Epilepsy Diagnostic Workup

What You'll Learn

EEG is the single most important ancillary test — routine EEG detects IEDs in ~25–35% on first study; cumulative yield approaches 80–90% in many series with 3–4 repeated studies including sleep (figures vary by population and whether sleep is included)
MRI with epilepsy protocol at 3T is preferred (HARNESS-MRI 2019); incremental yield over a dedicated 1.5T epilepsy protocol is ~10–15%, larger when compared with non-dedicated 1.5T. A high-quality 1.5T epilepsy protocol is acceptable when 3T is unavailable (especially FCD, hippocampal sclerosis)
First seizure labs: glucose, BMP (Na, Ca, Mg), CBC, tox screen — identify provoked causes before committing to ASM therapy
Surgical evaluation after failure of 2 appropriate ASMs — video-EEG, FDG-PET, ictal SPECT, MEG, neuropsychological testing
Autoimmune workup when new-onset refractory seizures, FBDS, limbic encephalitis features, or APE2 ≥4 — send serum AND CSF panels
Genetic testing highest yield in neonatal/infantile seizures and DEEs (Dravet >80%, BFNS ~80%, DEE 30–50%)
Prolactin elevated post-GTCS and focal impaired awareness (not absence, not PNES) — limited sensitivity; draw 10–20 min AFTER the event and compare to baseline drawn ≥6 h later

HighYield Pearls

Routine 30-min EEG sensitivity ~30–50% in known epilepsy: a single normal EEG does NOT exclude epilepsy — epilepsy remains a clinical diagnosis
Sleep-deprived EEG increases yield to ~80%: sleep deprivation activates IGE and focal IEDs — order this when routine EEG is nondiagnostic but suspicion remains high
MRI epilepsy protocol = 3T with thin-slice coronal hippocampi + FLAIR + T1 IR + GRE/SWI: looks for hippocampal sclerosis, FCD, cavernoma, DNET/ganglioglioma, encephalomalacia — standard brain MRI is insufficient
Hippocampal sclerosis triad: volume loss + T2/FLAIR hyperintensity + loss of internal architecture on coronal T2 perpendicular to hippocampus
FDG-PET shows interictal HYPOmetabolism at the epileptogenic zone (NOT hypermetabolism) — classic board trick
Ictal SPECT: Tc-99m HMPAO injected during seizure (ideally <30 sec from onset) vs baseline interictal; co-registered with MRI = SISCOM for localization
Video-EEG LTM is essential for PNES vs epileptic: capture of the habitual spell with no EEG correlate AND incongruent semiology — confront with multidisciplinary team
cEEG for ICU/altered MS to detect NCSE — subclinical seizures in 10–30% of acute brain injury patients
Genetic testing for DEEs: gene panel first (Dravet SCN1A, CDKL5, STXBP1, KCNQ2, KCNT1, PCDH19); WES if panel negative; CSF glucose for GLUT1 (SLC2A1)
Do NOT misread benign variants as epileptic: wicket spikes, BETS/SSS, 14-and-6 positive spikes, 6-Hz phantom spike-wave, SREDA, BETS-of-sleep — all are normal variants

🔍 Quick ReferenceEEG patterns · MRI / imaging · Workup pearls

EEG patterns / findings

Spike, sharp wave, spike-wave, polyspike-wave → epileptiform discharges (define lateralization/localization)
3 Hz generalized spike-wave activated by HV → childhood absence epilepsy (CAE)
Photoparoxysmal response (PPR) — generalized SW to photic stim → IGE / photosensitive epilepsy (esp JME); 5% normal but pathologic if seizure occurs
Hypsarrhythmia → infantile spasms (West syndrome)
Centrotemporal sharps activated by sleep → self-limited epilepsy with centrotemporal spikes (BECTS)
Wicket spikes / BETS-SSS / 14-and-6 / 6-Hz phantom SW / SREDA → BENIGN variants — do NOT call epileptic
Captured habitual spell with NO EEG correlate → PNES (especially if incongruent semiology)
NREM sleep recording → maximally activates IEDs (REM suppresses)

MRI / imaging

Coronal T2/FLAIR hippocampal atrophy + signal hyperintensity + loss of internal architecture → hippocampal sclerosis (mTLE)
Transmantle sign on FLAIR (linear hyperintensity cortex-to-ventricle) → focal cortical dysplasia type IIb (Taylor type, balloon cells)
Popcorn lesion with hemosiderin rim on SWI/GRE → cavernoma (cavernous malformation)
Cortical/subcortical “bubbly” T2-hyperintense temporal lobe mass in young patient → DNET
Cystic temporal lobe mass with enhancing mural nodule → ganglioglioma
Interictal FDG-PET HYPOmetabolism at seizure focus → epileptogenic zone (80–90% mTLE; 45–60% extratemporal)
Ictal SPECT hyperperfusion subtracted from interictal & overlaid on MRI → SISCOM localization
Encephalomalacia / gliosis on FLAIR → post-traumatic / post-stroke epilepsy

