What is the likelihood of a patient with Temporal Lobe Epilepsy (TLE) having a normal electroencephalogram (EEG), normal 7-Tesla (7T) Magnetic Resonance Imaging (MRI), and normal 7T Positron Emission Tomography-MRI (PET-MRI)?

Likelihood of Normal Advanced Imaging in Temporal Lobe Epilepsy

While uncommon, it is possible for a patient with TLE to have normal 48-hour EEG, normal 7T MRI, and normal 7T PET-MRI, occurring in approximately 5-20% of cases depending on the specific modality, though having all three simultaneously normal is rare and should prompt reconsideration of the diagnosis or consideration of very focal epileptogenic zones.

Diagnostic Sensitivity by Modality

EEG Limitations

• Extended EEG monitoring can miss epileptiform activity even in confirmed TLE cases, particularly when seizures are infrequent or the epileptogenic focus is deeply located in mesial temporal structures 1
• The timing of EEG relative to last seizure significantly impacts yield—interictal recordings should ideally be performed at least 48 hours after focal impaired awareness seizures for optimal detection 2

MRI-Negative TLE Prevalence

• Up to 20-30% of temporal lobe epilepsy patients have no clear lesion visible on MRI despite having confirmed epileptogenic foci 3
• Even with advanced 7T MRI technology, approximately 30% of TLE cases remain MRI-negative, representing a well-recognized clinical entity with distinct characteristics from lesional TLE 4
• Normal MRI does not preclude mesial temporal seizure onset, as demonstrated by SEEG studies showing 72% of MRI-negative TLE patients had exclusively mesial temporal seizure origins 1

PET-MRI Detection Rates

• [18F]FDG PET demonstrates a pooled sensitivity of 79-95% for detecting epileptic brain regions in TLE, meaning 5-21% of cases may show normal metabolism 2
• The sensitivity of interictal FDG-PET is approximately 63-67% when MRI is normal or shows nonspecific findings 5
• Hybrid PET/MRI systems provide improved detection through simultaneous multimodal acquisition, but still miss some cases particularly when hypometabolism is subtle or timing relative to seizures is suboptimal 2

Critical Factors Affecting Detection

Timing Considerations

• Interictal imaging should be performed at least 24 hours after focal aware seizures and 48 hours after focal impaired awareness seizures for optimal PET sensitivity 2
• Seizure frequency, antiseizure medications, delay between last seizures, and type of last seizure can all reduce [18F]FDG uptake patterns 2

Medication Effects

• Benzodiazepines and certain antiseizure medications can suppress both EEG abnormalities and metabolic changes on PET imaging 2
• Current medication regimens should be documented as they may mask epileptiform activity and metabolic abnormalities 2

Clinical Implications

When All Studies Are Normal

• Normal memory function does not preclude mesial temporal seizure onset—94% of MRI-negative TLE patients with normal memory still showed interictal SEEG abnormalities in mesial temporal structures 1
• Extratemporal seizure onset is rare when video-EEG and semiology are consistent with focal TLE, even with normal advanced imaging 1
• The combination of [18F]FDG PET/MRI with magnetoencephalography (MEG) can improve epileptogenic zone localization to 94.5% of cases, suggesting additional modalities may be needed when standard imaging is normal 6

Prognostic Considerations

• Patients with MRI-negative TLE have worse surgical outcomes compared to lesional TLE, with seizure-free rates of 60-80% when focal lesions are identified versus lower rates when imaging is normal 3, 4
• The absence of structural abnormalities on advanced imaging complicates presurgical workup but does not exclude surgical candidacy 4

Common Pitfalls to Avoid

• Do not dismiss the diagnosis of TLE based solely on normal advanced imaging—clinical semiology, video-EEG findings, and neuropsychological testing remain critical diagnostic components 1
• Avoid performing interictal PET too soon after seizures, as this reduces sensitivity for detecting hypometabolic patterns 2
• Do not assume that normal imaging across all modalities rules out surgically remediable epilepsy—consider additional evaluation with SEEG or MEG when clinical suspicion remains high 1, 6
• Recognize that approximately 5-20% of genuine TLE cases may have completely normal advanced imaging, representing the lower end of detection sensitivity across modalities 2, 3, 4