What are the diagnostic criteria and treatment options for temporal lobe epilepsy in a patient presenting with complex partial seizures and a history of potential underlying causes such as head trauma or genetic predisposition?

Diagnosis of Temporal Lobe Epilepsy

Formal Diagnostic Criteria

Temporal lobe epilepsy is formally diagnosed when a patient has at least two unprovoked seizures occurring more than 24 hours apart, or one unprovoked seizure with a high probability of recurrence (similar to the general recurrence risk after two unprovoked seizures over the next 10 years), or diagnosis of a specific epilepsy syndrome. 1

Initial Diagnostic Workup Algorithm

Clinical Seizure Characterization

• Seizures should be classified as focal onset (with or without impaired awareness), generalized onset, or unknown onset 1
• Complex partial seizures arising from mesial temporal lobe structures are the defining feature of mesial temporal lobe epilepsy 2
• Focal seizure features on history increase the likelihood of detecting structural abnormalities on imaging 3

Electroencephalography (EEG)

• Interictal scalp EEG demonstrates paroxysmal abnormalities in 96% of temporal lobe epilepsy patients during prolonged monitoring 4
• Anterior temporal localization of interictal discharges occurs in 94% of patients with confirmed temporal lobe epilepsy 4
• Bilateral independent paroxysmal activity occurs in 42% of patients, but is preponderant over the side of seizure origin in half of these cases 4
• Ictal EEG changes are rarely detected at clinical seizure onset, but lateralized buildup of rhythmic seizure activity during the seizure occurs in 80% of patients 4
• Lateralized postictal slowing, when present, is a very reliable lateralizing finding 4

Critical pitfall: In 13% of patients, scalp EEG seizure buildup may be contralateral to the actual side of seizure origin as determined by depth EEG, so discordant findings warrant invasive monitoring 4

Neuroimaging Protocol

MRI as First-Line Imaging

• MRI of the brain without IV contrast is the preferred initial imaging modality in non-emergent settings, with superior sensitivity (70-80%) compared to CT (approximately 30%) for detecting epileptogenic lesions 1, 3, 5

Dedicated Seizure Protocol Components

• Coronal T1-weighted imaging (3mm) perpendicular to the long axis of the hippocampus 3
• High-resolution 3D T1-weighted gradient echo (GRE) with 1mm isotropic voxels 3
• Coronal T2-weighted sequences 3
• Coronal and axial (or 3D) fluid-attenuated inversion recovery (FLAIR) sequences 3
• 3T MRI is preferred over 1.5T when available for improved lesion detection 3

MRI Findings in Temporal Lobe Epilepsy

• MRI is very sensitive in detecting subtle medial temporal abnormalities, present in 82% (23 of 28) of patients with temporal lobe epilepsy, corresponding with mesial temporal sclerosis on pathological examination 4
• MRI provides superior visualization of hippocampal abnormalities, which are the most common cause of temporal lobe seizures, with a detection rate of 70-80% 5

Important limitation: 20-30% of temporal lobe epilepsy patients have no clear lesion seen on MRI despite having epileptogenic foci 5

When to Use CT Instead

• CT head without IV contrast is appropriate in emergent situations when rapid assessment is needed for immediate intervention, patient requires ready access during scanning, acute trauma is suspected, or patient is unstable 3
• CT is useful for assessment of calcification pathologies such as tuberous sclerosis 6

Critical pitfall: Assuming a normal CT excludes structural abnormality is dangerous, as MRI may still reveal significant pathology in 29% of cases 3

Functional Neuroimaging for Surgical Planning

FDG-PET/CT

• FDG-PET demonstrates high sensitivity (86% predictive value) for presurgical localization of epileptogenic foci, typically manifesting as focal hypometabolism on interictal examinations 6
• FDG-PET can identify focal abnormalities in the setting of a negative anatomic MRI brain scan 6
• FDG-PET co-registered with MRI serves as an additional tool to enhance detection of lesions and provide information on good prognostic surgical outcome 6

Important consideration: Poor seizure outcomes following surgery have been described in the setting of bilateral temporal lobe hypometabolism 6

SPECT Imaging

• Ictal SPECT provides assessment of regional cerebral blood flow, with statistical ictal SPECT co-registered to MRI identifying hyperperfusion focus in 84% of patients 3
• Comparison of interictal PET and ictal SPECT demonstrated localization of lesions in 77.7% and 7.3% of patients, respectively, favoring PET for routine use 6

Neuropsychological Testing

• Neuropsychological testing provides lateralizing findings concordant with the side of seizure origin in 73% of patients 4
• When neuropsychological testing produces discordant results or nonlateralizing findings, patients are usually found to have right temporal seizure origin 4
• Intracarotid amobarbital (Wada) testing demonstrates absent or marginal memory functions on the side of seizure onset in 63% of patients, but 37% have bilaterally intact memory 4

Magnetoencephalography (MEG)

• MEG records brain electrical activity with 85% of patients with concordant and specific MEG findings achieving seizure freedom following surgery, compared with only 37% with nonspecific or discordant findings 6
• MEG demonstrates 70% sensitivity in detecting epileptic activity in large case series 6
• MEG is useful as a complementary modality for assessment of seizure location and identification of eloquent cortex to determine safe resection margins 6

Underlying Etiologies to Investigate

Structural Causes

• Tumors (especially low-grade epilepsy-associated brain tumors) 6
• Vascular malformations 1
• Traumatic brain injury 1
• Infarction 1
• Infection 1

Developmental Abnormalities

• Malformations of cortical development (MCD) including focal cortical dysplasia, polymicrogyria, and hemimegalencephaly 6
• Focal lesions such as hamartomas and heterotopias, generally considered to have been present at birth 7
• Mesial temporal sclerosis, the most frequent pathological finding in temporal lobe epilepsy, may represent a sequela of disturbed neuroembryogenesis rather than solely acquired injury 7

Genetic Factors

• Recent investigations emphasize the role of genetic background for acquisition of epilepsy, including variants of neurodevelopmental genes 8
• Mutations in neurodevelopmental transcription factors may innately increase hippocampal vulnerability to develop epilepsy following injury 8

When to Proceed to Invasive Monitoring

Stereoelectroencephalography (sEEG) electrode implantation is medically necessary when non-invasive methods (scalp EEG, MRI, PET) are insufficient to localize the epileptogenic zone in drug-resistant epilepsy patients being evaluated for definitive surgical intervention. 1

• Invasive monitoring is essential in patients with prior surgery and altered anatomy, where scalp EEG and non-invasive imaging have reduced sensitivity 1
• Precise localization is critical before surgical intervention to maximize seizure freedom rates (approximately 65% with correct identification) while preserving eloquent cortex 1

Treatment Implications Based on Diagnosis

Medical Management

• Valproate is FDA-approved as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to age 10 years 9
• Initial dosing: 10-15 mg/kg/day, increased by 5-10 mg/kg/week to achieve optimal clinical response 9
• Therapeutic valproate serum concentrations range from 50-100 μg/mL 9
• Approximately 25% of patients with structural epilepsy require a second antiepileptic drug to control seizure activity 1

Surgical Considerations

• Patients are more likely to be seizure-free after surgery (60-80% success rate) when focal circumscribed lesions are identified on presurgical MRI 5
• Surgical intervention could lead to seizure freedom in approximately 65% of patients with drug-resistant focal epilepsy when the epileptogenic zone is correctly identified 1
• Approximately 30% of epilepsy patients develop drug-resistant epilepsy and should be considered for surgical evaluation 1