Epilepsy syndromes
An epilepsy syndrome is defined as "a characteristic cluster of clinical and Electroencephalography features, often supported by specific etiology|etiological findings."
Syndromes are characterized by seizure types and specific findings on EEGs. Epilepsy syndromes often begin, and may remit, at specific ages. Identification of an epilepsy syndrome may provide important clues to the likely cause, the most effective treatment and the risk of comorbidity|comorbidities such as learning problems, intellectual disability, Attention Deficit Hyperactivity Disorder, or other problems.
Not everyone with epilepsy can be defined as having an epilepsy syndrome. Epilepsy syndromes are most commonly found in children with epilepsy onset before 3 years of age and are less common in adult-onset epilepsy.
This article reflects the 2017 ILAE Classification of the Epilepsies, and its more detailed follow-up papers, produced for the International League Against Epilepsy by a number of specialist clinicians. Some syndromes in earlier classifications have been renamed or redefined, but these are retained at the end of the article for convenience.
Classification of epilepsy syndromes
Epilepsy syndromes are now classified based on the type of epilepsy as well as by the age at onset.Type of epilepsy
Syndromes are characterized into 4 groups based on epilepsy type:Age at onset
Regarding the age at onset when the syndrome first appears, the following sistinctions are made: syndromes with onset in neonates and infancy, beginning prior to 2 years of age, syndromes with onset in childhood, and syndromes that begin at a variable age. This group includes syndromes that can begin either in childhood or adulthood.Epilepsy syndromes with onset in neonates and infants
Epilepsy syndromes are identified in over half of children with epilepsy onset before 2 years of age. Almost two thirds of these syndromes are developmental and epileptic encephalopathy|encephalopathies, which are associated with significant developmental impairment and frequent seizures which often respond poorly to antiseizure medication. Of the remainder of infants with an epilepsy syndrome, most will have a self-limited focal epilepsy, which does not impact development, and is typically outgrown by early childhood.Self-limited neonatal, infantile or neonatal-infantile epilepsy
As their names suggest, these epilepsies begin at specific ages in otherwise healthy babies and are caused by changes in specific genes. In some cases, the genetic changes are passed on from parent to child, and thus the syndromes are said to be familial. In other cases, the genetic change occurs de novo in the baby and there is no family history of other persons with early life seizures. De novo means that the child is affected but neither parent has the genetic variant. De novo variants typically may occur in the egg or sperm, or in early embryonic life.Seizures are focal in onset but less commonly may progress to involve both sides of the body and bloodwork is normal however genetic testing often shows a causal genetic variant, among others, are examples of very early onset prenatal phenotypes, with gestational pathologies resulting in cortical malformations.
Infantile epileptic spasms syndrome
Infantile epileptic spasms syndrome is the most common DEE that begins in early life. Infants present with a characteristic seizure type called infantile spasms. The EEG is always severely abnormal and often shows a pattern called hypsarrhythmia. Many children will have a preceding history of developmental delay and neurological concerns however this syndrome can also affect previously healthy babies. Typically if the seizures are not controlled quickly, infants may have plateauing or even regression of their development. An underlying cause can be found in most babies with infantile epileptic spasms syndrome. In many cases, the MRI scan will show evidence of a prior brain injury or abnormal brain development. Genetic causes are also relatively common and can include a large number of genetic variants. Metabolic causes are less commonly found.Infantile spasms are most commonly treated with either Steroid|oral steroids, Adrenocorticotropic hormone|ACTH or vigabatrin. The long-term outcome is often worrisome. While infantile spasms often stop with medication, many babies will develop other seizure types over time and most will be left with intellectual disability. The outcome is best predicted by the underlying cause of the spasms and whether the infant's development before onset of spasms. Rapid treatment with effective medication has also been shown to improve longterm developmental outcome.
Dravet syndrome
Dravet syndrome is a DEE beginning in infancy and characterized by severe epilepsy that does not respond well to treatment. This syndrome was described in 1978 by Charlotte Dravet, a French psychiatrist and epileptologist, while working at the Centre Saint Paul at the University of Marseille. The prevalence of this disorder is approximately 1/16,00 live births. Seizures begin before 20 months of age and in most cases, the first seizures occur with fever and are generalized tonic-clonic or unilateral convulsions. These seizures are often prolonged, and may lead to status epilepticus, a medical emergency. In time, seizures increase in frequency and begin to occur without fever. Additional seizure types appear, most often these are myoclonic, atypical absence, and focal seizures.Seizures persist despite treatment with medication, however several medications including valproic acid, stiripentol, clobazam, fenfluramine and pharmaceutical grade cannabidiol are often helpful to decrease seizure burden. Development is normal at the time of seizure onset, however developmental typically plateaus around age 2 years, and by adulthood, intellectual disability of varied severity is seen. Additional features that are seen in significant numbers of patients with Dravet syndrome may include a crouch gait, autism spectrum disorder, sleep problems, dysautonomia, and problems with growth and nutrition. Persons with Dravet syndrome also have an increased risk of early death, particularly due to SUDEP.