An epilepsy syndrome is defined as "a characteristic cluster of clinical and Electroencephalography (EEG) features, often supported by specific etiological findings (structural, genetic, metabolic, immune, and infectious)."
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 comorbidities such as learning problems, intellectual disability, Attention Deficit Hyperactivity Disorder (ADHD), 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: a. Generalized onset epilepsy syndromes. These epilepsy syndromes have only generalized-onset seizures and include both the idiopathic generalized epilepsies (specifically childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy and epilepsy with generalized tonic- clonic seizures alone), as well as other genetic generalized epilepsies.
b. Focal onset epilepsy syndromes. These epilepsy syndromes have only focal onset seizures and include both the self-limited focal epilepsies in infants and children as well as other focal epilepsy syndromes.
c. Generalized and focal onset epilepsy syndromes. These syndromes have seizures which can be both of generalized or focal onset.
d. Developmental and epileptic encephalopathies (DEEs) or syndromes with progressive neurological deterioration. Developmental and epileptic encephalopathies are disorders that typically onset early in life and are associated with developmental impairment that is due to both the underlying cause of the epilepsy (developmental encephalopathy) as well as frequent seizures and/or epileptiform discharges on EEG (epileptic encephalopathy). Epilepsy syndromes associated with cognitive impairment or other neurological regression that begin after a period of prolonged normal development are termed syndromes with progressive neurological deterioration. Both the DEEs and syndromes with progressive neurological deterioration are amongst the most severe types of epilepsy, with frequent seizures and high rates of drug resistance.
Age at onset Regarding the age at onset when the syndrome first appears, the following distinctions 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 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 (variants) 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 (focal to bilateral convulsive seizure. The babies have a normal examination and attain normal developmental milestones. The MRI, interictal EEG (between seizures) and bloodwork is normal however genetic testing often shows a causal genetic variant (most commonly KCNQ2 or KCNQ3 in self-limited neonatal epilepsy, PRRT2 or less commonly SCN2A or SCN8A in self-limited infantile epilepsy and SCN2A or KCNQ2 in self-limited neonatal-infantile epilepsy. These epilepsies are generally outgrown by the early preschool years and antiseizure medication is not needed after that time.
Genetic variants identified in the sodium channel SCN3A, and Na+/K+,ATPase (ATP1A3), 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 (repetitive spells of body crunching, each spell lasting less than 2-3 seconds, but which occur in brief clusters). 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 oral steroids, 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 1/16,000 live births. Seizures begin before 20 months of age and in most cases, the first seizures occur with fever and are generalized tonic-clonic (grand mal) or unilateral (one-sided) 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.
Epilepsy syndromes with onset in childhood Epilepsy syndromes can be identified in up to one third of children with epilepsy. Syndromes with onset at this age are divided into the self-limited focal epilepsies, the genetic generalized epilepsies (including childhood absence epilepsy) and the developmental and epileptic encephalopathies.
A. Self-limited focal epilepsies (SeLFEs) SeLFEs account for approximately one quarter of epilepsies that begin in childhood. They occur in otherwise healthy children with normal development and are not correlated with any brain abnormality on MRI. In most cases, children outgrow this epilepsy type by adolescence and do not need long-term antiseizure medication. These epilepsy syndromes are associated with characteristic seizures and EEG findings, specific for each syndrome.
i. Self-limited epilepsy with centrotemporal spikes (SeLECTS) SeLECTS, (previously known as benign epilepsy of childhood with centrotemporal spikes or benign Rolandic epilepsy) is a focal epilepsy of unknown cause that most commonly occurs in early to mid school-aged children. Apart from their seizure disorder, these patients are otherwise normal. Seizures usually involve facial muscles and frequently cause drooling and difficulty with speech, although the child is aware throughout the seizure. Although most episodes are brief, seizures that occur in sleep may spread to both sides of the body with convulsive activity. Seizures are typically associated with sleep, most commonly being seen shortly after falling asleep or just before waking. The EEG shows epileptic discharges that occur over the centrotemporal region and are most frequent during drowsiness or light sleep. Seizures are outgrown by puberty. Seizures may require antiseizure medication treatment, but sometimes are infrequent enough to allow physicians to defer treatment.
ii. Self-limitied epilepsy with autonomic seizures (SeLEAS) SeLEAS (formerly known as benign occipital epilepsy of childhood or Panayiotopoulos syndrome) is a focal epilepsy of unknown cause that most commonly presents in the preschool years. Seizures are typically infrequent although can be prolonged. Seizures typically have a prominent autonomic component, most commonly retching but also including pallor, nausea, abdominal pain or even syncope. Seizures may evolve with head and eye deviation to one side, followed by focal or bilateral convulsive activity. Children often have retained awareness early on, but as the seizure evolves, awareness is often impaired. The EEG shows a normal background with epileptiform discharges that are maximal over the posterior head region and typically occur in sleep. As seizures are not frequent, daily antiseizure medication is not needed in many cases. In most cases, this epilepsy type is outgrown within a few years after onset, and longterm antiseizure medication is not required.
B. Genetic Generalized Epilepsy