Impact of timing of antiseizure medication withdrawal on seizure recurrence in glioma patients: a retrospective observational study.

BACKGROUND: Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk for recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment. METHODS: In this retrospective observational study, the primary outcome was time to recurrent seizure, from the starting date of no ASM treatment up to 36 months follow-up. Cox proportional hazards models were used to study the effect of risk factors on time to recurrent seizure. Stratification was done with information known at baseline. Short-term seizure freedom was defined as ≥ 3 months, but < 12 months; medium-term as 12-24 months; and long-term as ≥ 24 months seizure freedom from the date of last antitumour treatment. RESULTS: This study comprised of 109 patients; 31% (34/109) were in the short-term, 29% (32/109) in the medium-term, and 39% (43/109) in the long-term group. A recurrent seizure was experienced by 47% (16/34) of the patients in the short-term, 31% (10/32) in the medium-term, and 44% (19/43) in the long-term group. Seizure recurrence risk was similar between patients in the short-term group as compared to the medium-term (cause-specific adjusted hazard ratio [aHR] = 0.65 [95%CI = 0.29-1.46]) and long-term group (cause-specific aHR = 1.04 [95%CI = 0.52-2.09]). CONCLUSIONS: Seizure recurrence risk is relatively similar between patients with short-term, medium-term, and long-term seizure freedom after completion of antitumour treatment.

The challenges to control epilepsy in an isolated indigenous tribe in Brazil's Amazon: 15 years of follow-up.

BACKGROUND: Epilepsy is a common neurological disease that affects people all over the world, but it is rarely described in indigenous peoples. OBJECTIVE: To study the epilepsy characteristics and risk factors for seizure control in people from an isolated indigenous population. METHODS: This is a retrospective and historical cohort study conducted from 2003 to 2018 (15 years), at a neurology outpatient clinic, of 25 Waiwai tribes' indigenous individuals with epilepsy, inhabitants of an isolated forest reserve in the Amazon. Clinical aspects, background, comorbidities, exams, treatment, and response were studied. Factors that impacted seizure control over 24 months were identified using Kaplan-Meier curves and Cox and Weibull regression models. RESULTS: The majority of cases started in childhood, with no difference regarding gender. Focal epilepsies were predominant. Most patients had tonic-clonic seizures. A quarter of them had a family history, and 20% had referred febrile seizures. There was intellectual disability in 20% of patients. Neurological examination and psychomotor development were altered in one third of the participants. The treatment controlled 72% of the patients (monotherapy in 64%). Phenobarbital was the most prescribed anti-seizure medication, followed by carbamazepine and valproate. The most relevant factors that impacted seizure control over time were abnormal neurological exam and family history. CONCLUSION: Family history and abnormal neurological exam were predicted risk factors for refractory epilepsy. Even in an isolated indigenous tribe, the partnership between the indigenous people and the multidisciplinary team ensured treatment adherence. The public healthcare system must guarantee modern anti-seizure medications, mainly for this vulnerable population, which has no other source of treatment.

ANTECEDENTES: A epilepsia é uma doença neurológica que afeta povos do mundo todo, mas raramente é descrita em povos indígenas. OBJETIVOS: Estudar as características da epilepsia e os fatores de risco para o controle das crises em pessoas de uma população indígena isolada. MéTODOS: Este é um estudo de coorte retrospectivo e histórico, conduzido de 2003 a 2018 (15 anos) no ambulatório de neurologia, de 25 indígenas Waiwai com epilepsia, habitantes de uma reserva florestal na Amazônia. Aspectos clínicos, antecedentes, comorbidades, exames, tratamento e resposta foram estudados. Identificou-se os fatores que afetaram o controle das crises ao longo de 24 meses usando curvas de Kaplan-Meier e modelos de regressão de Cox e Weibull. RESULTADOS: A maioria dos casos teve início na infância, sem diferença quanto ao gênero. Predominavam as epilepsias focais. A maioria dos pacientes apresentava crises tônico-clônicas. Um quarto deles tinha história familiar e 20% referiram convulsões febris. Vinte por cento dos pacientes apresentava deficiência intelectual. Um terço tinha exame neurológico e desenvolvimento psicomotor alterados. O tratamento controlou 72% dos pacientes (monoterapia em 64%). Fenobarbital foi o medicamento mais prescrito, seguido por carbamazepina e valproate, e os fatores que mais impactaram o controle das crises ao longo do tempo foram exame neurológico anormal e história familiar. CONCLUSãO: História familiar e exame neurológico anormal foram fatores de risco preditores para epilepsia refratária. Mesmo em uma tribo indígena isolada, a parceria entre os indígenas e a equipe multidisciplinar garantiu a adesão ao tratamento. O sistema público de saúde deve garantir medicamentos modernos anticrise, principalmente para essa população vulnerável, que não tem outra fonte de tratamento.

