MRI in Epilepsy: Protocols & Lesions

Structural MRI is the preferred nonurgent imaging modality for patients with new-onset seizures and epilepsy because of its superior soft tissue resolution compared with CT. Neuroimaging plays a critical role in the evaluation of epilepsy: it can identify the underlying etiology, classify the epilepsy syndrome, predict treatment response, and determine candidacy for epilepsy surgery. The International League Against Epilepsy (ILAE) has recommended standardized MRI protocols — the Harmonized Neuroimaging of Epilepsy Structural Sequences (HARNESS) — to maximize diagnostic yield. Understanding the imaging characteristics of common epileptogenic lesions is essential for neurologists, as the presence and type of MRI lesion profoundly influence prognosis and surgical outcomes. Patients with hippocampal sclerosis and malformations of cortical development have the lowest rates of seizure freedom with medical therapy alone and should be referred early for surgical evaluation.

When to Order Neuroimaging

The decision to obtain neuroimaging and the choice of modality depend on the clinical scenario, the urgency of the presentation, and the suspected etiology.

HARNESS-MRI Protocol

The ILAE Neuroimaging Task Force convened in 2019 to recommend a standardized epilepsy MRI protocol to reduce variability across medical centers and ensure that critical sequences are included. The HARNESS-MRI protocol is optimized for 3T scanners but can be completed on 1.5T scanners without extended imaging time.

• All sequences should be thin-cut (1 mm isotropic for 3D sequences) and no gap to permit identification of small epileptogenic lesions
• 3D acquisitions can be reformatted in any plane, allowing the neuroradiologist to view lesions optimally
• The coronal T2 sequence must be oriented perpendicular to the long axis of the hippocampus for accurate assessment of hippocampal internal architecture

Hippocampal Sclerosis (Mesial Temporal Sclerosis)

Temporal lobe epilepsy, specifically mesial temporal lobe epilepsy (MTLE), is one of the most common forms of focal epilepsy. It is frequently drug-resistant and responds well to epilepsy surgery. Hippocampal sclerosis (HS) is the most common pathologic substrate of MTLE.

Pathology

The ILAE pathologic classification defines three types of hippocampal sclerosis based on the pattern of neuronal cell loss and astrogliosis in the cornu ammonis (CA) regions:

MRI Features

• Hippocampal atrophy: Reduced volume compared with the contralateral hippocampus; best assessed on thin-cut coronal T2 and 3D T1 sequences; quantitative volumetric analysis can detect asymmetry not apparent visually
• T2/FLAIR hyperintensity: Increased signal in the hippocampus on T2 and FLAIR sequences, reflecting gliosis and neuronal cell loss; compare the hippocampal signal to the ipsilateral insula to confirm true signal abnormality (the mesial temporal region is susceptible to imaging artifact)
• Loss of internal architecture: The normal hippocampal digitations (stratum-level layering visible on high-resolution coronal T2) are lost; the hippocampus appears featureless and homogeneously bright
• Secondary signs: Ipsilateral temporal horn dilation (ex vacuo from atrophy), loss of hippocampal head digitations, ipsilateral fornix atrophy, ipsilateral mammillary body atrophy

Focal Cortical Dysplasia

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant lesional epilepsy and is a frequent finding in surgical pathology specimens. The ILAE clinicopathologic classification system categorizes FCD into three types.

Classification

Key MRI Findings

• Blurring of the gray-white matter junction: The most common finding; results from abnormal neurons extending into the subcortical white matter; best seen on T1-weighted and coronal T2 sequences
• Transmantle sign: A radial band of T2/FLAIR hyperintensity extending from the dysplastic cortex to the ventricle; characteristic of Type IIb with balloon cells
• Cortical thickening: Abnormally thick cortex compared with homologous contralateral region
• Subtle features: Lesions can be very subtle; seizure semiology and EEG localization should guide the neuroradiologist to scrutinize the relevant cortical region
• Size underestimation: The true extent of the dysplasia is often underestimated on MRI; careful consideration of the surrounding cortex during surgical planning is essential

Tumors Associated with Epilepsy

Low-grade tumors are among the most common causes of focal epilepsy in young adults. Two tumor types — dysembryoplastic neuroepithelial tumors (DNETs) and gangliogliomas — are particularly associated with chronic epilepsy and fall into the category of long-term epilepsy-associated tumors (LEATs).

