How is epilepsy diagnosed and what are the first‑line anti‑seizure medications for focal versus generalized seizures?

Epilepsy Diagnosis and First-Line Anti-Seizure Medications

Diagnostic Approach

Epilepsy is diagnosed clinically through detailed seizure history and examination, with EEG and MRI serving as essential confirmatory tools rather than standalone diagnostic tests. 1

Clinical Diagnosis

• Epilepsy is defined as: at least two unprovoked seizures occurring more than 24 hours apart, one unprovoked seizure with >60% recurrence risk, or diagnosis of a specific epilepsy syndrome 2, 3
• Critical history elements include: onset timing relative to consciousness loss, movement patterns (symmetrical vs asymmetrical), number of movements, duration of unconsciousness, and presence of focal features 4
• Focal features to identify: unilateral motor activity, versive head/eye deviation, hemiparesis, aphasia, sensory symptoms referable to one brain region, or impaired awareness with lateralizing signs 5
• Distinguish from syncope: epileptic myoclonus begins at onset of unconsciousness with synchronous movements lasting 74-90 seconds, whereas syncope features ~10 asynchronous movements with <30 seconds unconsciousness 4

Electroencephalography (EEG)

• EEG is essential for confirming seizure type and localizing epileptogenic focus, though it should not be used routinely in non-specialized settings in resource-limited areas 1, 5
• Focal seizures show ictal discharges originating from one hemisphere 5
• Video-EEG monitoring should be pursued when routine EEG is nondiagnostic but clinical suspicion remains high 5
• Continuous EEG increases sensitivity for detecting epileptiform activity including status epilepticus compared to brief intermittent recordings 4

Neuroimaging

MRI with dedicated epilepsy protocol is the definitive imaging study for newly diagnosed seizures, while CT is reserved for emergent evaluation only. 1, 5

Acute/Emergency Setting

• Non-contrast CT rapidly identifies structural pathology requiring immediate intervention: intracranial hemorrhage, stroke, vascular malformation, hydrocephalus, and tumors 1
• CT limitations: only 30% detection rate in focal epilepsies, 6% in generalized seizures, and poor sensitivity for orbitofrontal/medial temporal lesions 1

Non-Emergent Evaluation

• MRI with epilepsy protocol (3T scanner, T1-weighted volumetric acquisition with 1mm isotropic voxels, high-resolution coronal slices for hippocampal pathology) achieves 84% sensitivity and 70% specificity for intractable seizures 5
• MRI detects abnormalities missed by CT in 47% of children with focal seizures 5
• MRI is rarely indicated in neurologically normal patients with generalized seizures (only 2% positive findings) given their genetic basis 2, 5

Laboratory Evaluation

• Check glucose in all patients with focal features, as hypoglycemia can present with focal neurologic deficits 5
• Glucose abnormalities and hyponatremia are the most frequent metabolic causes, usually predicted by history and physical examination 5
• Toxicology screening when drug or toxin exposure is suspected 5
• Lumbar puncture is reserved for fever with focal seizures, persistent altered mental status, or signs of CNS infection 5

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First-Line Anti-Seizure Medications

Focal Seizures

For focal seizures, carbamazepine should be preferentially offered as first-line monotherapy, with phenobarbital as an alternative when cost is a primary consideration. 1

• Carbamazepine is the preferred first-line agent for children and adults with partial (focal) onset seizures 1
• Alternative monotherapy options include phenobarbital, phenytoin, and valproic acid, all demonstrating efficacy for focal seizures 1
• Phenobarbital should be offered as first option if acquisition costs are paramount and availability can be assured 1
• Focal seizures have 94% recurrence rate, considerably higher than generalized seizures at 72%, supporting early treatment initiation 5

Generalized Seizures

For generalized seizures, valproic acid is the first-line medication, with carbamazepine as an alternative when valproate is contraindicated. 1

Standard Recommendations

• Valproic acid is preferentially effective for generalized seizures including tonic-clonic, absence, and other motor types 1
• Carbamazepine may be considered as alternative monotherapy 1
• Phenobarbital and phenytoin are also effective but carry higher risk of behavioral adverse effects 1

Special Populations

• Women of childbearing potential: valproic acid should be avoided if possible due to teratogenicity; use minimum effective dose monotherapy if necessary 1
• Folic acid supplementation should be routine for women on antiepileptic drugs 1
• Intellectual disability with epilepsy: consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects 1

Treatment Principles

• Monotherapy with standard antiepileptic drugs should be offered initially 1
• Do not routinely prescribe antiepileptic drugs after a first unprovoked seizure 1
• Consider discontinuation after 2 seizure-free years, with decision involving patient and family consideration of clinical, social, and personal factors 1
• Breastfeeding remains appropriate for phenobarbital, phenytoin, carbamazepine, and valproic acid 1

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Status Epilepticus Management

Without IV Access

• Rectal diazepam should be administered 1
• IM phenobarbital may be considered when rectal diazepam is not possible due to medical or social reasons 1
• IM diazepam is not recommended due to erratic absorption 1

With IV Access

• IV benzodiazepine (lorazepam preferred over diazepam) should be administered first 1
• For sustained control: IV phenobarbital or phenytoin should be administered 1
• Alternative agents for refractory status epilepticus include IV valproate 30 mg/kg or levetiracetam 30 mg/kg 1

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Common Pitfalls

• Avoid misclassifying focal seizures as generalized: in children <3 years, 37% of apparently generalized seizures actually originate from focal cortical activity 5
• Do not rely on EEG alone: >60% of persons with idiopathic generalized epilepsies have atypical EEG abnormalities that can be misleading 6
• Recognize secondary bilateral synchrony: focal epilepsies can produce generalized-appearing EEG patterns 6
• Failure to return to baseline within several hours after seizure suggests structural abnormality requiring urgent neuroimaging 5
• Avoid narrow-spectrum medications for unclassified seizures: misdiagnosis of focal epilepsy when generalized epilepsy is present leads to inappropriate medication selection 7