title: Structural and physiological MRI correlates of occult cerebrovascular disease in late-onset epilepsy.
abstract: Late-onset epilepsy (LOE), with onset after 50 years of age, is often attributed to underlying occult cerebrovascular disease. LOE is associated with a three-fold increase in subsequent stroke risk, therefore it is important to improve our understanding of pathophysiology. In this exploratory study, we aimed to determine whether established structural magnetic resonance imaging markers and novel physiological imaging markers of occult cerebrovascular disease were more common in patients with LOE than age-matched controls. Sixteen patients with LOE (mean age ± SD: 67.6 ± 6.5 years) and 15 age-matched control subjects (mean age: 65.1 ± 3.9 years) underwent a 3 T MRI scan protocol. T1-weighted images and T2-weighted fluid attenuated inversion recovery (FLAIR) images were used to determine cortical grey matter volume and white matter hyperintensity (WMH) volume respectively, whilst multiple delay time arterial spin labelling (ASL) images were collected at rest and during a hypercapnic challenge. Cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from ASL data under both normocapnic and hypercapnic conditions. Cerebrovascular reactivity was also calculated for both CBF and AAT relative to the change in end-tidal CO2. Patients with LOE were found to have significantly lower cortical volume than control subjects (33.8 ± 3.8% of intracranial volume vs. 38.0 ± 5.5%, p = 0.02) and significantly higher WMH volume (1339 ± 1408 mm3 vs. 514 ± 481 mm3, p = 0.047). Baseline whole brain AAT was found to be significantly prolonged in patients with LOE in comparison to control subjects (1539 ± 129 ms vs. 1363 ± 167 ms, p = 0.005). Voxel-based analysis showed the significant prolongation of AAT to be predominantly distributed in the frontal and temporal lobes. Voxel-based morphometry showed the lower cortical volume to be localised primarily to temporal lobes. No significant differences in CBF or cerebrovascular reactivity were found between the two groups. Baseline whole brain AAT and cortical volume differences persisted upon further analysis to take account of differences in smoking history between patients and control subjects. These findings suggest that occult cerebrovascular disease is relevant to the pathophysiology of LOE.
authors.affiliation: Centre for Imaging Science, Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK ; Department of Neurology, Royal Preston Hospital, Preston, UK.
authors.forename: Martha F
authors.initials: MF
authors.lastname: Hanby
authors.affiliation: Centre for Imaging Science, Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Al-Bachari
authors.affiliation: Centre for Imaging Science, Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Fadiyah
authors.initials: F
authors.lastname: Makin
authors.affiliation: Centre for Imaging Science, Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Rishma
authors.initials: R
authors.lastname: Vidyasagar
authors.affiliation: Centre for Imaging Science, Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Parkes
authors.affiliation: Department of Neurology, Royal Preston Hospital, Preston, UK ; Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Hedley C A
authors.initials: HC
authors.lastname: Emsley
mesh_terms: D000368:Aged; D001921:Brain / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D004827:Epilepsy / Q000150:complications*; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology
keywords: AAT, arterial arrival time; ASL, arterial spin labelling; Arterial spin labelling; CBF, cerebral blood flow; CT, computerised tomography; CVD, cerebrovascular disease; CVR, cerebrovascular reactivity; Cerebral blood flow; Cerebrovascular disease; EEG, electroencephalogram; ETCO2, end-tidal CO2; FLAIR, fluid attenuated inversion recovery image; FWHM, full width half maximum; GM, grey matter; ICV, intracranial volume; LOE, late-onset epilepsy; Late-onset epilepsy; MRI, magnetic resonance imaging; MoCA, Montreal cognitive assessment; SVD, small vessel disease; Seizures; VBA, voxel-based analysis; VBM, voxel-based morphometry.; Voxel-based morphometry; WMH, white matter hyperintensity; oCVD, occult cerebrovascular disease