3.2 Generic Studies in Epilepsy
3.2.4 Malformations of Cortical Development
Diffusion measures evolve with brain maturation so may assist the detection of malformations of cortical development (MCD). Widespread diffusion changes comprising reduced FA and increased MD extending beyond the visible abnormality have been identified in MCD (Eriksson et al. 2001) and in other focal lesions (Dumas de la Roque et al. 2005). In tuberous sclerosis, ADC is elevated in both epileptic and non- epileptic tubers, but more so in the former (Jansen et al. 2003). In focal cortical dysplasia (FCD), fibre connectivity assessed by FA is reduced in subcortical white matter adjacent to the abnormality (Lee et al. 2004b) and is accompanied by a rise in MD although this may not extend to FCD without white matter
Paper Patients/ Controls
Pathology Laterality Analysis Regions Positive findings
Arfanakis et al. 2002
15 / 15 TLE (HS or MRI-negative)
- ROI EC/CC/IC EC/CC (FA, RD)
Concha et al. 2005
8 / 9 MTLE (HS) 6L, 2R Tractography Fornix, cingulum Bilateral fornix (FA, RD), cingulum (FA, MD, RD)
Thivard et al. 2005
35 / 36 MTLE (any) 18L, 17R ROI Hippocampus Contralateral MD
SPM Whole brain Ipsilateral hippocampus, temporal, posterior extratemporal (FA and/or MD); contralateral hippocampus, amygdala, temporal pole (MD) Kimiwada
et al. 2006
14 / 14 (children)
TLE (any) 11L, 3R ROI Hippocampus, thalamus,
lentiform
Bilateral hippocampus (FA), ipsilateral hippocampus (MD)
Gross et al. 2006
11 / 14 MTLE (HS) 7L, 4R ROI Hippocampus, EC/CC/IC EC/CC (FA, MD)
Yu et al. 2006
14 / 14 MTLE (HS or MRI-negative)
5L, 9R ROI Hippocampus Bilateral MD (ipsilateral greater)
Rodrigo et al. 2007
Focke et al. 2008
33 / 37 MTLE (HS) 21L, 12R SPM Whole brain LHS: Ipsilateral TL/FL, bilateral thalamus/cingulate (FA); ipsilateral TL/cingulum, bilateral FL (MD)
RHS: Ipsilateral TL (FA); ipsilateral hippocampus/TL (MD)
TBSS Whole brain LHS: Ipsilateral TL/fornix, bilateral thalamus/cingulate, bilateral FL (FA); ipsilateral TL/thalamus, bilateral cingulum/CC/EC (MD)
RHS: Ipsilateral TL/PHG/fornix, bilateral cingulum/CC (FA); ipsilateral TL/FL, bilateral parietal (MD)
Govindan et al. 2008 13 / 12 (children) TLE (MRI- negative)
All left Tractography UF, ILF, AF, CST Bilaterally in all (FA) - reversed asymmetry of AF
Gong et al. 2008
17 / 26 TLE (HS) 11L, 6R ROI Thalamus Reduced FA, increased MD bilaterally
10 / same TLE (no HS) 4L, 2R, 4 bilateral
No significant differences
Kim et al. 2008
10 / 10 TLE (any) 4L, 6R ROI Corpus callosum Reduced FA/AD, increased RD in splenium
Nilsson et al. 2008
8 / 10 (children)
TLE (any) 7L, 1R Tractography Temporal, cingulate Bilateral changes (MD, AD, RD)
Concha et al. 2009
17 / 25 TLE (HS) - ROI EC/CC EC/CC (FA, MD, RD) (both except MD in CC HS only)
13 / same TLE (MRI- negative)
6L, 2R, 5 bilateral
Tractography Fornix, cingulum, CC Bilateral cingulum (FA, MD, RD; both groups), bilateral fornix (FA, RD; HS only)
Knake et al. 2009
12 / 12 MTLE (HS) All left ROI Hippocampus, PHG, TL,
FL, CC
Ipsilateral hippocampus, PHG, CC (FA)
VBA (unspecified)
Whole brain Bilateral TL, CC, ipsilateral frontal (FA)
Ahmadi et al. 2009
21 / 21 TLE (any) 10L, 11R Tractography Cingulum, PHG, SLF, ILF, UF, fornix, ATR, IFOF
LTLE: reduced ipsilateral (6 tracts) and contralateral (4 tracts) RTLE: reduced ipsilateral (4 tracts)
Shon et al. 2010
19 / 20 TLE (HS) 12L, 7R SPM Whole brain LHS: Ipsilateral hippocampus, TL, FL, cingulate
RHS: Medial temporal/frontoparietal
18 / same TLE (non-HS) 10L, 8R LTLE: Ipsilateral posterior limbic (PHG/cingulate)
RTLE: No changes Bonilha et
al. 2010
23 / 34 MTLE (HS) 8L, 15R NPM Whole brain Medial TL, frontotemporal, orbitofrontal ipsi>contra (FA); FL, TL (MD in RHS)
Kim et al. 2010
9 / 16 TLE (HS) 5L, 4R ROI Thalamus Asymmetrical reduced FA
Bilateral increased MD 9 / same TLE (dysplasia) 5L, 4R Asymmetrical reduced FA Bilateral increased MD Meng et al. 2010 8 / 8 (children)
TLE (any) 6L, 2R ROI CC/EC/IC Bilateral IC/splenium (FA)
Bilateral IC/EC (MD) Kemmotsu
et al. 2011
36 / 36 TLE (any) 18L, 18R ROI (atlas) Fornix, PHG, UF, ILF, IFOF, AF
Bilateral changes (FA), more marked ipsilateral and LTLE (especially UF, ILF)
Afzali et al. 2011
19 / 12 TLE (any) 11L, 8R SPM/TBSS Whole brain TL/PHG/FL/EC/fornix/CC (FA)
