1. Epilepsy Surgery Overview
Anumeha Sharma
Fellow, clinical neurophysiology - EEG
University of Cincinnati Medical Center

2. Case - GT
36 year old RHM seen in clinic for a 7 year history of episodes of panic, nausea, déjà vu initially diagnosed as panic attacks. Subsequently additional behaviors of patting, slapping with right hand and confusion, asking strange questions – “When does school start again? What grade am I in?”
Frequency – Clusters of upto 9 seizures every 2-3 months
EEG – normal
MRI – normal
Medications tried - Topamax (aggression – NE), Lamictal - NE)
Current medications – Keppra (depression), Zonisamide

3. What would be the next step in management?
Start lacosamide
Refer for presurgical evaluation
Refer for VNS placement
Refer to psychiatry

4. Prognosis of epilepsy Prevalence ~ 0.5% to 1.0% (Hauser, 1998)
~ 70 % (35- 82%) have complete control with medications
Generalized %
Focal onset % (strokes and vascular malformations respond better than trauma, CD, MTS, tumors)
~ 20 – 40 % have drug resistant* disease
~ 4-16% chance of seizure freedom with additional drug trials

5. Prognosis of epilepsy over time
Sillanpaa et al NEJM 1998

6. Diminishing returns of multiple AED trials
Kwan NEJM 2000;342:314-9NEJM 2Kwan000;342:314-9.

7. Pharmacoresistance Introduction of newer AEDs
~ 25-50% responder rate (50% seizure reduction)
5% of previously refractory patients become seizure free (French et al 2004)
~ 5-10 % discontinue the medications due to adverse effects (Singhvi et al 2000)
VNS has a very low chance of achieving seizure freedom in MRE
Should not be considered before resective surgery
Reserved for poor candidates (palliative)

8. Pharmacoresistence
No agreement over the frequency and duration of epilepsy to constitute intractability
Pharmacoresistance should be established within a few years of starting AED therapy (Berg et al, 2003; Devinsky, 1999)
Absolute seizure freedom is the only outcome associated with improved quality of life

9. Medically Refractory Epilepsy
ILAE definition - Failure of adequate trials of two tolerated and and appropriately used AED regimens as monotherapy or in combination to achieve seizure freedom
Treatment failure due to lack of clinical efficacy
Seizure freedom should be at least 1 year or 3 times the pretreatment seizure free interval

10. Predictors of therapy resistance
Early age at seizure onset
Tonic or myoclonic seizures
Symptomatic etiologies
History of status epilepticus
(Chen et al, 2002; Ko and Holmes, 1999).

11. Risks of refractory Epilepsy
Mortality
SMR 5.1 compared to in general epilepsy population
Successful epilepsy surgery decreases mortality (Sperling et al, 1996)
Sudden unexpected death in epilepsy (SUDEP) - 0.5% per year, cumulative over lifetime (Sillanpaa et al, 1998)
Increased seizure frequency
Increasing number of AEDs (ever used)
Early onset of epilepsy
Frequent changes of AEDs
GTCs
Nilsson et al. 1999; Langan et al 2005, Beran et al. 2004,

12. Risks of Refractory Epilepsy
Cognitive - Slowly progressive cortical atrophy and Cognitive decline (Jokeit and Ebner, 1999)
Psychiatric – Depression
~1.8x in patients with epilepsy vs. general population,
20-55% in MRE vs. 3-9 % in well controlled epilepsy patients
High seizure frequency, focal onset seizures, female gender (JJ Barry et al 2008)
Injury
Quality of life, Driving, School and Employment

13. Candidates for surgery
~ 50 % of MRE patients are candidates for focal resective surgery
Rest can be considered for a variety of palliative procedures i.e. VNS, RNS or diets
Symptomatic focal onset related epilepsy - most likely to receive seizure freedom from surgery

14. Temporal lobectomy vs. medication
Wiebe et al, NEJM, 2001

15. AAN Practice parameter 2003
One Class I RCT of surgery for MTLE
58% of patients randomized in the surgical arm (64% of those who received surgery) were free of disabling seizures, compared with 8% seizure freedom in the medical arm
Improvement in quality of life and driving, employment, mortality, some neuropsychological parameters

16. AAN practice parameter 2003
“Patients with disabling complex partial seizures, with or without secondarily generalized seizures, who have failed appropriate trials*of first-line antiepileptic drugs should be considered for referral to an epilepsy surgery center”(Engel et al 2003)

17. Surgical outcome - summary
Epilepsy
Outcome (seizure free)
Temporal lobe lesion
~ 80%
Mesial temporal sclerosis
~ 70%
“Normal” temporal lobe
~ 60%
Lesional extratemporal
Nonlesional extratemporal
< 50%

18. Morbidity and mortality
Infections, hemorrhage, and neurological deficits, ~ transient
Principal post surgical complication – cognitive
Some decline in verbal or non verbal memory or language
Transiently worsened anxiety or depression in % (Engel et al 2003)
In general, overall risk of surgery is lower than risk of refractory epilepsy (Engel et al 2003)
mortality in RCTS of AEDS ~ 0.78% per year

19. Who is not a surgical candidate?
Clear evidence of more than one focus or bilateral onset
Progressive disease (multiple sclerosis, cerebral vasculitis, HIV, meningitis, and high-grade malignant brain tumors)
Diffuse neuropsychological deficits
Significant psychiatric disease

20. Epilepsy Surgery Evaluation - Initial
History and examination
Video and (scalp) EEG monitoring
Structural Imaging – MRI
Functional Imaging – PET, Ictal and Interictal SPECT
Tests for functional localization – Wada, Neuropsychometric testing, functional MRI

21. Structural Imaging - MRI
Best available tool for identification of epileptogenic lesions
Provides information about
Presumptive pathology
Anatomic location
Coronal T1 and FLAIR with thin cuts – MTS, CD
GRE – cavernoma
Hamartomas, polymicrogyria, neuronal migration disorders, AVM, low grade tumors

22. MRI Lesion on MRI may or may not reflect the epileptogenic zone
The success rates for epilepsy surgeries done on patients with “unremarkable” MRI is much lower
Use of 3 Tesla magnets has lead to increased number of patients eligible for surgery (knake et al, 2005)

23. MRI – GT

24. Long term video EEG monitoring
Both ictal and interictal EEG
Essential to capture complete sample of typical seizures to clarify region(s) of seizure onset
Ictal EEG gives valuable lateralizing and localizing information with regard to the seizure focus (Jobst et al, 2001)
Temporal lobe seizures higher yield than extratemporal 76 – 83 vs 47 – 65%

26. Phase I scalp EEG - GT

27. Phase I scalp EEG - GT

28. Functional Imaging - PET scan
Metabolic maps of the brain
Especially useful in non lesional MRI
18F FDG provides measure of interictal regional glucose metabolism
Decreased metabolism represents functional deficit zone ( % of TLE patients)
Unilateral temporal lobe hypometabolism on 18F-FDG-PET strongly predicts seizure freedom with resection of that temporal lobe, independent of MRI findings (Theodore et al 1992)

29. PET Scan - GT
Coronal and axial images

32. Functional localization
Eloquent cortices essential for language, memory, motor, or sensory functions must often be delineated
Resection can be tailored to avoid causing functional deficits.
Neuropsychometric testing
Functional MRI
IAP (Wada) test
Magnetoencephalography

33. Neuropsychometric testing
Quantify, lateralize and localize cognitive deficits
Predict cognitive decline after epilepsy surgery
Obtained pre and post operatively to determine if new deficits have developed
Correlated with seizure foci identified using other techniques

34. Wada test
Functions as the transient mimic of the effects of the proposed surgery
Amobarbital is injected into the ICA , temporarily disrupting function on that side, while language and memory tests are performed
The best validated method of determining
Language dominant hemisphere
Assess risk of postoperative memory deterioration after temporal lobectomy

35. Predictors of higher risk of cognitive decline after temporal lobectomy
Intact baseline cognitive ability
Dominant temporal lobe resection
Later age of epilepsy onset
Normal MRI results
Female gender
Loss of memory function during injection of amobarbital into the carotid artery on the side of planned surgery

36. Summary of phase 1 evaluation - GT
MRI – Non lesional
PET – bilateral hypometabolism, non lateralizing
Video EEG - 1 clear right and 4 likely left temporal seizures, no post ictal language delay
Temporal lobe onset, unclear lateralization

37. Summary of phase 1 evaluation - GT
Neuropsychometric testing
Not well localized or lateralized anatomically
Excellent cognitive abilities overall
High risk for cognitive decline post operatively
Wada test
Left sided language dominance
Slightly decreased memory on the left
No major risk of post-operative amnesia with surgery on either side

38. Phase II (intracranial) evaluation
Precisely delineate the extent of a epileptogenic zone and its relationship to areas of eloquent functional cortex.
Determine if right or left onset
10-20% of temporal lobe, 40%-70% extratemporal cases
~75% of implanted patients go on to have resective surgery.
Complications – minor, 1% to 2% of cases (Siegel, 2004)

39. Depth electrodes Multiple contact needles
Provide direct access to deep structures
Very detailed but focused sampling
Lower complication rate, implanted through burr holes
Can be left in place for days and weeks with low risk of infections permitting longer monitoring

40. Subdural Electrodes
Used if seizure focus cannot be located with scalp EEG or other diagnostic tests
Grids or strips
Placed on brain surface, grids and strips are placed through craniotomy and burr holes respectively
More precise recording especially for neocortical seizures
Cortical mapping for functional areas can occur
Higher complication rate especially for grids

41. Grid and Strip

42. Intracranial electrode placement- GT

43. Phase II intracranial EEG – GT

44. Phase II monitoring – GT
4 typical seizures arising from left depth electrode (left mesial temporal region)
Risk vs. benefits of surgery were discussed
Patient elected to undergo left anterior temporal lobectomy
3 month follow up – No seizures, mild anomia, resolved with steroids.

45. Epilepsy surgery Timing and trends in the US
Time interval between onset of seizures and referral for pre-surgical evaluation – years
Comparison of referral data for patients with TLE from 1995 to 1998 and 2005 to 2008
Determine whether AAN practice parameter resulted in a change in referral patterns for surgical evaluation
No improvement in timing of referral for pre-surgical evaluation

46. sharm 112,026 hospitalizations for medically refractory focal epilepsy
6,653 (5.9%) resective surgeries from 1990 to 2008.
A trend of increasing hospitalizations over time but overall trend of decreasing surgery rates

47. Thank You
David Ficker, MD
Mariano Fernandez Ulloa, MD