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MRI-negative epilepsy: A systematic review and meta-analysis
Ravnoor S Gill1, Francesco Deleo2, Boris Bernhardt3
1Neuroimaging of Epilepsy Laboratory and Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
Objective:
Drug-resistant focal epilepsy is commonly dichotomized based on magnetic resonance imaging (MRI) lesion visibility into positive (MRI-pos) and negative (MRI-neg). Yet, the criteria used to ascribe such categorization are variable. We used a systematic review and meta-analysis to synthesize evidence for the designation of MRI-neg status.
Methods:
In accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, the systematic review (1990-2025) across Embase, Cochrane, and Medline databases identified cohorts with MRI-neg epilepsy. Unsupervised clustering stratified studies based on co-occurrence of imaging modalities. Within identified classes, we assessed the consistency of reporting MRI parameters, rater expertise, post-processing, and stereo-electroencephalography (SEEG). Meta-analyses evaluated the effects of post-processing on diagnostic yield and MRI-neg status on post-surgical outcome.
Results:
We screened 2622 records and assessed the eligibility of 448 full-text articles, 246 of which met the inclusion criteria for systematic review: 108 (44%) provided data only on MRI-neg and 138 (56%) on mixed adult cohorts, for a total of 10.463 MRI-neg and 7436 MRI-pos patients. Compared to MRI-pos, MRI-neg patients underwent SEEG more frequently (75% vs 54%, p < 0.05), underwent surgery less frequently (73% vs 84%; odds ratio [OR] = 1.14, p < 0.001), and had less favorable outcomes (61% vs 72%, p < 0.05). Clustering identified three classes: MRI-dominant, typified by consistent reporting of MRI parameters (ORs >3.11, p < 0.001), rater-expertise (ORs >9.94, p < 0.001), and post-processing (ORs >3.38, p < 0.03), as opposed to Limited-MRI (χ2 = 41.08, p < 0.001); MRI-and-nuclear-imaging class was typified by use of SEEG (ORs >3.33, p < 0.02). Meta-analyses showed a 39% gain in diagnostic yield after post-processing (11.10, 95% confidence interval [CI] 7.45-16.53) and a higher proportion of favorable surgical outcome in MRI-pos compared to MRI-neg (75% vs 58%; χ2 = 19.10, p < 0.001). Time-based sensitivity analyses did not affect results.
Significance:
The designation of MRI-neg is ambiguous, with most studies lacking details on imaging parameters and reader expertise. Given a 39% gain in diagnostic yield, MRI post-processing should be performed systematically as part of a modern multimodal approach to epilepsy surgery before ascribing MRI-neg status.
Insights
The designation of MRI-negative epilepsy is inconsistent. Systematic MRI post-processing improves diagnostic yield by 39% and is crucial before classifying epilepsy as MRI-negative.
Area of Science:
- Neurology
- Radiology
- Epileptology
Background:
- Drug-resistant focal epilepsy is often categorized as MRI-positive or MRI-negative based on lesion visibility.
- The criteria for classifying epilepsy as MRI-negative are inconsistent across studies.
- This ambiguity impacts diagnostic accuracy and treatment strategies.
Purpose of the Study:
- To systematically review and synthesize evidence regarding the designation of MRI-negative epilepsy.
- To assess the consistency of reporting imaging parameters, rater expertise, and post-processing in studies of MRI-negative epilepsy.
- To evaluate the impact of MRI post-processing on diagnostic yield and surgical outcomes.
Main Methods:
- A systematic review and meta-analysis adhering to PRISMA guidelines (1990-2025) was conducted.
- Studies were identified across Embase, Cochrane, and Medline databases.
- Unsupervised clustering stratified studies by imaging modalities; meta-analyses assessed post-processing effects and MRI-negative status on outcomes.
Main Results:
- 246 articles were included, encompassing 10,463 MRI-negative and 7,436 MRI-positive patients.
- MRI-negative patients underwent SEEG more frequently but had less frequent surgery and less favorable outcomes.
- Clustering revealed distinct study classes based on imaging modality reporting and expertise; post-processing yielded a 39% gain in diagnostic yield.
Conclusions:
- The classification of MRI-negative epilepsy lacks standardized criteria, with frequent omissions in reporting imaging parameters and reader expertise.
- Systematic MRI post-processing is essential for improving diagnostic yield and should be a routine part of multimodal epilepsy evaluations.
- Accurate classification is critical for optimizing epilepsy surgery and patient outcomes.
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