Keller et al. 2013
10 / 81 TLE (MRI- negative)
All left SPM Whole brain Bilateral TL/CC/EC/thalamus (FA), CC/thalamus (MD)
Keller et al. 2012
62 / 68 TLE (HS) 41L, 21R ROI TL, FL, CC, IC,
brainstem, hippocampus, PHG, putamen, thalamus
LHS: bilateral hippocampus, PHG, TL, CC, FL, IC, brainstem (FA) RHS: right PHG, bilateral thalamus/CC (FA)
Liacu et al. 2012
9 / 10 TLE (HS) 7L, 2R Tractography Cingulum, fornix Bilateral changes (FA, RD)
9 / same TLE (MRI- negative)
8L, 1R Ipsilateral all (FA), cingulum (RD), no contralateral changes
Oguz et al. 2013
44 / 44 MTLE (HS) 22L, 22R TBSS Whole brain Temporal/extra-temporal especially ipsilateral (FA, MD); FA changes greatest in male/left, MD in female/right
Table 3.1 - Summary of cross sectional DTI studies in epilepsy
Pathology: HS = hippocampal sclerosis; Analysis: ROI = region-of-interest based, SPM = statistical parameter mapping, TBSS = tract-based spatial statistics, VBA = voxel-based analysis; Regions and Tracts: AF = arcuate fasciculus, ATR = anterior thalamic radiation, CC = corpus callosum, CST = corticospinal tract, EC = external capsule, FL = frontal lobe, IC = internal capsule, IFOF = inferior
fronto-occipital fasciculus, ILF = inferior longitudinal fasciculus, PHG = parahippocampal gyrus, SLF = superior longitudinal fasciculus, TL = temporal lobe, UF = uncinate fasciculus; Positive
Paper Patients/ Controls
Pathology Laterality Surgery Timepoints Analysis Regions Positive findings
Concha et al. 2006
3 / 1 Various - Corpus
callosotomy
0w/1w/2-4m Tractography Corpus callosum 1w: decreased FA/AD (axonal degradation) 2-4m: decreased FA, increased MD/RD (myelin degradation) Concha et al. 2007 8 / 22 HS 6L, 2R ATLR (3) or SAH (5) 0y/1y Tractography ROI Fornix, cingulum EC/genu/splenium
0: reduced FA, increased MD/RD bilateral fornix, cingulum, EC
1y: ipsilateral fornix/cingulum reduced FA/increased MD/RD; contralateral fornix, cingulum, EC did not normalise
Thivard et al. 2007
24 / 36 HS 12L, 12R ATLR (20)
or SAH (4)
0m/8m ROI Hippocampus 0: Increased MD ipsilateral, decreased MD
contralateral 8m: contralateral MD normalised Schoene- Bake et al. 2009 40 / 28 HS 19L, 21R ATLR (3) or SAH (37) No pre-op 3-11y
TBSS Whole brain LHS: reduced FA ipsilateral SLF, cingulum, CC, forceps minor, UF, IFOF, ILF, CST, contralateral ILF
RHS: reduced FA ipsilateral SLF, cingulum, CC, UF, ATR, IFOF, ILF, CST, contralateral posterior cingulum
McDonald et al. 2010
7 / none TLE 3L, 4R ATLR 0m/2m/12m ROI (atlas) Fornix, UF, PHC,
ATR, SLF, IFOF, ILF, CST, cingulum
2m: decreased FA ipsilateral ILF, PHC, UF, IFOF, CC, bilateral fornix
12m: no further change Yogarajah
et al. 2010
46 / none TLE 26L, 20R ATLR 0m/4m TBSS Whole brain LHS: reduced FA ipsilateral OR, PHG, SLF,
UF; bilateral ILF, fornix, AC; increased FA corona radiata, IC, EC; increased MD ipsilateral ILF, UF, AC, EC
RHS: reduced FA ipsilateral OR, PHG, SLF, UF, IFOF; bilateral ILF, fornix, AC; increased FA corona radiata; increased MD ipsilateral UF, AC, EC, bilateral fornix
Nguyen et al. 2011 22 / none (only 10 in post-op) HS 11L, 11R ATLR 0m/2-7m TBSS (left flipped)
Whole brain 0: reduced FA ipsilateral HIP/fornix/UF/CC, widespread increased MD
2-7m: increased MD ipsilateral anterior temporal
Faber et al. 2013
20 / none HS All left SAH 0m/3-
6m/12m
TBSS Whole brain 3-6m: reduced FA left cingulum, fornix 12m: in addition, reduced FA UF Liu et al. 2013 6 / 3 TLE 3L, 3R ATLR (4) or SAH (2) Many e.g. 0, 1/2/3/6d, 2m
Tractography Fornix Ipsilateral MD/AD/RD reduced by 2 days FA reduced/MD/RD rises by 1-4m
Table 3.2 - Summary of longitudinal DTI studies in epilepsy
Pathology and Analysis: as Table 3.1; Surgery: ATLR = anterior temporal lobe resection, SAH = selective amygdalohippocampectomy; Region and Tracts: AC = anterior commissure, ATR = anterior
The reduced FA could be a result of increased or abnormally located grey matter or pathological white matter with abnormal myelination or ectopic neurons whilst the increase in MD could reflect defective neurogenesis or cellular loss increasing the extracellular space (Eriksson et al. 2001). Improved diffusion models to study the extracellular volume could help disentangle these possibilities (Chapter 13).