Ganglioglioma

• Location: Most commonly temporal lobe
• MRI features: Cyst with a mural nodule; the mural nodule may be poorly visualized on non-contrast images but enhances after gadolinium administration
• Key point: Contrast-enhanced imaging is necessary to properly visualize the mural nodule
• Surgical outcome: Seizure-freedom rate near 78% after resection

Dysembryoplastic Neuroepithelial Tumor (DNET)

• Location: Most commonly temporal lobe
• MRI features: "Bubbly" appearance on T1 (multiple tiny intracortical cysts); T2/FLAIR hyperintensity with no FLAIR suppression of the signal (unlike CSF); typically no contrast enhancement; often involves the cortex with cortical expansion
• Surgical outcome: Seizure-freedom rate near 78% after resection; low recurrence risk due to WHO Grade I designation

Vascular Malformations

Cavernous Hemangiomas (Cavernomas)

• The most commonly seen vascular malformation in epilepsy clinics for both new-onset and chronic epilepsy
• Seizure prevalence: Up to 80% of individuals with a cavernoma develop seizures; the epileptogenicity is related to hemosiderin deposition in the surrounding cortex from microhemorrhages
• MRI features:
  • "Popcorn ball" appearance: mixed signal characteristics (hyperintense and hypointense regions) on T1 and T2 imaging due to blood products at various stages of evolution
  • Hemosiderin ring: dark rim on T2-weighted imaging surrounding the lesion
  • Blooming artifact: SWI and gradient echo sequences overestimate the size of the cavernoma due to susceptibility effects of hemosiderin
• Surgical timing: Early treatment with lesionectomy including a surrounding margin has superior seizure-freedom outcomes compared with surgery performed later; surgery ≥5 years after epilepsy onset is an independent predictor of surgical failure

Malformations of Cortical Development

Malformations of cortical development (MCDs) comprise a wide spectrum of brain lesions resulting from abnormal brain development. They are classified based on which developmental process is disrupted first.

Tuberous Sclerosis Complex

• Incidence: 1 per 6,000–10,000 live births; associated with TSC1 or TSC2 gene variants (mTOR pathway regulation)
• CNS imaging findings:
  • Cortical tubers: Multiple cortical/subcortical lesions; FLAIR-hyperintense; often multifocal; remain stable in number and location throughout life; these are the epileptogenic lesions
  • Subependymal nodules: Small calcified nodules along the ventricular walls; typically non-epileptogenic
  • Subependymal giant cell tumors (SEGAs): Slow-growing tumors near the foramen of Monro; require periodic imaging for obstructive hydrocephalus
• Epilepsy: Onset often within the first year of life, frequently presenting as infantile spasms; surgical resection of the epileptogenic tuber achieves seizure freedom in 60–65% initially, decreasing to 46–51% over time

Periventricular Nodular Heterotopia

• Gray matter neurons that fail to migrate from the periventricular zone
• MRI features: Nodules of gray matter signal intensity along the ventricular walls; can be singular, multiple, or longitudinally extensive; require differentiation from normal structures (caudate nucleus)
• Often require intracranial EEG to determine which nodule is epileptogenic; seizure onset may arise from both the heterotopia and the overlying cortex

Subcortical Band Heterotopia

• Bilateral bands of gray matter in the subcortical white matter resulting from arrested neuronal migration
• MRI features: Band of gray matter signal between the cortex and ventricle; overlying cortex is often thinned; T1-weighted axial images show the characteristic "double cortex" appearance

MRI-Negative Epilepsy

Approximately 20–30% of patients with focal epilepsy have no identifiable lesion on conventional MRI. These patients represent a significant diagnostic and therapeutic challenge.

