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May 2, 2012

Altered microstructural connectivity in juvenile myoclonic epilepsy
The missing link

C. Vollmar, MD, J. O'Muircheartaigh, PhD, M.R Symms, PhD, G.J. Barker, PhD, P. Thompson, PhD, V. Kumari, PhD, J. Stretton, MSc, J.S. Duncan, FMedSci, FRCP, M.P. Richardson, FRCP, PhD, and M.J. Koepp, MD, PhDAuthors Info & Affiliations
May 15, 2012 issue
78 (20) 1555-1559
https://doi.org/10.1212/WNL.0b013e3182563b44
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Abstract

Objectives:

Juvenile myoclonic epilepsy (JME) is characterized by myoclonic jerks of the upper limbs, often triggered by cognitive stressors. Here we aim to reconcile this particular seizure phenotype with the known frontal lobe type neuropsychological profile, photosensitivity, hyperexcitable motor cortex, and recent advanced imaging studies that identified abnormal functional connectivity of the motor cortex and supplementary motor area (SMA).

Methods:

We acquired fMRI and diffusion tensor imaging (DTI) in a cohort of 29 patients with JME and 28 healthy control subjects. We used fMRI to determine functional connectivity and DTI-based region parcellation and voxel-wise comparison of probabilistic tractography data to assess the structural connectivity profiles of the mesial frontal lobe.

Results:

Patients with JME showed alterations of mesial frontal connectivity with increased structural connectivity between the prefrontal cognitive cortex and motor cortex. We found a positive correlation between DTI and fMRI-based measures of structural and functional connectivity: the greater the structural connectivity between these 2 regions, the greater the observed functional connectivity of corresponding areas. Furthermore, connectivity was reduced between prefrontal and frontopolar regions and increased between the occipital cortex and the SMA.

Conclusion:

The observed alterations in microstructural connectivity of the mesial frontal region may represent the anatomic basis for cognitive triggering of motor seizures in JME. Changes in the mesial frontal connectivity profile provide an explanatory framework for several other clinical observations in JME and may be the link between seizure semiology, neurophysiology, neuropsychology, and imaging findings in JME.

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Information & Authors

Information

Published In

Neurology®
Volume 78 • Number 20 • May 15, 2012
Pages: 1555-1559
PubMed: 22551729

Copyright

Copyright © 2012 by AAN Enterprises, Inc.

Publication History

Received: August 15, 2011
Accepted: January 17, 2012
Published online: May 2, 2012
Published in issue: May 15, 2012

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Disclosure

Dr. Vollmar, Dr. O'Muircheartaigh, and Dr. Symms report no disclosures. Prof. Barker received honoraria for teaching for and serving on scientific advisory boards of General Electric Healthcare. Dr. Thompson, Prof. Kumari, and J. Stretton report no disclosures. Prof. Duncan serves on scientific advisory boards for and/or has received funding for travel from GE Healthcare. Prof. Richardson reports no disclosures. Prof. Koepp served on a scientific advisory board of GE. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

C. Vollmar, MD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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J. O'Muircheartaigh, PhD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
M.R Symms, PhD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
G.J. Barker, PhD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
GE Healthcare
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
GE Healthcare
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
National Institute for Health Research, unknown, co-investigator, April 2011 for 5 years; European Commission, unknown, co-investigator, Sept 2010 for 5 years; National Institute for Health Research, PB-PG-0807-14152, co-investigator, Jun 2010 for 3 years; Medical Research Council, G0701310, Supervisor for Clinical Training Fellowship, Aug 2008 for 3 years
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Epilepsy Research UK; Wellcome Trust, 091300/Z/10/Z; Guy’s and St Thomas’ Charity, R090767; Epilepsy Research UK; The Wellcome Trust, 079474; Baily Thomas Charitable Fund
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
P. Thompson, PhD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Seizure, Editorial Board, 10 years
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
V. Kumari, PhD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
J. Stretton, MSc
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
J.S. Duncan, FMedSci, FRCP
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
GE Healthcare, 2008; Eisai, 2011; Sanofi- Aventis, 2008; UCB, 2011
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
UCB, 2011
Editorial Boards:
1.
Seizure, 2002-present
Patents:
1.
A miniaturized wearable apnea detector
Publishing Royalties:
1.
Eyelid myoclonia and typical absences. Libbey, 1995
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Cyberonics, 2010-11; UCB, 2009, 2010, 2011; GSK, 2010, 2011; Eisai 2010, 2011
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
I have an active practice in epilepsy surgery
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Wellcome Trust, Programme Grant;
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
M.P. Richardson, FRCP, PhD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Neurology Neurosurgery and Psychiatry, editorial board, 2011-present; Epilepsy Research, guest editor, 2011
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
M.J. Koepp, MD, PhD
From the Department of Clinical and Experimental Epilepsy (C.V., M.R.S., P.T., J.S., J.S.D.), UCL Institute of Neurology, London, UK; Department of Neurology, Epilepsy Center (C.V.), University of Munich, Munich, Germany; and Departments of Neuroimaging (J.O., G.J.B.), Psychology (V.K.), and Clinical Neurosciences (M.P.R.), Institute of Psychiatr, King's College London, London, UK.
Disclosure
Scientific Advisory Boards:
1.
GE, scientific advisory board
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Honoraria from UCB, EISAI and BIAL (Portugal; funding for travel from UCB, Pfizer and Desitin
Editorial Boards:
1.
Epilepsy Research, Editorial Board
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
MRC, EU-Framework 7 programme
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Wellcome Trust Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
Shares in GSK
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author

Notes

Study funding: Supported by the Wellcome Trust (project grant 079474), the Big Lottery Fund, the Wolfson Trust, and the Epilepsy Society. Infrastructure support was provided by the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London. Part of this work was undertaken at University College London Hospitals, which received a proportion of funding from the NIHR, Biomedical Research Centres funding scheme.
Correspondence & reprint requests to Prof. Koepp: [email protected].

Author Contributions

Dr. Vollmar: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis. Dr. O'Muircheartaigh: drafting/revising the manuscript. Dr. Symms: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, contribution of vital reagents/tools, study supervision, obtaining funding. Prof. Baker: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, study supervision. Dr. Thompson: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, study supervision. Prof. Kumari: drafting/revising the manuscript, study concept or design, obtaining funding. J. Stretton: study concept or design, acquisition of data. Prof. Duncan: drafting/revising the manuscript, analysis or interpretation of data, study supervision, obtaining funding. Prof. Richardson: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, study supervision, obtaining funding. Prof. Koepp: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis, study supervision, obtaining funding.

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