es

1. Dr Ravi Goyal
SR Neurology
GMC Kota

2.  REASONS FOR EPILEPSY SURGERY :
 About one-third of epilepsy patients have seizures that
cannot be controlled with medication.
 Surgical therapy is an important and underutilized treatment
in patients with drug resistant focal epilepsy.

4.  Pharmaco resistant Epilepsy has severe consequences :
 – interference with school and work
 – loss of independence and social isolation and
 – increased risk of injury, depression and suicide
 Also leads to a significantly increased long-term mortality
rate (1.59% per year), with sudden unexpected death in
epilepsy (SUDEP) being the most common cause .
 Uncontrolled temporal lobe epilepsy - associated with slowly
progressive cortical atrophy and cognitive deterioration.

5.  Surgery ranges from focal resection of the epileptogenic
cortex (antero-mesial temporal lobe and other focal cortical
resections)
 to interventions that remove or isolate the cortex of a
grossly diseased hemisphere (functional hemispherectomy,
anterior corpus callosotomy, multiple subpial transections).
 The latter procedures are most often performed in children.

6.  Factors that may suggest sustained intractability, and thus support
early surgery (Langfitt and Wiebe 2008) :-
 – Lower efficacy towards first appropriate AED
 – Larger number of medications (even with high doses) tried, with
all causes of Pseudo resistance ruled out (Nonepileptic events,
syndromes, inappropriate medications)
 – Longer duration of seizures
 – History of status epilepticus
 – Mental retardation
 – Non-idiopathic epilepsy

7.  Mesial temporal lobe epilepsy (prototype).
 Lesional epilepsy due to focal structural pathology, such as a low-
grade glial tumor, cavernous malformation, or malformation of cortical
development (MCD) with medically refractory seizure.
 Neocortical epilepsy with normal brain MRI .
 Diffuse lesions limited to one hemisphere such as hemi -
megencephaly, Sturge–Weber syndrome, and large porencephalic cysts
 Rasmussen’s encephalitis.
 Gelastic seizures associated with hypothalamic hamartomas.

8.  Patients who are typically not surgical candidates
include:-
 Clear evidence of bilateral onset of seizures
 those with severe psychiatric or medical comorbidities
 increasing surgical risk or compromising recovery
 those with rapidly progressive CNS disease, and
 those with primary generalized epilepsy.

9.  GOAL :-
 (1) Localize the epileptogenic zone.
 (2) Identify incongruent evidence that may indicate the need for
additional tests including invasive EEG
 (3) Determine whether planned surgical resection poses risk to
cerebral functions.
 The Epileptogenic zone :- zone whose resection is necessary
and sufficient to eliminate seizures
 This zone cannot be directly defined by any test but can be
estimated by a number of other zones.

10.  The Ictal onset zone (Seizure onset zone or Pacemaker zone):-
 Area of cortex that is generating seizures .
 This zone, if accurately defined, is contained within the
epileptogenic zone and smaller than it.
 Identifying and defining the ictal onset zone challenging, as the
earliest detected ictal activity may have already undergone
considerable spread.
 Even with Intracranial EEG recording, the ictal onset zone may
be missed unless the electrodes placed directly over that zone.

11. The Irritative zone :-
• Zone that generates interictal epileptiform discharges.
• Usually localized within the epileptogenic zone.
The Ictal symptomatogenic zone :-
• Region that produces the seizure manifestations.
• This zone may be more valuable for lateralization than exact
localization, because most likely that seizures will spread
within the hemisphere of origin before spreading to the
contralateral hemisphere.(not always)

12. The Functional deficit zone:-
• Responsible for functional deficit .
• it may include the epileptogenic zone, it is often
considerably larger.
The Epileptogenic lesion :-
• Structural brain abnormality that is presumed to be the
cause of the epilepsy and usually identified on MRI.
• The relationship of the epileptogenic lesion to the seizure
onset zone is variable.

13.  Upon referral, the patient undergoes :
 – Detailed neurologic history and examination
 – Neuroimaging
 – Video-EEG monitoring
 – Neuropsychological testing.

