Imaging in epilepsy has two missions: (1) identify a structural cause (lesion-driven) and (2) localize the seizure focus when MRI is non-lesional, using advanced techniques. The single highest-yield finding is mesial temporal sclerosis (MTS); the most missed are focal cortical dysplasia (FCD), bottom-of-sulcus dysplasia, and small DNETs / gangliogliomas. A dedicated epilepsy MRI protocol (HARNESS-MRI) on 3T transforms the yield.

The Epilepsy MRI Protocol (HARNESS-MRI)

• 3T strongly preferred over 1.5T (catches more FCDs).
• 3D T1 MPRAGE: 1 mm isotropic; volumetric for hippocampal symmetry assessment + cortical morphology.
• 3D FLAIR: 1 mm isotropic; sensitive to FCD signal abnormality.
• High-resolution coronal T2 + FLAIR perpendicular to hippocampal long axis: 3 mm thin slices through the temporal lobe; essential for MTS detection.
• SWI: cavernoma, microbleeds.
• DWI: peri-ictal abnormalities, encephalitis, abscess.
• Post-contrast T1: tumors, abscess, neurocysticercosis.
• Optional: DTI (presurgical planning), MEG, fMRI (language / memory mapping).

Mesial Temporal Sclerosis (MTS)

Classical Findings

• Hippocampal atrophy: volume loss on coronal slices; compare to contralateral.
• T2 / FLAIR hyperintensity within hippocampus.
• Loss of internal architecture: blurring of the digitations (interdigitating gray-white pattern) on high-resolution coronal T2.
• Atrophy of ipsilateral mammillary body + fornix: secondary to hippocampal injury.
• Dilated temporal horn: ex-vacuo from hippocampal volume loss.
• FDG-PET: interictal temporal hypometabolism on the affected side.

Dual Pathology

• MTS + a second lesion (FCD, ganglioglioma, polymicrogyria) — affects surgical planning significantly.
• Search the rest of the temporal + adjacent neocortex carefully when MTS is found.

Focal Cortical Dysplasia (FCD)

Classification (Blümcke ILAE 2011)

• Type I: subtle architectural disorganization; commonly extratemporal; difficult to see on MRI.
• Type IIA: dysmorphic neurons without balloon cells.
• Type IIB: dysmorphic neurons + balloon cells; classically demonstrates transmantle sign (T2/FLAIR hyperintense band extending from cortex toward ventricle).
• Type III: FCD associated with another lesion (Type IIIa with MTS; IIIb with tumor; IIIc with vascular; IIId with other).

Classical MRI Findings

• Cortical thickening.
• Blurring of gray-white junction.
• T2 / FLAIR hyperintensity within cortex / subcortical white matter.
• Transmantle sign (FCD IIB): funnel-shaped or band-like FLAIR hyperintensity radiating from cortex to ventricle.
• Abnormal gyral / sulcal pattern.
• Often non-lesional on standard MRI: 7T / higher-resolution / morphometric maps (cortical thickness, gradient, extension) increase yield.

Other Structural Substrates

Ganglioglioma

• Cortical-based, temporal lobe predominantly.
• Solid + cystic + calcification often.
• Variable enhancement.
• Slow-growing; typically benign; epileptogenic.

Dysembryoplastic Neuroepithelial Tumor (DNET)

• Cortical-based, often temporal.
• “Bubbly” multicystic appearance on T2.
• Minimal mass effect.
• Usually non-enhancing.
• Benign, indolent.

Polymicrogyria

• Excessive small folds in cortex → bumpy / “lumpy” cortical surface.
• Perisylvian most common location.
• Bilateral perisylvian polymicrogyria → opercular syndrome with epilepsy.

Subcortical Band Heterotopia / “Double Cortex”

• Layer of gray matter (heterotopic neurons) deep to normal cortex, separated by thin white matter band.
• X-linked (DCX) in females; LIS1 in lissencephaly.

Periventricular Nodular Heterotopia

• Nodules of gray matter signal abutting ventricles.
• X-linked (FLNA) — females; males usually lethal in utero.
• Cardiac valve disease, intestinal pseudo-obstruction in some.

Schizencephaly

• Full-thickness gray-matter-lined cleft from cortex to ventricle.
• Open-lip (separated walls) vs closed-lip (apposed walls).
• Associated with epilepsy + motor / cognitive deficits.

Tuberous Sclerosis (TSC)

• Cortical / subcortical tubers: T2/FLAIR hyperintense; non-enhancing.
• Subependymal nodules: along lateral ventricle walls; often calcified; enhance.
• Subependymal giant cell astrocytoma (SEGA): at foramen of Monro; enhancing; can obstruct CSF flow.
• Radial migration lines: linear T2/FLAIR hyperintensity from subependymal to cortex.
• White matter heterotopia.

Lissencephaly / Agyria

• Smooth or simplified cortex with thickened gyri (“smooth brain”).
• Inverted four-layer cortical pattern.
• Severe epilepsy + intellectual disability.
• Causes: LIS1, DCX, TUBA1A, RELN, etc.

