Probability of Remission of the Main Epileptic Syndromes in Childhood

Aim To determine the long-term probability of remission without antiepileptic treatment of common epileptic syndromes and of children without a specific syndromic diagnosis. Patients and methods All children less than 14 years old with 2 or more unprovoked seizures seen at our hospital between June 1, 1994, and March 1, 2011 (n = 680), were included and prospectively followed up until August 15, 2020. Syndromic diagnosis was made retrospectively but blinded to subsequent evolution, employing the data available at 6 months after diagnosis and under predefined operational criteria. Results The Kaplan-Meier estimate of the probability of achieving a remission period of at least 5 years, with neither seizures nor antiepileptic treatment at 14 years was 97% for well-defined childhood epilepsy with centrotemporal spikes, 82% for uncertain childhood epilepsy with centrotemporal spikes, 85% for well-defined Panayiotopoulos syndrome, 88% for uncertain Panayiotopoulos syndrome, 93% for nonfamilial self-limited infantile epilepsy, 100% for familial self-limited infantile epilepsy, 86% for absence epilepsy, 6% for juvenile myoclonic epilepsy, 71% for cryptogenic West syndrome, 72% for patients with no associated neurologic deficits and no specific syndromic diagnosis, 65% for symptomatic West syndrome, and 40% for patients with associated neurologic deficits and no specific syndromic diagnosis. Conclusions The study results highlight the long-term outcomes of the main epileptic syndromes and also of the patients with no syndromic diagnosis.

Response to Levetiracetam Treatment and Long-Term Follow-Up in Dogs With Reactive Seizures Due to Probable Exogenous Toxicity

Limited information is available on the long-term follow-up and seizure recurrence in dogs with reactive seizures due to suspected exogenous toxicity. The purpose of this study was to report the long-term follow-up of 13 dogs referred to a single referral hospital, diagnosed with reactive seizures and treated with a standardized levetiracetam protocol. All dogs received a loading levetiracetam dose of 60 mg/kg/IV once, followed by a maintenance dose of 20 mg/kg every 8 h as part of an open-label clinical study. Levetiracetam was withdrawn after a 6-months seizure-free period by reducing levetiracetam to 20 mg/kg every 12 h for a 4-week seizure-free period, followed by levetiracetam 20 mg/kg every 24 h for a 4-week seizure-free period, before levetiracetam treatment was stopped. No adverse effects of the treatment were reported. No dogs experienced any seizures after discharge or after levetiracetam withdrawal. Median follow-up time from time of discharge was of 78 months (=6 years 6 months). The result of this study supports the use of levetiracetam for treatment of reactive seizures due to exogenous substance intoxication. Moreover, our results do not support the need for long-term antiepileptic treatment in cases of reactive seizures due to exogenous intoxication.

Influence of Different Antiepileptic Drugs on Blood Ammonia and Homocysteine Levels in Children with Epilepsy

In this study, we performed a study on 106 children with epilepsy who were treated with sodium valproate (the VPA group, n = 37), oxcarbazepine (the OXC group, n = 34), or levetiracetam (the LEV group, n = 35). In addition, the clinical data of epileptic children who were newly diagnosed in the same period without antiepileptic drug (AED) treatment (the untreated group, n = 35) and normal children who received physical examination in our hospital (the healthy group, n = 35) were selected as controls. We analyzed the efficacy and safety of different AEDs, used blood ammonia and homocysteine levels as the observation indicators, and calculated the incidence of hyperammonemia (VAH) and hyperhomocysteinemia (HHcy) treated with different AEDs. And, based on the effect of epilepsy status on the cognitive function of patients, we also analyzed the effect of different AED treatments on children’s cognitive function. Our results show that sodium valproate, oxcarbazepine, and levetiracetam are all effective in the treatment of children with epilepsy and can be used as the first-line choice of antiepileptic treatment for children with epilepsy. However, compared with sodium valproate, levetiracetam and oxcarbazepine have a lower incidence of adverse drug reactions and do not cause an increase in blood ammonia and Hcy levels, so they have higher safety of drug treatment. In addition, compared with sodium valproate, levetiracetam and oxcarbazepine have better recovery of cognitive function in children with epilepsy and so they have better application value.

