What is the underlying cause of focal seizures?

Underlying Causes of Focal Seizures

Focal seizures arise from structural brain lesions in the majority of cases, with the most common etiologies being hippocampal sclerosis in adults, malformations of cortical development in children, and acquired lesions including tumors, stroke, traumatic brain injury, vascular malformations, and infections. 1, 2

Primary Structural Causes by Age Group

Adults

• Hippocampal sclerosis is the most common cause of temporal lobe focal seizures 1
• Acquired structural lesions including:
  • Stroke and cerebral infarction 1
  • Traumatic brain injury (subdivided into immediate seizures from injury force and late seizures occurring later) 1, 2
  • Brain tumors (particularly low-grade epilepsy-associated brain tumors) 1, 3
  • Vascular malformations 1, 3
  • Infections 1, 3

Pediatric Population

• Malformations of cortical development (MCD) are the most common cause of medically refractory focal epilepsy in children 1, 4
• Focal cortical dysplasia (FCD) is the most frequent MCD subtype, presenting as focal irregularity of cortical morphology and thickness 1, 4
• Birth-related lesions including perinatal stroke or hemorrhages 1
• Low-grade epilepsy-associated brain tumors (LEAT) 1
• Polymicrogyria (PMG) - excessive number of abnormally small cerebral gyri with cortical overfolding 1
• Hemimegalencephaly - congenital unilateral disorder with cortical malformation 1

Developmental and Genetic Causes

• Genetic defects underlying many MCDs, occurring as isolated disorders or associated with developmental delay and motor abnormalities 1
• Complex etiology involving interaction between genetic background and early pre- or perinatal injury or stress 5
• mTOR pathway mutations identified in a subset of FCD cases 5

Location-Specific Patterns

Temporal Lobe

• Hippocampal sclerosis predominates 1
• Mesial temporal sclerosis is the primary cause in adults 1

Frontal Lobe

• Type II cortical dysplasia shows predilection for frontal lobes in children 4
• More extensive changes occur outside temporal lobe 4

Extratemporal Locations

• Tumors, vascular malformations, and developmental abnormalities more common 1

Critical Diagnostic Considerations

MRI is essential for identifying structural causes, with detection rates up to 55% in children with focal seizures and significantly higher sensitivity than CT (which detects lesions in only 30% of focal epilepsies) 1, 6. The American College of Radiology emphasizes that certain seizure types are likely associated with structural brain lesions, making neuroimaging mandatory in focal seizures 1, 2.

High-Risk Features Requiring Aggressive Workup

• Focal neurologic examination findings (97% correlation with symptomatic seizures) 2
• Focal seizure characteristics 2
• Predisposing conditions 2
• Nearly 50% of children with focal seizures show positive imaging findings (compared to only 6% in generalized seizures) 2, 6

Special Population Etiologies

Immunocompromised Patients (HIV)

• CNS toxoplasmosis 2
• Primary CNS lymphoma 2
• Cryptococcal meningitis 2
• HIV encephalopathy 2

Neonates

• Hypoxic-ischemic injury (46-65% of cases) 2
• Underlying cause identifiable in approximately 95% of neonatal seizures 2

Common Pitfalls to Avoid

Do not rely on CT alone - it misses small cortical lesions and orbitofrontal/medial temporal region pathology 1, 2. Do not assume normal MRI excludes structural cause - Type I focal cortical dysplasia often shows normal or minimal MRI findings despite being epileptogenic 4. The lesion seen on MRI may be smaller than the actual seizure-generating region 4.

Do not overlook metabolic and autoimmune causes in the appropriate clinical context, as these represent important treatable etiologies 3. In immunocompromised patients, infectious etiologies occur at significantly higher rates than in immunocompetent individuals 2.