The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS)

the participating investigators

doi:10.1111/epi.16305

The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS)

the participating investigators

Research output: Contribution to journal › Article (Academic Journal) › peer-review

76 Citations (Scopus)

Abstract

Objective: To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment. Methods: Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD-10). Results: A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi-square 4.3, P =.037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P =.037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi-square 0.35, P =.55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead-time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P =.62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy. Significance: This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.

Original language	English
Pages (from-to)	1861-1869
Number of pages	9
Journal	Epilepsia
Volume	60
Issue number	9
DOIs	https://doi.org/10.1111/epi.16305
Publication status	Published - 16 Aug 2019

Bibliographical note

Funding Information:
This research was sponsored by the Royal United Hospitals Bath National Health Service (NHS) Foundation Trust and we thank their R&D department for all their input and support for the trial. The trial website was hosted by the University of Bath. This research was also supported by the National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We thank the parents who gave their time and their permission for their infants to take part in the study at a difficult and traumatic moment. We also thank the members of the Data Monitoring and Ethics Committee who freely gave their time to review untoward events and the progress of the trial: Richard Purvis, Chairman, Linda Hunt, Jane Schulte, and John Wilson. We thank Catherine Carter and Mark Scholefield for their time and input as Parent Advisors to the trial. We thank Gordon Taylor who provided the randomization sequences. Administrative assistance was provided by Patricia Sheppard throughout the trial and also by Ros Conacher, Rowan Dalley‐Smith, Jessica Graysmark, Veronica Kerr, Ewa Mapstone, Christina Padovani, and Kathryn Wheeler. Carol Jackson, pediatric pharmacist, provided frequent help and advice. Phillip Lunt, Thomas Trentham, and Richard Wood provided IT advice. Karen Giles built the results database. We also owe a massive debt of thanks to the clinicians and the EEG and MRI departments who took part. We thank the local research nurses for their help and assistance. The trial was funded by the Castang Foundation; significant additional funding was provided by the Bath Unit for Research in Paediatrics, the NIHR, and the R&D department at the Royal United Hospital, with smaller contributions from the BRONNER‐BENDER Stiftung/Gernsbach and the University Children's Hospital Zurich: we are extremely grateful to them all.

Funding Information:
During the course of this study, F.J.K.O'C., S.W.E., E.H., A.L.L., and J.P.O. received a payment from Marathon Pharmaceuticals for intellectual property. The study sponsor has received a payment from UCB Biopharma for intellectual property. D.R. received a grant from the Bonner‐Bender stiftung. F.D.A., M.C.B., A.L.J., C.R.K., M.L., M.T.M., A.M.M., R.W.N., M.N., R.P., B.S., and C.M.V. declare no competing interests. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Publisher Copyright:
Wiley Periodicals, Inc. © 2019 International League Against Epilepsy

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

etiology
infantile spasms
West syndrome

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10.1111/epi.16305

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@article{30b364eee8264838a945a03e4ed3829a,

title = "The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS)",

abstract = "Objective: To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment. Methods: Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD-10). Results: A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi-square 4.3, P =.037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P =.037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi-square 0.35, P =.55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead-time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P =.62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy. Significance: This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.",

keywords = "etiology, infantile spasms, West syndrome",

author = "{the participating investigators} and Osborne, {John P.} and Edwards, {Stuart W.} and {Dietrich Alber}, Fabienne and Eleanor Hancock and Johnson, {Anthony L.} and Kennedy, {Colin R.} and Marcus Likeman and Lux, {Andrew L.} and Mark Mackay and Andrew Mallick and Newton, {Richard W.} and Melinda Nolan and Ronit Pressler and Dietz Rating and Bernhard Schmitt and Verity, {Christopher M.} and O'Callaghan, {Finbar J.K.}",

note = "Funding Information: This research was sponsored by the Royal United Hospitals Bath National Health Service (NHS) Foundation Trust and we thank their R&D department for all their input and support for the trial. The trial website was hosted by the University of Bath. This research was also supported by the National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We thank the parents who gave their time and their permission for their infants to take part in the study at a difficult and traumatic moment. We also thank the members of the Data Monitoring and Ethics Committee who freely gave their time to review untoward events and the progress of the trial: Richard Purvis, Chairman, Linda Hunt, Jane Schulte, and John Wilson. We thank Catherine Carter and Mark Scholefield for their time and input as Parent Advisors to the trial. We thank Gordon Taylor who provided the randomization sequences. Administrative assistance was provided by Patricia Sheppard throughout the trial and also by Ros Conacher, Rowan Dalley‐Smith, Jessica Graysmark, Veronica Kerr, Ewa Mapstone, Christina Padovani, and Kathryn Wheeler. Carol Jackson, pediatric pharmacist, provided frequent help and advice. Phillip Lunt, Thomas Trentham, and Richard Wood provided IT advice. Karen Giles built the results database. We also owe a massive debt of thanks to the clinicians and the EEG and MRI departments who took part. We thank the local research nurses for their help and assistance. The trial was funded by the Castang Foundation; significant additional funding was provided by the Bath Unit for Research in Paediatrics, the NIHR, and the R&D department at the Royal United Hospital, with smaller contributions from the BRONNER‐BENDER Stiftung/Gernsbach and the University Children's Hospital Zurich: we are extremely grateful to them all. Funding Information: During the course of this study, F.J.K.O'C., S.W.E., E.H., A.L.L., and J.P.O. received a payment from Marathon Pharmaceuticals for intellectual property. The study sponsor has received a payment from UCB Biopharma for intellectual property. D.R. received a grant from the Bonner‐Bender stiftung. F.D.A., M.C.B., A.L.J., C.R.K., M.L., M.T.M., A.M.M., R.W.N., M.N., R.P., B.S., and C.M.V. declare no competing interests. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Publisher Copyright: Wiley Periodicals, Inc. {\textcopyright} 2019 International League Against Epilepsy Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = aug,

