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, Silvana Franceschetti

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
JournalNeurology
DOIs
Publication statusE-pub ahead of print - 2017

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Unverricht-Lundborg Syndrome
Myoclonus
Seizures
Age of Onset
Cystatin B
Proportional Hazards Models
Mutation

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Canafoglia, L., Ferlazzo, E., Michelucci, R., Striano, P., Magaudda, A., Gambardella, A., ... Franceschetti, S. (2017). Variable course of Unverricht-Lundborg disease: Early prognostic factors. Neurology. https://doi.org/10.1212/WNL.0000000000004518

Variable course of Unverricht-Lundborg disease : Early prognostic factors. / Canafoglia, Laura; Ferlazzo, Edoardo; Michelucci, Roberto; Striano, Pasquale; Magaudda, Adriana; Gambardella, Antonio; Pasini, Elena; Belcastro, Vincenzo; Riguzzi, Patrizia; Fanella, Martina; Granata, Tiziana; Beccaria, Francesca; Trentini, Claudia; Bianchi, Amedeo; Aguglia, Umberto; Panzica, Ferruccio; Franceschetti, Silvana.

In: Neurology, 2017.

Research output: Contribution to journalArticle

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 & Franceschetti, S 2017, 'Variable course of Unverricht-Lundborg disease: Early prognostic factors', Neurology. https://doi.org/10.1212/WNL.0000000000004518
Canafoglia, Laura ; Ferlazzo, Edoardo ; Michelucci, Roberto ; Striano, Pasquale ; Magaudda, Adriana ; Gambardella, Antonio ; Pasini, Elena ; Belcastro, Vincenzo ; Riguzzi, Patrizia ; Fanella, Martina ; Granata, Tiziana ; Beccaria, Francesca ; Trentini, Claudia ; Bianchi, Amedeo ; Aguglia, Umberto ; Panzica, Ferruccio ; Franceschetti, Silvana. / Variable course of Unverricht-Lundborg disease : Early prognostic factors. In: Neurology. 2017.
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AU - Ferlazzo, Edoardo

AU - Michelucci, Roberto

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AU - Magaudda, Adriana

AU - Gambardella, Antonio

AU - Pasini, Elena

AU - Belcastro, Vincenzo

AU - Riguzzi, Patrizia

AU - Fanella, Martina

AU - Granata, Tiziana

AU - Beccaria, Francesca

AU - Trentini, Claudia

AU - Bianchi, Amedeo

AU - Aguglia, Umberto

AU - Panzica, Ferruccio

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