[Optimal Use of Perampanel in the Treatment of Patients with Epilepsy Based on the Clinical Evidence and Characteristics].

Perampanel (PER) has been used clinically as monotherapy and adjunctive therapy for focal seizures and as adjunctive therapy for generalized tonic-clonic seizures in epilepsy patients in Japan. In recent years in Japan and worldwide, clinical studies have been conducted on patients with various seizure types of epilepsy. The results have shown that PER has broad spectrum properties. The pooled analysis of controlled trials (PERMIT study) showed PER efficacy in patients with status epilepticus, myoclonic seizures, and absence seizures. In addition, PER has been shown to be safe and effective in patients with juvenile myoclonic epilepsy, Lennox-Gastaut syndrome, and elderly-onset epilepsy that are often difficult to treat with narrow-spectrum ASM. In this review article, we summarize the latest findings on PER, and overview the broad spectrum characteristics of PER. In addition, we discuss the optimal use of PER for patients with epilepsy, focusing on low-dose initiation and on slow titration of PER to minimize adverse events. (Received December 7, 2021; Accepted March 29, 2022; Published July 1, 2022).

Approach to the Medical Treatment of Epilepsy.

PURPOSE OF REVIEW: This article discusses the use of antiseizure medications in the treatment of focal and generalized epilepsies using an evidence-based approach. RECENT FINDINGS: In recent years, several new antiseizure medications with differing mechanisms of action have been introduced in clinical practice, and their efficacy and safety has been evaluated in randomized controlled clinical trials. Currently, all antiseizure medications can prevent seizure occurrence, but they have no proven disease-modifying or antiepileptogenic effects in humans. The choice of therapy should integrate the best available evidence of efficacy, tolerability, and effectiveness derived from clinical trials with other pharmacologic considerations, the clinical expertise of the treating physicians, and patient values and preferences. After the failure of a first antiseizure medication, inadequate evidence is available to inform policy. An alternative monotherapy (especially if the failure is because of adverse effects) or a dual therapy (especially if failure is because of inadequate seizure control) can be used. SUMMARY: Currently, several antiseizure medications are available for the treatment of focal or generalized epilepsies. They differ in mechanisms of action, frequency of administration, and pharmacologic properties, with a consequent risk of pharmacokinetic interactions. Major unmet needs remain in epilepsy treatment. A substantial proportion of patients with epilepsy continue to experience seizures despite two or more antiseizure medications, with a negative impact on quality of life. Therefore, more antiseizure medications that could provide higher seizure control with good tolerability and that could positively affect the underlying disease are needed.

Is there a ceiling lamotrigine serum level in epileptic children in remission?

