Article Navigation
- < Previous
- Next >
Journal Article
Get access
, Emma Macdonald-Laurs Department of Neurology, The Royal Children’s Hospital , Parkville, Victoria 3052 Australia Department of Neuroscience, Murdoch Children’s Research Institute , Parkville 3052 , Australia Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Correspondence to: Emma Macdonald-Laurs Department of Neurology, The Royal Children’s Hospital 50 Flemington Road, Parkville, 3052, Australia E-mail: emma.macdonald-laurs@rch.org.au Search for other works by this author on: Oxford Academic Aaron E L Warren Department of Neuroscience, Murdoch Children’s Research Institute , Parkville 3052 , Australia Department of Medicine (Austin Health), The University of Melbourne , Heidelberg 3084 , Australia Search for other works by this author on: Oxford Academic Peter Francis Department of Medical Imaging, The Royal Children’s Hospital , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic Simone A Mandelstam Department of Neuroscience, Murdoch Children’s Research Institute , Parkville 3052 , Australia Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Department of Medical Imaging, The Royal Children’s Hospital , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic Wei Shern Lee Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Department of Genomic Medicine, Bruce Lefroy Centre, Murdoch Children’s Research Institute , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic Matthew Coleman Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Department of Genomic Medicine, Bruce Lefroy Centre, Murdoch Children’s Research Institute , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic Sarah E M Stephenson Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Department of Genomic Medicine, Bruce Lefroy Centre, Murdoch Children’s Research Institute , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic Sarah Barton Department of Neurology, The Royal Children’s Hospital , Parkville, Victoria 3052 Australia Department of Neuroscience, Murdoch Children’s Research Institute , Parkville 3052 , Australia Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic Colleen D’Arcy Department of Pathology, The Royal Children’s Hospital , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic Paul J Lockhart Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Department of Genomic Medicine, Bruce Lefroy Centre, Murdoch Children’s Research Institute , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic
https://orcid.org/0000-0002-9894-4610 , Richard J Leventer Department of Neurology, The Royal Children’s Hospital , Parkville, Victoria 3052 Australia Department of Neuroscience, Murdoch Children’s Research Institute , Parkville 3052 , Australia Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic A Simon Harvey Department of Neurology, The Royal Children’s Hospital , Parkville, Victoria 3052 Australia Department of Neuroscience, Murdoch Children’s Research Institute , Parkville 3052 , Australia Department of Paediatrics, The University of Melbourne , Parkville 3052 , Australia Search for other works by this author on: Oxford Academic
Brain, Volume 147, Issue 4, April 2024, Pages 1264–1277, https://doi.org/10.1093/brain/awad379
Published:
06 November 2023
Article history
Received:
30 June 2023
Revision received:
20 September 2023
Accepted:
22 October 2023
Published:
06 November 2023
Corrected and typeset:
12 March 2024
- Views
- Article contents
- Figures & tables
- Video
- Audio
- Supplementary Data
-
Cite
Cite
Emma Macdonald-Laurs, Aaron E L Warren, Peter Francis, Simone A Mandelstam, Wei Shern Lee, Matthew Coleman, Sarah E M Stephenson, Sarah Barton, Colleen D’Arcy, Paul J Lockhart, Richard J Leventer, A Simon Harvey, The clinical, imaging, pathological and genetic landscape of bottom-of-sulcus dysplasia, Brain, Volume 147, Issue 4, April 2024, Pages 1264–1277, https://doi.org/10.1093/brain/awad379
Close
Search
Close
Search
Advanced Search
Search Menu
Abstract
Bottom-of-sulcus dysplasia (BOSD) is increasingly recognized as a cause of drug-resistant, surgically-remediable, focal epilepsy, often in seemingly MRI-negative patients. We describe the clinical manifestations, morphological features, localization patterns and genetics of BOSD, with the aims of improving management and understanding pathogenesis.
We studied 85 patients with BOSD diagnosed between 2005–2022. Presenting seizure and EEG characteristics, clinical course, genetic findings and treatment response were obtained from medical records. MRI (3 T) and 18F-FDG-PET scans were reviewed systematically for BOSD morphology and metabolism. Histopathological analysis and tissue genetic testing were performed in 64 operated patients. BOSD locations were transposed to common imaging space to study anatomical location, functional network localization and relationship to normal MTOR gene expression.
