Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES: A functional framework

Anne T. Berg; Deborah Gaebler-Spira; Greta Wilkening; Frank Zelko; Kelly Knupp; Tracy Dixon-Salazar; Nicole Villas; Mary Anne Meskis; Vinez Harwell; Tina Thompson; Scotty Sims; Gerry Nesbitt

doi:10.1016/j.yebeh.2020.107287

Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES: A functional framework

Anne T. Berg^*, Deborah Gaebler-Spira, Greta Wilkening, Frank Zelko, Kelly Knupp, Tracy Dixon-Salazar, Nicole Villas, Mary Anne Meskis, Vinez Harwell, Tina Thompson, Scotty Sims, Gerry Nesbitt

^*Corresponding author for this work

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

34 Scopus citations

Abstract

Rationale: Developmental epilepsies and encephalopathies (DEEs) are characterized by many severe developmental impairments, which are not well-described. A functional framework could facilitate understanding of their nature and severity and guide the selection instruments to measure improvements in therapeutic trials. Methods: An online survey administered through several parent-organized foundations utilized accepted functional classifications and questionnaires derived from common instruments to determine levels of mobility, fine motor, communication, and feeding functions. Statistical analyses focused on overall levels of function and across-group comparisons adjusted for age. Results: From 6/2018 to 2/2020, 252 parents provided information for one or more functional domains. Median age was 7.2 years (interquartile range (IQR): 3.9 to 11.8), and 128 (51%) were females. DEE groups were Dravet syndrome (N = 72), KCNQ2-DEE (N = 80), KCNB1-DEE, (N = 33), Lennox–Gastaut syndrome (LGS; N = 26), electrographic status epilepticus in sleep (ESES; N = 15), and others (N = 26). Overall, functional hand grasp was absent in 48 (20%). Of children ≥ 2 years old, 60/214 (28%) could not walk independently, 85 (40%) were dependent on someone else for feeding, and 153 (73%) did not effectively communicate with unfamiliar people. Impairments entailing absence or near absence of independent function (profound impairment) were observed in 0, 1, 2, 3, and 4 domains for 58 (25%), 78 (34%), 40 (17%), 33 (14%), and 22 (10%) children, respectively. After adjustment for age, impairment levels varied substantially across DEE group for mobility (p < 0.0001), feeding (p < 0.0001), communication (p < 0.0001), hand grasp (p < 0.0001), and number of profoundly impaired domains (p < 0.0001). Three or four profoundly affected domains were reported in 44% of KCNQ2-DEE participants, followed by LGS (29%), KCNB1-DEE (27%), ESES (7%), and Dravet syndrome (6%). Conclusions: Many children with DEEs experience severe functional impairments, and few children have typical function. As precision therapies will emphasize nonseizures consequences of DEEs, understanding the nature of abilities and impairments will be critical to selecting appropriate outcome measures in therapeutic trials.

Original language	English (US)
Article number	107287
Journal	Epilepsy and Behavior
Volume	111
DOIs	https://doi.org/10.1016/j.yebeh.2020.107287
State	Published - Oct 2020

Funding

This work was supported by the Stanley Manne Children's Research Institute and Ann & Robert H. Lurie Children's Hospital of Chicago under the Precision Medicine Strategic Research Initiative and by a grant from the Pediatric Epilepsy Research Foundation, Dallas, TX. This work was supported by the Stanley Manne Children’s Research Institute and Ann & Robert H. Lurie Children’s Hospital of Chicago under the Precision Medicine Strategic Research Initiative and by a grant from the Pediatric Epilepsy Research Foundation , Dallas, TX.

Keywords

Epilepsy
Functional ability
Outcome measures
Precision medicine

ASJC Scopus subject areas

Neurology
Clinical Neurology
Behavioral Neuroscience

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10.1016/j.yebeh.2020.107287

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Berg, A. T., Gaebler-Spira, D., Wilkening, G., Zelko, F., Knupp, K., Dixon-Salazar, T., Villas, N., Meskis, M. A., Harwell, V., Thompson, T., Sims, S., & Nesbitt, G. (2020). Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES: A functional framework. Epilepsy and Behavior, 111, Article 107287. https://doi.org/10.1016/j.yebeh.2020.107287

