Diagnostic and Treatment Approach: Seizure Pathology vs Brain Pathology
Understanding the Fundamental Distinction
The critical distinction is that "seizure pathology" refers to functional epileptogenic changes in brain tissue (like hippocampal sclerosis or cortical dysplasia), while "brain pathology" refers to structural lesions that secondarily cause seizures (like tumors, hemorrhage, or infection)—both require different diagnostic approaches but similar initial imaging strategies. 1, 2
The key clinical principle: certain seizure types strongly suggest underlying structural brain lesions, including tumors, infection, infarction, traumatic brain injury, vascular malformations, developmental abnormalities, and seizure-associated brain pathology. 1, 2
Initial Diagnostic Algorithm
Emergency vs Non-Emergency Pathway
In emergent presentations (acute seizure with altered mental status, focal deficits, or trauma):
- Obtain non-contrast CT head immediately to identify life-threatening pathology requiring urgent intervention: intracranial hemorrhage, stroke, vascular malformation, hydrocephalus, or mass effect. 1, 2, 3
- CT is appropriate when the patient requires ready access during scanning or is unstable. 1, 3
Critical limitation to avoid: CT detects only 18-30% of epileptogenic lesions compared to MRI's 55% detection rate, and misses 29% of abnormalities in orbitofrontal and medial temporal regions. 1, 3 Never assume a normal CT excludes structural pathology. 3
In non-emergent presentations (stable patient, first unprovoked seizure):
- MRI head with dedicated epilepsy protocol is the definitive initial study. 1, 2, 3
- MRI should be performed in all patients with epilepsy, with rare exceptions for neurologically normal patients with clear generalized seizures (only 2% yield). 1, 2
Identifying High-Risk Features for Structural Brain Pathology
Obtain urgent neuroimaging (preferably MRI, or CT if emergent) when any of these features are present:
- Focal neurological deficits on examination (hemiparesis, aphasia, visual field defects, sensory disturbances). 4, 2, 3
- Focal seizure features: Any focal characteristic independently predicts clinically relevant neuroimaging abnormalities. 2
- Recent head trauma (immediate vs late seizures have different implications). 1, 2, 3
- Persistent headache following seizure. 3
- Abnormal EEG findings showing focal discharges. 2, 3
- Post-ictal sleep or prolonged confusion (suggests focal pathology). 4
In pediatric patients: Approximately 4% of children with first-time afebrile focal seizures have urgent intracranial pathology, most commonly infarction, hemorrhage, and thrombosis. 2
Optimal MRI Protocol for Seizure Evaluation
The dedicated epilepsy protocol must include (preferably at 3T): 1, 3
- Coronal T1-weighted imaging (3mm) perpendicular to hippocampal long axis. 3
- High-resolution 3D T1-weighted gradient echo with 1mm isotropic voxels. 1, 3
- Coronal T2-weighted sequences. 3
- Coronal and axial FLAIR sequences. 3
When to add IV contrast (not routine): 3
- Initial non-contrast images are insufficient
- Neoplasm suspected
- Inflammatory condition suspected
- Infection suspected
For intractable/refractory epilepsy: MRI with dedicated epilepsy protocols achieves 84% sensitivity and 70% specificity, making it the most sensitive anatomic imaging technique. 2
Advanced Imaging for Surgical Planning
When MRI is normal but seizures persist and surgery is considered:
- FDG-PET/CT shows 87-90% sensitivity for temporal lobe epilepsy and 38-55% for extra-temporal lobe epilepsy. 3
- SPECT with statistical ictal SPECT co-registered to MRI identifies hyperperfusion focus in 84% of patients. 3
- Specialized PET tracers (11C-flumazenil for GABA receptors, alpha-[11C]methyl-L-tryptophan for tuberous sclerosis and cortical dysplasia) may provide additional localization. 1
EEG Integration
EEG is mandatory as an extension of the neurologic examination: 5
- Focal seizures show ictal discharges originating from one hemisphere. 2
- Critical pitfall: A normal interictal EEG cannot rule out epilepsy and must be interpreted in clinical context—clinical diagnosis takes precedence. 4
- Consider video-EEG monitoring when diagnosis remains uncertain after initial workup. 5
Distinguishing Seizure-Onset Patterns by Pathology
Seven distinct intracranial EEG seizure-onset patterns exist, with some pathology-specific signatures: 6
- Low-voltage fast activity (43%): Occurs across multiple pathologies, associated with larger seizure-onset zones. 6
- Low-frequency high-amplitude periodic spikes (21%): Specific to mesial temporal sclerosis—this pattern is a signature finding. 6
- Delta brush (4%): Exclusive to focal cortical dysplasia. 6
- Other patterns (sharp activity ≤13 Hz, spike-and-wave, burst of polyspikes, burst suppression) occur across various pathologies. 6
Important caveat: Some seizure-onset patterns can also appear in regions of spread, so morphology alone cannot definitively define the epileptogenic zone. 6
Treatment Implications
The distinction between seizure pathology and brain pathology determines management:
- Structural brain pathology (tumor, infection, hemorrhage) requires treatment of the underlying lesion plus antiepileptic therapy. 1, 2
- Seizure pathology (hippocampal sclerosis, cortical dysplasia) may require surgical resection if medically refractory. 2, 7
For adjunctive antiepileptic therapy:
- Levetiracetam demonstrates effectiveness across seizure types: 26.8% reduction in partial onset seizures, 60.4% responder rate for myoclonic seizures in JME, and 77.1% reduction in primary generalized tonic-clonic seizures. 8
- Behavioral monitoring is essential: 37.6% of levetiracetam-treated patients experience behavioral symptoms (agitation, hostility, depression) vs 18.6% on placebo. 8
- Withdraw antiepileptic drugs gradually to minimize increased seizure frequency risk. 8
Common Pitfalls to Avoid
- Never rely on CT alone when focal features are present—29% of abnormalities are missed. 3
- Never dismiss epigastric sensations as anxiety or GI symptoms—they are characteristic focal seizure auras. 4
- Never assume normal interictal EEG excludes epilepsy—clinical diagnosis supersedes EEG findings. 4
- Never confuse brief post-ictal sleep with normal tiredness—it indicates seizure activity. 4
- Never delay MRI in neurologically normal patients with generalized seizures if any atypical features exist—the 2% yield applies only to truly typical presentations. 2