Hospital from March 2016 to March 2017

Background: Preeclampsia and eclampsia have been increasing at an alarming rate. It is a challenging task for doctors and pregnant mothers. Preeclampsia defined as new onset of hypertension (≥140mmHg systolic or ≥90mm Hg diastolic on at least two occasions 6 hours apart) and proteinuria (at least 1+ on dipstick or ≥300mg in a 24-hour urine collection) after 20 weeks of gestation. Eclampsia defined as neurologic involvement in the form of generalized tonic-clonic convulsions in women with preeclampsia is termed eclampsia if the seizures cannot be attributed to any other cause such as epilepsy, cerebral infection, tumor or ruptured aneurysm. Aim: This study aims to find the association of risk factors for preeclampsia and eclampsia. The risk factors for preeclampsia and eclampsia are obesity, primigravida, multiple pregnancies, diabetes, pre-existing hypertension, family history, expecting mother’s age, nutritional status, and socioeconomic status. The study was carried out by using descriptive research and data were collected from medical records in Sanglah hospital which has 140 cases. Results: The results for preeclampsia are highest in expecting the age of 20-35 years old, primigravida women with gestational age > 37 weeks, overweight and overnourished women, a middle socioeconomic status and also without risk factors. The results for eclampsia are dominant in expecting age of 20-35 years old, primigravida women with gestational age > 37 weeks, women with middle socioeconomic status and majority without risk factors, and women who are overweight and overnourished. Conclusion: Preeclampsia and eclampsia cases are highest in expecting age of 20-35 years old, primigravida women with gestational age >37 weeks, overweight and overnourished women, majority women without risk factors and from middle socioeconomic status.

Исследование противосудорожных и противогипоксических свойств гемисукцината 2-этил-6-метил-3-гидроксипиридина

Изучены противосудорожные и антигипоксические свойства гемисукцината (2-этил-6-метил-3-гидроксипиридина) в сравнении с мексидолом. Показано, что в тесте антагонизма с максимальным электрошоком гемисукцинат (50 и 100 мг/кг) превосходит по противосудорожному действию мексидол (200 мг/кг), что проявляется в защите животных от гибели и устранении тонической фазы судорог у мышей. В тесте антагонизма с коразолом гемисукцинат (50 и 100 мг/кг), в отличие от мексидола (200 мг/кг), не устраняет клонико-тонические судороги и не защищает животных от гибели. В условиях модели нормобарической гипоксии с гиперкапнией в гермообъеме гемисукцинат (50 и 100 мг/кг), аналогично мексидолу (200 мг/кг), увеличивает время жизни животных. Полученные результаты свидетельствуют о различиях в спектре противосудорожной активности гемисукцината и мексидола.

Synthesis and Anticonvulsive Activity of 3- and 4-Benzoylpyridine Oxime Derivatives

We present here the synthesis of 3- and 4-benzoylpyridine oxime derivatives with potential anticonvulsant action. The most active compound in the maximum electric shock test was 4-benzoylpyridine O-2-morpholinoethyloxime oxalate (1a), i.p. doses of 60 – 150 mg/kg of which increased the survival of mice to 100%. The best effect in the corasol antagonism test was obtained with 4-benzoylpyridine O-(isonicotinoyl)oxime (2c), i.p. doses of 12.5 mg/kg of which increased the survival of mice to 67% and the latent period of onset of generalized tonic-clonic convulsions to 52 sec. Compound 1a had low toxicity (the i.p. LD50 in mice was 316 mg/kg) and a therapeutic index of 21.

Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy

BackgroundIn juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.MethodsUsing Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase (ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds ratios in case–control associations, and allele frequencies in the Genome Aggregation Database. We performed functional tests of the effects of variants on mitosis, apoptosis, and radial neuroblast migration in vitro and conducted video-EEG studies in mice lacking a copy of Ick.ResultsA variant, K305T (c.914A→C), cosegregated with epilepsy or polyspikes on EEG in 12 members of the family affected with juvenile myoclonic epilepsy. We identified 21 pathogenic ICK variants in 22 of 310 additional patients (7%). Four strongly linked variants (K220E, K305T, A615T, and R632X) impaired mitosis, cell-cycle exit, and radial neuroblast migration while promoting apoptosis. Tonic–clonic convulsions and polyspikes on EEG resembling seizures in human juvenile myoclonic epilepsy occurred more often in knockout heterozygous mice than in wild-type mice (P=0.02) during light sleep with isoflurane anesthesia.ConclusionsOur data provide evidence that heterozygous variants in ICK caused juvenile myoclonic epilepsy in 7% of the patients included in our analysis. Variant ICK affects cell processes that help explain microdysgenesis and polyspike networks observed on EEG in juvenile myoclonic epilepsy. (Funded by the National Institutes of Health and others.)

