Convulsive Phase Research Articles

Bilateral Todd's paralysis in a patient with left fronto-opercular epilepsy.

Postictal paresis ("Todd's paralysis") is commonly observed as a unilateral, transient motor weakness, lasting minutes to hours, after focal or focal to bilateral tonic-clonic seizures, contralateral to the epileptogenic zone. Bilateral postictal paresis is exceedingly rare and could be misinterpreted, especially if the preceding convulsive phase was not witnessed. An 18-year-old right-handed male patient with refractory focal epilepsy with seizure onset at age 3 years, was admitted for presurgical video-EEG monitoring. His seizures were predominantly nocturnal, consisting of a laryngeal somatosensory aura, occasionally evolving to bilateral tonic or tonic-clonic seizures with occasional asymmetrical limb extension during the tonic phase (right arm extension). Postictally, consciousness recovery was fast, if ever lost. At that stage, we documented severe dysarthria and bilateral symmetrical arm paresis lasting several minutes. The ictal pattern and interictal epileptiform activity were projected on the fronto-central midline. Brain MRI was highly suggestive of a bottom-of-sulcus dysplasia with underlying transmantle sign on the left premotor, fronto-opercular region and an FDG-PET-CT showed a concordant left fronto-operculo-insular hypometabolism. A complete lesionectomy was performed, with the additional guidance of intraoperative electrocorticography, resulting in sustained seizure freedom. Anatomo-pathology confirmed a type 2b focal cortical dysplasia. We speculate that, in our patient, a left fronto-opercular ictal onset with an early spread to both primary motor cortices and relative sparing of consciousness networks allowed the emergence of a clinically detectable postictal bilateral paresis.

Outpatient management of prolonged seizures and seizure clusters to prevent progression to a higher-level emergency: Consensus recommendations of an expert working group.

The management of prolonged seizures (PS) and seizure clusters (SC) is impeded by the lack of international, evidence-based guidance. We aimed to develop expert recommendations regarding consensus definitions of PS, SC, and treatment goals to prevent progression to higher-level emergencies such as status epilepticus (SE). An expert working group, comprising 12 epileptologists, neurologists, and pharmacologists from Europe and North America, used a modified Delphi consensus methodology to develop and anonymously vote on statements. Consensus was defined as ≥75% voting "Agree"/"Strongly agree." All group members strongly agreed that termination of an ongoing seizure in as short a time as possible is the primary goal of rapid and early seizure termination (REST) and that an ideal medication for REST would start to act within 2 min of administration to terminate ongoing seizure activity. Consensus was reached on the terminology defining PS (with proposed thresholds of 5 min for prolonged focal seizures and 2 min for prolonged absence seizures and the convulsive phase of bilateral tonic-clonic seizures) and SC (an abnormal increase in seizure frequency compared with the individual patient's usual seizure pattern). All group members strongly agreed or agreed that patients who have experienced a PS should be offered a REST medication, and all patients who have experienced a SC should be offered an acute cluster treatment (ACT). Further, when prescribing a REST medication or ACT, a seizure action plan should be agreed upon in consultation with the patient and caregiver. The expert working group had a high level of agreement on the recommendations for defining and managing PS and SC. These recommendations will complement the existing guidance for the management of acute seizures, with the possibility of treating them earlier to potentially avoid progression to more severe seizures, including SE.

Surface modified PLGA nanoparticles of gabapentin: Biodistribution and pharmacodynamic investigation via intranasal route

Epilepsy is a chronic condition and is caused by abnormal electrical conduction by nerve cells. It can affect people from different age groups. The prime objective of epilepsy therapeutics is the targeted and sustained release of drugs at the site of action i.e. in the brain. In the present study, PLGA nanoparticles of gabapentin, coated with Polysorbate 80 were prepared with the aim of delivering the drug to the brain through the nasal route. The said nanoparticles were formulated by the method of double emulsion and solvent evaporation. Thereafter, the prepared nanoparticles were characterized for particle size, Zeta potential, and Surface morphology of the nanoparticles was evaluated by SEM &TEM In vitro release in PBS (pH 7.4) and SNF (pH 5.5). In addition, FTIR and DSC techniques were used to confirm the P80 coating around the nanoparticle's surface. In vitro, cell assays like Cytotoxicity studies, and quantitative and qualitative cell uptake studies were studied on Neuro-2a cells. The nasal mucosa of the goat was used to perform histopathological studies to evaluate the toxicity of nanoparticles. A biodistribution study was performed on Swiss albino mice and the results showed that the concentration of the drug reaching the brain in the case of P80 modified nanoparticles was maximum as compared to Plain PLGA nanoparticle, and aqueous solution of the drug. Pharmacodynamic studies were performed to assess the delay in different phases of convulsion and the results showed that the modified nanoparticles of gabapentin were able to significantly delay the episodes of convulsion. Overall, results demonstrate that modified nanoparticles are potential drug carriers in the brain for the management of epilepsy.

