The Seizure Workup: What to Do When It's the First Time

The Seizure Workup: What to Do When It's the First Time

A patient comes in after their first seizure. Maybe they were brought in by ambulance with a confused family member trying to explain what happened. Maybe they walked in themselves, still foggy from the post-ictal state. Either way, you're about to do one of the most common and most consequential workups in internal medicine.

Getting this right matters. A provoked seizure might just need a sodium correction or alcohol detox. An unprovoked seizure could be the first sign of epilepsy, a brain tumor, or something in between. The difference between "discharge with neurology follow-up" and "admit for monitoring" often comes down to how thoroughly you sort through the details.

Step One: Figure Out What Actually Happened

The history is your most important diagnostic tool, period. No EEG or MRI replaces a good witness account.

Start with the patient if they're alert enough. Ask about any aura — sensory phenomena like a rising epigastric sensation, visual changes, strange smells, or emotional experiences like sudden fear or déjà vu. An aura is not a warning sign of a seizure. It is the first part of the seizure itself, just a focal onset before generalization.

Then get the witness account. This is where things get interesting.

Eye position tells you a lot. Eyes open during the event favors seizure or syncope. Eyes closed favors psychogenic nonepileptic seizures (PNES). It sounds simple, but studies show this single feature has decent specificity.

Movement pattern matters. True tonic-clonic seizures are symmetrical and synchronous — both arms and legs moving together in a rhythmic pattern. PNES tends to be asymmetrical, asynchronous, with waxing and waning movements. Pelvic thrusting and side-to-side head movements are classic for PNES and essentially never seen in epileptic seizures.

Duration is a clue. True convulsive seizures typically last 60-120 seconds of motor activity. Events lasting more than 5 minutes should raise suspicion for PNES, though status epilepticus is obviously on the differential too.

Tongue biting has specificity. Lateral tongue biting — biting the side of the tongue — is highly specific for generalized tonic-clonic seizure. Tip of the tongue biting can happen in syncope or falls and doesn't carry the same weight.

The recovery phase is diagnostic gold. Prolonged post-ictal confusion (minutes to hours) points toward seizure. Rapid, complete recovery within seconds to a minute points toward syncope. Variable recovery with preserved awareness during "unconsciousness" points toward PNES.

Provoked Versus Unprovoked: The Critical Distinction

Up to 40% of first seizures are provoked, also called acute symptomatic seizures. These happen in the setting of an identifiable acute insult and carry a much lower risk of recurrence once the trigger is removed.

Metabolic causes lead the list. Severe hyponatremia (below 115 mEq/L) is the most common metabolic cause. Hypocalcemia, hypomagnesemia (especially in alcohol use disorder), hypoglycemia, severe hyperglycemia, and uremia from renal failure all lower the seizure threshold.

Toxic causes are everywhere in the ED. Alcohol withdrawal is the leading cause of provoked seizures in emergency departments. Benzodiazepine withdrawal follows a similar pattern. Drug overdoses — particularly cocaine, tricyclic antidepressants, and other sympathomimetics — can trigger seizures through various mechanisms.

Infectious causes include meningitis, encephalitis, and CNS abscess. Any febrile patient with a seizure needs this considered first.

Acute structural causes like stroke, intracranial hemorrhage, or acute head trauma can present with seizures as the initial symptom.

Neuroimaging: MRI Is Your Friend

For any first unprovoked seizure, an MRI with an epilepsy protocol should be your first-line imaging study. The yield is significant — abnormalities are found in roughly 30% of patients overall, and up to 47% have potentially epileptogenic lesions detected.

The key is using the right protocol. A dedicated epilepsy protocol adds coronal oblique T2-weighted and FLAIR sequences perpendicular to the hippocampus, high-resolution MPRAGE, and susceptibility-weighted imaging (SWI). This approach detects 100% of mesial temporal sclerosis cases and finds 37% more lesions than a standard brain MRI.

The yield is highest in patients with focal-onset seizures — up to 81% have detectable abnormalities. If the clinical picture suggests a generalized seizure, the yield drops but is still meaningful enough to justify the scan.

When to get a CT instead: In the emergency setting, you'll often start with a non-contrast head CT. This is appropriate when there's a focal neurological deficit, fever or suspected infection, persistent headache, anticoagulant use, known malignancy, immunocompromise, or acute head trauma. CT is fast and rules out hemorrhage and mass effect, but it misses the subtle cortical and hippocampal abnormalities that MRI catches.

EEG: Timing Matters

An EEG should be performed within 72 hours of the first seizure. The earlier, the better — ideally within 48 hours.

Here's what the numbers look like. If early EEGs (within 48 hours) show epileptiform discharges, the recurrence risk jumps to 83%. If the EEG is consistently normal, recurrence risk drops to about 12%. That's a massive difference that directly impacts management decisions.

