What are the causes of a first seizure?

Causes of First Seizure in Adults

Primary Classification Framework

First seizures are fundamentally divided into provoked (acute symptomatic) and unprovoked categories, with provoked seizures occurring within 7 days of an acute insult, while unprovoked seizures occur without acute precipitating factors. 1

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Provoked (Acute Symptomatic) Seizures

These represent seizures with an identifiable, acute precipitating cause occurring at the time of or within 7 days of the insult. 1

Metabolic Derangements

• Hypoglycemia is a critical, immediately reversible cause requiring point-of-care glucose testing in all seizure patients 1, 2
• Hyperglycemia, particularly in diabetic emergencies, can precipitate seizures 1
• Hyponatremia is one of the most common electrolyte abnormalities causing seizures 1, 3
• Hypocalcemia can trigger seizures at any age, even without prior seizure history, particularly in patients with renal failure or parathyroid dysfunction 1, 4
• Hypomagnesemia, especially in chronic alcoholics, causes seizures 1
• Uremia in renal failure patients is a known seizure precipitant 1

Clinical pitfall: History and physical examination predict most metabolic abnormalities, but approximately 2-3 cases per 100 seizure patients will have unexpected findings like hypoglycemia or subdural hematomas. 2 Therefore, laboratory testing including glucose, electrolytes, calcium, magnesium, and renal function is essential even when clinical suspicion is low. 5

Toxic Ingestions and Medications

• Cocaine causes seizures in approximately 10% of cocaine-related medical admissions, with 70% being single, generalized seizures 5
• Tricyclic antidepressants are significant seizure precipitants 1
• Antihistamines and theophylline can cause seizures, with phenytoin being ineffective for theophylline-induced seizures 1, 3
• Tramadol and other prescribed medications can lower seizure threshold 4
• Alcohol withdrawal is a common cause, though clinicians must eliminate other symptomatic causes before labeling seizures as withdrawal-related 5, 2

Acute Structural/Neurological Causes

• Stroke and cerebral infarction are among the most common causes, with incidence increasing with age 1, 6
• Traumatic brain injury causes both immediate seizures (within 7 days) 1
• Intracranial hemorrhage, including subdural hematomas, particularly in elderly or anticoagulated patients 1
• CNS infections including meningitis and encephalitis require urgent intervention 1
  • Fever with seizure warrants strong consideration of CNS infection, with 55% likelihood of CNS infection in febrile seizure patients 2
  • Blood culture, urine culture, and empirical antibiotics should be initiated immediately when infection is suspected 2

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Unprovoked Seizures

These occur without acute precipitating factors and include both idiopathic cases and remote symptomatic seizures. 1

Idiopathic/Cryptogenic

• Idiopathic epilepsy represents 27-44% of first seizure cases, defined as seizures without identifiable structural or metabolic cause 1, 2, 6

Remote Symptomatic Causes (>7 days from insult)

• Prior stroke occurring more than 7 days before seizure onset 1
• Remote traumatic brain injury 1
• CNS tumors and brain masses are significant causes requiring neuroimaging 1, 6
• Vascular malformations 1, 6
• Malformations of cortical development 1

Special Populations

HIV-infected patients now represent an important group with first seizures (8.2% of all first seizures, 20% in the 15-45 age group), requiring consideration of: 6

• CNS toxoplasmosis
• Primary CNS lymphoma
• Cryptococcal meningitis
• HIV encephalopathy
• Critical finding: 40% of HIV patients with new-onset seizures have acute lesions necessitating admission 2

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Diagnostic Approach Algorithm

Immediate Assessment

1. Point-of-care glucose testing is mandatory to exclude hypoglycemia immediately 2
2. Vital signs and fever assessment - fever dramatically increases likelihood of CNS infection to 55% 2
3. Focused neurologic examination - focal findings have 97% correlation with symptomatic seizures 1

Laboratory Evaluation

All patients require: 5

• Complete blood count
• Comprehensive metabolic panel (glucose, sodium, calcium, magnesium, BUN, creatinine)
• Toxicology screen when appropriate

Note: Approximately 8% of seizure patients have correctable metabolic abnormalities, with only 2 cases being unpredictable by history/examination. 5, 2

Neuroimaging

• CT scan is essential in evaluation of all adults with first seizure to identify structural lesions 6
• MRI is preferred when available and reveals additional lesions in 22% of patients with normal CT, though it rarely changes acute management 6
• Emergent neuroimaging is required for patients with persistent focal deficits or failure to return to baseline within several hours 5

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Treatment Principles

For provoked seizures, identify and treat the underlying cause rather than initiating long-term antiseizure medications. 4 Most patients with acute symptomatic seizures do not have epilepsy and should not be labeled as such. 3

• Correct metabolic abnormalities as primary treatment 4, 3
• Use short-acting anticonvulsants (lorazepam) only for active or recurrent seizures 4
• Long-term anticonvulsant therapy is reserved for patients with recurrent unprovoked seizures or uncorrectable predisposing factors 3, 7