DYRK1B haploinsufficiency in a Holstein cattle with epilepsy.

In this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6-month-old Holstein heifer. The seizures were characterized by a brief pre-ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic-clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter-seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice-site variant in DYRK1B (NM_001081515.1: c.-101-1G>A), most likely resulting in haploinsufficiency owing to loss-of-function. This represents a report of a DYRK1B-associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy.

Mucuna pruriens (Velvet bean) seed extract ameliorates epilepsy and anxiety against in vivo experimental models: A histopathological analysis

Introduction: the plant Mucuna pruriens is traditionally used in Indian system ofmedicine for the therapy of several neurological disorders. Chemical investigationson the plant have established the presence of levodopa and tryptamine which areresponsible for treating the neurological disorders like Parkinsonism. Objective:the objective of this research was to scientifically explore and ascertain its antiepilepticand anxiolytic activity in preclinical studies on Swiss albino mice. Materialand Method: the antiepileptic and anxiolytic effect of ethanolic extract of Mucunapruriens (EEMP) tested against maximal electroshock (MES) pentylenetetrazol(PTZ)-induced convulsions, Elevated Plus Maze, and light and dark arena. Actophotometertest performed to evaluate its potential locomotor activity deficitinducing action. Result: treatment of mice with EEMP significantly upturned theMES-induced convulsions, which was reflected by diminution in the time interval(sec) of entire phases of MES-induced convulsions, with an improvement in GABAlevels. In the PTZ model, pretreatment with EEMP delayed the latency and reducedthe intensity to clonic convulsions (p< 0.0001), and also delayed the latency oftonic convulsions as well as decrease the mortality mice in the treated groups ina dose-dependent manner. EEMP intervention dose dependently restored brainGABA levels. Assessment of GABA in mice’s brain after administration of EEMPexhibits significant modulation of GABA levels. Conclusion: overall, the findingssuggest that Mucuna pruriens has anticonvulsant and anxiolytic properties that aremediated by positive GABAergic neurotransmission hence could be used to treatepileptic seizures, petitmal and grandmal epilepsy.

Microwave Assisted Synthesis and Evaluation of Anticonvulsant Activity of Some 3-(3-(Substituted benzylidine)amino)phenyl-2-phenylquinazolin-4(3H)-ones

Herein, the synthesis of 3-(3-(substituted benzylidine)amino)phenyl-2-phenylquinazolin-4(3H)-ones from 3-aminophenyl-2-phenyl-quinazolin-4(3H)-ones is reported. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1H NMR and 13C NMR studies. All compounds were evaluated for their anticonvulsant activity against maximal electroshock seizure method. The LD50 value was found to be 550 mg/Kg and the duration of tonic phase was reduced upto 1.1 s and that of stupor phase was reduced upto 70 s. The structure activity relationship of the compounds revealed that Schiff bases viz. 3-(3-benzylidineamino)phenyl-2-phenylquinazolin-4(3H)-one, 3-(3-(3- chlorobenzylidine)amino)phenyl-2-phenylquinazolin-4(3H)-one, 3-(3-(3- nitrobenzylidine)amino)phenyl-2-phenylquinazolin-4(3H)-one by significantly shorten the tonic and stupor phases of convulsions compared to controls, thus thereby these compounds demonstrated strong anticonvulsant potential.

