Encephalopathies and progressive epilepsy syndromes

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Read about the causes, symptoms and treatments for encephalopathies and progressive syndromes.

Key points

  • Epileptic encephalopathies are a group of epilepsy syndromes in which seizures are linked with developmental delay or mental impairment.
  • Many children with these seizures stop developing psychomotor skills.
  • These types of seizures are often difficult to treat with medication.

Encephalopathy is a general term that means brain disease. The epileptic encephalopathies are a group of epilepsy syndromes in which seizures are associated with developmental delay or intellectual disability. In these conditions, the seizures are often frequent and difficult to control with medication. In some epileptic encephalopathies, there is a progressive decline in function.

Early myoclonic encephalopathy

Early myoclonic encephalopathy begins when a baby is less than three months old. The first seizures are isolated myoclonic jerks. Later, the child has partial seizures, massive myoclonic seizures or tonic spasms. The child’s psychomotor development (learning skills that involve controlled movement) stops.

Children with this syndrome often have a family history of the syndrome, but no genetic pattern has been identified. It is possible that one or several inherited metabolic disorders play a role.

Early infantile epileptic encephalopathy (EIEE)

EIEE is also known as Ohtahara syndrome or early infantile epileptic encephalopathy with suppression bursts. It begins before the child is three months old, and usually within the first 10 days of life. We do not know how common the syndrome is.

The syndrome is usually caused by structural brain problems, but in some cases no cause can be identified. It is possible that EIEE, infantile spasms and Lennox-Gastaut syndrome represent the brain’s reactions to various external factors at specific stages of development.

The child usually has tonic spasms. They may also have partial seizures and, rarely, myoclonic seizures. They will also have a characteristic “suppression-burst” EEG pattern while they are awake and asleep. An EEG and neuroimaging studies are both important for diagnosis.

EIEE has a poor prognosis. Children with this syndrome have severe psychomotor retardation; they are unable to learn new psychomotor skills (skills that involve controlled movement) and may not make eye contact with others. Their seizures continue, and are very difficult to control. Children with this syndrome may later develop infantile spasms, Lennox-Gastaut syndrome or severe partial epilepsy.

Severe myoclonic epilepsy in infancy (SMEI or Dravet syndrome)

Severe myoclonic epilepsy in infancy is rare. It is estimated to affect between one child in 40,000 and one in 20,000, although this estimate may change as more becomes known. It affects boys more often than girls. The syndrome is strongly associated with various mutations on the SCN1A gene, which helps control sodium ion channels, although not every child with SMEI has a mutation on this gene. Mutations on the SCN1A gene are associated with a spectrum of epilepsy syndromes, ranging from the relatively benign generalized epilepsy with febrile seizures plus to SMEI. They are inherited in an autosomal dominant fashion, although they can also arise spontaneously.

Children with SMEI begin to have febrile seizures when they are between two and 10 months old. The seizures may be generalized or one-sided, affecting each side of the body alternately. Their EEG patterns are normal at first, but over time they develop generalized spike wave abnormalities. Within one or two years, children with SMEI develop seizures without fever; the seizures may be a mixture of myoclonic, atonic, atypical absence, or partial seizures. Despite the name of the syndrome, not all children have myoclonic seizures. They may have one or more episodes of convulsive or myoclonic status epilepticus. The seizures usually become less frequent as the syndrome progresses, and most children begin to stabilize after age four.

Before the onset of seizures, children develop normally. In the second year of life, children with SMEI begin to lose skills they have already acquired or fail to gain new skills. They may also develop other neurological problems, including problems with language, learning, communication, behaviour, and coordination.

Seizures with SMEI are difficult to treat. As with many other forms of epilepsy, treatment for SMEI depends on the individual child. Status epilepticus can be prevented with medication and some anti-epileptic drugs appear to reduce the number of seizures, although there is no one anti-epileptic drug that is always effective. Valproate, topiramate, clobazam, clonazepam, and stiripentol may be helpful; however, stiripentol can be difficult to access. Some anti-epileptic drugs, including lamotrigine, carbamazepine, oxcarbazepine, vigabatrin, phenytoin, and fosphenytoin​, may make seizures worse. Other treatments, including the ketogenic diet and vagus nerve stimulation, may be helpful and are still being studied in children with SMEI. Epilepsy surgery is not considered effective.

High body temperature can trigger seizures, so it is important to treat fever aggressively and avoid hot baths and overheating. Children with SMEI are at higher risk of status epilepticus and sudden unexpected death.

As with many forms of epilepsy, the outlook is variable. SMEI cannot be completely cured, and the seizures are difficult to control. Children with SMEI may be dependent on others for help with dressing and eating into adulthood. However, we still know very little about the course of SMEI over the long term.

Genetic testing may be suggested for children with symptoms of SMEI.

Progressive myoclonus epilepsies

The progressive myoclonus epilepsies (PMEs) are rare; no more than 1% of people with epilepsy have one of these syndromes. The three characteristic symptoms are:

  • myoclonic jerks
  • progressive neurological deterioration with dementia, cerebellar ataxia (lack of muscle coordination due to disease of the cerebellum), neuropathy (nerve disease) and myopathy (muscle disease)
  • epilepsy with generalized tonic-clonic seizures and possibly other seizure types as well

They are usually caused by autosomal recessive mutations. Examples of progressive myoclonus epilepsies are:

  • Lafora’s disease
  • myoclonus epilepsy with ragged red fibres (MERRF)
  • neuronal ceroid lipofuscinoses
  • type I sialidosis
  • type 3 Gaucher’s disease
  • Unverricht-Lundborg disease

The age of onset and the disease course of the different progressive myoclonus epilepsies vary. Some cause rapid degeneration and death. Others, such as Unverricht-Lundborg disease, progress more slowly, and with proper treatment the person can live for a normal lifespan.

These syndromes are diagnosed with a thorough personal and family history and laboratory tests, which may include molecular genetic testing and muscle biopsies.

There is no cure at present for the progressive myoclonus epilepsies; people with these syndromes will be prescribed anti-epileptic drugs to control the seizures and myoclonic jerks.

Genetic counselling is possible for family members of people with most progressive myoclonus epilepsies, because they have a clear inheritance pattern.

Last updated: February 4th 2010