Epilepsy Surgery

by Michael Wong, MD, PhD

PREOPERATIVE EVALUATION

EEG

  1. Ictal Epileptiform Activity: Patients with unilateral temporal lobe ictal onset by invasive monitoring had better outcome (60-70% seizure-free) compared to bilateral ictal foci (10-30%) (Hufnagel et al. 1994, Weinand et al. 1992).
  2. Interictal Epileptiform Activity:
    1. When interictal activity is restricted to one focus, ~95% will be concordant with ictal onset, but ~5% will be falsely lateralizing (Weinand et al. 1992). 100% concordant lateralization of interictal and ictal activity results in excellent outcome (~90% seizure-free)
    2. (Hufnagel et al. 1994). Degree of lateralization of interictal activity by itself (>90% lateralization) predicts a better outcome (Chung et al. 1991).
    3. When interictal activity is bilateral or multifocal, ~50% of patients with unilateral ictal onset will still become seizure-free (Holmes et al. 1997, Hufnagel et al. 1994, Weinand et al. 1992).
    4. When interictal activity is concordant with unilateral hippocampal atrophy, ictal EEG is always unilateral, suggesting that ictal EEG may not be necessary (Cendes et al. 2000)
  3. Scalp vs Invasive Monitoring
    1. Scalp recording only: When interictal and ictal scalp EEG and MRI data converged to one temporal lobe focus, ~80% of patients without invasive monitoring were seizure-free at 4 years (Thadani et al. 1995).
    2. Patients with and without invasive monitoring had similar seizure outcome (Wyllie et al. 1998), but patients with invasive monitoring represent more difficult cases.

MRI

  1. Methodology: resolution ~3 mm; thin contiguous cuts, volumetric hippocampal analysis, and pulse sequence techniques have greatly increased sensitivity of MRI in detecting epileptic lesions.
  2. Sensitivity/Specificity: Pooled data from 809 patients (Spencer 1994) gave a sensitivity of 55% and specificity of 78% for temporal lobe and sensitivity of 43% and specificity of 95% for extratemporal regions, compared to EEG localization.
  3. Identification of a lesion on MRI predicts a better outcome (Berkovic et al. 1995, Jack et al. 1992).

SPECT

  1. Interictal SPECT: resolution ~10 mm; pooled data from 539 patients (Spencer 1994) gave a sensitivity of 66% and specificity of 68% for temporal lobe and sensitivity of 60% and specificity of 93% for extratemporal regions, compared to EEG localization; false localization in 10-25%.
  2. Flumazenil: flumazenil-PET had similar diagnostic sensitivity than FDG-PET, but gave complementary information in specific clinical situations (Ryvlin et al. 1998).

PET

  1. Flurodeoxyglucose: resolution ~5 mm; pooled data from 312 patients (Spencer 1994) gave a sensitivity of 84% and specificity of 86% for temporal lobe and sensitivity of 33% and specificity of 95% for extratemporal regions, compared to EEG localization; false localization in ~2% (temporal) to 10% (extratemporal).
  2. Flumazenil: flumazenil-PET had similar diagnostic sensitivity than FDG-PET, but gave complementary information in specific clinical situations (Ryvlin et al. 1998).

Comparative Studies

  1. Several studies have compared various modalities of EEG, MRI, SPECT, and PET (Ho et al. 1995; Markand et al. 1997, Spencer 1994, Won et al. 1999). While some differences exist between studies, overall the various modalities are fairly comparable in diagnostic sensitivity and accuracy. In individual cases, however, different modalities may reveal different or complementary
    information.
  2. Lesion (MRI)/Focus (EEG) Incongruence: In patients where a MRI lesion and EEG ictal focus occurred in completely separate locations, one study reported good outcome when the EEG focus was resected (Holmes et al. 1999); however, another study found better outcome in patients where the lesion was resected compared to patients where the focus was resected (Clarke et al. 1996).

PREDICTORS OF OUTCOME

Multivariate Analyses

  1. Study #1 (Radhakrishnan et al. 1998): 175 patients with anterior temporal lobectomy and 2 year follow-up.
    1. Presurgical factors: unilateral hippocampal atrophy and concordance of location of interictal and ictal discharges predicted excellent outcome (Engel I/II)
    2. Postsurgical factors: seizure-free during 1st postoperative year.
  2. Study #2 (Armon et al. 1996): 116 patients with any focal resection and 2 year follow-up.
    1. Presurgical factors: percentage of epileptiform EEG activity from resected site and localization of imaging abnormality to resected site predicted good outcome.
    2. Postsurgical factors: seizures within 2 months postop predicted poor outcome.
  3. Study #3 (Berg et al. 1998): 214 patients from 2 centers with one-year follow-up.
    1. Presence of mesial temporal sclerosis on pathological analysis, known etiology, and partial seizures only (no secondarily generalized seizures) independently predicted good outcome.

Univariate and Bivariate Analyses: General Trends

  1. Location of Resection: Temporal resections have better outcome than extratemporal (Engel et al. 1993, Wyllie et al. 1998).
  2. Lesions: Lesional resections have better outcome than non-lesional (Arruda et al. 1996, Berkovic et al. 1995, Engel et al. 1993, Wyllie et al. 1998).
  3. Etiology: Neoplastic lesions have better outcome than non-neoplastic (dysplasia, sclerosis) (Berkovic et al. 1995, Wyllie et al. 1998, Zentner 1996).
  4. Type of Temporal Resection: For temporal resection, selective amygdalohippocampectomy and anterior temporal lobectomy have similar outcomes (Arruda et al. 1996, Engel et al. 1993).
  5. Completeness of resection: Patients with complete resection of epileptogenic zone did better than incomplete resection (Paoliuchi et al. 2000).
  6. Age: Age at operation does not significantly change outcome when comparing adult to pediatric studies and different pediatric ages (Wyllie et al. 1998).
  7. Postoperative EEG: Epileptiform EEG abnormalities over the resected region at 12 months post-op were associated with a higher risk of poor outcome (29%) versus patients with normal EEGs (0%) (Patrick et al. 1995).

OUTCOME DATA: SEIZURES

Classification of Seizure Outcome (Engel et al. 1993):

  1. Class I: Free of disabling seizures – a. completely seizure free since surgery, b. nondisabling simple partial seizures, c. some disabling seizures, but free of disabling seizures for at least 2 years (“running down”), d. generalized convulsion with AED withdrawal only.
  2. Class II: Rare disabling seizures – a. rare disabling seizures since surgery (? <3/yr), b. more than rare disabling seizures initially, but only rare seizures for at least 2 years, c. nocturnal seizures only.
  3. Class III: Worthwhile improvement – a. significant reduction in seizure frequency (? >75% reduction), b. prolonged seizure-free intervals amounting to greater than half the follow-up period of at least 2 years.
  4. Class IV: No worthwhile improvement – insignificant reduction, no change, or increase in seizure frequency.

Temporal Lobe Resection

  1. Randomized Controlled Trial: Despite decades of experience with epilepsy surgery, the first randomized-controlled trial of epilepsy vs antiepileptic drug treatment was published in 2001. In 80 patients with intractable temporal lobe epilepsy using an intention-to-treat analysis (4 of the 40 patients in the “surgical” group did not receive surgery), 58% of patients in the surgical group were seizure-free at one year follow-up, compared to only 8% of the medical group (Wiebe et al. 2001).
  2. Second International Palm Desert Conference (Engel et al. 1993): data from 6009 primarily adult patients from 100 epilepsy centers between 1986-1990 with at least one-year follow-up.
    1. anterior temporal lobectomy (n=3579): 68% Class I, 24% Class II/III.
    2. amygdalohippocampectomy (n=413): 69% Class I, 22% Class II/III.
  3. Cleveland Clinic Pediatric Study (Edwards et al 2000, Mohamed et al. 2001, Wyllie et al. 1998): data from 136 children and adolescents from 3 months to 20 years old receiving temporal, extratemporal resection, and hemispherectomy, with at least one-year follow-up.
    1. overall (n=72 for temporal lobectomy): 78% Class I; age did not affect outcome.
    2. etiology: tumor (86% Class I), hippocampal sclerosis (67%), dysplasia (56%).
  4. Selective amygdalohippocampectomy (SAH) vs. anterior temporal lobectomy (ATL) (Arruda et al. 1996): 74 adults with at least one-year follow-up.
    1. overall: 72% Class I, 10% Class II.
    2. procedure: no significant difference between SAH (68% Class I) and ATL (76%).
    3. MRI findings: unilateral atrophy (85% class I, 9% Class II) had better outcome than bilateral atrophy (47% Class I, 18% Class II) and no atrophy (50% Class I, 0% Class II).
  5. Other Single-Center Adult Studies (Berkovic et al. 1995, Foldvary et al. 2000, Patrick et al. 1995, Salanova et al. 1994): most single-center studies have found at least a 60% Class I overall outcome.

Extratemporal Resection

  1. Second International Palm Desert Conference (Engel et al. 1993):
    1. neocortical resection (including non-lesional) (n=805): 45% Class I, 35% Class II/III.
    2. extratemporal lesionectomy (n=100): 66% Class I, 22% Class II/III.
  2. Cleveland Clinic Pediatric Study (Wyllie et al. 1998)
    1. overall (n=48), 54% Class I; age did not affect outcome.
    2. etiology: neoplastic (75% Class I) lesions had better outcome than dysplasia (50%).
    3. lesion: lesional (56% Class I) cases had better outcome than non-lesional (33%).
  3. Adult Study (Zentner et al. 1996): n=60 adults, mean follow-up 4 years.
    1. overall: 54% Class I, 32% Class II/III.
    2. etiology: neoplastic lesions (80% Class I) had better outcome than non-neoplastic lesion (52%) and no lesion (20%).
    3. location of resection (frontal, parietal, occipital) did not affect outcome.

Hemispherectomy

  1. Second International Palm Desert Conference (Engel et al. 1993): n=190, 67% Class I, 21% Class II/III.
  2. Cleveland Clinic Pediatric Study (Wyllie et al. 1998): n=16, 69% Class I.
  3. Johns Hopkins Pediatric Study (Vining et al. 1997): n=58, 54% Class I, 24% ~Class II.

Corpus Callosotomy

  1. Second International Palm Desert Conference (Engel et al. 1993): n=563, 5% Class I, 61% Class II/III.
  2. Review of 15 Studies of Callosotomy (Carmant and Holmes 1994):
    1. Overall, most studies report at least 50% of patients having “worthwhile improvement” in seizures, with >50% reduction in generalized seizures.
    2. Seizure type: outcome clearly dependent on seizure type; drop attacks of tonic or myoclonic origin have the best response, other generalized seizures with good response, and partial seizure the poorest response.

OUTCOME DATA: QUALITY OF LIFE

Adult Studies

  1. Measures of health-related quality of life (HRQOL), such as the Epilepsy Surgery Inventory (ESI)-55, correlate with seizure outcome; seizure-free postoperative patients have higher HRQOL scores than post-op patients with frequent seizures (Kellett et al. 1997, Vickrey et al. 1995) or pre-op patients awaiting surgery (Gilliam et al. 1999).
  2. Seizure-free patients also had higher HRQOL scores than patients who were evaluated but did not receive epilepsy surgery (Kellett et al. 1997).
  3. Little prospective data exists comparing HRQOL scores before and after epilepsy surgery (???).

Pediatric Studies

  1. Few studies of HRQOL in children exist.
  2. One study (Gilliam et al. 1997) found that HRQOL scores assessed by the Child Health Questionaire were lower in post-surgical epilepsy patients compared to age-matched controls, but the study did not compare to pre-operative scores or assess relationship of scores to seizure outcome.

POSTOPERATIVE AND NEUROLOGICAL COMPLICATIONS

Mortality: A large series of 429 primarily adult patients undergoing 708 diagnostic and therapeutic procedures had no mortality (Behrens et al. 1997). However, 2 (1.3%) of 149 patients in a pediatric series died on the first postoperative day (Wyllie et al. 1998).

Surgical Morbidity (Behrens et al. 1997): Overall, 3% and 8% surgical complications occurred following diagnostic and therapeutic procedures, respectively. Wound infection (3-4%), meningitis (1-2%), hydrocephalus (1%), and subdural hemorrhage (2%) were the most common.

Neurological Morbidity (Behrens et al. 1997): Overall, 1-2% and 5% unexpected neurological complications occurred following diagnostic and therpeutic procedures, respectively, with approximately half being transient. Hemiparesis (3%), unexpected hemianopia (1%), dysphasia/dysgraphia (1%) were most common.

Neuropsychological Morbidity (Szabo et al. 1998): Verbal memory decreased after temporal lobectomy in children, especially in patients with high baseline memory function and undergoing left temporal lobectomy.

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