Natural Course Of Epilepsy Research Articles

Antiepileptic and cognition-enhancing effects of Citrus aurantium peel extract in animal model of epilepsy

Background: History of epilepsy is intertwined with the chronicles of humankind, with millions of people worldwide living with epilepsy, still the current available antiepileptic drugs (AEDs) only suppress seizures without correcting the natural course of epilepsy. Growing limitations of available AEDs have motivated this study to divert our attention towards other safe and natural resources available for the treatment of epilepsy. Aim and Objective: This study aims to investigate the antiepileptic and cognition-enhancing effects of Citrus aurantium (CA) in a mouse model of pentylenetetrazole (PTZ)-induced generalized tonic–clonic seizures. Materials and Methods: Kindling was induced by administering 35 mg/kg PTZ to 6-month-old Swiss albino mice for 28 days. Mice were divided into following groups: PTZ control group; CA peel extract group, and Valproic acid (VA) group. The methods used for validating the antiepileptic and cognition-enhancing effects were Behavioral seizure evaluation and Cook’s pole climbing apparatus. Results: Acute treatment with CA effectively attenuated the seizures induced by PTZ. The antiepileptic and cognition-enhancing effects of CA peel extract were comparable with the standard treatment, that is, VA. Conclusion: CA showed remarkable antiepileptic and memory-enhancing effects in PTZ-induced seizures and the effects were comparable to VA.

THE IMPACT OF ANTIEPILEPTIC TREATMENT IN PREGNANCY ON PERINATAL OUTCOME IN CROATIA - A SINGLE-CENTER STUDY.

SUMMARYPregnancy can alter the natural course of epilepsy and affect pharmacokinetic profile of antiepileptic drugs (AEDs) making therapeutic management more demanding. Since there is no relevant population-based study in Croatia to date, we conducted this research with the aim to observe antiepileptic treatment policy in pregnancy and to determine if the number of AEDs affects pregnancy outcomes. The study included all women with epilepsy with singleton pregnancy exposed to one or more AEDs divided into two groups (group 1: one AED and group 2: more than one AED used). Data were collected retrospectively at the Department of Obstetrics and Gynecology, Zagreb University Hospital Centre, Zagreb, Croatia, and included 153 women from January 2010 to December 2018. Primary outcomes included rates of preterm delivery, major fetal malformations, gestational hypertension, cesarean section rate, and appearance of seizures during pregnancy. We found higher rates of all pregnancy complications examined than in the general population, while comparison of the two study groups yielded significant differences. Preterm labor was detected in 30% of deliveries in polytherapy group compared to 16.6% in monotherapy group (p=0.03). Gestational hypertension was recorded in 20% of women in polytherapy group vs. 4.90% in monotherapy group (p=0.009). There was also a high rate of cesarean deliveries in polytherapy group (27.5%). Seizures during pregnancy occurred in 48.4% of patients in polytherapy group, which was significantly higher than the rate recorded in monotherapy group (p=0.015). In this single-center retrospective study, women with epilepsy using AEDs during pregnancy had a higher rate of gestational hypertension and preterm delivery than the general population of pregnant women. To the best of our knowledge, this is the first study in Croatia observing antiepileptic treatment policy in pregnancy with regards to AED regimen and perinatal outcome.

Christianson syndrome: An underestimated cause of electrical status epilepticus in sleep?

Objective: Christianson syndrome (CS) is a syndromic form of X-linked severe ID associated to progressive microcephaly, ataxia, autistic behaviour, near absent speech and epilepsy in 90% of cases. The natural history of seizures and EEG abnormalities is insufficiently known. We report two additional families including patients with electrical status epilepticus in sleep (ESES) previously described in only two patients. Methods: We describe two unrelated families with CS caused by SLC9A6 mutations (one frameshift and one partial deletion), each including two boys. One family has been followed for over 20 years, providing insights into the natural course of epilepsy in this syndrome. Results: Onset of epilepsy occurred within the first two years of life in all patients. Seizures were of various types. First EEG recordings showed abnormal fast-background activity with poor antero-posterior organization as reported in the literature. In the two boys with a 20 year follow-up, epilepsy was drug-resistant during childhood, then became less active in early adolescence. EEG background rhythm slowed over time to 4–5Hz after the age of 8 years. One patient from the first family fulfilled the electrical criteria of ESES, between 6 and 8 years of age, while sleep-EEG had not been performed in his brother during this range of age. ESES was diagnosed in the older brother from the second family since the age of 4 years and 10 months. The four boys presented severe ID, autistic features with agitation limiting frequent sleep EEG recordings. Conclusion: Our observations and previous reports, suggest that ESES might be an underestimated feature in CS and may participate to the psychomotor degradation of the patients. Interestingly, SLC9A6 mutations underlie dysfunction in the sodium-hydrogen exchanger NHE6 implicated in plasticity of glutamatergic synapses. Sleep EEGs should be performed in these infants between 4 and 8 years of age.

