Causes of Seizures
Classification Framework
Seizures are fundamentally divided into provoked (acute symptomatic) and unprovoked categories, with provoked seizures occurring at the time of or within 7 days of an acute insult, while unprovoked seizures occur without acute precipitating factors. 1
Provoked (Acute Symptomatic) Seizures
Metabolic Causes
- Hypoglycemia is a critical and reversible metabolic cause requiring immediate recognition 2
- Hyperglycemia can precipitate seizures, particularly in diabetic emergencies 1
- Hyponatremia and other electrolyte abnormalities are common precipitants 1, 2
- Hypocalcemia and hypomagnesemia, particularly in patients with renal failure or chronic alcoholism 1
- Uremia in renal failure patients 1
Toxic and Withdrawal Causes
- Alcohol withdrawal is a frequent cause of provoked seizures 1, 3
- Toxic ingestions including cocaine, tricyclic antidepressants, antihistamines, and theophylline 1
- Medication toxicity from antibiotics, antivirals, antidepressants, and antipsychotics 4
- Drug withdrawal from various substances 5
Infectious Causes
- Encephalitis is a critical infectious etiology requiring urgent intervention 1, 2
- CNS infections including meningitis (cryptococcal, herpes zoster, cytomegalovirus in immunocompromised patients) 1
- In neonates, seizures occurring beyond day 7 of life are more likely infection-related 1, 2
Structural/Neurological Causes
- CNS mass lesions including tumors and brain masses 1
- Stroke and cerebral infarction are common causes, with incidence increasing with age 1
- Traumatic brain injury can cause both immediate and late seizures 1, 6
- Intracranial hemorrhage including subdural hematomas 1
- Vascular malformations 1
Unprovoked Seizures
Idiopathic/Genetic
- Idiopathic epilepsy represents seizures without identifiable structural or metabolic cause 1
- Genetic epilepsy syndromes, particularly in pediatric populations 1
Remote Symptomatic Causes
- Prior stroke occurring more than 7 days before seizure onset 1, 6
- Remote traumatic brain injury 1, 6
- Malformations of cortical development 1, 2
- History of CNS infections 6
Age-Specific Considerations
Neonatal Seizures (0-29 days)
- Hypoxic ischemic injury is by far the most common cause (46-65% of cases) 1, 2
- Intracranial hemorrhage and perinatal ischemic stroke (10-12%) 1, 2
- Approximately 90% of hypoxic ischemic encephalopathy seizures occur within 2 days of birth 1
- An underlying cause can be identified in approximately 95% of neonatal seizures 1
Special Populations
- HIV patients with new-onset seizures require consideration of CNS toxoplasmosis, lymphoma, cryptococcal meningitis, and HIV encephalopathy 1
- Immunocompromised patients have higher rates of infectious etiologies 1
Critical Clinical Pearls
Diagnostic Approach
- History and physical examination predict most metabolic abnormalities except occasional cases of hypoglycemia and subdural hematomas 1
- Fever in seizure patients warrants strong consideration of CNS infection, with 5 of 9 febrile patients in one series having confirmed CNS infections 1
- Focal neurologic examination findings have 97% correlation with symptomatic seizures 1
Common Pitfalls
- Do not label seizures as "alcohol withdrawal" without excluding other symptomatic causes first - the withdrawal hypothesis lacks strong statistical support, and increased alcohol consumption itself increases seizure risk 1
- Phenytoin is ineffective for seizures secondary to alcohol withdrawal, theophylline toxicity, or isoniazid toxicity 5
- Most patients with provoked seizures do not have epilepsy and should not be labeled as such - this distinction is critical for patient counseling 5
Reversibility and Prognosis
- Reactive seizures from toxic or metabolic causes carry the possibility of complete elimination if the underlying cause is detected and corrected 7
- Only patients with recurrent seizures and uncorrectable predisposing factors require long-term anticonvulsant therapy 5
- The latent period between brain insult and late unprovoked seizures may offer a therapeutic window, though anticonvulsant administration following acute brain insults has not yet proven effective in preventing late epilepsy 6