Workup / pitfalls

Single normal routine EEG → does NOT exclude epilepsy — repeat with sleep / sleep deprivation
SEEG (depth electrodes) → deep/bilateral/multilobar hypotheses; lower morbidity than grids; no large-area cortical mapping
Subdural grids → superficial neocortical focus needing extensive language/functional mapping
MEG dipole localization → superior for deep/tangential sources; cortical mapping
CSF/serum glucose ratio <0.4 (fasting LP) → GLUT1 deficiency (SLC2A1) — treat with ketogenic diet
IV pyridoxine 100 mg with dramatic seizure cessation on EEG → pyridoxine-dependent epilepsy (ALDH7A1); trial PLP for PNPO
HV-induced posterior slowing in adolescent → NORMAL response — not absence

First Seizure Evaluation: Children vs. Adults

Component	Children	Adults
History	Witness/video; birth hx (HIE, prematurity); developmental milestones; febrile seizure hx; family hx; vaccination timing	Witness/video; prior unrecognized events (staring, morning myoclonus); alcohol/drug use; sleep deprivation; driving/occupational risk
Labs	Glucose, BMP (Na, Ca, Mg), CBC; metabolic workup in neonates (lactate, ammonia, amino acids); tox screen in adolescents	Glucose, BMP (Na, Ca, Mg), CBC, LFTs, ammonia, tox screen; prolactin (limited — draw 10–20 min after event, compare to baseline ≥6 h later)
When to CT	Emergent: trauma, focal deficits, persistent AMS, VP shunt; NOT routine for simple febrile seizure	Emergent: focal deficits, persistent AMS, trauma, anticoagulation, cancer hx, immunocompromised, meningeal signs
When to MRI	All focal seizures; DD + seizures; abnormal exam; NOT required if classic IGE with typical EEG (e.g., CAE with 3 Hz spike-wave)	ALL adults with unprovoked seizures — epilepsy protocol; 3T preferred (HARNESS-MRI 2019), dedicated 1.5T epilepsy protocol acceptable when 3T unavailable; CT alone is insufficient
EEG timing	Within 24–48 h; first routine EEG with sleep captures IEDs in ~50–60% of children; yield drops substantially without sleep — sleep recording essential in children	Within 24–48 h; IED ~25–35% on first routine EEG; sleep-deprived or prolonged EEG if initial nondiagnostic
EEG yield	Higher yield than adults; pathognomonic patterns (hypsarrhythmia, 3 Hz spike-wave, centrotemporal spikes)	Yield 80–90% after 3–4 routine EEGs with sleep deprivation and longer recording

💎 Board Pearl

EEG within 24–48 h has the HIGHEST yield — IEDs are most likely captured in the early postictal period
Classic IGE in children (CAE, JAE, JME) with typical EEG may NOT require MRI — any atypical feature mandates imaging

When to Order EEG

Routine EEG (20–40 min)

First-line test for any suspected seizure or epilepsy
IED detection: ~25–35% on first routine EEG; cumulative yield approaches 80–90% in many series with 3–4 repeated studies including sleep (numbers vary by population and inclusion of sleep recordings)
Should include wakefulness + drowsiness/sleep for maximal yield
Normal EEG does NOT exclude epilepsy — epilepsy is a clinical diagnosis

Sleep-Deprived EEG

Sleep-deprived EEG adds ~20% incremental yield over routine awake EEG
Recording during NREM sleep (regardless of sleep deprivation) activates most IEDs — capturing sleep is the key driver of yield
Particularly useful for: suspected IGE (JME, CAE), temporal lobe epilepsy, nondiagnostic routine EEG

Prolonged / Ambulatory EEG (24–72 h)

When routine EEG is nondiagnostic but clinical suspicion remains high
Captures interictal and potentially ictal events; correlates symptoms with EEG changes
Home ambulatory EEG is an alternative to inpatient monitoring for selected patients

Continuous EEG (cEEG) — ICU Indications

Unexplained altered mental status / encephalopathy
Post-cardiac arrest (detect nonconvulsive SE; prognostication)
Refractory SE (titrate IV anesthetics to electrographic seizure suppression; burst suppression is commonly used in deeper coma but is not the only evidence-based endpoint)
Comatose patients with suspected subclinical seizures
Acute brain injury (TBI, SAH, ICH) — subclinical seizures in 10–30%
Per ACNS 2015: ≥24 h cEEG in non-comatose patients with unexplained altered mental status; ≥48 h in comatose patients (yield rises from ~50% at 24 h to ~80–90% at 48 h in coma)

Activation Procedures

Procedure	Mechanism	Key Clinical Utility
Hyperventilation (3–5 min)	Hypocapnia → vasoconstriction → hyperexcitability	Provokes absence seizures >90%; activates 3 Hz spike-wave in CAE
Photic stimulation	Intermittent flashing light (1–30 Hz)	PPR: generalized spike-wave; seen in IGE (especially JME). Distinguish from photic driving
Sleep	NREM disinhibits cortical networks	NREM activates most IEDs; REM suppresses them. Adds 20–30% yield

Clinical Pearl

Hyperventilation is the single best activation procedure for absence epilepsy — triggers 3 Hz spike-wave in >90% of untreated CAE. If a board question describes staring spells with a normal interictal EEG, the answer is hyperventilation during the EEG, not a repeat study.

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