Microangiopathy in temporal lobe epilepsy with diffusion MRI alterations and cognitive decline.


Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
08 Oct 2024
Historique:
received: 01 08 2024
accepted: 28 09 2024
revised: 23 09 2024
medline: 8 10 2024
pubmed: 8 10 2024
entrez: 8 10 2024
Statut: epublish

Résumé

White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05-0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorβ and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE.

Identifiants

pubmed: 39377933
doi: 10.1007/s00401-024-02809-8
pii: 10.1007/s00401-024-02809-8
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

49

Subventions

Organisme : Wellcome Trust
ID : 221934/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221934/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221934/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221934/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221934/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221934/Z/20/Z
Pays : United Kingdom

Informations de copyright

© 2024. The Author(s).

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Auteurs

Joan Liu (J)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Department of Neuroscience, University of Westminster, London, UK.

Lawrence Binding (L)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Centre for Medical Image Computing, Department of Computer Science, UCL, London, UK.

Isha Puntambekar (I)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Smriti Patodia (S)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Yau Mun Lim (YM)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Alicja Mryzyglod (A)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Fenglai Xiao (F)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Shengning Pan (S)

Department of Statistical Science, University College London, Gower St., London, UK.

Remika Mito (R)

Department of Neuroscience and Mental Health, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia.

Jane de Tisi (J)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

John S Duncan (JS)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Sallie Baxendale (S)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Matthias Koepp (M)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

Maria Thom (M)

Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK. M.Thom@ucl.ac.uk.

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