title: Alternating Hemiplegia of Childhood: Pharmacological treatment of 30 Italian patients.
abstract: BACKGROUND
  Alternating Hemiplegia of Childhood (AHC) is a severe disorder. Several drugs have been administered as prophylaxis for paroxysmal attacks, however, no therapy is completely effective.
  
  
  METHODS
  Our aim is to review the pharmacological data related to the prophylactic and acute treatment of a cohort of 30 patients (16M, 14F, age range 5-42years) and to correlate them with the clinical and genetic data collected through the Italian Biobank and Clinical Registry for AHC.
  
  
  RESULTS
  Flunarizine was the most commonly used long-term treatment in the cohort; it reduced duration and frequency of attacks in 50% of patients and decreased intensity in 32.1%. In younger patients, flunarizine seemed significantly more effective in reducing intensity. We found no correlation between the effectiveness of flunarizine and genotype, or between developmental outcome and duration of treatment. In particular, 3 of our patients affected by E815K mutation presented rapid neurological deterioration despite ongoing treatment. Among the other administered prophylactic therapies, few proved to be effective (benzodiazepines, niaprazine, acetazolamide, melatonin, olanzapine, ketogenic diet). No clear rationale exists regarding their use, but these therapies may work by reducing the triggering factors.
  
  
  CONCLUSIONS
  The presented data are retrospective, but they are aimed at filling a gap given the rarity of the disease and the lack of randomized and controlled studies. Besides their usefulness in clarifying the pathophysiology of the disease, prospective studies involving larger cohorts of ATP1A3 mutated AHC patients are needed to provide a rationale for testing other molecules.
authors.affiliation: Child Neuropsychiatry Unit, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genoa, Genoa, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.affiliation: Child Neuropsychiatry Unit, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genoa, Genoa, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Gherzi
authors.affiliation: Child Neuropsychiatry Unit, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genoa, Genoa, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Stagnaro
authors.affiliation: Epidemiology, Biostatistics and Committees Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Calevo
authors.affiliation: Child Neurology Unit, Maggiore Hospital, Bologna, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Giannotta
authors.affiliation: IAHCRC International Consortium, Lyon, France.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Vavassori
authors.affiliation: Child Neuropsychiatry Unit, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genoa, Genoa, Italy.
authors.forename: Edvige
authors.initials: E
authors.lastname: Veneselli
authors.affiliation: Child Neuropsychiatry Unit, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genoa, Genoa, Italy. Electronic address: elisadegrandis@gaslini.org.
authors.forename: Elisa
authors.initials: E
authors.lastname: De Grandis
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D005444:Flunarizine / Q000627:therapeutic use*; D006429:Hemiplegia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D055815:Young Adult
chemical_list: C488756:ATP1A3 protein, human; D000927:Anticonvulsants; D000254:Sodium-Potassium-Exchanging ATPase; D005444:Flunarizine
keywords: ATP1A3; Alternating Hemiplegia; Flunarizine; Genotype; Phenotype; Treatment