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January 22, 2019; 92 (4) Article

Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients

Saud Alhusaini, Magdalena A. Kowalczyk, Clarissa L. Yasuda, Mira K. Semmelroch, Marilise Katsurayama, Matheus Zabin, Tamires Zanão, Mateus H. Nogueira, Marina K.M. Alvim, Victória R. Ferraz, Meng-Han Tsai, Mary Fitzsimons, Iscia Lopes-Cendes, Colin P. Doherty, Gianpiero L. Cavalleri, Fernando Cendes, Graeme D. Jackson, Norman Delanty
First published December 26, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006834
Saud Alhusaini
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Magdalena A. Kowalczyk
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Clarissa L. Yasuda
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Mira K. Semmelroch
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Marilise Katsurayama
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Matheus Zabin
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Tamires Zanão
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Mateus H. Nogueira
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Marina K.M. Alvim
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Victória R. Ferraz
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Meng-Han Tsai
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Mary Fitzsimons
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Iscia Lopes-Cendes
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Colin P. Doherty
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Gianpiero L. Cavalleri
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Fernando Cendes
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Graeme D. Jackson
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Norman Delanty
From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.
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Citation
Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients
Saud Alhusaini, Magdalena A. Kowalczyk, Clarissa L. Yasuda, Mira K. Semmelroch, Marilise Katsurayama, Matheus Zabin, Tamires Zanão, Mateus H. Nogueira, Marina K.M. Alvim, Victória R. Ferraz, Meng-Han Tsai, Mary Fitzsimons, Iscia Lopes-Cendes, Colin P. Doherty, Gianpiero L. Cavalleri, Fernando Cendes, Graeme D. Jackson, Norman Delanty
Neurology Jan 2019, 92 (4) e351-e358; DOI: 10.1212/WNL.0000000000006834

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Abstract

Objective To examine cerebral cortex thickness in asymptomatic first-degree relatives of patients with mesial temporal lobe epilepsy (MTLE).

Methods We investigated 127 asymptomatic first-degree relatives of patients with MTLE due to hippocampal sclerosis (HS) (mean age ± SD = 39.4 ± 13 years) and 203 healthy control individuals (mean age ± SD = 36.0 ± 11 years). Participants underwent a comprehensive clinical evaluation and structural brain MRI at 3 study sites. Images were processed simultaneously at each site using a surface-based morphometry method to quantify global brain measures, hippocampal volumes, and cerebral cortical thickness. Differences in brain measures between relatives of patients and controls were examined using generalized models, while controlling for relevant covariates, including age and sex.

Results None of the asymptomatic first-degree relatives of MTLE + HS patients showed evidence of HS on qualitative image assessments. Compared to the healthy controls, the asymptomatic relatives of patients displayed no significant differences in intracranial volume, average hemispheric surface area, or hippocampal volume. Similarly, no significant cerebral cortical thinning was identified in the relatives of patients. This was consistent across the 3 cohorts.

Conclusion Lack of cortical thickness changes in the asymptomatic relatives of patients indicates that the previously characterized MTLE + HS-related cortical thinning is not heritable, and is likely driven by disease-related factors. This finding therefore argues for early and aggressive intervention in patients with medically intractable epilepsy.

Glossary

FS=
febrile seizures;
GLM=
generalized linear model;
HS=
hippocampal sclerosis;
ICV=
intracranial volume;
MTLE=
mesial temporal lobe epilepsy;
TE=
echo time;
TI=
inversion time;
TR=
repetition time

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received February 6, 2018.
  • Accepted in final form September 20, 2018.
  • © 2018 American Academy of Neurology
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