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Early infantile epileptic encephalopathy (NORD)

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Central nervous system disorders
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Content Reviewers:

Yifan Xiao, MD

With early infantile epileptic encephalopathy, epilepsy means seizure disorder, encephalopathy means brain dysfunction, often due to damage, and ‘early infantile’ refers to the age of onset of the disease, which is usually within the first three months of life.

So, early infantile epileptic encephalopathy, or EIEE, is a disorder characterized by recurrent and unprovoked seizures during early infancy, which can result in severe brain damage.

The nervous system is made up of specialized cells called neurons which receive and send signals from other neurons.

The two neurons communicate at the synapse, where one neuron sends neurotransmitters to the next neuron.

Excitatory neurotransmitters, like glutamate, bind to the receptors on neurons and tell them to open up ion channels and relay an electrical signal.

Inhibitory neurotransmitters like GABA can close the ion channels and dampen down electrical signals.

The most common causes of EIEE are structural brain abnormalities like hemi-megalencephaly where one half of the brain is larger than the other; absence of the corpus callosum, which is a large fiber bundle connecting the left and right hemispheres; and dysplasia, or abnormal development of the cerebral cortex.

Other causes include metabolic disorders like nonketotic hyperglycemia; and mutations in the genes coding for normal development of the neurons.

These include the ARX, or Aristaless-related homeobox, gene, and STXBP1, or syntaxin-binding protein 1, gene.

Regardless of the cause, defective neurons fire synchronously (at the same time) and excessively, resulting in a seizure.

Infants with EIEE typically present with seizures within the first 3 months of life, often in the first 10 days.

The seizures can occur during wakefulness and sleep.

They’re usually generalized tonic-clonic seizures, which means that the muscles in the trunk and extremities suddenly become stiff, the tonic phase, and then jerk, the clonic phase.

Some individuals might have myoclonic seizures which cause short muscle twitches.

In general, seizures are brief, lasting less than 10-20 seconds, but there can be more than 100 seizures in a day!

Although the exact mechanism is unknown, repeated firing of neurons causes changes in the synapse, which interferes with normal impulse conduction.

Also, abnormal firing during sleep can affect brain areas involved in memory and learning.

The end result is severe and permanent impairment in brain function and a delay in the developmental milestones like sitting and babbling.