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

Zianka Fallil; Heath Pardoe; Robert Bachman; Benjamin Cunningham; Isha Parulkar; Catherine Shain; Annapurna Poduri; Robert Knowlton; Ruben Kuzniecky; Bassel Abou-Khalil; Brian Alldredge; Eva Andermann; Jocelyn Bautista; Sam Berkovic; Alex Boro; Gregory Cascino; Damian Consalvo; Patricia Crumrine; Orrin Devinsky; Dennis Dlugos; Michael Epstein; Miguel Fiol; Nathan Fountain; Jacqueline French; Daniel Friedman; Eric Geller; Tracy Glauser; Simon Glynn; Sheryl Haut; Jean Hayward; Sandra Helmers; Andres Kanner; Heidi Kirsch; Eric Kossoff; Rachel Kuperman; Daniel Lowenstein; Shannon McGuire; Paul Motika; Edward Novotny; Ruth Ottman; Juliann Paolicchi; Jack Parent; Kristen Park; Neil Risch; Lynette Sadleir; Ingrid Scheffer; Renee Shellhaas; Elliot Sherr; Jerry Shih; Shlomo Shinnar; Rani Singh; Joseph Sirven; Michael Smith; Joe Sullivan; Liu Lin Thio; Anu Venkatasubramanian; Eileen Vining; Gretchen Von Allmen; Judith Weisenberg; Peter Widdess-Walsh; Melodie R. Winawer; Emily Acton; Samantha Hagopian; Sarah Sanchez

doi:10.1016/j.yebeh.2015.07.041

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

Zianka Fallil, Heath Pardoe, Robert Bachman, Benjamin Cunningham, Isha Parulkar, Catherine Shain, Annapurna Poduri, Robert Knowlton, Ruben Kuzniecky, Bassel Abou-Khalil, Brian Alldredge, Eva Andermann, Jocelyn Bautista, Sam Berkovic, Alex Boro, Gregory Cascino, Damian Consalvo, Patricia Crumrine, Orrin Devinsky, Dennis DlugosMichael Epstein, Miguel Fiol, Nathan Fountain, Jacqueline French, Daniel Friedman, Eric Geller, Tracy Glauser, Simon Glynn, Sheryl Haut, Jean Hayward, Sandra Helmers, Andres Kanner, Heidi Kirsch, Eric Kossoff, Rachel Kuperman, Daniel Lowenstein, Shannon McGuire, Paul Motika, Edward Novotny, Ruth Ottman, Juliann Paolicchi, Jack Parent, Kristen Park, Neil Risch, Lynette Sadleir, Ingrid Scheffer, Renee Shellhaas, Elliot Sherr, Jerry Shih, Shlomo Shinnar, Rani Singh, Joseph Sirven, Michael Smith, Joe Sullivan, Liu Lin Thio, Anu Venkatasubramanian, Eileen Vining, Gretchen Von Allmen, Judith Weisenberg, Peter Widdess-Walsh, Melodie R. Winawer, Emily Acton, Samantha Hagopian, Sarah Sanchez

Neurology

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

12 Scopus citations

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 language	English (US)
Pages (from-to)	321-327
Number of pages	7
Journal	Epilepsy and Behavior
Volume	51
DOIs	https://doi.org/10.1016/j.yebeh.2015.07.041
State	Published - Oct 1 2015

Bibliographical note

Funding Information:
This study was supported by NINDS U01 NS 053998 , as well as planning grants from the Finding a Cure for Epilepsy and Seizures ( FACES ) Foundation, the Andrew's Foundation and the Richard Thalheimer Philanthropic Fund . A.P. was supported by the NINDS ( K23 NS069784 ).

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Epilepsy
Epilepsy Phenome/Genome Project
Periventricular nodular heterotopia

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Fallil, Z., Pardoe, H., Bachman, R., Cunningham, B., Parulkar, I., Shain, C., Poduri, A., Knowlton, R., Kuzniecky, R., Abou-Khalil, B., Alldredge, B., Andermann, E., Bautista, J., Berkovic, S., Boro, A., Cascino, G., Consalvo, D., Crumrine, P., Devinsky, O., ... Sanchez, S. (2015). Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy. Epilepsy and Behavior, 51, 321-327. https://doi.org/10.1016/j.yebeh.2015.07.041

Fallil, Z, Pardoe, H, Bachman, R, Cunningham, B, Parulkar, I, Shain, C, Poduri, A, Knowlton, R, Kuzniecky, R, Abou-Khalil, B, Alldredge, B, Andermann, E, Bautista, J, Berkovic, S, Boro, A, Cascino, G, Consalvo, D, Crumrine, P, Devinsky, O, Dlugos, D, Epstein, M, Fiol, M, Fountain, N, French, J, Friedman, D, Geller, E, Glauser, T, Glynn, S, Haut, S, Hayward, J, Helmers, S, Kanner, A, Kirsch, H, Kossoff, E, Kuperman, R, Lowenstein, D, McGuire, S, Motika, P, Novotny, E, Ottman, R, Paolicchi, J, Parent, J, Park, K, Risch, N, Sadleir, L, Scheffer, I, Shellhaas, R, Sherr, E, Shih, J, Shinnar, S, Singh, R, Sirven, J, Smith, M, Sullivan, J, Thio, LL, Venkatasubramanian, A, Vining, E, Von Allmen, G, Weisenberg, J, Widdess-Walsh, P, Winawer, MR, Acton, E, Hagopian, S & Sanchez, S 2015, 'Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy', Epilepsy and Behavior, vol. 51, pp. 321-327. https://doi.org/10.1016/j.yebeh.2015.07.041

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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.",

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author = "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 Eric Kossoff 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 Shlomo Shinnar and Rani Singh and Joseph Sirven and Michael Smith and Joe Sullivan and Thio, {Liu Lin} and Anu Venkatasubramanian and Eileen Vining and {Von Allmen}, Gretchen and Judith Weisenberg and Peter Widdess-Walsh and Winawer, {Melodie R.} and Emily Acton and Samantha Hagopian and Sarah Sanchez",

note = "Funding Information: This study was supported by NINDS U01 NS 053998 , as well as planning grants from the Finding a Cure for Epilepsy and Seizures ( FACES ) Foundation, the Andrew's Foundation and the Richard Thalheimer Philanthropic Fund . A.P. was supported by the NINDS ( K23 NS069784 ). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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T1 - Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

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

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 - Shinnar, Shlomo

AU - Singh, Rani

AU - Sirven, Joseph

AU - Smith, Michael

AU - Sullivan, Joe

AU - Thio, Liu Lin

AU - Venkatasubramanian, Anu

AU - Vining, Eileen

AU - Von Allmen, Gretchen

AU - Weisenberg, Judith

AU - Widdess-Walsh, Peter

AU - Winawer, Melodie R.

AU - Acton, Emily

AU - Hagopian, Samantha

AU - Sanchez, Sarah

N1 - Funding Information: This study was supported by NINDS U01 NS 053998 , as well as planning grants from the Finding a Cure for Epilepsy and Seizures ( FACES ) Foundation, the Andrew's Foundation and the Richard Thalheimer Philanthropic Fund . A.P. was supported by the NINDS ( K23 NS069784 ). Publisher Copyright: © 2015 Elsevier Inc.

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.

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KW - Epilepsy Phenome/Genome Project

KW - Periventricular nodular heterotopia

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ER -

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

Abstract

Bibliographical note

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