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ALTERNATING HEMIPLEGIA OF CHILDHOOD: RATIONALE FOR THERAPY WITH GAMMA-HYDROXY-BUTYRATE
Objectives:. To determine if therapeutic innovation with gammahyodrxy- butyrate (GHB) may ameliorate the acute events and improve long-term neurological outcome of alternating hemiplegia of childhood (AHC): an idiopathic disorder with unknown mechanisms underlying recurrent episodes of acute hemiplegia before 18 months of age.
Methods: A prospective N=1 study of an 18 month old infant girl was undertaken, with approval by the Research Ethics Board, on an in-patient basis over 10 days: pre-GHB monitoring for 6 months of approximately 20 episodes of hemiparesis, despite therapy with flunarizine and clonazepam, on occasion lasting up to 2 weeks' duration. Baseline EEG and MRI were normal. GHB therapy was initiated in hospital, with careful monitoring of neurovital signs and respiratory functions. EEG monitoring with polygraphic recording of EKG, respirations, EOG and EMG was undertaken prior to GHB therapy, during titration of GHB from 10mg/kg to 30mg/kg/day in 3 divided doses, reaching a maximal dose of 90mg/kg/day maintenance. Neurological and RT assessment at onset and on maintenance GHB therapy were undertaken. After discharge, oral maintence of GHB at a tolerable dose was followed by careful neurological and developmental assessment. The EEG was repeated at 3 and 6 months, and an MRI of the brain on GHB at 6 months.
Results: The pre-GHB studies were all normal: MRI, EEG with polygraphic monitoring, biochemistry and lactate. Apart from mild sedation, no severe adverse effects are encountered at 10–30mg/kg GHB therapy within the dosage range used. Neurological, OT and EEG showed no other adverse effects. The infant was developmentally delayed to a moderate degree prior to GHB: groß, fine motor and language, but AHC episodes were decreased by 10mg/kg tid dose of GHB at 3 months followup.
Conclusion: AHC is a rare disorder of unknown etiology, indeterminate pathophysiology and has no specific therapy, although cohort studies have used calcium-channel blocker (flunarizine) and benzodiazepines (clonazepam). This preliminary study suggests an early response to low-dose GHB in the therapy of AHC, but a longer study of a larger cohort is needed.