How Owners of Epileptic Dogs Living in Italy Evaluate Their Quality of Life and That of Their Pet: A Survey Study

Epilepsy is the most common chronic neurological disorder of dogs and requires a substantial commitment by the pet owner. The aim of this study was to evaluate how Italian owners of epileptic dogs receiving long-term treatment perceived their own quality of life (QoL) and that of their pet, using a list of key questions. A questionnaire was sent to owners of dogs affected by recurrent seizures and treated with antiepileptic drugs for at least three months. The questions included signalment, medical history and physical, social and psychological aspects associated with managing an epileptic dog. Eighty complete questionnaires were obtained. Most owners surveyed had a positive opinion on their dog’s QoL and they did not believe that commitment to managing their animals was a limitation of QoL. Dog QoL, seizure, frequency and severity were considered the most important factors in evaluating the efficacy of the antiepileptic treatment. The evaluation of the different aspects of QoL can help veterinary professionals understand the need for correct and exhaustive information provided to owners and the development of therapeutic plans and follow up, corresponding to the needs of dogs and owners.

Recent advancements to enhance the therapeutic efficacy of antiepileptic drugs

Epilepsy is a multifactorial neurological disorder characterized by recurrent or unprovoked seizures. Over the past two decades, many new antiepileptic drugs (AEDs) were developed and are in use for the treatment of epilepsy. However, drug resistance, drug-drug interaction and adverse events are common problems associated with AEDs. Antiepileptic drugs must be used only if the ratio of efficacy, safety, and tolerability of treatment are favorable and outweigh the disadvantages including treatment costs. The application of novel drug delivery techniques could enhance the efficacy and reduce the toxicity of AEDs. These novel techniques aim to deliver an optimal concentration of the drug more specifically to the seizure focus or foci in the CNS without numerous side-effects. The purpose of this article is to review the recent advancements in antiepileptic treatment and summarize the novel modalities in the route of administration and drug delivery, including gene therapy, for effective treatment of epilepsy.

Variant in CACNA1G as a Possible Genetic Modifier of Neonatal Epilepsy in an Infant with a De Novo SCN2A Mutation

Mutations in SCN2A genes have been described in patients with epilepsy, finding a large phenotypic variability, from benign familial epilepsy to epileptic encephalopathy. To explain this variability, it was proposed the existence of dominant modifier alleles at one or more loci that contribute to determine the severity of the epilepsy phenotype. One example of modifier factor may be the CACNA1G gene, as proved in animal models. We present a 6-day-old male newborn with recurrent seizures in which a mutation in the SCN2A gene is observed, in addition to a variant in CACNA1G gene. Our patient suffered in the first days of life myoclonic seizures, with pathologic intercritical electroencephalogram pattern, requiring multiple drugs to achieve adequate control of them. During the next weeks, the patient progressively improved until complete remission at the second month of life, being possible to withdraw the antiepileptic treatment. We propose that the variant in CACNA1G gene could have acted as a modifier of the epilepsy syndrome produced by the mutation in SCN2A gene in our patient.

Cytotoxic lesion of the corpus callosum in a patient with aphasic status epilepticus

A 47-year-old man with a history of aphasic seizures presented to the emergency room with a 12-hour global aphasia. Upon admission, brain MRI did not reveal acute lesions, and EEG showed sharp waves in the left frontal-temporal region. An Aphasic Status Epilepticus was diagnosed and antiepileptic treatment was initiated with adequate response. A week after the episode, a new brain MRI showed a high-signal ovoid lesion on T2-weighted and FLAIR sequences in the central part of the splenium of the corpus callosum. On diffusion-weighted images (DWI) the lesion was hyperintense with decreased apparent diffusion coefficient (ADC) values, indicating restricted diffusion consistent with a cytotoxic lesion of the corpus callosum (CLOCC). Follow-up MRI one month later showed complete image resolution. CLOCCs are secondary lesions associated with various entities in which high levels of cytokines and extracellular glutamate cause intracellular edema and reduced diffusion, a condition called cytotoxic edema, which affects vulnerable brain regions such as the splenium of the corpus callosum. In epileptic patients, CLOCCs may be due to the effect of seizures, especially prolonged ones, as well as antiepileptic treatment itself. CLOCCs are rare radiological findings and must be recognized to avoid misdiagnosis.