All patients presented with stereotyped focal seizures with rapidly escalating frequency, prompting hospitalization in 48%. Despite 42% patients having seizure remissions, usually with sodium channel blocking medications, most eventually became drug-resistant and underwent surgery (86% seizure-free). Prior developmental delay was uncommon but intellectual, language and executive dysfunction were present in 24%, 48% and 29% when assessed preoperatively, low intellect being associated with greater epilepsy duration.
BOSDs were missed on initial MRI in 68%, being ultimately recognized following repeat MRI, 18F-FDG-PET or image postprocessing. MRI features were grey-white junction blurring (100%), cortical thickening (91%), transmantle band (62%), increased cortical T1 signal (46%) and increased subcortical FLAIR signal (26%). BOSD hypometabolism was present on 18F-FDG-PET in 99%. Additional areas of cortical malformation or grey matter heterotopia were present in eight patients. BOSDs predominated in frontal and pericentral cortex and related functional networks, mostly sparing temporal and occipital cortex, and limbic and visual networks.
Genetic testing yielded pathogenic mTOR pathway variants in 63% patients, including somatic MTOR variants in 47% operated patients and germline DEPDC5 or NPRL3 variants in 73% patients with familial focal epilepsy. BOSDs tended to occur in regions where the healthy brain normally shows lower MTOR expression, suggesting these regions may be more vulnerable to upregulation of MTOR activity.
Consistent with the existing literature, these results highlight (i) clinical features raising suspicion of BOSD; (ii) the role of somatic and germline mTOR pathway variants in patients with sporadic and familial focal epilepsy associated with BOSD; and (iii) the role of 18F-FDG-PET alongside high-field MRI in detecting subtle BOSD. The anatomical and functional distribution of BOSDs likely explain their seizure, EEG and cognitive manifestations and may relate to relative MTOR expression.
focal cortical dysplasia, MRI-negative, epilepsy surgery, mechanistic target of rapamycin
© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)
Issue Section:
Original Article
You do not currently have access to this article.
Download all slides
Sign in
Get help with access
Personal account
- Sign in with email/username & password
- Get email alerts
- Save searches
- Purchase content
- Activate your purchase/trial code
Sign in Register
Institutional access
- Sign in through your institution
- Sign in with a library card Sign in with username/password Recommend to your librarian
Institutional account management
Sign in as administrator
Get help with access
Institutional access
Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:
IP based access
Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.
Sign in through your institution
Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution’s website and Oxford Academic.
- Click Sign in through your institution.
- Select your institution from the list provided, which will take you to your institution's website to sign in.
- When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If your institution is not listed or you cannot sign in to your institution’s website, please contact your librarian or administrator.
Sign in with a library card
Enter your library card number to sign in. If you cannot sign in, please contact your librarian.
Society Members
Society member access to a journal is achieved in one of the following ways:
Sign in through society site
Many societies offer single sign-on between the society website and Oxford Academic. If you see ‘Sign in through society site’ in the sign in pane within a journal:
- Click Sign in through society site.
- When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If you do not have a society account or have forgotten your username or password, please contact your society.
Sign in using a personal account
Some societies use Oxford Academic personal accounts to provide access to their members. See below.
Personal account
A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.
Some societies use Oxford Academic personal accounts to provide access to their members.
Viewing your signed in accounts
Click the account icon in the top right to:
- View your signed in personal account and access account management features.
- View the institutional accounts that are providing access.
Signed in but can't access content
Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.
Institutional account management
For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.
Purchase
Subscription prices and ordering for this journal
Purchasing options for books and journals across Oxford Academic
Short-term Access
To purchase short-term access, please sign in to your personal account above.
Don't already have a personal account? Register
The clinical, imaging, pathological and genetic landscape of bottom-of-sulcus dysplasia - 24 Hours access
EUR €51.00
GBP £44.00
USD $55.00
Rental
This article is also available for rental through DeepDyve.
Advertisem*nt
Citations
Views
533
Altmetric
More metrics information
Email alerts
Article activity alert
Advance article alerts
New issue alert
Subject alert
Receive exclusive offers and updates from Oxford Academic
Citing articles via
Google Scholar
-
Latest
-
Most Read
-
Most Cited
More from Oxford Academic
Medicine and Health
Neurology
Neuroscience
Science and Mathematics
Books
Journals
Baltimore, Maryland
Brockville, Ontario
, Vermont
Advertisem*nt
