What are the potential causes and diagnostic approaches for seizures in patients across different age groups, including pediatric, adult, and geriatric populations, with varying medical histories and presenting symptoms?

Differential Diagnosis of Seizures

Primary Diagnostic Categories

Seizures must first be classified as either acute symptomatic (provoked) or unprovoked, as this fundamentally determines both etiology and management approach. 1, 2

Acute Symptomatic (Provoked) Seizures

These occur within 7 days of an acute insult and include: 1

• Metabolic disturbances - hypoglycemia, hyponatremia, hypocalcemia, hypomagnesemia, hyperglycemia 2, 3, 4
• Toxic ingestions - cocaine, theophylline, isoniazid, antihistamines 5, 1
• Substance withdrawal - alcohol, benzodiazepines 5, 1, 4
• CNS infections - meningitis, encephalitis, HIV encephalopathy 5, 2
• Acute brain injury - stroke, traumatic brain injury, intracranial hemorrhage 5, 6
• Organ failure - renal failure, hepatic failure 4, 7
• Hypertensive encephalopathy 4

Unprovoked Seizures

These occur without acute precipitating factors and include: 1, 6

• Remote symptomatic seizures - prior stroke (>7 days), old traumatic brain injury, cortical malformations 1, 2
• CNS mass lesions - primary brain tumors, metastatic disease, lymphoma 5, 2, 7
• Progressive CNS disease - neurodegenerative conditions 6
• Idiopathic/cryptogenic - no identifiable cause despite workup 5

Age-Specific Differential Considerations

Pediatric Population (0-18 years)

Febrile seizures are the most common cause in children aged 6 months to 5 years and require no neuroimaging for simple febrile seizures. 2

• Neonates (0-29 days) - hypoxic-ischemic injury, metabolic disorders, congenital malformations, CNS infections 2
• Infants/young children - febrile seizures, genetic epilepsy syndromes, metabolic disorders 1, 2
• School-age/adolescents - idiopathic generalized epilepsy, juvenile myoclonic epilepsy, drug/alcohol exposure 1, 2

Adult Population (18-65 years)

In adults, the most common etiologies are idiopathic, alcohol-related, and cerebrovascular disease. 5, 8

• Alcohol withdrawal - most common in this age group but should be diagnosis of exclusion 5, 2, 3
• Drug-related - cocaine, prescription medications, withdrawal states 5, 1
• Structural lesions - tumors, vascular malformations, prior trauma 5, 2
• HIV-related - HIV encephalopathy, CNS toxoplasmosis, cryptococcal meningitis, progressive multifocal leukoencephalopathy, CNS lymphoma 5

Geriatric Population (>65 years)

Cerebrovascular disease and brain tumors become the predominant etiologies in elderly patients, with incidence increasing significantly after age 60. 7, 6

• Stroke - both acute and remote 5, 7, 6
• Brain tumors - primary and metastatic 7
• Neurodegenerative disease - Alzheimer's disease, other dementias 7
• Toxic-metabolic - polypharmacy, renal insufficiency, diabetes complications 7

Diagnostic Approach Algorithm

Step 1: Confirm True Seizure Event

Approximately 28-48% of suspected first seizures have alternative diagnoses including syncope, nonepileptic seizures, and panic attacks. 2

• Features suggesting true seizure: tonic-clonic movements that are prolonged and begin simultaneously with loss of consciousness, postictal confusion, tongue biting, incontinence 2
• Alternative diagnoses to exclude: transient ischemic attacks, syncope, psychiatric disorders, cardiac arrhythmias 7

Step 2: Identify High-Risk Features Requiring Emergent Evaluation

Patients with any of the following require immediate comprehensive workup including emergent neuroimaging: 1, 2

• Persistent altered mental status or failure to return to baseline 1, 2
• Focal neurologic deficits or postictal Todd's paralysis 1, 2
• Fever with concern for CNS infection 1, 2
• Recent head trauma 1, 2
• History of malignancy or immunocompromised state 1, 2
• Age >40 years with first-time seizure 2
• Patients on anticoagulation 2

Step 3: Essential Laboratory Testing

For all adult patients, obtain serum glucose and sodium levels, as these are the only laboratory tests that consistently alter acute management. 2, 3