The caveat: a normal EEG does not rule out epilepsy. Up to 10% of patients with established epilepsy have an initially normal EEG. The sensitivity improves with sleep-deprived EEGs, prolonged monitoring, or repeat studies, but a single routine EEG has limited negative predictive value.

Focal epileptiform activity carries the highest recurrence risk and should prompt more aggressive management consideration.

Labs: Keep It Focused

You don't need a fishing expedition. The routine panel should include:

• Serum electrolytes (sodium is the big one)
• Glucose
• Complete blood count
• Renal and liver function tests
• Urinalysis
• Pregnancy test in women of childbearing age

Add a toxicology screen if you're in the ED setting or the history suggests substance use. A lumbar puncture is reserved for patients where CNS infection is suspected — febrile patients, immunocompromised individuals, or those with meningeal signs.

The Mimics: Syncope and PNES

Two conditions regularly masquerade as seizures, and confusing them can lead to unnecessary treatment.

Convulsive syncope is the most common seizure mimic. The mechanism is straightforward: cerebral hypoperfusion causes loss of consciousness, and brief myoclonic jerks can follow. These jerks typically last less than 15 seconds, and patients recover quickly with full orientation. The prodrome is classic — dizziness, nausea, diaphoresis, pallor, and tunnel vision. If a patient describes feeling "faint" before losing consciousness, think syncope first.

Psychogenic nonepileptic seizures (PNES) are increasingly recognized. The AAN published their first-ever guidelines for functional seizure management in January 2026, reflecting growing awareness of this condition. Key semiological features include asymmetrical movements, eyes closed during the event, prolonged duration (often 10-30 minutes), pelvic thrusting, and side-to-side head movements. Patients may retain awareness or recall the event afterward, which is inconsistent with true generalized seizures.

The gold standard for diagnosing PNES is video-EEG monitoring, where clinical events are captured without corresponding epileptiform EEG changes. The AAN's new guidelines emphasize semiology-based diagnosis and psychological interventions rather than antiseizure medications, which are ineffective for PNES.

Treatment After the First Seizure: To Treat or Not to Treat?

This is where the rubber meets the road. The AAN/AES 2015 practice guideline gives us the evidence-based framework, and the answer is: it depends.

Starting an antiseizure medication (ASM) immediately after a first unprovoked seizure reduces recurrence risk by approximately 35% in the first two years. But here's the catch — it does not improve long-term prognosis beyond three years, may not improve quality of life, and carries its own adverse event rate of 7-31%, though most side effects are mild and reversible.

The decision should be individualized. Consider the patient's recurrence risk factors:

• Abnormal EEG with epileptiform abnormalities
• Significant brain imaging abnormality (stroke, tumor, prior CNS insult)
• Nocturnal seizure
• Remote symptomatic etiology
• Todd's paresis after the event
• Prior febrile seizures
• Family history of epilepsy

A young patient with a normal EEG, normal MRI, and no risk factors might reasonably defer treatment until a second seizure occurs. A patient with focal epileptiform discharges and a structural lesion on MRI is in a different category entirely.

When treatment is chosen, the common first-line options are:

• Levetiracetam — broad spectrum, minimal drug interactions, rapid titration. The go-to in many hospitals.
• Lamotrigine — excellent tolerability profile but requires slow titration over weeks to avoid Stevens-Johnson syndrome.
• Lacosamide — particularly useful for focal seizures with a favorable side effect profile.
• Valproate — broad spectrum but teratogenic. Avoid in women of childbearing potential unless no alternatives exist.

Patient Education and Safety

The workup isn't complete without addressing practical safety issues. Driving restrictions vary by jurisdiction but typically require 3-12 months seizure-free before returning to the road. Patients should avoid unsupervised swimming, prefer showers over baths, and stay away from heights and heavy machinery.

Teach seizure first aid: protect from injury, turn the patient on their side, do not put anything in their mouth, and time the event. Call emergency services if the seizure lasts more than 5 minutes, if seizures repeat without recovery, or if there's any injury during the event.

Refer to neurology within two weeks. That's the recommendation, and it should be a firm plan, not a vague suggestion.

Bottom Line

The first seizure workup is a balance between thoroughness and pragmatism. Get a good history with witness accounts. Check basic labs. Order an MRI with epilepsy protocol and an EEG within 72 hours. Distinguish provoked from unprovoked. Consider the mimics. And have an honest conversation with your patient about the risks, benefits, and uncertainties of starting treatment after just one event.

The evidence supports shared decision-making over reflexive medication prescriptions. Your job is to give them the data they need to make that choice — not to make it for them.