What diagnostic work‑up and first‑line treatment are recommended for a patient with focal seizures involving the right lower limb?

Focal Seizures Involving the Right Lower Limb: Diagnostic Work-Up and First-Line Treatment

Immediate Diagnostic Work-Up

MRI brain with a dedicated epilepsy protocol is the essential imaging study for any patient with focal seizures involving the right lower limb, as it detects structural abnormalities in 55% of focal seizure patients compared to only 18% with CT. 1, 2

Neuroimaging Strategy

• Perform MRI brain with epilepsy protocol including coronal T1-weighted imaging, high-resolution 3D T1-weighted gradient echo, coronal T2-weighted sequences, and coronal/axial FLAIR sequences as the primary imaging modality 2, 3
• Use 3T MRI when available for superior lesion detection over 1.5T scanners 3
• Reserve emergent non-contrast CT only for situations where MRI is unavailable and you need to rapidly exclude intracranial hemorrhage, stroke, mass lesion, or hydrocephalus 2, 4
• MRI is superior because 29% of abnormal intracranial findings in focal seizures are missed on initial CT 2

Electroencephalography

• Obtain EEG as a core component of the neurodiagnostic work-up to confirm focal seizure diagnosis and localize the epileptogenic focus 2, 5
• Proceed to video-EEG monitoring if routine EEG is nondiagnostic but clinical suspicion remains high 2
• Focal seizures show ictal discharges originating from one hemisphere 2

Laboratory Testing

• Check serum glucose and sodium levels in all patients, as these are the most frequent metabolic abnormalities causing focal neurologic deficits and the only tests that consistently alter acute management 4, 3
• Obtain pregnancy test if the patient has reached menarche 4
• Consider toxicology screening if drug exposure is suspected 4

When to Perform Lumbar Puncture

• Reserve lumbar puncture for cases with fever plus focal seizures, persistent altered mental status, or immunocompromised status suggesting meningitis or encephalitis 2, 4
• Routine LP is not indicated for uncomplicated focal seizures 4

Structural Pathologies to Identify

The MRI should specifically evaluate for:

• Focal cortical dysplasia (most common epileptogenic lesion requiring dedicated protocol) 3
• Hippocampal sclerosis 3
• Developmental abnormalities 1, 3
• Neoplasms 1, 3
• Vascular malformations 3
• Prior infarction, hemorrhage, or thrombosis (approximately 4% of first-time focal seizures have urgent intracranial pathology) 1, 3
• Gliosis from prior injury 3

First-Line Treatment Approach

For a first unprovoked focal seizure, do not initiate antiepileptic drugs in the acute setting unless the seizure occurred in the context of remote symptomatic brain disease (prior stroke, traumatic brain injury >7 days ago, tumor, or chronic CNS disease). 4

When to Start Treatment

• Defer AED initiation for most first unprovoked focal seizures, as starting treatment reduces 1-2 year recurrence risk but does not affect long-term remission rates or mortality 4
• The number needed to treat to prevent one recurrence within two years is 14, exposing many patients to medication adverse effects without proven mortality benefit 4
• Consider starting AED only when focal seizures occur with remote symptomatic brain disease or injury 4

First-Line Medication Options

When treatment is indicated, carbamazepine, phenytoin, or valproic acid are rated as first-line drugs for focal seizures, with Level A evidence supporting seven drugs for initial monotherapy showing no clear superiority of one over another. 5, 6

Specific Drug Choices:

• Lamotrigine, gabapentin, topiramate, and oxcarbazepine have monotherapy indications in many countries for focal seizures 5
• Levetiracetam is an effective option with favorable tolerability profile 7, 6
• Lacosamide is available in both oral and IV forms and is considered safe, though loading doses are not well-studied 4
• Cenobamate represents the latest approved option for focal seizures 6

Drug Selection Factors:

• Consider adverse-effect profiles, age, pregnancy potential, concomitant diseases, and medication interactions 5
• Avoid valproate in women of childbearing potential due to high teratogenic risk 4
• Newer AEDs generally have better tolerability than older agents, though evidence for superiority is limited 5, 6

Loading Dose Strategies (When Immediate Treatment Required):

• Carbamazepine: 8 mg/kg oral suspension as single loading dose (suspension preferred over tablets due to erratic absorption) 4
• Lamotrigine: 6.5 mg/kg oral load only in patients on lamotrigine >6 months without prior rash; contraindicated in AED-naïve patients due to Stevens-Johnson syndrome risk requiring slow titration over weeks 4

Disposition and Follow-Up

• Discharge patients who have returned to clinical baseline with normal neurologic exam and reliable outpatient follow-up 4
• Admit patients with persistent abnormal neurologic findings, abnormal investigation results requiring inpatient management, or failure to return to baseline 4
• Arrange outpatient neurology follow-up for EEG and treatment decisions 4

Seizure Recurrence Risk

• Focal seizures have a recurrence rate up to 94%, considerably higher than generalized seizures at 72% 2
• Mean time to first recurrence is 121 minutes (median 90 minutes), with >85% occurring within 6 hours 4
• Risk factors for higher recurrence include abnormal EEG, remote symptomatic seizures, Todd's paralysis, and abnormal neurological examination 4

Common Pitfalls to Avoid

• Do not rely on CT alone for focal seizure evaluation, as MRI detects abnormalities missed by CT in 47% of children with focal seizures 2
• Do not miss structural lesions by failing to perform appropriate neuroimaging with epilepsy protocol 4
• Do not assume alcohol withdrawal as the cause in first-time focal seizures without excluding symptomatic causes first 4
• Do not fail to return patient to baseline before making disposition decisions—failure to regain baseline alertness within several hours suggests underlying structural abnormality requiring urgent neuroimaging 2