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Clinical
Epilepsy
20 notes available
1 Last Minute Review 2 Seizure Semiology & Localization 3 Epilepsy Diagnostic Workup 4 Neonatal & Infantile Encephalopathies 5 Childhood Epileptic Encephalopathies 6 Self-Limited & Absence Epilepsies 7 Temporal Lobe & Focal Epilepsies 8 Idiopathic Generalized Epilepsies 9 Progressive Myoclonic & Reflex Epilepsies 10 First Seizure & Acute Symptomatic 11 Status Epilepticus 12 Autoimmune Epilepsy 13 ASM Selection & Treatment 14 Individual ASM Profiles & PK 15 Presurgical Evaluation 16 Epilepsy Surgery 17 Neuromodulation (VNS, RNS, DBS) 18 Special Populations & SUDEP 19 Driving Regulations 20 Epilepsy Mimics & DDx
Clinical › Epilepsy

Presurgical Evaluation

Presurgical Evaluation

What Do You Need to Know?

  • Drug-resistant epilepsy = failure of 2 appropriate ASMs; probability of seizure freedom drops to ~5% per subsequent agent — refer early
  • Phase I (noninvasive): video-EEG, 3T MRI epilepsy protocol, FDG-PET, ictal SPECT/SISCOM, MEG/MSI, neuropsychological testing
  • Phase II (invasive): SEEG has largely replaced subdural grids in North America; required in 30–40% of surgical candidates
  • Language lateralization: fMRI has largely replaced Wada (>90% concordance); Wada still needed for memory lateralization
  • Concordance model: all modalities agree → >70% seizure-free outcome; discordance → poorer outcomes or need for Phase II
  • MRI-negative epilepsy: 30–45% Engel I (vs. 60–70% for lesional TLE); PET, MEG, SEEG become critical
  • Best prognostic factors: identifiable MRI lesion, mTLE with HS, concordance across modalities, shorter epilepsy duration
When to Refer for Epilepsy Surgery
  • Drug-resistant epilepsy (ILAE definition): failure to achieve seizure freedom after adequate trials of 2 tolerated, appropriately chosen ASMs
  • Probability of seizure freedom drops to ~5% with each subsequent ASM after 2 failures
  • Earlier referral = better outcomes: average delay from drug resistance to surgery is 10–20 years in many series
  • ERSET trial: early surgery for mTLE = 73% seizure-free vs. 0% continued medical therapy
  • ILAE recommends referral as soon as drug resistance is identified, regardless of epilepsy type
  • Comprehensive epilepsy center care reduces premature mortality — even in patients who do not undergo surgery
💎 Board Pearl

Drug-resistant epilepsy = failure of 2 ASMs. After 2 failures, each additional ASM adds only ~5% chance of seizure freedom. Do NOT wait for 5+ ASM failures before referring. Boards test this threshold repeatedly.

Phase I (Noninvasive) Evaluation
Modality What It Shows Sensitivity / Specificity Key Points
Video-EEG monitoring Capture habitual seizures; identify seizure-onset zone; classify semiology Gold standard for seizure localization Typically 5–14 days; capture ≥3–5 habitual seizures; ASMs often reduced; interictal IEDs lateralize irritative zone
3T MRI epilepsy protocol Structural lesion identification (HS, FCD, tumors, vascular malformations) 1.5T misses ~20% of lesions detected at 3T Key sequences: 3D T1 (1 mm), 3D FLAIR, coronal T2 perpendicular to hippocampus, SWI; NOT a “routine brain MRI”
FDG-PET Interictal hypometabolism in epileptogenic zone 80–90% sensitivity for mTLE; 45–60% extratemporal More sensitive than MRI for some subtle lesions; concordance with EEG strengthens surgical candidacy
Ictal SPECT (SISCOM) Ictal hyperperfusion at seizure-onset zone 70–90% for TLE; lower for extratemporal Must inject radiotracer within 30 sec of seizure onset; SISCOM = subtraction ictal SPECT coregistered to MRI
MEG / MSI Magnetic source imaging of interictal epileptiform discharges Complementary to EEG; better for neocortical foci Most useful in MRI-negative cases; detects tangential dipoles (sulcal cortex) better than EEG; guides SEEG placement
Neuropsychological testing Baseline cognitive function; lateralization of language/memory Supports lateralization; predicts postop deficits Verbal memory deficit = left temporal; visuospatial deficit = right temporal; establishes preoperative baseline