Onset of intractability and its course over time: The Dutch study of epilepsy in childhood

Intractability in epilepsy is difficult to define, and little is known about its onset, course, and duration. We investigated these aspects (as well as the occurrence of intractability) during long-term follow-up in patients with epilepsy, focusing on possible explanations for the variation in time of onset and duration of intractability. After diagnosis, 453 patients with childhood-onset epilepsy had a 5-year follow-up with regular visits and data collection. Ten years later they received a questionnaire with items concerning epilepsy, which was completed by 413 patients resulting in a mean follow-up of 15 years. Intractability during the first 5 years was compared with that in the last year of follow-up. Intractability was defined as having no 3-month remission during a 1-year period despite adequate medical treatment. At least 12.1% of the cohort had a period of intractability during the 15-year follow-up, and 8.5% were intractable in the final year. Of the patients with idiopathic etiology 4.3% had a period of intractability versus 17.0% for those with cryptogenic, and 22.6% for those with remote symptomatic etiology (p < 0.001). Other risk factors at baseline were younger age at first seizure, generalized cryptogenic/symptomatic or localization-related symptomatic epilepsy, mental retardation, and febrile convulsions before enrollment. The cumulative risk of a period of intractability was 6.1% (95% confidence interval [CI] 3.7-8.5) at 2 years follow-up and 8.2% (95% CI 5.4-11.0) at 5 years. The mean time to onset of intractability during the first 5 years of follow-up was 1.6 (95% CI 1.3-2.0; median 1.0) years and the mean duration of intractability during these 5 years was 3.3 (95% CI 2.8-3.8; median 3.6) years. Fifteen patients were intractable only during the first 5 years of follow-up (group A), and 19 subjects were intractable both during the first 5 years and the last year of follow-up (group B). Compared with group A, group B had shorter remission and a longer time to intractability during the first 5 years and more were intractable in the fifth year of follow-up. Sixteen other patients had a late onset of intractability after 5 years of follow-up, sometimes after long periods of remission (group C). No significant differences in baseline characteristics were found among groups A, B, and C, but slightly more children in groups B and C became mentally retarded during the follow-up. In all groups, antiepileptic drugs were of little use in preventing and ending intractability. There is a large unpredictable variation in time of onset, course, and duration of intractability, with a higher chance of final intractability after a poor course during the first 5 years of follow-up. The natural course of epilepsy probably best explains the variable course of intractability. The effect of medication seems to be minor.

Short-duration swimming exercise decreases penicillin-induced epileptiform ECoG activity in rats.

The aim of the present study is to understand the basic relationship between swimming exercise and natural course of epilepsy in animals by performing an electrophysiological study. For this purpose, male Wistar rats were submitted to daily swimming exercise program of three different durations. Animals were swim-exercised for 90 days with either 15 minutes, 30 minutes or 60 minutes/day. Thereafter, the epileptiform activity was induced by a single microinjection of penicillin (500 units) into the left somatomotor cortex. Short-duration swimming exercise (15 min per day for 90 days) decreased the mean frequency and amplitude of penicillin-induced epileptiform activity in the 70 and 90 minutes after penicillin injection compared to penicillin administered group, respectively. Moderate-duration (30 min per day for 90 days) and long-duration (60 min per day for 90 days) swimming exercise did not alter either the frequency or amplitude of epileptiform activity. The results of the present study provide electrophysiologic evidence that short-duration swimming exercise partially inhibits penicillin-induced epileptiform activity. These data also suggest that moderate and long-duration swimming exercise do not increase either the frequency or severity of seizure in the model of penicillin-induced epilepsy.