@article{e878889bd7fc400dbeb2d0d5b63ebc44,

title = "Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES: A functional framework",

abstract = "Rationale: Developmental epilepsies and encephalopathies (DEEs) are characterized by many severe developmental impairments, which are not well-described. A functional framework could facilitate understanding of their nature and severity and guide the selection instruments to measure improvements in therapeutic trials. Methods: An online survey administered through several parent-organized foundations utilized accepted functional classifications and questionnaires derived from common instruments to determine levels of mobility, fine motor, communication, and feeding functions. Statistical analyses focused on overall levels of function and across-group comparisons adjusted for age. Results: From 6/2018 to 2/2020, 252 parents provided information for one or more functional domains. Median age was 7.2 years (interquartile range (IQR): 3.9 to 11.8), and 128 (51%) were females. DEE groups were Dravet syndrome (N = 72), KCNQ2-DEE (N = 80), KCNB1-DEE, (N = 33), Lennox–Gastaut syndrome (LGS; N = 26), electrographic status epilepticus in sleep (ESES; N = 15), and others (N = 26). Overall, functional hand grasp was absent in 48 (20%). Of children ≥ 2 years old, 60/214 (28%) could not walk independently, 85 (40%) were dependent on someone else for feeding, and 153 (73%) did not effectively communicate with unfamiliar people. Impairments entailing absence or near absence of independent function (profound impairment) were observed in 0, 1, 2, 3, and 4 domains for 58 (25%), 78 (34%), 40 (17%), 33 (14%), and 22 (10%) children, respectively. After adjustment for age, impairment levels varied substantially across DEE group for mobility (p < 0.0001), feeding (p < 0.0001), communication (p < 0.0001), hand grasp (p < 0.0001), and number of profoundly impaired domains (p < 0.0001). Three or four profoundly affected domains were reported in 44% of KCNQ2-DEE participants, followed by LGS (29%), KCNB1-DEE (27%), ESES (7%), and Dravet syndrome (6%). Conclusions: Many children with DEEs experience severe functional impairments, and few children have typical function. As precision therapies will emphasize nonseizures consequences of DEEs, understanding the nature of abilities and impairments will be critical to selecting appropriate outcome measures in therapeutic trials.",

keywords = "Epilepsy, Functional ability, Outcome measures, Precision medicine",

author = "Berg, {Anne T.} and Deborah Gaebler-Spira and Greta Wilkening and Frank Zelko and Kelly Knupp and Tracy Dixon-Salazar and Nicole Villas and Meskis, {Mary Anne} and Vinez Harwell and Tina Thompson and Scotty Sims and Gerry Nesbitt",

note = "Funding Information: This work was supported by the Stanley Manne Children's Research Institute and Ann & Robert H. Lurie Children's Hospital of Chicago under the Precision Medicine Strategic Research Initiative and by a grant from the Pediatric Epilepsy Research Foundation, Dallas, TX. Funding Information: This work was supported by the Stanley Manne Children{\textquoteright}s Research Institute and Ann & Robert H. Lurie Children{\textquoteright}s Hospital of Chicago under the Precision Medicine Strategic Research Initiative and by a grant from the Pediatric Epilepsy Research Foundation , Dallas, TX. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = oct,

doi = "10.1016/j.yebeh.2020.107287",

language = "English (US)",

volume = "111",

journal = "Epilepsy and Behavior",

issn = "1525-5050",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES

T2 - A functional framework

AU - Berg, Anne T.

AU - Gaebler-Spira, Deborah

AU - Wilkening, Greta

AU - Zelko, Frank

AU - Knupp, Kelly

AU - Dixon-Salazar, Tracy

AU - Villas, Nicole

AU - Meskis, Mary Anne

AU - Harwell, Vinez

AU - Thompson, Tina

AU - Sims, Scotty

AU - Nesbitt, Gerry

N1 - Funding Information: This work was supported by the Stanley Manne Children's Research Institute and Ann & Robert H. Lurie Children's Hospital of Chicago under the Precision Medicine Strategic Research Initiative and by a grant from the Pediatric Epilepsy Research Foundation, Dallas, TX. Funding Information: This work was supported by the Stanley Manne Children’s Research Institute and Ann & Robert H. Lurie Children’s Hospital of Chicago under the Precision Medicine Strategic Research Initiative and by a grant from the Pediatric Epilepsy Research Foundation , Dallas, TX. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/10

