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 language | English |
|---|---|
| Journal | Neurology |
| DOIs | |
| Publication status | E-pub ahead of print - 2017 |
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ASJC Scopus subject areas
- Clinical Neurology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Variable course of Unverricht-Lundborg disease
T2 - Early prognostic factors
AU - Canafoglia, Laura
AU - Ferlazzo, Edoardo
AU - Michelucci, Roberto
AU - Striano, Pasquale
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
AU - Franceschetti, Silvana
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031406634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031406634&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000004518
DO - 10.1212/WNL.0000000000004518
M3 - Article
C2 - 28931642
AN - SCOPUS:85031406634
JO - Neurology
JF - Neurology
SN - 0028-3878
ER -