MRI Epilepsy Protocol — Key Sequences

  • 3D T1 (1 mm isotropic): cortical thickness, gray-white junction blurring (FCD), volumetric analysis
  • 3D FLAIR (1 mm isotropic): hippocampal signal abnormalities, FCD, gliosis
  • Coronal T2 (2–3 mm): perpendicular to long axis of hippocampus — essential for HS detection
  • SWI/GRE: cavernous malformations, calcifications, hemosiderin deposits
  • 7T MRI: detects subtle FCD and hippocampal subfield abnormalities missed on 3T

PET vs. SPECT — Key Distinctions

  • FDG-PET: interictal study; shows hypometabolism; hypometabolism extends beyond epileptogenic zone (localizing but not precise)
  • Ictal SPECT: inject within 30 sec of seizure onset; >45 sec = shows propagation, NOT onset; SISCOM increases accuracy
💎 Board Pearl

FDG-PET = interictal hypometabolism. Ictal SPECT = ictal hyperperfusion. These are OPPOSITE findings, both localizing to the epileptogenic zone. SPECT must be injected within 30 seconds of seizure onset — late injection shows propagation, not origin.

Language & Memory Lateralization

Language Dominance

  • Left hemisphere dominant: 95% of right-handers; ~70% of left-handers; bilateral/right language more common with early left-hemisphere lesions

fMRI vs. Wada Test

Feature fMRI Wada Test
Language lateralization >90% concordance with Wada; preferred first-line Gold standard but invasive; declining use
Memory lateralization Hippocampal fMRI protocols exist but not yet validated as Wada replacement Remains the standard for memory lateralization
Invasiveness Noninvasive; repeatable Invasive (catheter angiography); stroke risk <1%
Availability Widely available Limited to select centers; declining expertise

When Is the Wada Test Still Needed?

  • fMRI shows atypical or bilateral language representation
  • Memory lateralization before temporal lobe resection (esp. left TLE with concern for memory decline)
  • fMRI nondiagnostic due to motion artifact, poor task performance, or technical failure
  • Concern for contralateral hippocampal insufficiency (bilateral hippocampal abnormalities)
💎 Board Pearl

fMRI has replaced Wada for LANGUAGE lateralization (>90% concordance). Wada is still needed for MEMORY lateralization — especially before left temporal resection. Left hemisphere = language dominant in 95% of right-handers, 70% of left-handers.

Phase II (Invasive) Evaluation

Indications for Intracranial EEG

  • Discordant/inconclusive Phase I data; MRI-negative with lateralized EEG
  • Seizure onset from or near eloquent cortex; bilateral independent temporal onsets
  • Extratemporal epilepsy with broad localization; 30–40% of surgical candidates require Phase II

SEEG vs. Subdural Grids

Feature SEEG (Depth Electrodes) Subdural Grids
Implantation Stereotactic via twist-drill holes; robot-assisted Open craniotomy
Spatial coverage Deep structures (hippocampus, insula, cingulate); bilateral feasible Cortical surface; limited deep access; difficult bilateral placement
Complication rate Hemorrhage 1–4%; infection 1–2%; overall lower Overall 10–15% (hemorrhage, infection, CSF leak, edema)
Cortical mapping Limited by electrode geometry Excellent for detailed motor/sensory/language mapping
Current trend Has largely REPLACED grids in North America since ~2015 Declining; reserved for specific cortical mapping indications
Seizure-free outcomes Engel I at 1 year: ~58% Engel I at 1 year: ~46%

SEEG Technical Points

  • Typically 8–16 depth electrodes (8–18 contacts each); hypothesis-driven placement based on Phase I data
  • Robotic-assisted implantation (ROSA, Neuromate) — target error <2 mm; monitoring 7–14 days
  • SEEG-guided thermocoagulation: can ablate small foci at electrodes — minimally invasive therapeutic option
💎 Board Pearl

SEEG has largely replaced subdural grids in North America. SEEG = lower complications (1–4% hemorrhage vs. 10–15% overall for grids), better for deep structures (hippocampus, insula, cingulate), and allows bilateral implantation. Grids are reserved for cortical surface functional mapping.

Concordance Model & Surgical Decision-Making
  • All modalities concordant (semiology + EEG + MRI + PET + neuropsych) → >70% seizure-free outcome
  • Discordance among modalities → poorer outcomes; may need Phase II or may not proceed with surgery
  • No single test is sufficient — convergence of multiple independent data sources is the fundamental principle
  • Final decision at multidisciplinary epilepsy surgery conference (epileptologist, neurosurgeon, neuroradiologist, neuropsychologist)

