Early Infantile Epileptic Encephalopathy (EIEE) describes a group of severe neurological conditions that affect infants, typically appearing within the first three months of life. It is not a single disorder but rather a collection of syndromes characterized by frequent and challenging-to-control seizures, alongside significant developmental challenges. The condition leads to severe brain dysfunction, which can manifest as developmental regression or arrest in affected children.
What is EIEE
EIEE is a severe epileptic encephalopathy characterized by seizures beginning very early in life, often within the first 10 days. These seizures are frequently drug-resistant, meaning they do not respond well to standard anti-seizure medications. The encephalopathy indicates widespread brain dysfunction, profoundly impacting an infant’s developing brain.
Children with EIEE experience frequent and continuous epileptic activity, disrupting normal brain development. This persistent activity contributes to developmental regression or arrest. EIEE is sometimes referred to as Ohtahara syndrome, especially with tonic spasms and a specific EEG pattern. It can also transition into other epileptic syndromes like West syndrome or Lennox-Gastaut syndrome later in childhood.
Genetic Roots of EIEE
EIEE is primarily caused by genetic factors, with many cases resulting from new gene mutations not inherited from either parent. These mutations can occur in various genes, disrupting normal brain function. Over half of infants with EIEE have an identified genetic change.
Specific genes often implicated in EIEE include SCN1A, KCNQ2, CDKL5, and STXBP1. Mutations in these genes can affect how nerve cells communicate, for instance, by altering ion channels or synaptic proteins. Such disruptions lead to neuronal hyperexcitability, making the brain more prone to frequent and severe seizures.
Recognizing Symptoms and Diagnosis
Infants with EIEE present with diverse seizure types, sometimes within hours of birth. Common manifestations include tonic spasms, where the body stiffens, or myoclonic seizures, characterized by brief, sudden muscle jerks. These seizures can occur hundreds of times a day and may not be affected by wakefulness or sleep. Beyond seizures, affected infants often show severe developmental delays, poor muscle tone, and abnormal movements.
Diagnosing EIEE involves a comprehensive clinical evaluation, assessing the infant’s seizure patterns and neurological presentation. An electroencephalogram (EEG) is a test to measure brain activity and is an important diagnostic tool. The EEG in EIEE frequently shows a distinctive “burst suppression” pattern, characterized by periods of high-amplitude electrical bursts alternating with periods of very low electrical activity. This pattern is continuous and present during both sleep and wakefulness. Genetic testing, such as whole exome sequencing, is also performed to identify the specific genetic mutation, which can help guide treatment and provide prognostic information.
Treatment and Living with EIEE
Managing EIEE involves a multi-faceted approach, as seizures are often resistant to standard treatments. Anti-seizure medications are typically the first line of pharmacological treatment, though many EIEE cases do not respond fully. The goal of medication is to reduce seizure frequency and severity.
When medications are not effective, other therapies may be considered. These include the ketogenic diet, a high-fat, low-carbohydrate diet that can help control seizures in some patients by altering brain metabolism. Vagus nerve stimulation (VNS), involving a surgically implanted device that sends electrical pulses to the brain via the vagus nerve, is another option that can reduce seizure frequency and improve quality of life. In specific cases where a focal brain abnormality is identified, epilepsy surgery might be considered.
Beyond seizure control, comprehensive supportive care is important for children living with EIEE. This includes physical therapy to address motor challenges, occupational therapy to assist with daily living skills, and speech therapy to support communication development. The long-term outlook for individuals with EIEE often involves significant physical and intellectual disabilities, and some children may die early in life due to complications. However, ongoing research aims to understand the causes and develop more effective treatments, offering hope for improved outcomes.