Seizure Differential Diagnosis and Diagnostic Workup
Immediate Bedside Assessment
The first priority is to determine if the event was truly a seizure versus a seizure mimic, with syncope being the most common alternative diagnosis in 28-48% of suspected first seizures. 1
Key Historical Features That Distinguish Seizure from Syncope
Findings strongly suggesting seizure: 2
- Tonic-clonic movements that are prolonged and begin simultaneously with loss of consciousness
- Hemilateral clonic movements or clear automatisms (chewing, lip smacking, frothing)
- Tongue biting (particularly lateral tongue)
- Aura preceding the event (unusual smell, déjà vu)
- Prolonged post-ictal confusion or muscle aching
Findings suggesting syncope instead: 2
- Brief tonic-clonic movements (<15 seconds) that start after loss of consciousness
- Prodrome of nausea, vomiting, pallor, sweating, or feeling cold
- Rapid return to baseline without confusion
Clinical pitfall: Incontinence, injury, headache, and sleepiness after the event have low specificity and occur in both seizures and syncope. 2
Essential Laboratory Testing
For all adults with new-onset seizures, obtain serum glucose and sodium levels—these are the only two laboratory tests that consistently alter acute management. 1, 3
Core Laboratory Panel
- Serum glucose: Hypoglycemia is a common treatable cause; check immediately 1, 4
- Serum sodium: Hyponatremia can both cause and result from seizure activity 4
- Pregnancy test: Required for all women of childbearing age, as this affects testing, disposition, and antiepileptic drug selection 1, 3
Additional Testing Based on Clinical Context
Obtain these only when suggested by specific clinical findings: 1
- Calcium: In patients with known cancer or renal failure 2, 3
- Magnesium: In patients with suspected alcohol-related seizures 2, 3
- Complete metabolic panel: When history suggests metabolic derangement (vomiting, diarrhea, dehydration) 1
- Toxicology screen: If substance exposure suspected, particularly in pediatric patients 1
Important caveat: Prospective studies show that only 8% of patients have correctable laboratory abnormalities, and in most cases these are predicted by history and physical examination. 2 Only hypoglycemia and hyponatremia consistently require immediate intervention. 1
Neuroimaging Decision Algorithm
Emergent Head CT Without Contrast
Perform emergent CT in the ED if ANY of the following high-risk features are present: 1
- Age >40 years
- New focal neurological deficits
- Persistent altered mental status
- Fever or persistent headache
- Recent head trauma
- History of malignancy or immunocompromised state
- Anticoagulation use
- Focal (partial) seizure onset before generalization
Yield: 41% of first-time seizure patients have abnormal CT findings when high-risk features are present. 1
Deferred Outpatient MRI
For low-risk patients (young, returned to baseline, normal neurologic exam, reliable follow-up), deferred outpatient MRI is acceptable. 1
However: 22% of patients with normal neurologic examinations still have abnormal imaging, so MRI should not be omitted entirely. 1 MRI is the preferred imaging modality for non-emergent evaluation as it is more sensitive than CT for detecting epileptogenic lesions. 2, 1
Special Imaging Considerations
For children with focal seizures: MRI with dedicated epilepsy protocol is indicated, as nearly 50% will have positive findings. 2
For children with primary generalized seizures who are neurologically normal: MRI is rarely indicated, with only 2% showing abnormal findings. 2
For refractory epilepsy: MRI with 3T scanner using dedicated epilepsy protocol (1mm isotropic T1 volumetric acquisition, high-resolution coronal slices for hippocampal evaluation) has 84% sensitivity. 2
Lumbar Puncture Indications
Lumbar puncture should be performed primarily when there is concern for meningitis or encephalitis. 1
Specific Indications
- Fever with meningeal signs 2
- Immunocompromised patients (after head CT to rule out mass effect) 1, 3
- Persistent altered mental status without alternative explanation 2
Important note: In one study of HIV-positive patients, 2 afebrile patients without meningeal signs had positive CSF findings (cryptococcal and herpes zoster meningitis), suggesting lower threshold for LP in immunocompromised populations. 2
Routine lumbar puncture is NOT indicated for uncomplicated first-time seizures. 1
Electroencephalography (EEG)
EEG is recommended as part of the neurodiagnostic evaluation for all patients with apparent first unprovoked seizure. 1
Timing consideration: Abnormal EEG findings predict increased risk of seizure recurrence, but EEG does not need to be performed emergently unless there is concern for non-convulsive status epilepticus in a patient with persistent altered consciousness. 1, 4
Autoimmune Encephalitis Considerations
When autoimmune encephalitis (AE) is suspected based on polysyndromic presentation, subacute onset, or atypical features, additional workup is required: 2
- Brain MRI with contrast (bilateral limbic encephalitis on MRI is sufficient for definite AE diagnosis) 2
- CSF analysis for inflammatory markers and neural antibody testing 2
- Serum neural antibody panel 2
- Cancer screening in high-risk patients (smokers, elderly, unintentional weight loss) 2
Clinical clue: A preceding viral infection or viral-like prodrome is common in AE. 2 Faciobrachial dystonic seizures are highly specific for LGI1-antibody encephalitis. 2
Disposition and Recurrence Risk
Emergency physicians need not admit patients with a first unprovoked seizure who have returned to their clinical baseline in the ED. 1
Consider Admission If:
- Persistent abnormal neurologic examination 1
- Abnormal investigation results requiring inpatient management 1
- Patient has not returned to baseline 1
Recurrence Risk Data
The mean time to first seizure recurrence is 121 minutes (median 90 minutes), with >85% of early recurrences occurring within 6 hours of ED presentation. 1
- Overall 24-hour recurrence rate: 19% 1
- Nonalcoholic patients with new-onset seizures: 9.4% (lowest risk) 1
- Alcoholic patients with seizure history: 25.2% (highest risk) 1
- When alcohol-related events and focal CT lesions are excluded: 9% recurrence rate 1
Long-term recurrence: Risk at 1 year ranges from 14-36%, with higher risk in patients with abnormal neurological examination, abnormal EEG, remote symptomatic seizures, or Todd's paralysis. 1
Common Diagnostic Pitfalls to Avoid
Alcohol withdrawal seizures should be a diagnosis of exclusion, especially in first-time seizures. 3 Always search for symptomatic causes before labeling as withdrawal seizures. 2
Do not miss structural lesions by failing to perform appropriate neuroimaging in high-risk patients. 1
Do not fail to identify treatable metabolic causes (hypoglycemia, hyponatremia) that may be precipitating the seizure. 1
Consider non-convulsive status epilepticus in any patient with confusion or coma of unclear cause—obtain emergent EEG. 5