14.  Identifying specific risk factors in the history can help
predict the epileptogenic lesion .
 The description of the seizure aura and other early
seizure semiology helps with localization of Ictal
symptomatogenic zone.
 The description of seizure semiology by witnesses is
also helpful particularly for lateralization .

15.  Cornerstone of the presurgical evaluation.
 The interictal focal attenuation and focal slow activity -
Functional deficit zone
 Interictal epileptiform discharges – define the irritative zones
 Electrographic localization of seizure onset helps define - ictal
onset zone.
 Additional closely spaced electrodes may help such as anterior
temporal electrodes, sphenoidal electrodes, zygomatic
electrodes, or cheek electrodes.

16.  The analysis of seizure semiology by video-EEG provides
several localizing and lateralizing signs that help define
the ictal symptomatogenic zone .

17.  Performed when non invasive testing suggests a
resectable epileptic focus with some uncertainty.
 Invasive video-EEG can also more precisely delineate
the extent of a neocortical epileptogenic zone and its
relationship to areas of eloquent functional cortex.
 It continues to be used commonly in patients with
neocortical focal epilepsy, particularly those with a
normal MRI or bilateral seizure foci.

18.  Defined as: events with at least 4 consecutive oscillations between
80Hz and 500Hz that clearly rise above baseline.
 studies have pointed to the high frequency oscillation (HFO) recorded in
intracranial EEG (iEEG) as a new indicator for the Epileptogenic zone .
 To record HFOs, the intracranial EEG needs to be sampled at least at
2,000Hz
 At present, HFOs are further sub-classified in ripples (80–250Hz) and
fast ripples (250–600Hz).
 High frequency oscillations (HFOs) are recognized as biomarkers for
epileptogenic brain tissue

20.  All patients should have a high-resolution brain MRI with
sequences optimized for visualization of the hippocampus
and gray-white matter junction.
 It include coronal or oblique-coronal T1- and T2-weighted
and FLAIR sequences.
 In patients with mesial temporal sclerosis, the most
common imaging alteration is hippocampal atrophy with a
signal intensity change that reflects gliosis.

22.  it also has a high diagnostic yield in patients with
tumors or vascular malformations.
 The latter are often best visualized on gradient echo
sequences, which are sensitive for blood products.
 In patients with focal cortical dysplasia, MRI findings
may be subtle and include mild cortical thickening,
 a prominent deep sulcus, a cortical signal intensity
change, blurring of the gray-white junction or aberrant
cortical architecture.

24.  Advanced MRI techniques —
 In Quantitative MRI techniques, MRI-based volumetric
studies of the hippocampal formation shows unilateral
reduction in hippocampal volume that is a reliable
indicator of the epileptogenic temporal lobe in patients
with medically refractory focal epilepsy.

25.  Almost always an interictal study , ictal PET difficult to plan.
 FDG-PET defines the functional deficit zone.
 80% patients have a discrete region of hypometabolism -
has a good correlation epileptic focus in Temporal lobe
epilepsy.
 FDG-PET particularly useful in patients without MRI
abnormalities.

27.  Ictal SPECT studies are used to map increased cerebral blood
flow during seizures to assist in localizing the epileptogenic
zone .
 it is particularly useful in patients with a conflicting
noninvasive epilepsy evaluation with regard to localization of
the epileptic brain tissue .
 Subtraction ictal SPECT coregistered to MRI (SISCOM) is a
modification of the ictal SPECT technique that superimposes
ictal and interictal SPECT images and brain MRI .


28.  It has been used in patients with :
 Normal MRI studies
 Those with multifocal EEG or MRI abnormalities
 Individuals with intractable epilepsy who are being
considered for reoperation.

30.  Eloquent cortices essential for language, motor, or sensory
functions must often be delineated
 so resection can be tailored to avoid causing deficits.
 Preoperatively, functional MRI and the intracarotid
amobarbital procedure (also called the Wada test) are two
methods used to assess language localization and predict
postoperative language and memory outcomes.
 Functional MRI is generally preferred over intracarotid
amobarbital given its superior safety profile .