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Characteristics of epilepsy in severely mentally retarded individuals

In order to clarify the characteristics of epilepsy in patients with severe mentally retarded (SMR) subjects, we analyzed 52 SMR subjects with epilepsy from the institute for SMR subjects at Kikuchi National Hospital, Kumamoto, Japan. A total of 61.5% patients had uncontrolled seizures which were resistant to treatment. The most common combinations of seizure types in those not responding to conventional anticonvulsants were generalized tonic-clonic seizures (GTCS) with tonic seizure and GTCS with atypical absence. Their clinical features were characterized by spastic paralysis associated with a slower background electroencephalogram and abnormal computed tomography scans of the head, suggesting the involvement of cortical damage. These findings suggest that a large proportion of epilepsy in SMR subjects does not respond to treatment and that the severity of organic brain damage may therefore affect the natural course of epilepsy in such patients.

Seizure-inducing effects of antiepileptic drugs: a review.

Seizure-inducing effects can be observed in the treatment of epileptic patients with antiepileptic drugs (AED). This may be a paradoxical reaction (for example the increase of complex focal seizures due to carbamazepine, vigabatrin or phenytoin treatment) or a result of AED-induced encephalopathy (commonly induced by valproate in patients with complex focal seizures). A seizure increase during intoxication with AED is a rare phenomenon, thus, it is not directly related to this condition. An incorrect choice of drugs in the treatment of an epileptic syndrome or seizure type may provoke seizures (as for example the provocation of absences due to carbamazepine or phenytoin). The possible seizure-inducing effect of AEDs has to be differentiated from seizure occurrence due to the natural course of epilepsy. This may be especially difficult in patients suffering from West syndrome or Lennox-Gastaut syndrome, in whom seizure frequency may vary even without medication. However, especially in these patients, drug-induced worsening of seizure manifestation is often observed. In general, a seizure-inducing effect of antiepileptic drugs has to be considered when a seizure increase is observed soon after the initiation of therapy, when a stepwise increase of the dosage is followed by a further increase of seizures, a decrease of seizures is seen with tapering of the dosage and a renewed increase of seizures can be observed after this therapy has been reestablished. Finally, one knows that the clinical condition of encephalopathy due to valproate or carbamazepine is accompanied by seizure increase. In spite of these clinical aspects, the underlying mechanisms of seizure increase mostly remain unclear. From animal experiments it is obvious that especially carbamazepine and phenytoin may provoke generalized seizures as absences or myoclonic seizures. A seizure increase during vigabatrin therapy has been attributed to the increase of the cerebral amount of gamma-amino butyric acid, which is known to possibly exhibit inhibitory or excitatory neuronal effects. The occurrence of tonic seizures in patients with Lennox-Gastaut syndrome has been attributed to the sedative effect of the drugs; however, this conclusion is controversial. From a clinical point of view, one should consider young age of the patient, mental retardation, antiepileptic polytherapy, high frequency of seizures or prominent epileptic activity in the electroencephalogram previous to medication as risk factors for a possible seizure-inducing effect of antiepileptic drugs.

Controversies in Management: Do anticonvulsants alter the natural course of epilepsy? Treatment should be started as early as possible

Throughout this century the pharmacological treatment of epilepsy has been based on the Jacksonian concept, reinforced after Berger's discovery of the electroencephalograph, that seizures represent neuronal discharges that need to be suppressed by antiepileptic drugs. According to this view, when antiepileptic drugs are withdrawn seizures may be expected to recur unless the seizure disorder has gone into spontaneous remission, which apparently happens in a high percentage or cases.1 A more recent view, which has some neglected historical roots,2 suggests that antiepileptic drugs may also influence the natural history of epilepsy, that epilepsy should be viewed as a process that has the potential to develop into an intractable disorder, and that early effective treatment may reduce this risk of chronicity.3 4 Epilepsy used to be thought of as a chronic disorder in most patients, but recent community and hospital based studies of newly diagnosed patients have shown that only …

Controversies in Management: Commentary: reliable data are not yet available

Epilepsy is a syndrome of varying aetiology. Although drugs do not seem to be effective in head injured patients, the natural course of epilepsy in these patients …