Hemimegalencephaly

• Enlargement of one hemisphere with dysplastic cortex.
• Severe early-onset epilepsy.
• Hemispherectomy often required.

Rasmussen Encephalitis

• Progressive unilateral hemispheric atrophy.
• Refractory focal epilepsy + hemiparesis.
• Hemispherectomy in selected cases.

Sturge-Weber Syndrome

• Cortical / leptomeningeal angiomatosis.
• Hemispheric atrophy + tram-track calcifications on CT (gyriform cortical calcification).
• Pial enhancement + enlarged choroid plexus on post-contrast.
• Ipsilateral facial port-wine birthmark (V1).
• Genetics: somatic GNAQ R183Q in affected tissue (see Genetics page).

Cavernoma

• Popcorn appearance on MRI with complete dark hemosiderin rim.
• Multifocal → familial form (KRIT1, CCM2, PDCD10).
• Symptomatic with seizures from cortical lesions; surgical excision curative for epilepsy.

AVM

• Tangle of vessels with early venous drainage on CTA/DSA.
• SWI shows flow voids + adjacent hemosiderin.
• Can present with seizure or hemorrhage.

Neurocysticercosis (Common Cause Worldwide)

• Vesicular stage: thin-walled cyst with scolex inside (dot).
• Colloidal stage: enhancing wall + perilesional edema.
• Granular nodular stage: small enhancing nodule.
• Calcified stage: small calcification on CT/SWI.
• Multiple lesions of different stages classical.

Tumor + Epilepsy

• Low-grade glioma, ganglioglioma, DNET, oligodendroglioma — most epileptogenic.
• High-grade glioma + metastasis can also present with seizure.

Peri-Ictal Imaging

• Cortical T2/FLAIR hyperintensity + DWI restriction on the side of seizure focus.
• Ipsilateral thalamic involvement (especially pulvinar).
• Hippocampal swelling and signal change.
• Splenium of corpus callosum: cytotoxic lesion (MERS-like).
• Gyriform enhancement can appear (laminar necrosis pattern).
• Most peri-ictal changes resolve over days to weeks.

When MRI Is Non-Lesional (Localization Tools)

• 3T → 7T MRI: 7T detects more FCDs.
• Morphometric analysis: cortical thickness, gradient, extension maps highlight subtle FCD.
• Interictal FDG-PET: hypometabolism at seizure focus.
• Ictal SPECT (HMPAO injected during seizure) + SISCOM: subtraction of interictal from ictal scan, registered to MRI; highly specific.
• MEG: magnetic dipole localization of interictal spikes.
• EEG-fMRI: simultaneous EEG + BOLD; investigative.
• Intracranial EEG: stereotactic EEG (SEEG) or subdural grids — definitive.

Presurgical Planning

• Wada test: intracarotid amobarbital; lateralizes language and memory; being replaced by fMRI + intracranial EEG in many centers.
• fMRI: language lateralization (Broca, Wernicke), motor mapping.
• DTI / tractography: Meyer’s loop (visual radiations) preservation in anterior temporal lobectomy.
• Cortical stimulation mapping: intraoperative or via intracranial electrodes; gold standard for eloquent cortex.

Pitfalls and Pearls

• Always read coronal hippocampal slices on epilepsy MRI — MTS lives here.
• FCD IIB transmantle sign: linear FLAIR hyperintensity from cortex to ventricle — pathognomonic.
• “Bumpy cortex”: polymicrogyria. Don’t miss bilateral perisylvian pattern.
• Heterotopia signal matches gray matter on all sequences — distinguishes from gliosis.
• Hippocampal symmetry matters; mild asymmetry can be normal — use volumetric quantification when uncertain.
• Dual pathology: search beyond the first lesion when MTS is found.
• Peri-ictal MRI can mimic stroke (DWI restriction + cortical FLAIR) — clinical and EEG correlation essential.
• 3T is markedly better than 1.5T for FCD detection.
• Non-lesional MRI does not mean no lesion — escalate to higher-resolution + advanced techniques.
• HARNESS-MRI protocol standardizes the workup — ensure your facility offers it for any refractory focal epilepsy.
• Wada test is being replaced in many centers by fMRI + intracranial mapping.
• Don’t miss cavernoma on SWI — single most surgically curable epileptogenic lesion.

References

1. Bernasconi A, Cendes F, Theodore WH, et al. Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: a consensus report from the International League Against Epilepsy. Epilepsia. 2019;60(6):1054-1068.
2. Blümcke I, Thom M, Aronica E, et al. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of the ILAE Diagnostic Methods Commission. Epilepsia. 2011;52(1):158-174.
3. Cendes F. Mesial temporal lobe epilepsy syndrome: an updated overview. J Epilepsy Clin Neurophysiol. 2005;11(3):141-144.
4. Wagner J, Weber B, Urbach H, et al. Morphometric MRI analysis improves detection of focal cortical dysplasia type II. Brain. 2011;134(10):2844-2854.
5. Knowlton RC. The role of FDG-PET, ictal SPECT, and MEG in the epilepsy surgery evaluation. Epilepsy Behav. 2006;8(1):91-101.