Epilepsy Surgery Overview
Anumeha Sharma
Fellow, clinical neurophysiology - EEG
University of Cincinnati Medical Center
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
What would be the next step in
management?
A. Start lacosamide
B. Refer for presurgical evaluation
C. Refer for VNS placement
D. Refer to psychiatry
Prognosis of epilepsy
• Prevalence ~ 0.5% to 1.0% (Hauser, 1998)
• ~ 70 % (35- 82%) have complete control
with medications
• Generalized - 74- 82%
• Focal onset - 35-58% (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
Prognosis of epilepsy over time
Sillanpaa et al NEJM 1998
Diminishing returns of multiple
AED trials
Kwan NEJM 2000;342:314-9NEJM
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)
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
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
Predictors of therapy resistance
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Early age at seizure onset
Tonic or myoclonic seizures
Symptomatic etiologies
History of status epilepticus
•
(Chen et al, 2002; Ko and Holmes,
1999).
Risks of refractory Epilepsy
• Mortality
• SMR 5.1 compared to 1.6 - 2.3 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)
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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,
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
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
Temporal lobectomy vs.
medication
Wiebe et al, NEJM, 2001
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
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)
Surgical outcome - summary
Epilepsy
Outcome (seizure free)
Temporal lobe lesion
~ 80%
Mesial temporal sclerosis
~ 70%
“Normal” temporal lobe
~ 60%
Lesional extratemporal
~ 60%
Nonlesional extratemporal
< 50%
Morbidity and mortality
• Mortality <1%
• Morbidity 3-6%
• 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 20-40 % (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
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
Epilepsy Surgery Evaluation - Initial
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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
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
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)
MRI – GT
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%
Phase I scalp EEG - GT
Phase I scalp EEG - GT
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 (65 - 90% 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)
PET Scan - GT
• Coronal and axial images
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.
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Neuropsychometric testing
Functional MRI
IAP (Wada) test
Magnetoencephalography
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
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
Predictors of higher risk of cognitive
decline after temporal lobectomy
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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
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
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
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)
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
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
Grid and Strip
Intracranial electrode placementGT
Phase II intracranial EEG – GT
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.
Epilepsy surgery Timing and trends
in the US
• Time interval between onset of seizures and referral for presurgical evaluation – 18- 25 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
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
Thank You
• David Ficker, MD
• Mariano Fernandez Ulloa, MD