day = "16",

doi = "10.1111/epi.16305",

language = "English",

volume = "60",

pages = "1861--1869",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Wiley-Blackwell",

number = "9",

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TY - JOUR

T1 - The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS)

AU - the participating investigators

AU - Osborne, John P.

AU - Edwards, Stuart W.

AU - Dietrich Alber, Fabienne

AU - Hancock, Eleanor

AU - Johnson, Anthony L.

AU - Kennedy, Colin R.

AU - Likeman, Marcus

AU - Lux, Andrew L.

AU - Mackay, Mark

AU - Mallick, Andrew

AU - Newton, Richard W.

AU - Nolan, Melinda

AU - Pressler, Ronit

AU - Rating, Dietz

AU - Schmitt, Bernhard

AU - Verity, Christopher M.

AU - O'Callaghan, Finbar J.K.

N1 - Funding Information: This research was sponsored by the Royal United Hospitals Bath National Health Service (NHS) Foundation Trust and we thank their R&D department for all their input and support for the trial. The trial website was hosted by the University of Bath. This research was also supported by the National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We thank the parents who gave their time and their permission for their infants to take part in the study at a difficult and traumatic moment. We also thank the members of the Data Monitoring and Ethics Committee who freely gave their time to review untoward events and the progress of the trial: Richard Purvis, Chairman, Linda Hunt, Jane Schulte, and John Wilson. We thank Catherine Carter and Mark Scholefield for their time and input as Parent Advisors to the trial. We thank Gordon Taylor who provided the randomization sequences. Administrative assistance was provided by Patricia Sheppard throughout the trial and also by Ros Conacher, Rowan Dalley‐Smith, Jessica Graysmark, Veronica Kerr, Ewa Mapstone, Christina Padovani, and Kathryn Wheeler. Carol Jackson, pediatric pharmacist, provided frequent help and advice. Phillip Lunt, Thomas Trentham, and Richard Wood provided IT advice. Karen Giles built the results database. We also owe a massive debt of thanks to the clinicians and the EEG and MRI departments who took part. We thank the local research nurses for their help and assistance. The trial was funded by the Castang Foundation; significant additional funding was provided by the Bath Unit for Research in Paediatrics, the NIHR, and the R&D department at the Royal United Hospital, with smaller contributions from the BRONNER‐BENDER Stiftung/Gernsbach and the University Children's Hospital Zurich: we are extremely grateful to them all. Funding Information: During the course of this study, F.J.K.O'C., S.W.E., E.H., A.L.L., and J.P.O. received a payment from Marathon Pharmaceuticals for intellectual property. The study sponsor has received a payment from UCB Biopharma for intellectual property. D.R. received a grant from the Bonner‐Bender stiftung. F.D.A., M.C.B., A.L.J., C.R.K., M.L., M.T.M., A.M.M., R.W.N., M.N., R.P., B.S., and C.M.V. declare no competing interests. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Publisher Copyright: Wiley Periodicals, Inc. © 2019 International League Against Epilepsy Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/8/16

Y1 - 2019/8/16

N2 - Objective: To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment. Methods: Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD-10). Results: A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi-square 4.3, P =.037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P =.037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi-square 0.35, P =.55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead-time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P =.62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy. Significance: This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.

AB - Objective: To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment. Methods: Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD-10). Results: A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi-square 4.3, P =.037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P =.037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi-square 0.35, P =.55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead-time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P =.62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy. Significance: This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.

KW - etiology

KW - infantile spasms

KW - West syndrome

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U2 - 10.1111/epi.16305

DO - 10.1111/epi.16305

M3 - Article (Academic Journal)

C2 - 31418851

AN - SCOPUS:85070764049

SN - 0013-9580

VL - 60

SP - 1861

EP - 1869

JO - Epilepsia

JF - Epilepsia

IS - 9

ER -

The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS)

Abstract

Bibliographical note

Keywords

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