Maternal Mortality in Eclampsia after Cesarean Section versus Vaginal Delivery

Preeclampsia with generalized tonic-clonic convulsions is termed as eclampsia. Eclampsia isassociated with multiple maternal and fetal complications. Eclampsiais an obstetric emergency and quick decision making is required to save lives. The objective of the study was to compare the maternal mortalityafter cesarean section versus vaginal delivery among eclampsiapatients. It is a descriptive case series conducted in Department of Obstetrics and Gynecology, Lady Willingdon Hospital, from December 2014 to June 2015. In our study, 62.86 % (n=88) patients were between18-25 years of age and 37.14 % (n=52) werebetween 26-35 years of age. The mean+SD was calculated as 25.12+4.53 years. Frequency ofvaginal delivery in patients with eclampsia was 30.71 % (n=43) while69.29 % (n=97) were delivered through cesarean section. Comparisonof maternal mortality in two groups was recorded, where out of 43 spontaneous vaginal deliveries mortality was recorded in 6.98 % (n=3). Out of 97 cesarean deliveries, mortality was recorded in 17.53% (n=17). We concluded that mortality rates are higher in patients undergoing cesarean section.

Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.

Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.

Camphor Induced Seizures in an Adult- A Revisit

In Nineteenth century camphor was produced by distillation of the tree bark of camphor (Cinnamomum camphora) however now a days it is obtained artificially from oils like turpentine. Camphor is used to relieve pain, coryza, haemorrhoids, osteoarthritis and is an ingredient in of many over-the-counter drugs. In India the most popular use of camphor still remains in the spiritual prayers and pujas offered daily even in an ordinary household. Seizures can occur as soon as minutes after ingestion of camphor. Seizures associated with camphor have been reported in young children after accidental ingestion, dermal, and inhalational exposure. We report a case of camphor self-ingestion in an elderly female who experienced generalized tonic clonic convulsions with no previous history of seizure disorder. On evaluation she had no other plausible explanation for seizures but for camphor toxicity. She was treated supportively with no seizure recurrence.

Antepartum Eclampsia and Partial HELLP Syndrome in a Patient with Bell\'s Palsy

Bell's palsy affects pregnant women three times more often than nonpregnant women, with majority of cases occurring in the third trimester (71%) and early postpartum period (21%). Bell's palsy during pregnancy has been associated with preeclampsia, with 22% of these women developing preeclampsia. A 26-year-old G3P1 L1A1 diagnosed with Bell's palsy 2 weeks earlier, presented at 33-week period of gestation with a chief complaint of progressive bilateral pedal edema for 1 week, blood pressure (BP) - 150/100 mmHg and dipstick urine - 3+. Laboratory screening of HELLP syndrome was normal. Six days later, she had an episode of generalized tonic–clonic convulsion, magnesium sulfate was given, and emergency laboratory investigations revealed partial HELLP syndrome (platelet - 80,000, serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase - 281/222 U/L) with normal coagulation profile. Lower segment caesarean section was performed with delivery of a 2ks neonate with APGAR of 7/10 and 9/10 at 1 and 5 minute respectively. Postoperative day 3, all laboratory reports including magnetic resonance imaging brain were normal. BP was stabilized and she was discharged on the third postnatal day, with some right-sided residual facial weakness. All obstetricians must be aware of association of Bell's palsy with hypertensive disorders of pregnancy and aggressively screen for the same as soon as diagnosed, to prevent complications such as eclampsia and HELLP. Since Bell's palsy is not associated with adverse perinatal outcomes, it should not prompt obstetricians for hastening deliveries prematurely.