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.
Diagnosis of EIEE is made with an electroencephalography, or EEG, which is done by placing electrodes
on the scalp and monitoring the brain’s activity. It shows a typical burst suppression
pattern, where there are bursts of high amplitude spikes alternated with periods of suppressed
electrical activity. The frequent EEG abnormalities between seizures can also impair development
as the brain ‘never has a chance to be free of disruptive epilepsy waves’. Also, brain
imaging (MRI is preferred) can identify potential structural abnormalities, and blood tests
can be done to look for underlying metabolic or genetic disorders.
Unfortunately, seizures due to EIEE are difficult to treat since they usually don’t respond
to antiseizure medications. Corticosteroid therapy with prednisolone or adrenocorticotropic
hormone, or ACTH, can help control seizures in some infants. Another option is a ketogenic
diet, which forces the body and the brain to use fat instead of carbohydrates for energy.
Although the exact mechanism is unknown, this can reduce seizures in many cases. In addition,
correcting the underlying cause wherever possible can help reduce seizures.
Regardless of treatment, EIEE usually has a poor prognosis. Some children die within
the first 2 years of life and those who survive are left with severe physical and intellectual
disabilities. In survivors, there can be a transition of EIEE into other epileptic syndromes
like West syndrome and Lennox-Gastaut syndrome; which have similar underlying etiologies.
All right, as a quick recap, Early infantile epileptic encephalopathy, or EIEE, is a disorder
characterized by recurrent and unprovoked seizures beginning in the first three months
of life, resulting in severe brain damage. The seizures can be very frequent. On an EEG,
there’s a typical burst suppression pattern that can be frequent and can impair brain
function. EIEE seizures usually don’t respond to antiseizure medication, so treatment with
corticosteroid therapy and ketogenic diet are recommended.