Alternating hemiplegia is a rare neurological disorder that develops in childhood, most often before the child is 18 months old. The disorder is characterized by recurrent episodes of paralysis that involve one or both sides of the body, multiple limbs, or a single limb. The paralysis may affect different parts of the body at different times and maybe brief or last for several days. Oftentimes these episodes will resolve after sleep. Affected children may also have abnormal movements involving stiffening or "dance-like" movements of a limb, as well as walking and balance problems. Some children have seizures. Children may have normal or delayed development. There are both benign and more serious forms of the disorder.
The episodes of hemiplegia or uncontrolled movements can be triggered by certain factors, such as stress, extreme tiredness, cold temperatures, or bathing, although the trigger is not always known. A characteristic feature of alternating hemiplegia of childhood is that all symptoms disappear while the affected person is sleeping but can reappear shortly after awakening. The number and length of the episodes initially worsen throughout childhood but then begin to decrease over time. The uncontrollable muscle movements may disappear entirely, but the episodes of hemiplegia occur throughout life. Alternating hemiplegia of childhood also causes mild to severe cognitive problems. Almost all affected individuals have some level of developmental delay and intellectual disability. Their cognitive functioning typically declines over time.
Patients who fit the Aicardi Alternating Hemiplegia of Childhood clinical criteria of any age. The Aicardi Criteria are six. (1) Paroxysmal hemiplegia episodes. (2) Bilateral hemiplegia or quadriplegia episodes. (3) Other paroxysmal manifestations, such as abnormal eye movements, nystagmus, strabismus, ataxia, dystonia, choreoathetosis, tonic spells, or autonomic disturbances. (4) Evidence of permanent neurological dysfunction, which can manifest as cognitive impairment, developmental delay, and/or persistent motor deficits such as spastic diplegia/quadriplegia, hypotonia, ataxia, choreoathetosis, or dystonia. (5) Sleep relieves symptoms, although attacks may resume soon after awakening. (6) First signs of dysfunction occur prior to the age of 18 months. Patients having some but not all the above criteria and have the mutation in ATP1A3 gene can be included.
AHC affects males and females in equal numbers. It is estimated to occur in approximately 1 in 1,000,000 births. However, since cases may go unrecognized or misdiagnosed, it is difficult to determine the true frequency of AHC in the general population. Symptoms usually become apparent within the first 18 months.
Alternating hemiplegia of childhood is primarily caused by mutations in the ATP1A3 gene. Very rarely, a mutation in the ATP1A2 gene is involved in the condition. These genes provide instructions for making very similar proteins. They function as different forms of one piece, the alpha subunit, of a larger protein complex called Na+/K+ ATPase; the two versions of the complex are found in different parts of the brain. Both versions play a critical role in the normal function of nerve cells (neurons). Na+/K+ ATPase transports charged atoms (ions) into and out of neurons, which is an essential part of the signaling process that controls muscle movement.
Mutations in the ATP1A3 or ATP1A2 gene reduce the activity of the Na+/K+ ATPase, impairing its ability to transport ions normally. It is unclear how a malfunctioning Na+/K+ ATPase causes episodes of paralysis or uncontrollable movements characteristic of alternating hemiplegia of childhood.
Drug therapy including verapamil may help to reduce the severity and duration of attacks of paralysis associated with the more serious form of alternating hemiplegia
Children with the benign form of alternating hemiplegia have a good prognosis. Those who experience the more severe form have a poor prognosis because intellectual and mental capacities do not respond to drug therapy, and balance and gait problems continue. Over time, walking unassisted becomes difficult or impossible.
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Journal of Clinical & Experimental Neuroimmunology