Alternating hemiplegia of childhood (AHC)
General description
Alternating hemiplegia of childhood (AHC) is a rare, rare neurodevelopmental disorder almost invariably beginning within the first 18 months of life and caused predominantly by heterozygous mutations in the ATP1A3 gene. The principal pathological mechanism involves dysfunction of the neuronal Na⁺/K⁺‐ATPase α3 subunit, producing disrupted ion gradients, neuronal hyperexcitability, and impaired neurotransmitter homeostasis.
Clinically, AHC presents with recurrent, transient unilateral or bilateral paresis episodes that resolve with sleep, accompanied by oculomotor disturbances, dystonia, choreoathetosis, and varying degrees of developmental delay and epilepsy.
References
- Sasaki, Masayuki, et al. "Progressive brain atrophy in alternating hemiplegia of childhood." Movement Disorders Clinical Practice 4.3 (2017): 406-411.
Acute phase
During or immediately after severe hemiplegic episodes, diffusion-weighted imaging may demonstrate restricted diffusion with corresponding low apparent diffusion coefficient values with increased signal of T2 and FLAIR imaging in the affected cortical gyri.
Chronic phase
Patients with severe motor and intellectual deterioration show progressive frontal‐dominant cerebral atrophy with compensatory enlargement of frontal horns of the lateral ventricles.
Bilateral hippocampal atrophy and occasional mesial temporal sclerosis have been described in AHC patients with status epilepticus or refractory seizures, suggesting seizure‐related excitotoxic injury in regions with dense α3 subunit expression.
Diffuse cerebellar atrophy reflects Purkinje‐cell sensitivity to ionic homeostasis disruption, correlating clinically with ataxia and movement disorders.