Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

for the EPGP Investigators

Research output: Contribution to journalArticle

Abstract

Purpose: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Methods: Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. Key findings: We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. Significance: A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalEpilepsy and Behavior
Volume51
DOIs
StatePublished - Oct 1 2015

Fingerprint

Periventricular Nodular Heterotopia
Epilepsy
Seizures
Malformations of Cortical Development
Choristoma
Febrile Seizures
Age of Onset
Neuroglia

Keywords

  • Epilepsy
  • Epilepsy Phenome/Genome Project
  • Periventricular nodular heterotopia

ASJC Scopus subject areas

  • Clinical Neurology
  • Behavioral Neuroscience
  • Neurology

Cite this

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy. / for the EPGP Investigators.

In: Epilepsy and Behavior, Vol. 51, 01.10.2015, p. 321-327.

Research output: Contribution to journalArticle

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title = "Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy",
abstract = "Purpose: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Methods: Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. Key findings: We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6{\%}. There was at least one other family member with epilepsy in 36.9{\%} of this population. Developmental delay was present in 21.8{\%}. Focal onset seizures were the most common type of seizure presentation (79.3{\%}). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. Significance: A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.",
keywords = "Epilepsy, Epilepsy Phenome/Genome Project, Periventricular nodular heterotopia",
author = "{for the EPGP Investigators} and Zianka Fallil and Heath Pardoe and Robert Bachman and Benjamin Cunningham and Isha Parulkar and Catherine Shain and Annapurna Poduri and Robert Knowlton and Ruben Kuzniecky and Bassel Abou-Khalil and Brian Alldredge and Eva Andermann and Jocelyn Bautista and Sam Berkovic and Alex Boro and Gregory Cascino and Damian Consalvo and Patricia Crumrine and Orrin Devinsky and Dennis Dlugos and Michael Epstein and Miguel Fiol and Nathan Fountain and Jacqueline French and Daniel Friedman and Eric Geller and Tracy Glauser and Simon Glynn and Sheryl Haut and Jean Hayward and Sandra Helmers and Andres Kanner and Heidi Kirsch and Kossoff, {Eric H} and Rachel Kuperman and Daniel Lowenstein and Shannon McGuire and Paul Motika and Edward Novotny and Ruth Ottman and Juliann Paolicchi and Jack Parent and Kristen Park and Neil Risch and Lynette Sadleir and Ingrid Scheffer and Renee Shellhaas and Elliot Sherr and Jerry Shih and Vining, {Eileen P.G.}",
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T1 - Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

AU - for the EPGP Investigators

AU - Fallil, Zianka

AU - Pardoe, Heath

AU - Bachman, Robert

AU - Cunningham, Benjamin

AU - Parulkar, Isha

AU - Shain, Catherine

AU - Poduri, Annapurna

AU - Knowlton, Robert

AU - Kuzniecky, Ruben

AU - Abou-Khalil, Bassel

AU - Alldredge, Brian

AU - Andermann, Eva

AU - Bautista, Jocelyn

AU - Berkovic, Sam

AU - Boro, Alex

AU - Cascino, Gregory

AU - Consalvo, Damian

AU - Crumrine, Patricia

AU - Devinsky, Orrin

AU - Dlugos, Dennis

AU - Epstein, Michael

AU - Fiol, Miguel

AU - Fountain, Nathan

AU - French, Jacqueline

AU - Friedman, Daniel

AU - Geller, Eric

AU - Glauser, Tracy

AU - Glynn, Simon

AU - Haut, Sheryl

AU - Hayward, Jean

AU - Helmers, Sandra

AU - Kanner, Andres

AU - Kirsch, Heidi

AU - Kossoff, Eric H

AU - Kuperman, Rachel

AU - Lowenstein, Daniel

AU - McGuire, Shannon

AU - Motika, Paul

AU - Novotny, Edward

AU - Ottman, Ruth

AU - Paolicchi, Juliann

AU - Parent, Jack

AU - Park, Kristen

AU - Risch, Neil

AU - Sadleir, Lynette

AU - Scheffer, Ingrid

AU - Shellhaas, Renee

AU - Sherr, Elliot

AU - Shih, Jerry

AU - Vining, Eileen P.G.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Purpose: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Methods: Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. Key findings: We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. Significance: A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.

AB - Purpose: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Methods: Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. Key findings: We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. Significance: A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.

KW - Epilepsy

KW - Epilepsy Phenome/Genome Project

KW - Periventricular nodular heterotopia

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U2 - 10.1016/j.yebeh.2015.07.041

DO - 10.1016/j.yebeh.2015.07.041

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EP - 327

JO - Epilepsy and Behavior

JF - Epilepsy and Behavior

SN - 1525-5050

ER -