Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder characterized by recurrent episodes of hemiplegia and paroxysmal disturbances associated with persistent developmental delay and cognitive impairment. Incidence is estimated at 0.9 in 100,000 newborns. Onset occurs before 18 months of age. Paroxysmal ocular motor abnormalities (episodic nystagmus or deviation) are a frequent and early (often in the first 3 months of life) sign but often go unrecognized. Repeated episodes of hemiplegia lasting from a few minutes to several days and involving either side of the body are the most prominent early manifestation. Episodes of bilateral hemiplegia or quadriplegia also occur, either as a generalization of a hemiplegic attack or as a bilateral event from the onset. Other paroxysmal findings, occurring in isolation or during hemiplegic attacks, include tonic episodes, focal or unilateral attacks of dystonia (often occurring in the first 6 months of life), dyspnea and autonomic phenomena. Episodes can be triggered by a range of factors: environmental stress, water exposure, physical activities, light changes and certain foods. Episodic manifestations disappear immediately during sleep but may recur shortly after waking during long-lasting attacks. Other neurological manifestations include epilepsy, developmental delay, intellectual deficit, choreoathetosis, dystonia and ataxia. The etiology remains unclear. Mutations in the CACNA1A (19p13), SLC1A3 (5p13) and ATP1A2 (1q21-q23) genes have been identified in some cases but these patients generally presented with alternating hemiplegia associated with an atypical clinical picture and no mutations in any of these genes are detected in the majority of AHC patients. Diagnosis is primarily clinical with criteria for early diagnosis including onset of dystonic or hemiplegic events in the first 6 months of life, paroxysmal eye movements in the first 3 months of life and EEG studies revealing an absence of epileptiform changes during ictal events. AHC remains a diagnosis of exclusion, often requiring extensive examinations (magnetic resonance imagining and angiography, SPECT, analysis of CSF, video-EEG, and metabolic and genetic screening) to rule out other disorders such as vascular anomalies (Moyamoya disease), neurotransmitter deficiencies (aromatic L-amino acid decarboxylase (AADC) deficiency), mitochondrial disorders (MELAS and pyruvate dehydrogenase deficiency) and other disorders associated with infantile-onset epileptic encephalopathy (see these terms). Familial or sporadic hemiplegic migraine (FHM/SHM; see this term), which is associated with mutations in the CACNA1A, ATP1A2 and SCNA1 genes, shows some clinical overlap with AHC and should also be included in the differential diagnosis. Currently, no specific treatment is available for AHC patients and they should be managed by a multidisciplinary team with treatment strategies including prophylactic measures (such as avoiding triggers), acute management of attacks (including early induction of sleep), epilepsy management and educational therapy. AHC has an unrelenting disease course and the outcome is generally poor.
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