Neurological and Molecular Interactions of Phytoconstituents from Ricinus communis Root Extract- A Pharmacological and Computational Approach

The majority of epileptic patients takes numerous anticonvulsant medications and is still not treated successfully. These medications' produce chronic side effects and drug interactions, which restrict their use, constitute their major drawback. On the other hand, the fact that nature has given us plants that can be used as safe, all-natural treatments for illnesses with little side effects and minimal drug interactions has prompted researchers to focus on herbal remedies with anticonvulsant potential. The antiepileptic potential of the methanolic root extract of Ricinus communis was investigated in rodent models. Molecular docking studies using Schrodinger software was employed to study interactions with active site using PDB ID: 4MS4 (GABA agonist’s), 3WFG (glutamate antagonist), 5HCV (aspartate antagonist), 6J8G (sodium channel antagonist). At 30 and 60 minutes, MERC effectively diminished various convulsive phases and provided strong defence against the MES model. In PTZ, MERC extract treated groups at a dose (200 mg/kg and 400 mg/kg) showed significant antiepileptic activity with percentage protection of 24% and 33% respectively against seizures and significantly (* = p<0.0001) increased the latency of the seizures. Molecular docking studies confirmed the GABA agonist’s effects, and the results revealed that quercetin. gallic acid, luteolic acid, gentixic acid, catechin, vanillic acid, ricinoilc acid and standard phenytoin, clonazepam has highest Glide scores against all the selected proteins which indicates a stronger receptor -ligand binding affinity. From in vivo and molecular docking results it is clear that methanolic root extract of Ricinus communis possessed significant antiepileptic activity.

The antiepileptic potential of Vateria indica Linn in experimental animal models: Effect on brain GABA levels and molecular mechanisms

BackgroundEpilepsy is a neurodegenerative condition characterized by uncontrollable convulsions caused by a misalignment of the central nervous system's inhibitory and excitatory branches. Vateria indica is a medicinal herb with anti-inflammatory, anthelmintic, antiulcer, antitumor, and anticancer properties. ObjectivesTo investigate the antiepileptic activity of Vateria indica using maximal electrical shock (MES), pentylenetetrazole (PTZ), and isoniazid (INH) induced experimental animal models. MethodologyVateria indica bark was subjected to Soxhlet extraction using ethanol and quantitative and qualitative analysis was performed. The antiepileptic activity of Vateria indica bark extract (VIE) was investigated using different animal models in mice. GABA levels in the brain and antioxidant capacity in vitro were estimated. ResultsTreatment of mice with VIE significantly reversed the MES-induced convulsions, which was reflected by the decrease in the duration (sec) of all the phases of MES-induced convulsions, with an increment in the GABA levels. In the PTZ and INH models, pretreatment with VIE delayed the latency to clonic convulsions (p 0.001), reduced the intensity and duration of clonic convulsions, and reduced the mortality rate in the treatment groups in a dose-dependent manner. VIE intervention dose-dependently restored brain GABA levels. VIE also exhibited significant in-vitro antioxidant activity. ConclusionOverall, the findings imply that Vateria indica has substantial antiepileptic activities, mediated by positive GABAergic neurotransmission and antioxidant capabilities. To summarize, Vateria indica may provide adequate protection against epileptic seizures, suggesting that it could be used to treat petitmal and grandmal epilepsy. We plan to provide pure lead compounds derived from Vateria indica in the future in order to better understand the role it could play in the development of natural anticonvulsant drugs.