• Universal tests: glucose, sodium, pregnancy test for women of childbearing age 2, 3
• Selective testing based on clinical presentation: 3
  • Complete metabolic panel if altered mental status, vomiting, diarrhea, dehydration 2, 3
  • Calcium and magnesium in patients with known cancer, renal failure, or suspected alcohol withdrawal 2, 3
  • Toxicology screening if drug exposure suspected 1, 2

Critical pitfall: Only hypoglycemia and hyponatremia consistently require immediate intervention; other metabolic abnormalities are usually predictable from history and physical examination. 2, 3

Step 4: Neuroimaging Decision

Perform emergent CT head without contrast for: 2

• Any high-risk features listed above 2
• New focal neurological deficits 2
• Persistent altered mental status 2
• Fever or persistent headache 2
• History of cancer or immunocompromised state 2
• Patients over 40 years of age 2
• Partial-onset seizures before generalization 2

For low-risk patients (young, returned to baseline, normal neurologic exam, reliable follow-up), deferred outpatient MRI is acceptable. 2

• MRI is the preferred imaging modality for non-emergent evaluation as it is more sensitive than CT for detecting epileptogenic lesions 2
• For children with focal seizures, MRI with dedicated epilepsy protocol is indicated, as nearly 50% will have positive findings 2

Important caveat: 22% of patients with normal neurologic examinations still have abnormal imaging, but 41% of first-time seizure patients have abnormal CT findings overall. 2

Step 5: Lumbar Puncture Indications

Perform lumbar puncture (after head CT) when: 2, 3

• Fever with meningeal signs or concern for CNS infection 2
• Immunocompromised patients 2, 3
• Persistent altered mental status without alternative explanation 2
• Suspicion for autoimmune encephalitis 2

Step 6: EEG Timing

EEG is recommended as part of the neurodiagnostic evaluation for all patients with apparent first unprovoked seizure. 2

• Abnormal EEG findings predict increased risk of seizure recurrence 2
• Can be performed as outpatient in stable patients who have returned to baseline 2

Seizure Recurrence Risk Stratification

The mean time to first seizure recurrence is 121 minutes (median 90 minutes), with more than 85% of early recurrences occurring within 6 hours of ED presentation. 2

Low-Risk Features (9% recurrence rate):

• Nonalcoholic patients with new-onset seizures 2
• Normal neurological examination 2
• No focal CT lesions 2

High-Risk Features for Recurrence:

• Abnormal neurological examination 1, 2
• Abnormal EEG findings 2
• Remote symptomatic seizures from CNS or systemic insults 1, 2
• Todd's paralysis 2
• Alcoholic patients with seizure history (25.2% recurrence rate) 2

Disposition Decisions

Emergency physicians need not admit patients with a first unprovoked seizure who have returned to their clinical baseline in the ED. 2

Indications for Admission:

• Persistent abnormal neurologic examination 2
• Abnormal investigation results requiring inpatient management 2
• Patient has not returned to baseline 1, 2
• Recurrent seizures in the ED 5
• High-risk features requiring ongoing monitoring 1

Safe for Discharge:

• Returned to clinical baseline 2
• Normal neurologic examination 2
• No high-risk features 1, 2
• Reliable follow-up arrangements 2

Special Population Considerations

HIV-Positive Patients

HIV patients with new-onset seizures require CT and lumbar puncture either in ED or after admission, as 40% have acute lesions necessitating admission. 5

• Common etiologies: HIV encephalopathy, CNS toxoplasmosis, cryptococcal meningitis, CNS lymphoma, progressive multifocal leukoencephalopathy 5

Alcohol-Related Seizures

Alcohol withdrawal seizures should be a diagnosis of exclusion, especially in first-time seizures, and symptomatic causes should always be searched for before labeling as withdrawal seizures. 2

• 44% of patients with presumed alcohol withdrawal seizures have clinically significant intracranial lesions on CT 5
• Check magnesium levels in suspected alcohol-related seizures 3

Immunocompromised Patients

Immunocompromised patients require more extensive evaluation including lumbar puncture due to higher rates of CNS infections presenting with seizures. 3