Early Myoclonic Encephalopathy (EME)

What is EME?

Early Myoclonic Encephalopathy (EME) is a rare epilepsy syndrome seen in newborn infants. It is also known as neonatal myoclonic encephalopathy.
It is usually diagnosed before 3 months of age. In retrospect, the first seizure could be felt towards the last trimester of pregnancy (when the baby is in the mother’s womb) or is seen during the first 10 days of life.
Infants with EME are usually severely delayed in their development.
EME can affect both boys and girls equally.

What types of seizures are seen in EME?

Many seizure types may occur, but myoclonic seizures (very frequent, brief, single or repetitive, erratic, and nearly continuous body jerks) characterize this epilepsy syndrome and differentiate it from Ohtahara Syndrome (which has more tonic seizures). Some may also have focal motor seizures, tonic seizures, or rarely tonic spasms, which appear later.

What causes EME?

Though the cause can’t be found in some cases of EME, possible causes may include metabolic disorders, certain gene mutations, and rarely brain malformations.

Metabolic causes are common. A few of these include non-ketotic hyperglycinemia, amino and organic acid disorders, urea cycle disorders, mitochondrial disorders, pyridoxine and pyridoxal-5-phosphate disorders, sulfite oxidase deficiency, Menke syndrome, Zellweger syndrome, amongst many others.
An increasing number of genetic conditions are also being found that cause EME. One example is ErbB4.

How is EME diagnosed?

Diagnosing a baby with EME is based on clinical features (what signs or symptoms the baby has) and electroencephalograph (EEG) findings.

The EEG is the most important test in making a diagnosis of EME. The EEG in babies who are not treated with medications is very abnormal, with a burst suppression pattern (high amplitude spikes followed by little brain activity or flattening of the brain waves). These changes can be seen during sleep and when the infant is awake. As infants develop, the EEG may evolve to a hypsarrhythmia pattern, which is the term for an EEG with multifocal high amplitude spikes with a very abnormal background.

Magnetic resonance imaging (MRI) is a helpful way to look for structural changes in the brain that could cause EME. MRIs could be normal initially, but follow up MRIs can show atrophy (shrinkage) of the brain. Sometimes the MRI may be abnormal and the neurologist will determine if the abnormality is the cause of the EME.

Blood work will also be done to look for metabolic or genetic problems.

How is EME treated?

Anti-seizure medications are routinely used, but seizures with EME are usually difficult to control. Medications that are often tried include clobazam (Onfi), clonazepam (Klonopin), topiramate (Topamax), zonisamide (Zonegran), Phenobarbital, valproate (if the metabolic condition is known), or felbamate (Felbatol). Medications like vigabatrin (Sabril) may make seizures worse.
Epilepsy Surgery may be an option in children with seizures starting in one area or involving one side of the brain. In these situations, a focal resection (removal of one area) or a hemispherectomy (removing most of one side of the brain) may be considered.
Devices or dietary therapy: A vagus nerve stimulator, special diets depending on the underlying metabolic condition, or the ketogenic diet may also be considered when medicines don’t work well.
Correcting metabolic problems: All babies without a known cause for their EME should be considered fo a trial of pyridoxine (vitamin B6) in case they have pyridoxine dependent seizures or biotin in case they have biotinidase deficiency. Sometimes a metabolic disorder that affects how the brain works may lead to EME. While most of these metabolic disorders can’t be reversed, sometimes treating the underlying disorder can help.

What is the outlook for persons with EME?

The outlook for children with EME is often very worrisome. Many children progress to have infantile spasms (West Syndrome) or Lennox-Gastaut Syndrome (LGS). Some children with EME may die within the first year of life. Those who survive are typically left with severe physical and cognitive disabilities.