INTRODUCTION: Seizure control, in patients with epilepsy, is proportionally associated with health-related quality of life. Antiepileptic therapy leads to seizure remission in most cases. However, some patients are resistant to treatment despite achieving high doses which can be explained by interindividual variability of antiepileptic drugs' metabolism. A ceiling exposure, in epilepsy, helps to adapt the therapeutic strategy in a faster way and to prevent unnecessary exposure to adverse drug reactions. Due to the increasing use of new generations of antiepileptic drugs, we aimed to explore the distribution of lamotrigine (LMT) trough serum levels in epileptic children, stratified between remission and ongoing seizures, in order to determine whether there is a ceiling effect associated with remission. METHODS: We conducted a retrospective study (2012-2021) including children, with generalized epilepsy (2-18 years), addressed for a therapeutic drug monitoring of LMT trough serum levels. Patients in remission, should have as lasting three times the longest pre-treatment seizure-free interval and more than one year. RESULTS: The population of 114 children with generalized epilepsy was divided in to groups: epileptic children in remission (36) and epileptic children with ongoing seizures (78). There was no significant difference in age and sex in the two groups. Median LMT daily dose and trough serum levels were significantly higher in group 2. The highest LMT serum trough level was 11µg/mL in group 1 and 23.1µg/mL in group 2. Valproate was associated in 29%. There was no significant difference of the distribution of valproate in the two groups (P=0.08). CONCLUSIONS: Children in remission had a LMT trough serum levels under 11µg/mL and a daily dose of 3.36mg/kg/day or less. These results suggest that this LMT serum level and daily dose might be associated with a ceiling effect in epileptic children.

An Open Retrospective Study of a Standardized Cannabidiol Based-Oil in Treatment-Resistant Epilepsy.

Introduction: Cannabidiol (CBD) has antiseizure properties but no psychoactive effects. Randomized controlled trials of an oral, pharmaceutical formulation of highly purified CBD are promising; however, data regarding other formulations are sparse and anecdotal. We evaluated the effectiveness of add-on therapy with a standardized CBD-based oil in treatment-resistant epilepsy (TRE) patients. Materials and Methods: An open retrospective study was carried out on patients with refractory epilepsy of different etiology. We reviewed clinical data from medical charts and caregiver's information. Participants received add-on with 24% CBD-based oil, sublingually administered, at the starting dose of 5-10 mg/[kg·day] up to the maximum dose of 50 mg/[kg·day], based on clinical efficacy. Efficacy was evaluated based on patients being seizure free or experiencing at ≥50% improvement on seizure frequency. Tolerability and suspected adverse drug reaction data were also analyzed. Results: We included 37 patients (46% female) with a median age of 16.1 (range: 2-54) years. Twenty-two (60%) patients suffered from epileptic encephalopathy, 9 (24%) from focal epilepsy, and 6 (16%) from generalized epilepsy. Mean follow-up duration was 68 (range: 24-72) weeks. The average age at seizure onset was 3.8±2.1 years (range: 7 days-21 years). The median achieved CBD-based oil dose was 4.2±11.4 (range: 0.6-50) mg/[kg·day]. At 40-month follow-up, 7 (19%) patients were seizure free, 27 (73%) reported >50% improvement, 2 (5%) patients reported <50% improvement, and 1 patient discontinued therapy due to lack of efficacy. Weaning from concomitant antiepileptic drugs was obtained after 24 weeks from CBD introduction in 10 subjects. Mild and transitory adverse events, including somnolence or loss of appetite, occurred in nine (25%) patients. Discussion and Conclusion: We showed the efficacy of a CBD-based oil formulation with few significant side effects in patients with TRE of various etiologies.

Evaluation of optical coherence tomography findings in adolescents with genetic generalized epilepsy.

OBJECTIVE: To evaluate retinal nerve fiber layer (RNFL) thickness, central macular thickness (CMT), and subfoveal choroid thickness (CT) by using optical coherence tomography (OCT) in adolescents with newly diagnosed epilepsy and patients who had been using Na valproate (VPA) for at least 1 year. METHODS: We examined 60 patients with genetic generalized epilepsy (GGE) aged 8-17 years. Thirty patients with newly diagnosed GGE who were evaluated before the beginning of the therapy and another 30 patients who were chosen from among adolescents with epilepsy using VPA for at least 1 year were included in the study. RESULTS: Nasal quadrant RNFL thickness and CMT measurements were significantly lower in the monotherapy group compared with the newly diagnosed group (p = 0.044 and p = 0.032, respectively). CT measurements were not significantly different between the groups (p = 0.413). There was a negative correlation in regression analysis between the duration of drug use and RNFL thickness in all quadrants. CONCLUSION: According to our study, we observed thinning of the nasal RNFL and macular thickness in adolescents with epilepsy who were using Na valproate for at least 1 year and that as the duration of use increased, the thinning occurred in all RNFL quadrants. Further studies with larger series are needed to better understand the effects of both epilepsy and VPA on the eye.

