Alternating hemiplegia of childhood (AHC) is a rare genetic disorder characterized by 7 criteria: developmental delay, onset of symptoms in infancy, repeating spells of hemiplegia, intermittent generalization, paroxysmal neurological and autonomic symptoms, alleviation with sleep, and recurrence shortly after awakening. Epilepsy is comorbid in approximately 50% of patients. 80% of AHC is associated with the ATP1A3 mutation, leading to reduced ATPase activity without affecting protein expression, as seen in rapid-onset dystonia with parkinsonism (DYT12). There is no known acute intervention, but calcium-channel blockers are used for prophylaxis. Studies of similar channeolopathies (DYT12 and familial hemiplegic migraines) also report positive responses to Levetiracetam and Topiramate, independent of seizure control.

We present a 26-year old female with developmental delay and near-monthly episodes of lethargy, spastic hemiparesis, and aphasia, as well as rare occurrences of tonic-clonic movements with unresponsiveness. She was hospitalized for a typical, but particularly severe episode, empirically receiving Lorazepam and high-dose Levetiracetam for acute seizure treatment. Continuous video-EEG monitoring indicated a severe encephalopathy, but no clearly formed seizures. The EEG remained abnormal throughout clinical recovery, and only normalzied during sleep. Both AHC and epilepsy were diagnosed, with an expected dysfunctional electrographic background at baseline. In follow-up, episode frequency decreased with maintenance Levetiracetam, and even further with the addition of Verapamil. Molecular testing confirmed the ATP1A3 mutation. 

This is the first report of non-epileptic electrophysiological changes behind the active and recovery phases of a typical AHC episode, especially in correlation to sleep. This is also the first successful use of Levetiracetam as a disease-modifying agent in AHC.