Epilepsy: Seizure Types, Diagnosis, and Treatment Options

3.4 Million Americans Living Between Seizures

Epilepsy affects approximately 3.4 million Americans and 65 million people worldwide, making it the fourth most common neurological disorder after migraine, stroke, and Alzheimer's disease. Despite the prevalence, epilepsy remains one of the most misunderstood conditions in medicine. A single seizure does not constitute epilepsy — the diagnosis requires either two unprovoked seizures occurring more than 24 hours apart, one unprovoked seizure with a high probability of recurrence (greater than 60% over 10 years), or a diagnosis of an epilepsy syndrome. The distinction between a provoked seizure (caused by a reversible factor like low blood sugar, fever, or alcohol withdrawal) and an unprovoked seizure is clinically significant: provoked seizures generally do not require chronic antiseizure treatment.

ILAE 2017 Seizure Classification: A Revised Framework

The International League Against Epilepsy (ILAE) published a revised seizure classification in 2017 that updated decades-old terminology to reflect modern understanding of seizure onset and spread. The classification organizes seizures by onset type, awareness level, and motor manifestations.

• Focal onset seizures: Begin in one hemisphere, in a specific brain network. Divided by awareness — focal aware (formerly "simple partial") and focal impaired awareness (formerly "complex partial").
• Generalized onset seizures: Begin simultaneously in both hemispheres. Include tonic-clonic (formerly "grand mal"), absence (formerly "petit mal"), myoclonic, atonic, tonic, and clonic subtypes.
• Unknown onset seizures: When onset cannot be determined from available information.

The removal of the term "partial" and the adoption of "focal" were not cosmetic — they reflect the understanding that seizures arise from specific neural networks, not merely anatomical brain areas. The distinction between focal aware and focal impaired awareness has significant implications for driving restrictions, treatment selection, and disability documentation.

Diagnostic Evaluation: EEG and Neuroimaging

The electroencephalogram (EEG) is the primary diagnostic tool for epilepsy, recording electrical activity from scalp electrodes to detect abnormal discharges — interictal epileptiform discharges (IEDs) — that occur between seizures in most people with epilepsy. A routine awake EEG captures abnormalities in approximately 50% of people with epilepsy on the first recording; repeat EEGs, sleep EEGs, and prolonged ambulatory EEGs improve yield. Video-EEG monitoring — recording EEG simultaneously with video during a clinical event — is the gold standard for confirming the seizure type, localizing the seizure onset zone, and distinguishing epileptic seizures from psychogenic non-epileptic seizures (PNES).

MRI brain imaging is essential for identifying structural causes of epilepsy — hippocampal sclerosis, cortical dysplasia, tumors, cavernous malformations, and stroke. A standard brain MRI does not suffice; epilepsy protocol MRI uses thin-slice sequences specifically angled to visualize the hippocampus and cortex in detail. For patients being evaluated for surgical treatment, additional imaging — PET, SPECT, or MRI with surface-based analysis — may be needed to localize the epileptogenic zone.

First-Line Anti-Seizure Medications Compared

Drug-Resistant Epilepsy: The Two-Drug Threshold

The ILAE defines drug-resistant epilepsy (DRE) as failure of adequate trials of two tolerated and appropriately chosen anti-seizure medications (ASMs) to achieve sustained seizure freedom. This definition places the threshold for "drug resistance" at a relatively early stage — approximately 30–40% of people with epilepsy will not achieve seizure control with ASMs alone, regardless of how many additional drugs are tried. After two drug failures, the probability that a third drug will achieve seizure freedom is approximately 4%. Drug resistance is a fixed diagnosis, not a temporary state.

The identification of DRE should trigger referral to a comprehensive epilepsy center for evaluation of surgical options, neuromodulation devices, and diet therapies. Continuing to cycle through additional medications without surgical evaluation is a common and consequential error. Epilepsy surgery remains underutilized: only approximately 1% of surgical candidates actually undergo resection, despite success rates of 60–70% seizure freedom in the best candidates.

Neuromodulation: VNS, RNS, and DBS

For patients who are not surgical candidates, neuromodulation devices provide seizure control without removing brain tissue.

• Vagus Nerve Stimulator (VNS): An implanted pulse generator that delivers periodic electrical stimulation to the left vagus nerve, modulating brain excitability. Reduces seizures by 50% or more in approximately 50% of patients after 3 years. No significant systemic side effects; voice changes during stimulation are common.
• Responsive Neurostimulation (RNS/NeuroPace): A closed-loop device implanted directly in the skull that continuously monitors the EEG from two leads placed at the seizure onset zone and delivers brief electrical stimulation when it detects abnormal patterns. Median seizure reduction of 66–75% in clinical trials after 5 years. Uniquely provides longitudinal EEG data for clinical monitoring.
• Deep Brain Stimulation (DBS): Electrodes implanted in the anterior nucleus of the thalamus (ANT-DBS, FDA approved 2018) provide sustained stimulation. Reduces seizures by approximately 50% at five years in the SANTE trial, with continued improvement over time.

Ketogenic Diet: Mechanism and Evidence

The ketogenic diet (KD) — a high-fat, very low-carbohydrate diet that induces a ketotic metabolic state — has been used for epilepsy since the 1920s. The anticonvulsant mechanism is not fully understood but likely involves multiple pathways: ketone bodies (beta-hydroxybutyrate, acetoacetate) enhance GABA inhibitory tone, reduce glutamate excitatory activity, and provide an alternative fuel source that stabilizes neuronal energy metabolism. The diet is most studied and most effective in children; approximately 50% of children on the KD achieve a 50% or greater seizure reduction, and 10–15% become seizure-free. Modified versions — the modified Atkins diet and low glycemic index treatment — are more palatable and increasingly used in adolescents and adults.

SUDEP: The Silent Risk

Sudden Unexpected Death in Epilepsy (SUDEP) occurs when a person with epilepsy dies suddenly without a clear cause identifiable at autopsy. The risk is approximately 1 in 1,000 per year for the general epilepsy population, rising to 1 in 150 for people with drug-resistant epilepsy and frequent generalized tonic-clonic seizures. SUDEP accounts for up to 17% of all deaths in epilepsy and is the leading cause of premature death in people with epilepsy who are otherwise healthy. The mechanism likely involves seizure-related cardiac and respiratory dysfunction, possibly exacerbated by nocturnal seizures and prone sleeping position. Seizure control — by any means — is the primary protective strategy. The conversation about SUDEP risk belongs in every epilepsy clinic. It rarely happens.