Effects of ketamine on EEG in baboons with genetic generalized epilepsy.

Ketamine, a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, used as an anesthetic has been reported to induce seizures both in humans and baboons predisposed to epilepsy. In this study, we aimed to characterize the acute effects of ketamine on scalp (sc-EEG) and intracranial EEG (ic-EEG) in the baboon, which offers a natural model of genetic generalized epilepsy (GGE). We evaluated the electroclinical response to ketamine in three epileptic baboons. The raw EEG data were analyzed within 10 min of intramuscular ketamine (5-6 mg/kg) administration. Earliest EEG changes occurred after 30 s in sc-EEG and after 15 s in ic-EEG of ketamine administration. These initial changes involved increased paroxysmal fast activity (PFA) followed by slowing, the latter emerging first occipitally, and then spreading more anteriorly. Generalized spike-and-wave discharges (GSWDs) were evident on both sc-EEG and ic-EEG within two minutes, but focal occipital discharges were already increased on ic-EEG after 15 s. Occipital slowing emerged on ic-EEG after 30 s, before spreading fronto-centrally and orbito-frontally. By 60-120 seconds post-injection, ic-EEG demonstrated a parieto-occipital burst suppression (BS), which was not noted on sc-EEG. Ketamine waves and seizures, especially if the latter were subclinical, also appeared earlier on ic-EEG. This study highlights the anesthetic and proconvulsant effects of ketamine originate in the occipital lobes before fronto-central regions. We speculate that NMDAR concentration difference in cortical regions, such as the occipital and frontal cortices, are mainly involved in the expression of ketamine's EEG effects, both physiological and epileptic.

Safranal carried by nanostructured lipid vehicles inhibits generalized epilepsy in mice.

Safranal, a main component of Crocus sativus, is suggested to have neuroprotective effects. The aim of this study was to investigate the effect of safranal and nanostructured lipid vehicle (NLV) carried safranal in acute and chronic experimental mice models of epilepsy. In PILO acute seizure model, safranal dose-dependently extended latency to generalized seizure, decreased the highest seizure stages and the number of generalized seizures. Moreover, NLV carried safranal further enhanced the anti-seizure effect, which is comparable to the action of sodium valproate. Meanwhile, NLV carried safranal reduced and delayed the electroencephalogram spectra power after pilocarpine injection. In histological aspect, safranal dose-dependently reduced the loss of neurons induced by seizure and NLV system further improved this protection at the same dose. In MES acute model, safranal markedly increased the electroconvulsive threshold, where NLV further improved its effect. In PTZ chronic seizure model, NLV carried safranal significantly delayed the kindling rate of progress and the time it took to reach generalized seizures as compared to NLV control group. In conclusion, this study indicates that safranal inhibits generalized seizure in acute and chronic epilepsy models in mice and NLV can enhance this effect. So, NLV carried safranal may have potential value in treatment of generalized epilepsy.

Ventral pallidum deep brain stimulation attenuates acute partial, generalized and tonic-clonic seizures in two rat models.

Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged. The transition to brainstem seizures was prevented in almost all animals. VP-DBS immediately after rats exhibited their first partial forebrain stage 3 seizure did not affect the frequency of partial seizures but reduced median partial seizure duration from 271 to 54 s. Stimulation after partial seizures also reduced the occurrence and duration of secondarily generalized stage 4/5 seizures. VP-DBS prior to pilocarpine administration prevented the appearance of partial seizures in almost all animals. Lastly, VP-DBS delayed the onset of generalized tonic-clonic seizures (GTCSs) from 111 to 823 s in rats administered another chemoconvulsant, pentylenetetrazol (PTZ, 90 mg/kg). In this particular rat seizure model, stimulating electrodes placed more laterally in both VP hemispheres and more posterior in the left VP hemisphere provided greatest efficacy for GTCSs. In conclusion, our findings posit that VP-DBS can serve as an effective novel neuromodulatory approach for a variety of acute seizure phenotypes.

Varied responses to benzodiazepine treatment in cephalosporin-related generalized periodic discharges.