• Repeat imaging: All patients with drug-resistant epilepsy who had initial imaging on a non-epilepsy protocol or a 1.5T scanner should undergo repeat 3T MRI with the HARNESS protocol
• Post-processing techniques: Voxel-based morphometry, cortical thickness analysis, FLAIR signal intensity mapping, and junction image analysis can detect subtle FCD and other lesions not visible on conventional review
• Advanced imaging: FDG-PET, ictal SPECT/SISCOM, and MEG can help identify the epileptogenic zone in MRI-negative cases and guide surgical planning
• Surgical outcomes: Surgical outcomes are inferior in MRI-negative compared with MRI-positive epilepsy, but concordant multimodal data (EEG, PET, SPECT) can identify good surgical candidates. In one study, patients with focal seizures but without MRI abnormalities were more likely to be seizure-free on medical therapy (42%) than those with MRI lesions (25%)
• Repeat imaging in children: Children who had initial MRI before myelination completion should have repeat imaging after 18–24 months to detect lesions obscured by unmyelinated white matter

Traumatic Brain Injury and Epilepsy

• TBI is a common cause of epilepsy; the risk varies with injury severity (5% at 1 year and 17% over 20 years for severe TBI)
• MRI findings: Encephalomalacia, gliosis (FLAIR hyperintensity), hemosiderin deposition (SWI blooming); multifocal lesions are common and should be sought in multiple imaging planes
• Key principle: Review images in multiple planes to identify all lesions; some lesions (particularly parietal or posterior fossa) may only be apparent in specific orientations
• Patients with new-onset seizures should always be screened for prior traumatic brain injury, even if the injury occurred years to decades earlier

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 ILAE Neuroimaging Task Force. Epilepsia. 2019;60(6):1054–1068.
2. Zhu H, Scott J, Hurley A, et al. 1.5 versus 3 tesla structural MRI in patients with focal epilepsy. Epileptic Disord. 2022;24(2):274–286.
3. Blümcke I, Thom M, Aronica E, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy. Epilepsia. 2013;54(7):1315–1329.
4. 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.
5. Semah F, Picot MC, Adam C, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology. 1998;51(5):1256–1262.
6. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475–482.
7. Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84(16):1705–1713.
8. Harden CL, Huff JS, Schwartz TH, et al. Reassessment: neuroimaging in the emergency patient presenting with seizure. Neurology. 2007;69(18):1772–1780.
9. Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: update 2012. Brain. 2012;135(Pt 5):1348–1369.
10. Randle SC. Tuberous sclerosis complex: a review. Pediatr Ann. 2017;46(4):e166–e171.
11. Specchio N, Pepi C, de Palma L, et al. Surgery for drug-resistant tuberous sclerosis complex-associated epilepsy: who, when, and what. Epileptic Disord. 2021;23(1):53–73.
12. Vogt VL, Witt JA, Delev D, et al. Cognitive features and surgical outcome of patients with long-term epilepsy-associated tumors (LEATs) within the temporal lobe. Epilepsy Behav. 2018;88:25–32.
13. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069–1077.
14. Lapalme-Remis S. Neuroimaging of epilepsy. Continuum (Minneap Minn). 2022;28(2):306–338.
15. Hadady L, Sperling MR, Alcala-Zermeno JL, et al. Prediction tools and risk stratification in epilepsy surgery. Epilepsia. 2024;65(2):414–421.
16. Jehi LE, Palmini A, Aryal U, Coras R, Paglioli E. Cerebral cavernous malformations in the setting of focal epilepsies. Acta Neuropathol. 2014;128(1):55–65.
17. Yeon JY, Kim JS, Choi SJ, et al. Supratentorial cavernous angiomas presenting with seizures: surgical outcomes in 60 consecutive patients. Seizure. 2009;18(1):14–20.
18. Fordington S, Manford M. A review of seizures and epilepsy following traumatic brain injury. J Neurol. 2020;267(10):3105–3111.
19. Winston GP, Micallef C, Kendell BE, et al. The value of repeat neuroimaging for epilepsy at a tertiary referral centre. Epilepsy Res. 2013;105(3):349–355.
20. Knake S, Triantafyllou C, Wald LL, et al. 3T phased array MRI improves the presurgical evaluation in focal epilepsies. Neurology. 2005;65(7):1026–1031.