Key Concordance Domains

  • Seizure semiology • Scalp EEG (interictal + ictal) • MRI (structural lesion)
  • Neuropsychological profile • FDG-PET (hypometabolism) • Ictal SPECT (hyperperfusion) • MEG
MRI-Negative Epilepsy
  • Definition: no identifiable lesion on 3T MRI; affects up to 30% of drug-resistant focal epilepsy patients
  • Surgical outcomes: 30–45% Engel I (vs. 60–70% for lesional TLE) — counsel patients about lower probability
  • PET, MEG, SEEG become critical — concordance among these can substitute for a visible lesion
  • 7T MRI + computational postprocessing can reveal subtle FCD in 20–30% of previously MRI-negative cases
  • Most MRI-negative patients require SEEG before resection; if not feasible, consider neuromodulation (RNS, VNS, DBS)
Engel Classification of Surgical Outcomes
Engel Class Outcome Subclasses
Class I Free of disabling seizures Ia = completely seizure-free; Ib = only auras; Ic = some seizures postop but seizure-free ≥2 years; Id = only generalized seizures with drug withdrawal
Class II Rare disabling seizures Almost seizure-free; rare seizures after initial complete control
Class III Worthwhile improvement Meaningful seizure reduction but ongoing disabling seizures
Class IV No worthwhile improvement No significant change or worsening of seizures
💎 Board Pearl

Engel Ia = completely seizure-free (the goal). Engel Ib = only auras (still considered “free of disabling seizures”). Boards may describe a patient with only auras postop and ask you to classify — that is Engel Class Ib, NOT Class II.

Favorable Prognostic Factors for Surgery
  • Identifiable lesion on MRI — strongest single predictor (especially HS or low-grade tumor)
  • Concordance across all modalities (EEG, MRI, PET, semiology, neuropsych)
  • Mesial temporal lobe epilepsy with hippocampal sclerosis — 60–80% Engel I
  • Shorter duration of epilepsy before surgery — earlier surgery = better outcomes
  • Normal IQ (≥70)
  • Unilateral interictal epileptiform discharges concordant with MRI; single seizure type with consistent aura
  • Complete resection of the epileptogenic lesion; temporal lobe epilepsy (better outcomes than extratemporal)
💎 Board Pearl
  • Drug-resistant epilepsy = failure of 2 ASMs (not 3, not 5) — ~5% chance of seizure freedom per additional agent after 2 failures
  • FDG-PET = interictal HYPOmetabolism; Ictal SPECT = ictal HYPERperfusion — both localize to the epileptogenic zone but at different times
  • SISCOM = subtraction ictal SPECT coregistered to MRI; must inject within 30 sec of seizure onset for optimal localization
  • fMRI replaces Wada for language (>90% concordance), but Wada still needed for memory lateralization in selected patients (esp. left TLE)
  • SEEG has replaced subdural grids in most centers: lower complications, better for deep structures, allows bilateral sampling
  • Concordance = success: all modalities agree → >70% seizure-free; any discordance lowers expected outcomes
Clinical Pearls
  • A “normal MRI” does NOT mean the patient is not a surgical candidate. MRI-negative patients can achieve 30–45% seizure freedom with surgery. PET, MEG, and SEEG can localize the epileptogenic zone when MRI fails. Always use 3T with an epilepsy protocol — 1.5T misses ~20% of lesions.
  • The average delay from drug resistance to surgical referral is 10–20 years. Every year of ongoing seizures worsens cognitive outcomes, psychosocial disability, and SUDEP risk. If a patient has failed 2 appropriate ASMs, the conversation about surgery should begin immediately.

References

  1. Friedman D, Engel J. Surgical treatments, devices, and nonmedical management of epilepsy. Continuum (Minneap Minn). 2025;31(1):165–186.
  2. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069–1077.
  3. Jehi L, Jette N, Kwon CS, et al. Timing of referral to evaluate for epilepsy surgery: expert consensus recommendations from the Surgical Therapies Commission of the ILAE. Epilepsia. 2022;63(10):2491–2506.
  4. Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial (ERSET). JAMA. 2012;307(9):922–930.
  5. Tandon N, Tong BA, Friedman ER, et al. Analysis of morbidity and outcomes associated with use of subdural grids vs stereoelectroencephalography in patients with intractable epilepsy. JAMA Neurol. 2019;76(6):672–681.
  6. Jehi L, Morita-Sherman M, Love TE, et al. Comparative effectiveness of stereotactic electroencephalography versus subdural grids in epilepsy surgery. Ann Neurol. 2021;90(6):927–939.
  7. Mullin JP, Shriver M, Alomar S, et al. Is SEEG safe? A systematic review and meta-analysis of stereoelectroencephalography-related complications. Epilepsia. 2016;57(3):386–401.
  8. West S, Nolan SJ, Cotton J, et al. Surgery for epilepsy. Cochrane Database Syst Rev. 2015;(7):CD010541.
  9. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311–318.
  10. Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA. 2015;313(3):285–293.