Although benzodiazepines (BZDs) are used as the first-line treatment for status epilepticus, previous studies have shown inconsistent responses to BZDs in patients with cephalosporin-related non-convulsive status epilepticus. In this study, we investigated nine patients with cephalosporin-related impaired consciousness and their EEGs all showed generalized periodic discharges (GPDs). One of the patients received repetitive BZD injections without discontinuing cephalosporins, and neither his clinical symptoms nor GPDs on EEG responded to BZDs. Seven of the patients received BZDs after discontinuation of cephalosporins, but only two of them responded immediately to BZD administration. One of the patients did not receive BZDs or antiepileptic drugs, and this patient spontaneously recovered consciousness in one day after cephalosporins were discontinued. The changes in consciousness were reversible in all of the nine patients after cephalosporins were withdrawn. The administration of intravenous BZDs in cases with impairment of consciousness and GPDs secondary to cephalosporins may help in only a small number of patients. Cephalosporin withdrawal is ultimately mandatory in these patients.

1-Triacontanol cerotate; isolated from Marsilea quadrifolia Linn. ameliorates reactive oxidative damage in the frontal cortex and hippocampus of chronic epileptic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsilea quadrifolia Linn. (MQ) has been used for insomnia and epileptic disorders in traditional Indian medicine. The present study is to isolate the active component responsible for antiepileptic property of MQ by evaluating its ability to minimize the reactive oxidative damage in brain due to chronic epilepsy in rat. MATERIALS AND METHODS: 1-Triacontanol cerotate (1TAC) was isolated after chromatography on a silica gel from dried petroleum ether fraction of methanolic extract of MQ. Acute oral toxicity studies of 1TAC were carried out and efficacy of 1TAC on malondialdehyde (MDA) and reduced glutathione (GSH) production in different brain areas of chronic pentylenetetrazole (PTZ) induced epileptic rats were evaluated. RESULTS: Our results showed that PTZ-kindled chronic epileptic rats had an increase MDA and decreased GSH concentration in the frontal cortex as well as hippocampus, compared to the normal control. MDA and GSH concentrations in those brain areas were normalized after treatment with sodium valproate (SV) in 200 mg kg(-1)bw; as well as 1TAC in 40 and 80 mg kg(-1)bw doses. CONCLUSION: Production of reactive oxygen species (ROS) is known to worsen epileptogenesis. The isolated component 1TAC which reduced the reactive oxidative damage in hippocampus and frontal cortex of PTZ kindled rats could be responsible for antiepileptic property of MQ. Its action is found to be dose dependent, with 80 mg kg(-1)bw showing even better efficacy than 200 mg kg(-1)bw of SV.

Isovaline attenuates generalized epileptiform activity in hippocampal and primary sensory cortices and seizure behavior in pilocarpine treated rats.

Anti-seizure drugs are the most commonly employed treatment option for epilepsy and these generally provide effective management of seizures. However, 30% of patients with epilepsy are not adequately treated with anti-seizure medications and are considered intractable. Recently we reported that isovaline, a unique amino acid, could attenuate seizure like events (SLEs) in two in vitro hippocampal seizure models by selectively increasing the activity of interneurons, but not pyramidal neurons. Isovaline also attenuated hippocampal epileptiform activity and behavioral seizures in vivo in rats administered 4 aminopyridine (4AP). Here, we investigate whether isovaline is efficacious in attenuating secondarily generalized epileptiform activity and behavioral seizures in rats administered pilocarpine. We found that 150 mg/kg isovaline administered intravenously abolished pilocarpine-induced epileptiform activity in the primary sensory cortex and hippocampus and attenuated generalized forebrain behavioral seizures. We are the first to demonstrate that isovaline may be a plausible anti-seizure drug for secondarily generalized seizures and this could potentially lead to the development of a novel class of anti-seizure drugs focused around the unique mechanism(s) of isovaline.

Ifosfamide chemotherapy and nonconvulsive status epilepticus: case report and review of the literature.

