Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study

Marina Trivisano; Nicola Pietrafusa; Alessandra Terracciano; Carla Marini; Davide Mei; Francesca Darra; Patrizia Accorsi; Domenica Battaglia; Lorella Caffi; Maria P Canevini; Simona Cappelletti; Elisabetta Cesaroni; Luca de Palma; Paola Costa; Raffaella Cusmai; Lucio Giordano; Annarita Ferrari; Elena Freri; Lucia Fusco; Tiziana Granata; Tommaso Martino; Massimo Mastrangelo; Stefania M Bova; Lucio Parmeggiani; Francesca Ragona; Federico Sicca; Pasquale Striano; Luigi M Specchio; Ilaria Tondo; Elena Zambrelli; Nelia Zamponi; Caterina Zanus; Clementina Boniver; Marilena Vecchi; Carlo Avolio; Bernardo Dalla Bernardina; Enrico Bertini; Renzo Guerrini; Federico Vigevano; Nicola Specchio

doi:10.1111/epi.14600

Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study

Marina Trivisano, Nicola Pietrafusa, Alessandra Terracciano, Carla Marini, Davide Mei, Francesca Darra, Patrizia Accorsi, Domenica Battaglia, Lorella Caffi, Maria P Canevini, Simona Cappelletti, Elisabetta Cesaroni, Luca de Palma, Paola Costa, Raffaella Cusmai, Lucio Giordano, Annarita Ferrari, Elena Freri, Lucia Fusco, Tiziana GranataTommaso Martino, Massimo Mastrangelo, Stefania M Bova, Lucio Parmeggiani, Francesca Ragona, Federico Sicca, Pasquale Striano, Luigi M Specchio, Ilaria Tondo, Elena Zambrelli, Nelia Zamponi, Caterina Zanus, Clementina Boniver, Marilena Vecchi, Carlo Avolio, Bernardo Dalla Bernardina, Enrico Bertini, Renzo Guerrini, Federico Vigevano, Nicola Specchio

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors.

METHODS: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency.

RESULTS: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124).

SIGNIFICANCE: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.

Original language	English
Pages (from-to)	2260-2271
Number of pages	12
Journal	Epilepsia
Volume	59
Issue number	12
DOIs	https://doi.org/10.1111/epi.14600
Publication status	Published - Dec 2018

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10.1111/epi.14600

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Trivisano, M., Pietrafusa, N., Terracciano, A., Marini, C., Mei, D., Darra, F., Accorsi, P., Battaglia, D., Caffi, L., Canevini, M. P., Cappelletti, S., Cesaroni, E., de Palma, L., Costa, P., Cusmai, R., Giordano, L., Ferrari, A., Freri, E., Fusco, L., ... Specchio, N. (2018). Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study. Epilepsia, 59(12), 2260-2271. https://doi.org/10.1111/epi.14600

Trivisano, M, Pietrafusa, N, Terracciano, A, Marini, C, Mei, D, Darra, F, Accorsi, P, Battaglia, D, Caffi, L, Canevini, MP, Cappelletti, S, Cesaroni, E, de Palma, L, Costa, P, Cusmai, R, Giordano, L, Ferrari, A, Freri, E, Fusco, L, Granata, T, Martino, T, Mastrangelo, M, Bova, SM, Parmeggiani, L, Ragona, F , Sicca, F , Striano, P, Specchio, LM, Tondo, I, Zambrelli, E, Zamponi, N, Zanus, C, Boniver, C, Vecchi, M, Avolio, C, Dalla Bernardina, B, Bertini, E, Guerrini, R, Vigevano, F & Specchio, N 2018, 'Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study', Epilepsia, vol. 59, no. 12, pp. 2260-2271. https://doi.org/10.1111/epi.14600

@article{21161adde6fa472ab900e976d973ca8b,

title = "Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study",

abstract = "OBJECTIVE: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors.METHODS: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency.RESULTS: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124).SIGNIFICANCE: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.",

author = "Marina Trivisano and Nicola Pietrafusa and Alessandra Terracciano and Carla Marini and Davide Mei and Francesca Darra and Patrizia Accorsi and Domenica Battaglia and Lorella Caffi and Canevini, {Maria P} and Simona Cappelletti and Elisabetta Cesaroni and {de Palma}, Luca and Paola Costa and Raffaella Cusmai and Lucio Giordano and Annarita Ferrari and Elena Freri and Lucia Fusco and Tiziana Granata and Tommaso Martino and Massimo Mastrangelo and Bova, {Stefania M} and Lucio Parmeggiani and Francesca Ragona and Federico Sicca and Pasquale Striano and Specchio, {Luigi M} and Ilaria Tondo and Elena Zambrelli and Nelia Zamponi and Caterina Zanus and Clementina Boniver and Marilena Vecchi and Carlo Avolio and {Dalla Bernardina}, Bernardo and Enrico Bertini and Renzo Guerrini and Federico Vigevano and Nicola Specchio",

note = "Wiley Periodicals, Inc. {\textcopyright} 2018 International League Against Epilepsy.",

year = "2018",

month = dec,

doi = "10.1111/epi.14600",

language = "English",

volume = "59",

pages = "2260--2271",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Blackwell Publishing Inc.",

number = "12",

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TY - JOUR

T1 - Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy

T2 - A multicenter study

AU - Trivisano, Marina

AU - Pietrafusa, Nicola

AU - Terracciano, Alessandra

AU - Marini, Carla

AU - Mei, Davide

AU - Darra, Francesca

AU - Accorsi, Patrizia

AU - Battaglia, Domenica

AU - Caffi, Lorella

AU - Canevini, Maria P

AU - Cappelletti, Simona

AU - Cesaroni, Elisabetta

AU - de Palma, Luca

AU - Costa, Paola

AU - Cusmai, Raffaella

AU - Giordano, Lucio

AU - Ferrari, Annarita

AU - Freri, Elena

AU - Fusco, Lucia

AU - Granata, Tiziana

AU - Martino, Tommaso

AU - Mastrangelo, Massimo

AU - Bova, Stefania M

AU - Parmeggiani, Lucio

AU - Ragona, Francesca

AU - Sicca, Federico

AU - Striano, Pasquale

AU - Specchio, Luigi M

AU - Tondo, Ilaria

AU - Zambrelli, Elena

AU - Zamponi, Nelia

AU - Zanus, Caterina

AU - Boniver, Clementina

AU - Vecchi, Marilena

AU - Avolio, Carlo

AU - Dalla Bernardina, Bernardo

AU - Bertini, Enrico

AU - Guerrini, Renzo

AU - Vigevano, Federico

AU - Specchio, Nicola

PY - 2018/12

Y1 - 2018/12

N2 - OBJECTIVE: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors.METHODS: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency.RESULTS: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124).SIGNIFICANCE: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.

AB - OBJECTIVE: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors.METHODS: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency.RESULTS: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124).SIGNIFICANCE: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.

U2 - 10.1111/epi.14600

DO - 10.1111/epi.14600

M3 - Article

C2 - 30451291

SN - 0013-9580

VL - 59

SP - 2260

EP - 2271

JO - Epilepsia

JF - Epilepsia

IS - 12

ER -

Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study

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