Possible Protective Effects of Omega 3, Diazepam and their Combination Against Yohimbine-Induced Clonic Seizure in Mice: Comparative Study

Yohimbine is actually confirmed in the United States to be utilized for erectile dysfunction; and recently such drug has become commonly used in body-building communities for its presumed lipolytic and sympathomimetic effects. But ingestion of such drug can bring about epileptic neurotoxic effects. Many antiepileptic drugs can be utilized to counteract myoclonic seizure; furthermore, diazepam can be used to oppose such type of seizure; in addition, surrogate therapeutic options such as omega 3 may also be utilized. In this study, twenty-four (24) mice of both sexes weighing 20-25g were randomly-allocated into 4 groups (6 animals each group) as follows: Group I- Yohimbine-induced clonic seizure [mice orally-administered DMSO (10%), and after 30 min, animals Sc. injected with 45mg/kg yohimbine). Group II- Diazepam-treated as standard drug: It is Sc. injected at a dose of 2mg/kg, and after 30 minutes, yohimbine at a dose of 45mg/kg is Sc. injected. Group III- Omega 3 (40 mg/kg) is orally-administered, and after 30 min 45mg/kg yohimbine is Sc. injected. Group IV- Combination of omega 3 (40mg/kg) is orally-administered then and after ten minutes, diazepam was IP injected 2mg/kg then after 20 minute, 45mg/kg yohimbine is Sc. Injected. The result of this study showed that omega 3 has non-optimal antiepileptic effect; where, it is un-able to reduce the onset and frequency of epilepsy tone in mice during several time periods (30-120min); and data weren’t significantly different when compared to diazepam. But omega 3 reduced onset of epilepsy in combination with diazepam when compared with diazepam alone. As well as omega 3 caused small percent changes frequency of epilepsy tone through 120 min when compared with other groups. Conclusion: Omega 3 fatty acid had partial beneficial effect; where, alone it has a role for decreasing onset of epilepsy; but, its combination with diazepam had significant role for reducing onset of epilepsy against yohimbine-induced seizure model. Additionally, omega 3 alone and in combination with diazepam have negligible role for reduction frequency of epilepsy.

Case Report: Cerebral Phaeohyphomycosis Due to Chaetomium strumarium in a Child with Visceral Heterotaxy Syndrome

Chaetomium sp. is a mold, member of the phylum Ascomycota. Clinical disease in humans is rare, particularly in children, for which only five cases have been reported. We report a 7-months-old female patient with a diagnosis of visceral heterotaxy syndrome who was admitted to a private center in Mexico. After two episodes of focal myoclonic seizure, a brain magnetic resonance imaging (MRI) revealed a right porencephalic cyst and a right frontal abscess with ventriculitis. Seventy-two hours after temporal abscesses drainage procedure, the culture showed a rapidly growing pale white fungal colony. Sequencing of ITS and D1/D2 led to the identification of Chaetomium strumarium. Although Chaetomium sp. is a rare fungal infection in humans, clinicians should consider it as a plausible etiologic agent that can form brain abscess.

The Effects of Hydro-alcoholic Extract of Ocimum Basilicum Green Leaf on Pentylenetetrazole-induced Seizure in Male Mice

Background: Regarding the chronic nature of epilepsy, and drug resistance in many cases, herbal medicine has received remarkable interest. Objective The present study aimed to determine the anticonvulsant effects of hydro-alcoholic extract of Ocimum basilicum green leaf on Pentylenetetrazole (PTZ)-induced seizure in male mice. Methods: In this experimental study, 48 albino male mice, weighing 20-25 g were randomly divided into 6 groups. All study groups were injected intraperitoneally (IP). The negative and positive control groups received saline (10 mL/kg) and phenobarbital (40 mg/kg) respectively. The treatment groups received 100, 300, 500, and 1000 mg/kg doses of hydro-alcoholic extract Ocimum basilicum green leaf. To provoke convulsion, after 45 minutes, PTZ was injected (80 mg/kg) to all research groups; accordingly, the d initiation time of myoclonic and tonic-clonic seizures and the frequency of 24h death were measured. Results: The obtained results indicated that the extract delayed the initiation time of myoclonic and tonic-clonic seizures, compared with the controls. The delay was significant at doses of 1000 (P<0.001), 500, and 300 mg/kg (P<0.01) for myoclonic seizure as well as 1000, 500, and 300 mg/kg (P<0.001) and 100 mg/kg (P<0.05) for tonic-clonic seizure. Furthermore, the extract decreased the 24h death. This was significant at doses of 1000, 500, and 300 mg/kg (P<0.001). Conclusion: It seems that the hydro-alcoholic extract of Ocimum basilicum green leaf presented decremental effects on PTZ-induced seizure and death in male mice.