PROMISING ANTI CONVULSANT EFFECT OF A HERBAL DRUG IN WISTAR ALBINO RATS

Epilepsy is one of the most common chronic disease affecting human beings.This brain disorder is characterized by tendency for recurrent seizures or fits. The seizures can leads to loss of consciousness, disturbance of movement, muscle spasms, autonomic and mental functions. In Ayurveda the epilepsy is correlated to Apasmara by classical symptomatology especially under generalized tonic-clonic seizure.Treatment of epilepsy is a long-term process and usage of conventional antiepileptic drugs Carbamazepine, Valproic acid, Ethosuximide, Phenobarbital, Benzodiazepine and Phenytoin produce unpleasant side effects in long run. So a safe herbal medicine in this condition is a necessity. The traditional healers of kerala, in their practice they widely use one herbal drug called Guchapatra (Ruta graveolens L) commonly known as Aruta in Malayalam. The plant is administered as ghrita (a preparation with ghee as the main base) for the effective management of Apasmara (Epilepsy). Guchapatra (Ruta graveolens L) is a strongly odoriferous perennial herb belonging to the family Rutaceae. The claim of anti epileptic effect of Ghee prepared with Ruta graveolens is not proven scientifically till date. The aim of present study is to test Guchapatra (Ruta graveolens .L) for its anti-convulsant effect by Maximal electroshock seizure (MES) method in Albino rats. The drug was administered in the form of Ghrita. The experiment was carried out in 3 groups having 6 Wistar albino rats per group. Phenytoin was the standard drug. Group 1 (control – distilled water), Group 2 (standard drug - Phenytoin), Group 3 (Normal dose of Guchapatra ghritam (Ghee prepared with Ruta graveolens. L). Reduction in duration of Tonic Hind Limb Extension (THE) in seconds or the complete absence of tonic extensor phase of MES convulsions was taken as the assessment criteria for Anti-convulsant effect. The observations statistically analyzed using one way ANOVA and Post Hoc Tukeys multiple comparison tests. The in-vivo experiment revealed that the Guchapatra (Ruta graveolens. L) as a ghrita (Ghee) preparation posses equal anti- convulsant effect in comparison with standard drug Phenytoin.

Seizure Clusters, Seizure Severity Markers, and SUDEP Risk.

Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk.Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as two or more GCS in a 24-h period during the recording of prolonged video-electroencephalography in the Epilepsy monitoring unit (EMU). We measured heart rate variability (HRV), pulse oximetry, plethysmography, postictal generalized electroencephalographic suppression (PGES), and electroencephalography (EEG) recovery duration. A linear mixed effects model was used to study the difference between the first and subsequent seizures, with a level of significance set at p < 0.05.Results: We identified 112 GCS clusters in 105 patients with 285 seizures. GCS lasted on average 48.7 ± 19 s (mean 49, range 2–137). PGES emerged in 184 (64.6%) seizures and postconvulsive central apnea (PCCA) was present in 38 (13.3%) seizures. Changes in seizure features from seizure to seizure such as seizure and convulsive phase durations appeared random. In grouped analysis, some seizure features underwent significant deterioration, whereas others improved. Clonic phase and postconvulsive central apnea (PCCA) were significantly shorter in the fourth seizure compared to the first. By contrast, duration of decerebrate posturing and ictal central apnea were longer. Four SUDEP cases in the cluster cohort were reported on follow-up.Conclusion: Seizure clusters show variable changes from seizure to seizure. Although clusters may reflect epilepsy severity, they alone may be unrelated to SUDEP risk. We suggest a stochastic nature to SUDEP occurrence, where seizure clusters may be more likely to contribute to SUDEP if an underlying progressive tendency toward SUDEP has matured toward a critical SUDEP threshold.

Neuropsychological Screening on Acalypha indica Whole Plant Extract

Objectives: Herbal treatment is a natural form of healing or alternative therapy to cure ailments or diseases of cognitive disorders. Methods: The methanolic whole plant extract of Acalypha indica was screened for its Antiepileptic and anxiolytic activity in rodent models. Molecular docking studies were employed to study interactions with GABA agonist’s active site. Results: MEAI showed a significant reduction in various phases of convulsions at 30 and 60 minutes and afforded significant protection against MES model. In PTZ, MEAI at a dose of 200 mg/kg protected 66.66% of the animals against seizures and did not affect the latency of seizures to any significant extent at a dose of 400 mg/kg protected 33.33% of the mice against seizures and significantly (* = p Key words: Acalypha indica, Anti-epileptic, Anti-anxiolytic, GABA, Glidescore, Docking.

Effects of Huazhuo Jiedu Shugan Decoction on Cognitive and Emotional Disorders in a Rat Model of Epilepsy: Possible Involvement of AC-cAMP-CREB Signaling and NPY Expression.