Y1 - 2020/10

N2 - Rationale: Developmental epilepsies and encephalopathies (DEEs) are characterized by many severe developmental impairments, which are not well-described. A functional framework could facilitate understanding of their nature and severity and guide the selection instruments to measure improvements in therapeutic trials. Methods: An online survey administered through several parent-organized foundations utilized accepted functional classifications and questionnaires derived from common instruments to determine levels of mobility, fine motor, communication, and feeding functions. Statistical analyses focused on overall levels of function and across-group comparisons adjusted for age. Results: From 6/2018 to 2/2020, 252 parents provided information for one or more functional domains. Median age was 7.2 years (interquartile range (IQR): 3.9 to 11.8), and 128 (51%) were females. DEE groups were Dravet syndrome (N = 72), KCNQ2-DEE (N = 80), KCNB1-DEE, (N = 33), Lennox–Gastaut syndrome (LGS; N = 26), electrographic status epilepticus in sleep (ESES; N = 15), and others (N = 26). Overall, functional hand grasp was absent in 48 (20%). Of children ≥ 2 years old, 60/214 (28%) could not walk independently, 85 (40%) were dependent on someone else for feeding, and 153 (73%) did not effectively communicate with unfamiliar people. Impairments entailing absence or near absence of independent function (profound impairment) were observed in 0, 1, 2, 3, and 4 domains for 58 (25%), 78 (34%), 40 (17%), 33 (14%), and 22 (10%) children, respectively. After adjustment for age, impairment levels varied substantially across DEE group for mobility (p < 0.0001), feeding (p < 0.0001), communication (p < 0.0001), hand grasp (p < 0.0001), and number of profoundly impaired domains (p < 0.0001). Three or four profoundly affected domains were reported in 44% of KCNQ2-DEE participants, followed by LGS (29%), KCNB1-DEE (27%), ESES (7%), and Dravet syndrome (6%). Conclusions: Many children with DEEs experience severe functional impairments, and few children have typical function. As precision therapies will emphasize nonseizures consequences of DEEs, understanding the nature of abilities and impairments will be critical to selecting appropriate outcome measures in therapeutic trials.

AB - Rationale: Developmental epilepsies and encephalopathies (DEEs) are characterized by many severe developmental impairments, which are not well-described. A functional framework could facilitate understanding of their nature and severity and guide the selection instruments to measure improvements in therapeutic trials. Methods: An online survey administered through several parent-organized foundations utilized accepted functional classifications and questionnaires derived from common instruments to determine levels of mobility, fine motor, communication, and feeding functions. Statistical analyses focused on overall levels of function and across-group comparisons adjusted for age. Results: From 6/2018 to 2/2020, 252 parents provided information for one or more functional domains. Median age was 7.2 years (interquartile range (IQR): 3.9 to 11.8), and 128 (51%) were females. DEE groups were Dravet syndrome (N = 72), KCNQ2-DEE (N = 80), KCNB1-DEE, (N = 33), Lennox–Gastaut syndrome (LGS; N = 26), electrographic status epilepticus in sleep (ESES; N = 15), and others (N = 26). Overall, functional hand grasp was absent in 48 (20%). Of children ≥ 2 years old, 60/214 (28%) could not walk independently, 85 (40%) were dependent on someone else for feeding, and 153 (73%) did not effectively communicate with unfamiliar people. Impairments entailing absence or near absence of independent function (profound impairment) were observed in 0, 1, 2, 3, and 4 domains for 58 (25%), 78 (34%), 40 (17%), 33 (14%), and 22 (10%) children, respectively. After adjustment for age, impairment levels varied substantially across DEE group for mobility (p < 0.0001), feeding (p < 0.0001), communication (p < 0.0001), hand grasp (p < 0.0001), and number of profoundly impaired domains (p < 0.0001). Three or four profoundly affected domains were reported in 44% of KCNQ2-DEE participants, followed by LGS (29%), KCNB1-DEE (27%), ESES (7%), and Dravet syndrome (6%). Conclusions: Many children with DEEs experience severe functional impairments, and few children have typical function. As precision therapies will emphasize nonseizures consequences of DEEs, understanding the nature of abilities and impairments will be critical to selecting appropriate outcome measures in therapeutic trials.

KW - Epilepsy

KW - Functional ability

KW - Outcome measures

KW - Precision medicine

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Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox–Gastaut syndrome, ESES: A functional framework

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