Experimental Models for the Discovery of Novel Anticonvulsant Drugs: Focus on Pentylenetetrazole-Induced Seizures and Associated Memory Deficits

: Epilepsy is a chronic neurological disorder characterized by irregular, excessive neuronal excitability, and recurrent seizures that affect millions of patients worldwide. Currently, accessible antiepileptic drugs (AEDs) do not adequately support all epilepsy patients, with around 30% patients not responding to the existing therapies. As lifelong epilepsy treatment is essential, the search for new and more effective AEDs with an enhanced safety profile is a significant therapeutic goal. Seizures are a combination of electrical and behavioral events that can induce biochemical, molecular, and anatomic changes. Therefore, appropriate animal models are required to evaluate novel potential AEDs. Among the large number of available animal models of seizures, the acute pentylenetetrazole (PTZ)-induced myoclonic seizure model is the most widely used model assessing the anticonvulsant effect of prospective AEDs, whereas chronic PTZ-kindled seizure models represent chronic models in which the repeated administration of PTZ at subconvulsive doses leads to the intensification of seizure activity or enhanced seizure susceptibility similar to that in human epilepsy. In this review, we summarized the memory deficits accompanying acute or chronic PTZ seizure models and how these deficits were evaluated applying several behavioral animal models. Furthermore, major advantages and limitations of the PTZ seizure models in the discovery of new AEDs were highlighted. With a focus on PTZ seizures, the major biochemicals, as well as morphological alterations and the modulated brain neurotransmitter levels associated with memory deficits have been illustrated. Moreover, numerous medicinal compounds with concurrent anticonvulsant, procognitive, antioxidant effects, modulating effects on several brain neurotransmitters in rodents, and several newly developed classes of compounds applying computer-aided drug design (CADD) have been under development as potential AEDs. The article details the in-silico approach following CADD, which can be utilized for generating libraries of novel compounds for AED discovery. Additionally, in vivo studies could be useful in demonstrating efficacy, safety, and novel mode of action of AEDs for further clinical development.

The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy

This study aims to investigate the effects of the three potassium channel genes KCNA1, KCNA2, and KCNV2 on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control cohort (n = 595) consisted of 296 epileptic patients and 299 healthy individuals. Epileptic patients were recruited from the Pediatric Neurology clinic at the Queen Rania Al Abdullah Hospital (QRAH) in Amman, Jordan. A custom platform array search for genetic association in Jordanian-Arab epileptic patients was undertaken. The MassARRAY system (iPLEX GOLD) was used to genotype seven single nucleotide polymorphisms (SNPs) within three candidate genes (KCNA1, KCNA2, and KCNV2). Only one SNP in KCNA2, rs3887820, showed significant association with increased risk of susceptibility to generalized myoclonic seizure (p-value < 0.001). Notably, the rs112561866 polymorphism of the KCNA1 gene was non-polymorphic, but no significant association was found between the KCNA1 (rs2227910, rs112561866, and rs7974459) and KCNV2 (rs7029012, rs10967705, and rs10967728) polymorphisms and disease susceptibility or drug responsiveness among Jordanian patients. This study suggests that a significant association exists between the KCNA2 SNP rs3887820 and increased susceptibility to generalized myoclonic seizure. However, the present findings indicate that the KCNA1 and KCNV2 SNPs do not influence disease susceptibility and drug responsiveness in epileptic patients. Pharmacogenetic and case-control studies involving a multicenter and multiethnic approach are needed to confirm our results. To improve the efficacy and safety of epilepsy treatment, further studies are required to identify other genetic factors that contribute to susceptibility and treatment outcome.

P.011 Not just for babies: positive rolandic sharp waves in adult post-hypoxic myoclonus

Background: Post-hypoxic myoclonus is broadly divided into myoclonic status epilepticus (MSE) and Lance-Adams syndrome (LAS), where diagnosis depends on clinical and electroencephalographic (EEG) findings. Positive rolandic sharp waves (PRS) are a classic EEG finding in pre-term infants with white matter necrosis, but they are not known to be epileptogenic and have never been described in adults. Methods: We report a unique case of PRS correlated with myoclonic seizures in a post-hypoxic adult patient. Results: Shortly after cardiac arrest, a 21-year-old woman developed multifocal post-hypoxic myoclonus. Early development of myoclonus suggested MSE, but her EEG findings were atypical for MSE; initially, the only notable feature on EEG were subtle PRS. LAS did not fit the clinical picture or EEG findings. As myoclonus persisted over the following weeks, PRS evolved on EEG into positive rolandic predominant generalized polyspike-wave complexes that became definitively time-locked to each myoclonic jerk. PRS were diagnosed as epileptogenic and frequent myoclonic jerks were diagnosed as continuous myoclonic seizure. Myoclonus resolved to medication and mental status returned to baseline. Conclusions: We report for the first time that PRS can appear in adult patients and be epileptogenic, and produce a non-classical variant of post-hypoxic myoclonus that carries good prognosis.