University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Medicine and Radiology
  • Medicine and Radiology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Medicine and Radiology
  • Medicine and Radiology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype

    Thumbnail
    Download
    Published version (874.9Kb)

    Citations
    Scopus
    Web of Science
    Altmetric
    18
    14
    Author
    Jaffer, F; Avbersek, A; Vavassori, R; Fons, C; Campistol, J; Stagnaro, M; De Grandis, E; Veneselli, E; Rosewich, H; Gianotta, M; ...
    Date
    2015-10-01
    Source Title
    Brain: a journal of neurology
    Publisher
    OXFORD UNIV PRESS
    University of Melbourne Author/s
    Scheffer, Ingrid; GARRY, SARAH
    Affiliation
    Medicine and Radiology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Jaffer, F., Avbersek, A., Vavassori, R., Fons, C., Campistol, J., Stagnaro, M., De Grandis, E., Veneselli, E., Rosewich, H., Gianotta, M., Zucca, C., Ragona, F., Granata, T., Nardocci, N., Mikati, M., Helseth, A. R., Boelman, C., Minassian, B. A., Johns, S. ,... Sisodiya, S. M. (2015). Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype. BRAIN, 138 (Pt 10), pp.2859-2874. https://doi.org/10.1093/brain/awv243.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257702
    DOI
    10.1093/brain/awv243
    Abstract
    Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Medicine and Radiology - Research Publications [2347]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors