Variable course of Unverricht-Lundborg disease: Early prognostic factors

Laura Canafoglia, Edoardo Ferlazzo, Roberto Michelucci, Pasquale Striano, Adriana Magaudda, Antonio Gambardella, Elena Pasini, Vincenzo Belcastro, Patrizia Riguzzi, Martina Fanella, Tiziana Granata, Francesca Beccaria, Claudia Trentini, Amedeo Bianchi, Umberto Aguglia, Ferruccio Panzica

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To explore the course of Unverricht-Lundborg disease (EPM1) and identify the risk factors for severity, we investigated the time course of symptoms and prognostic factors already detectable near to disease onset.

METHODS: We retrospectively evaluated the features of 59 Italian patients carrying the CSTB expansion mutation, and coded the information every 5 years after the disease onset in order to describe the cumulative time-dependent probability of reaching disabling myoclonus, relevant cognitive impairment, and inability to work, and evaluated the influence of early factors using the log-rank test. The risk factors were included in a Cox multivariate proportional hazards regression model.

RESULTS: Disabling myoclonus occurred an average of 32 years after disease onset, whereas cognitive impairment occurred a little later. An age at onset of less than 12 years, the severity of myoclonus at the time of first assessment, and seizure persistence more than 10 years after onset affected the timing of disabling myoclonus and cognitive decline. Most patients became unable to work years before the appearance of disabling myoclonus or cognitive decline.

CONCLUSIONS: A younger age at onset, early severe myoclonus, and seizure persistence are predictors of a more severe outcome. All of these factors may be genetically determined, but the greater hyperexcitability underlying more severe seizures and myoclonus at onset may also play a role by increasing cell damage due to reduced cystatin B activity.

Original languageEnglish
Pages (from-to)1691-1697
Number of pages7
JournalNeurology
Volume89
Issue number16
DOIs
Publication statusPublished - Oct 17 2017

Keywords

  • Adolescent
  • Adult
  • Age of Onset
  • Analysis of Variance
  • Anticonvulsants
  • Cathepsin B
  • Electroencephalography
  • Evoked Potentials, Somatosensory
  • Female
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Phenytoin
  • Prognosis
  • Retrospective Studies
  • Unverricht-Lundborg Syndrome
  • Valproic Acid
  • Young Adult
  • Journal Article

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  • Cite this

    Canafoglia, L., Ferlazzo, E., Michelucci, R., Striano, P., Magaudda, A., Gambardella, A., Pasini, E., Belcastro, V., Riguzzi, P., Fanella, M., Granata, T., Beccaria, F., Trentini, C., Bianchi, A., Aguglia, U., & Panzica, F. (2017). Variable course of Unverricht-Lundborg disease: Early prognostic factors. Neurology, 89(16), 1691-1697. https://doi.org/10.1212/WNL.0000000000004518