We present a patient with peritoneal carcinosarcoma who was treated with the alkylating agent ifosfamide and experienced a rapid decline in mental status. Electroencephalogram (EEG) displayed generalized periodic epileptiform discharges, which raised suspicion for nonconvulsive status epilepticus (NCSE). Following administration of midazolam, the patient's clinical condition and EEG improved. We review the 8 documented cases of ifosfamide-induced NCSE, and demonstrate the similarity in clinical features when compared with ifosfamide neurotoxicity that is not classified as NCSE. EEG findings suggesting an ictal pattern are subtle and heterogeneous, but they are essential for a diagnosis. Since it is unlikely that EEGs are uniformly obtained in instances of ifosfamide neurotoxicity, many cases of NCSE may go unrecognized.

The effects of responsive and scheduled subicular high frequency stimulation in the intra-hippocampal kainic acid seizure model.

BACKGROUND: Responsive stimulation is a promising and newly emerging treatment for refractory temporal lobe epilepsy in which current is delivered to target areas following seizure occurrence. OBJECTIVE: We compared responsive and scheduled subicular high frequency stimulation (HFS) with a sham control group on acute seizures and seizure sensitivity two weeks later. We also investigated the role of status epilepticus (SE) on efficacy of both types of stimulation. METHOD: Adult Wistar rats received kainic acid (KA) injections intrahippocampally until they reached Stage V (Racine scale) on Day 1. Responsive, scheduled or sham HFS (125 Hz, 100 µs) was delivered in three groups while EEG was recorded. All rats received KA injections again on Day 15 to measure the excitability of animals to KA, again with EEG monitoring. RESULTS: All rats reached Stage V and 60% reached SE on Day 1. Focal seizures were suppressed in both stimulated groups (the scheduled group was slightly more effective) on both days in only non-SE rats. Similar stimulation effects were found on generalized seizures but mainly on Day 15. CONCLUSION: Both types of subicular HFS suppressed focal and generalized seizures, albeit differently. Scheduled stimulation seemed a bit more effective, and the amount of stimulation might be a factor that influences the differences between the stimulated groups. Beneficial effects of HFS were restricted to non-SE rats and HFS did not suppress or even worsen seizures in SE rats.

Possible nitric oxide mechanism in the protective effect of hesperidin against pentylenetetrazole (PTZ)-induced kindling and associated cognitive dysfunction in mice.

Epilepsy is a complex neurological disorder manifested by recurrent episodes of convulsive seizures, loss of consciousness, and sensory disturbances. Pentylenetetrazole (PTZ)-induced kindling primarily represents a model of generalized epilepsy. The present study has been undertaken to evaluate the neuroprotective potential of hesperidin and its interaction with nitric oxide modulators against PTZ-induced kindling and associated cognitive dysfunction in mice. The experimental protocol comprised of eleven groups (n=6), where a subconvulsive dose of PTZ (40 mg/kg, i.p.) had been administered every other day for a period of 12 days, and seizure episodes were noted after each PTZ injection over a period of 30 min. The memory performance tests were carried out on days 13 and 14 followed by the estimation of biochemical and mitochondrial parameters. Chronic administration of a subconvulsive dose of PTZ resulted in an increase in convulsive activity culminating in generalized clonic-tonic seizures, as revealed by a progressive increase in seizure score as well as alteration in antioxidant enzyme levels (lipid peroxidation, nitrite, glutathione, super oxide dismutase, and catalase) and mitochondrial complex (I, II, and IV) activities, whereas chronic treatment with hesperidin (200 mg/kg) significantly attenuated these behavioral, biochemical, and mitochondrial alterations. Further, treatment with l-arginine (100 mg/kg) or l-NAME (10 mg/kg) in combination with hesperidin significantly modulated the protective effect of hesperidin which was significant as compared to their effects per se in PTZ-treated animals. Thus, the present study suggests a possible involvement of the NO-cGMP pathway in the neuroprotective effect of hesperidin in PTZ-kindled mice.

Derivatives of valproic acid are active against pentetrazol-induced seizures in immature rats.

Propylisopropyl acetamide (PID) and valnoctamide (VCD) are two CNS-active constitutional isomers of valproic acid (VPA) corresponding amide (and prodrug) valpromide. VPA is a major antiepileptic drug (AED) used also in children. Consequently, the purpose of the current study was to see if PID, VCD and two of VCD stereoisomers are active also in juvenile anticonvulsant animal seizure models. Rat pups 7, 12, 18 and 25 days old were pretreated with PID, VCD or the VCD stereoisomers (2S,3S)-VCD, and (2R,3S)-VCD and 30 min later pentetrazol (100mg/kg s.c.) was administered. The incidence of seizures, their expression pattern and their latencies were registered and the severity was expressed by means of a five-point scale. All four tested compounds exhibited anticonvulsant activity against generalized tonic-clonic seizures. Lower doses suppressed specifically the tonic phase in 7-, 12- and 18-day-old rats, while higher doses abolished both phases of generalized seizures. This effect was most pronounced in 12-day-old rats. Twenty-five-day-old rats exhibited suppression of the entire pattern of generalized seizures. There were no significant differences among the drugs used. The CNS-active amide derivatives of VPA, VCD (racemate or individual stereoisomers) and PID exhibit potent anticonvulsant activity against generalized convulsive seizures in developing rats. The majority of these developmental effects are quantitative; while a specific selective action on the tonic phase of generalized seizures is the main qualitative change found in our study.

Effects of quercetin on oxidative stress and memory retrieval in kindled rats.

Flavonoids are a class of polyphenolic compounds present in fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich diets and the prevention of human diseases including neurodegenerative disorders. Thus, we assessed the effect of quercetin (3,3',4',5,7-pentahydroxyflavone) on oxidative stress and memory retrieval using a step-through passive avoidance task in kindled rats. Quercetin (25, 50, and 100 mg/kg) was administered intraperitoneally (i.p.) before pentylenetetrazole (PTZ) every other day prior to the training. Retention tests were performed to assess memory in rats. Compared to control, pretreatment with 50 mg/kg of quercetin could attenuate seizure severity from the beginning of the kindling experiment by lowering the mean seizure stages. Moreover, quercetin 50 mg/kg significantly increased the step-through latency of the passive avoidance response compared to the control in the retention test. Malondialdehyde (MDA) levels were significantly increased in the quercetin groups compared to the PTZ group in the hippocampus and cerebral cortex following PTZ kindling. In the quercetin groups, higher sulfhydryl (SH) contents were not observed compared to the PTZ group. These results indicate that quercetin at a specific dose results in decreased seizure severity during kindling and performance improvement in a passive avoidance task in kindled rats. All doses of quercetin led to increased oxidative stress in the hippocampi and cerebral cortices of kindled rats.

Activation and involvement of the lateral-posterior nucleus of the thalamus after a single generalized tonic-clonic seizure.

The lateral-posterior thalamic nuclei (LP) have been shown to play an important role in controlling epileptic activity. In addition, thalamic atrophy and neuronal loss have been observed in epilepsy. The objective of this study was to investigate whether lateral-posterior neuronal activation may be observed shortly after a single generalized seizure in rats submitted to the pilocarpine model of epilepsy. The results showed an increased lateral-posterior activation as soon as the seizure occurred, suggesting that neuronal loss in the thalamus is not only the consequence of chronic epilepsy.

Case report of a patient with bipolar disorder - migraines and epilepsy.

Bipolar disorder; migraines and epilepsy are three prevalent conditions, of which little is understood about their pathophysiological processes. Co-morbidities often present between two of these conditions, but it is uncommon for all three to co-exist in a patient. Here, we present a middle-aged gentleman, seen in the outpatient department of a district general hospital in England, who suffers from severe effects of all three disorders, with no other medical history. Clinical difficulties have arisen in the diagnosis and treatment of his bipolar disorder. Management of his depressive episodes with simple selective serotonin reuptake inhibitors and mood stabilisers were either ineffective, or precipitated complicating adverse effects. Persistent use of citalopram is likely to have triggered bipolar disorder, whilst quetiapine induced seizures. The clinical problems presented question the possibility that bipolar disorder; migraines and epilepsy may fall on the same spectrum of disorders. This could contribute towards the complexities in treating his conditions. Further insight into their link and interactions would facilitate diagnoses of these conditions, as well as improve treatment strategies when they are presented co-morbidly.