Background Huazhuo Jiedu Shugan decoction (HJSD), a traditional Chinese medicine (TCM), has been used to treat epileptic seizures for many years. Some ingredients in these herbs have been demonstrated to be effective for the treatment of brain damage caused by epilepsy. Aim of the Study The object of the study is to determine the effects of HJSD on cognitive and emotional disorders in a rat model of epilepsy. Materials and Methods After a predetermined time period, rats were intraperitoneally injected with pentylenetetrazol and observed in different phases of convulsions. The cognitive and emotional changes in the epileptic rats were assessed using behavioral and immunohistochemical tests. Results Compared with the epilepsy group, the seizure grade was reduced and seizure latency was prolonged following HJSD-H treatment (P < 0.01). Compared with the control group, the epilepsy group displayed marked worse performance on the animal behavior tests (P < 0.05) and the HJSD-H group displayed improved behavioral performance (P < 0.05). After HJSD-H treatment, the expression of adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP), cAMP-response element binding protein (CREB), and neuropeptide Y (NPY) immunoreactive cells markedly increased in the hippocampus, compared with that of the epilepsy group (P < 0.05). Conclusions The current results demonstrate that HJSD treatment in epileptic rats markedly inhibits epileptic seizures and improves cognitive and emotional disorders, which may be related to the regulation of AC-cAMP-CREB signaling and NPY expression in the hippocampus. The effects of the HJSD treatment may provide a foundation for the use of HJSD as a prescription medicinal herb in the TCM for the treatment of epilepsy.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

ANTICONVULSANT ACTIVITY OF CITRUS MAXIMUS LEAVES IN EXPERIMENTAL ANIMAL MODELS

ABSTRACTObjective: To assess the anticonvulsant activity of ethanolic extract of Citrus maximus (EECM) leaves of maximal electroshock seizure (MES) andpentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats and mice.Methods: Anticonvulsant activity was carried out by MES model and PTZ-induced clonic convulsions model; in each model, albino rats (Wistar strain)of either sex were taken and divided into five groups, each consisting of 6 rats. One group was used as control (3% w/v gum acacia), one as standard(phenytoin), and three groups for the test drug of EECM leaves (doses of 50, 100, and 200 mg/kg) treatment. The reduction in time or abolition of tonicextensor phase of MES-convulsions was recorded for all the animals. In PTZ model, either delay or complete abolition of convulsions in rats treatedwith diazepam and EECM leaves was noted for all the animals.Result: EECM leaves reduced the extensor phase of convulsion in MES in a dose-dependent manner and decrease in the duration of convulsions in PTZmodel with increasing dose. Anticonvulsant activity was seen maximum at the dose of 200 mg/kg.Conclusions: Thus, from the above two seizure models of MES and PTZ, it can be concluded that EECM leaves have got an anticonvulsant effect in anincreasing dose-dependent manner.Keywords: Anticonvulsant, Citrus maximus, Maximal electroshock seizure, Pentylenetetrazol.

2-methylpyridinium 5-(2,4-dinitrophenyl)-6-oxo-2-thioxo-1,2,3,6-tetrahydropyrimidin-4-olate: Synthesis, crystal structure, and biological evaluation

The titled complex is synthesized from the ethanolic solutions of 1-chloro-2,4-dinitrobenzene, 2-thiobarbituric acid, and 2-methylpyridine and characterized by spectral and elemental analyses. The single crystal X-ray diffraction results for the complex are compatible with the spectral observations. The titled complex exhibits anticonvulsant activity and reduces all phases of convulsion even at a low dosage. Acute toxicity studies of the complex are performed to understand the safer dose concentration for clinical trials.

The genetic audiogenic seizure hamster from Salamanca: The GASH:Sal.

The hamster has been previously described as a paroxysmal dystonia model, but our strain is currently recognized as a model of audiogenic seizures (AGS). The original first epileptic hamster appeared spontaneously at the University of Valladolid, where it was known as the GPG:Vall line, and was transferred to the University of Salamanca where a new strain was developed, named GASH:Sal. By testing auditory brainstem responses, the GASH:Sal exhibits elevated auditory thresholds that indicate a hearing impairment. Moreover, amplified fragment length polymorphism analysis distinguished genetic differences between the susceptible GASH:Sal hamster strain and the control Syrian hamsters. The GASH:Sal constitutes an experimental model of reflex epilepsy of audiogenic origin derived from an autosomal recessive disorder. Thus, the GASH:Sal exhibits generalized tonic-clonic seizures, characterized by a short latency period after auditory stimulation, followed by wild running, a convulsive phase, and finally stupor, with origin in the brainstem. The seizure profile of the GASH:Sal is similar to those exhibited by other models of inherited AGS susceptibility, which decreases after six months of age, but the proneness across generations is maintained. The GASH:Sal can be considered a reliable model of audiogenic seizures, suitable to investigate current antiepileptic pharmaceutical treatments as well as novel therapeutic drugs. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction.

The pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized electroencephalography (EEG) suppression (PGES) may follow generalized tonic-clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the epilepsy monitoring unit. We investigated for associations between PI duration and PGES, ictal/postictal oxygen saturation (SpO2 ), end-tidal CO2 (ETCO2 ), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures. Seventy patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p < 0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO2 nadir was lower in seizures with PGES (p = 0.046), ETCO2 peak change (p = 0.003) was higher, and duration of ETCO2 elevation (p = 0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration. The duration of PI and presence of PGES are associated with periictal RD. The duration of PI is also associated with the presence of PGES. Seizure duration or duration of the convulsive phase is not associated with PI or PGES. Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.

On the anticonvulsant effect of allopregnanolone (a neurosteroid) in neonatal rats.

Allopregnanolone has shown potent anticonvulsant activity in the adult brain. However, none of the studies have shown its effect in neonatal animal models of seizures. The current study explored the effect of allopregnanolone in animal models of neonatal status epilepticus. Allopregnanolone was administered 10min before administration of kainic acid or 4-aminopyridine in postnatal 9 (PN9) day old rats. Various phases of convulsions such as latency to myoclonic jerks, continuous clonic movements with loss of righting reflex (status epilepticus) and mortality were measured; the effect was compared with its effect in pentylenetetrazol (PTZ) -induced generalized tonic-clonic convulsions. Exogenous administration of kainic acid (2mg/kg., i.p.) or 4-aminopyridine (5mg/kg., i.p.) in rat pups (PN9) resulted in continuous clonic movements with loss of righting reflex (status epilepticus). Pre-treatment with allopregnanolone at doses of 5 and 10mg/kg., i.p. dose-dependently delayed the onset of status epilepticus, but not myoclonic jerks. Allopregnanolone did not prevent kainic acid-induced mortality at theses doses. In the kainic acid model, pretreatment of bumetanide before allopregnanolone delayed various phases of convulsions; the effect was significantly higher compared to per se groups. Allopregnanolone only at the higher dose extended the latency of 4-aminopyridine-induced seizures. In contrast, allopregnanolone at a low dose markedly shielded neonatal rats against PTZ convulsions. Allopregnanolone is protective in animal models of neonatal status epilepticus and generalized tonic-clonic convulsions and further clinical studies are required to establish its use in therapeutics.

Gamma-aminobutyric acid loaded halloysite nanotubes and in vitro-in vivo evaluation for brain delivery

Gamma-aminobutyric acid (GABA) is a key neurotransmitter where it usually inhibits impulse transmission. GABA release blockage or postsynaptic reaction were determined to provoke epileptic convulsions. The aim of the present study was the development of brain-targeted, nanosized, nontoxic, biocompatible, highly specific formulations. Incorporation of GABA into halloysite nanotubes (HNT) was performed using different methods. Particle size, zeta potential and pH measurements, morphological, thermal, XRD, FTIR analyses and GABA quantification by validated HPLC method were used for the characterization of the systems prepared. Release pattern of GABA from the nanotubes was determined using a dialysis membrane.Following successful incorporation of GABA into HNTs for brain delivery, nanotube formulation coded HNT–GABA H1 was selected for in vivo studies. Smaller particle size with narrow size distribution, possible HNT–GABA interaction indicated by thermal, XRD and FTIR analyses and prolonged release were the parameters considered in this selection. Moreover, HNT–GABA H1 remained stable for 3-month storage period and showed higher cell viability values than GABA. Rats were used in in vivo studies and potential of anticonvulsant effect of GABA was determined in the pentylenetetrazole model of seizure. HNT–GABA H1 was found to increase latency of seizure, decrease ending time of the convulsion, duration of severe convulsion and mortality rate significantly compared to pure GABA. After administration of HNT–GABA H1, GABA concentration in Stratum corsatum measured by enzyme immune assay showed that it was not significantly higher than GABA administered alone.These findings suggest that GABA loaded HNTs reduces the duration of all phases of convulsion indicating efficient delivery of GABA to all brain areas to interfere with epileptic mechanism.