Causes of Seizures
Seizures result from abnormal excessive or synchronous neuronal activity in the brain, with etiologies varying dramatically by age and clinical context—ranging from idiopathic/genetic causes to acute symptomatic causes including structural, infectious, metabolic, immune, and neurodegenerative disorders. 1
Age-Specific Etiological Framework
Neonatal Period (0-29 days)
In neonates, an underlying cause can be identified in approximately 95% of seizures, making this the age group where acute symptomatic causes dominate over idiopathic epilepsies 2:
Primary causes by frequency:
- Hypoxic-ischemic injury (46-65%) - by far the most common cause in both term and preterm infants, with 90% of cases presenting within 2 days of birth 2
- Intracranial hemorrhage and perinatal ischemic stroke (10-12%) 2
- Infections, genetic disorders, and malformations of cortical development - more likely when seizures occur beyond the seventh day of life 2
The incidence is substantially higher in preterm infants (57-132 per 1,000 live births) compared to term infants (3 per 1,000 live births) 2.
Pediatric Population (Beyond Neonatal Period)
The spectrum shifts toward a more heterogeneous mix of benign and serious etiologies 2:
- Idiopathic/genetic causes - constitute the majority when no structural lesion is identified
- Febrile seizures - affect 2-5% of children between 6 months and 5 years of age; simple febrile seizures require no imaging 2
- Structural abnormalities - malformations of cortical development, tumors
- Acute intracranial processes - infections, trauma
- Systemic/metabolic abnormalities
Approximately 470,000 children <17 years in the US have epilepsy, with 50,000 new cases diagnosed annually 2.
Adult Population
In adults, the etiological distribution shifts based on age group 1:
Young adults (13-35 years):
- Infectious etiologies dominate - tubercular and pyogenic meningitis, cerebral malaria 3
- Malignancy and metabolic causes follow in descending order 3
Middle-aged adults (36-55 years):
- Cerebrovascular accidents become the leading cause 3, 4
- CNS infections remain significant 3
- Metabolic derangements (13%) 4
- Alcohol withdrawal (10.9%) 4
Elderly (>55 years):
- Stroke is the dominant etiology (50.9% in this age group) 3, 5
- Brain tumors (15.5% overall) 5
- Vascular etiologies account for 28.3% overall but increase dramatically with age 5
Comprehensive Etiological Categories
The International League Against Epilepsy classification system organizes causes into six categories 6, 7:
1. Structural Etiologies
- Cerebrovascular accidents (most common in adults overall at 28.3-32.6%) 4, 5
- Traumatic brain injury - subdivided into immediate (from injury force) and late seizures 1
- Brain tumors
- Malformations of cortical development
- Intracranial hemorrhage
2. Genetic Etiologies
- Identified genetic causes: 10% of childhood epilepsy 8
- Presumed genetic: constitutes a large proportion when no structural cause found
- Channelopathies (e.g., KCNQ2/KCNQ3 variants causing self-limited familial neonatal epilepsy) 9
- Genetic factors likely play a role to varying degrees in all epilepsy 6
3. Infectious Etiologies
- Meningitis (tubercular, pyogenic) - particularly common in younger adults in developing countries 3
- Encephalitis
- Cerebral malaria 3
- Neuroinfections account for 26.8% of acute symptomatic seizures 4
4. Metabolic Etiologies
- Metabolic derangements cause 13% of acute symptomatic seizures 4
- Inborn errors of metabolism (particularly in neonates)
- Electrolyte disturbances
- Hypoglycemia/hyperglycemia
5. Immune-Mediated Etiologies
- Autoimmune encephalitis
- Autoimmune antibody-mediated seizures
6. Neurodegenerative Etiologies
- Growing importance in epilepsy classification 6
- More relevant in older populations
Critical Clinical Distinctions
These etiological categories are NOT mutually exclusive - many causes fall into multiple categories, and genetic factors likely contribute to seizure susceptibility across all etiologies 6.
Acute Symptomatic vs. Unprovoked Seizures
In emergency department presentations:
- 49.8% present with new-onset seizures 5
- 38.6% have previous epilepsy diagnosis 5
- 71% of acute symptomatic seizures present as a single episode 4
Unknown etiology remains significant:
- In adults with established epilepsy, acquired etiology identified in only 30% 7
- Remaining 70% have presumably genetic etiology 7
- In children, 47% still have unknown etiology despite modern diagnostics 8
Prognostic Implications
Seizure recurrence risk varies by etiology:
- Symptomatic remote seizures: 41% recurrence rate 5
- Brain tumors: 5.1-fold increased odds of recurrence 5
- Younger age and previous epilepsy diagnosis increase recurrence risk 5
Mortality considerations:
- Overall mortality at 1 year: 8.6% 5
- Symptomatic epilepsy: 6.3-fold increased hazard ratio for mortality 5
Key Clinical Pitfalls
Age-dependent diagnostic approach is essential - the differential diagnosis for a seizing neonate is fundamentally different from an elderly patient, and failure to consider age-appropriate etiologies leads to missed diagnoses and delayed treatment.
Timing matters in neonates - seizures within 2 days suggest hypoxic-ischemic injury, while onset after day 7 should prompt aggressive workup for infection, genetic disorders, or malformations 2.
In developing countries, maintain high suspicion for CNS infections in younger patients - infections dominate the young adult age group and require urgent identification and treatment 3.
Nonconvulsive seizures are common with structural etiologies - particularly with vascular causes and tumors, emphasizing the need for EEG monitoring beyond obvious convulsive activity 5.