Microangiopathy in temporal lobe epilepsy with diffusion MRI alterations and cognitive decline
Joan Liu1,2, Lawrence Binding1,3, Isha Puntambekar1
1Department of Clinical and Experimental Epilepsy, Department of Neuropathology, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Abstract:
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.
Insights
Temporal lobe epilepsy (TLE) involves white matter microvascular damage, including arteriolosclerosis and reduced vessel size, potentially causing cognitive decline. These changes correlate with MRI findings and epilepsy duration.
Area of Science:
- Neurology
- Neuroscience
- Pathology
Background:
- White matter microvascular alterations in temporal lobe epilepsy (TLE) may contribute to neurodegeneration and cognitive impairment.
- Understanding these changes is crucial for managing TLE-associated cognitive decline.
Purpose of the Study:
- To quantify microvascular changes, myelin, axonal, glial, and extracellular-matrix alterations in TLE white matter.
- To correlate these pathological findings with in vivo MRI diffusion measurements and cognitive function.
Main Methods:
- Analysis of surgical resections from 44 TLE patients and controls.
- Quantification of microvascular markers (collagen-4, PDGF-Rβ, SMA), myelin (MAG, PLP), and glial cells (Olig2, Iba1).
- Comparison with pre-operative MRI diffusion data and neuropsychological assessments.
Main Results:
- TLE showed increased arteriolosclerosis, reduced mean vascular size, and increased pericyte coverage compared to controls.
- Reduced myelin and increased glial numbers were observed, particularly in deep white matter.
- Microvascular changes correlated with MRI diffusivity, white matter abnormalities, and cognitive decline, especially increased perivascular space.
Conclusions:
- Acquired microangiopathic changes, including vascular sclerosis and altered small vessel function, are present in TLE.
- These pathological findings correlate with white matter diffusion MRI alterations.
- The observed microvascular changes may underlie cognitive decline in TLE patients.