31.  It can be used to map language, motor function
memory, and epileptic activity.
 blood oxygen level–dependent (BOLD) signal is
generated .
 The BOLD signal represents the ratio of oxyhemoglobin
concentration to deoxyhemoglobin concentration.

32.  Neuropsychological testing establishes baseline measurements of
any cognitive deficits, sometimes giving insight into the epileptic
focus location.
 Also allows comparison with postoperative testing to measure
cognitive outcomes.
 Predictors of higher risk of cognitive decline after temporal
lobectomy :-
 – Dominant temporal lobe resection
 – Later age of epilepsy onset
 – Normal MRI results
 – Female gender and
 – Loss of memory function during injection of amobarbital into the
carotid artery on the side of planned surgery (Wada test)

34.  The Engel classification system :- Devised in 1987, most
commonly used scale.
 This scale use subjective components, such as "worthwhile
improvement" or "significant reduction.“
 Divided in 4 classes :-
 Class 1 - Free of disabling seizures (completely seizure free , non
disabling, simple partial seizures only; some disabling seizures,
but free of disabling seizures for at least 2 years, generalize
convulsion with antiepileptic drug withdrawal only)

35.  Class II - Rare disabling seizures (initially free of disabling
seizures, but rare seizures now; rare disabling seizures since
surgery, more than rare disabling seizures, but rare seizures
for at least 2 years, nocturnal seizures only)
 Class III - Worthwhile improvement (worthwhile seizure
reduction; prolonged seizure-free intervals amounting to
more than half the follow-up period, but not less than 2 y)
 Class IV - No worthwhile improvement (significant seizure
reduction; no appreciable change, seizures worse)

36.  In 2001, the International League Against Epilepsy (ILAE)
proposed a new classification scheme for outcome with
respect to epileptic seizures after surgery.
 The goal of this classification scheme was to provide a
more objective measure of the number of seizures.
 Limitation - this scale too becomes ambiguous after level 3,
determining 50% reduction in seizures can be difficult to
assess, since patients often do not maintain accurate
seizure calendars.

37. • This classification system is as follows:
• classification 1 - Completely seizure free ,no auras
• classification 2 - Only auras , no other seizures
• classification 3 - 1 to 3 seizure days per year, ± auras
• classification 4 - 4 seizure days per year to 50% reduction of
baseline seizure days, ± auras
• classification 5 - Less than 50% reduction of baseline seizure days,
± auras
• classification 6 - More than 100% increase of baseline seizure
days, ± auras

38.  In addition to seizure freedom or reduction, other
outcome measures also considered :-
 such as developmental and cognitive outcome,
 behavioral and psychosocial outcome,
 Improvement in health-related quality of life (HRQOL)

39.  Mesial temporal sclerosis is the most common indication for epilepsy
surgery in adults, accounting for 75% of cases in adult surgical series.
 In adults, the most common surgical procedure for temporal lobe
epilepsy (TLE) involves
 an amygdalo hippocampectomy
 Anterior temoral lobectomy
 Wiebe et al found that at the end of 1 year, 58% of patients in the
surgical group were free from disable seizures, and 10-15% had little or
no improvement, compared with only 8% free from disabling seizures in
the medical group. also that quality of life (QOL) at 1 year was
significantly improved in the surgical group .

40.  In a Mayo Clinic series, The investigators found that 90% of patients
with unilateral temporal interictal spikes, concordant ictal onsets, and
unilateral hippocampal atrophy became seizure free after surgery.
 patients with bilaterally independent, temporal, interictal epileptiform
abnormalities did not have as good a seizure-free outcome rate (ie,
70%).
 In patients with MRI scans showing hippocampal atrophy and IEDs
discordant with ictal onset, only 60% had a seizure-free outcome
 In patients with normal MRI findings, surgical outcome was similar,
regardless of whether IEDs were concordant with ictal onset.

41.  A systematic review and meta-analysis by Engel et al
that included 32 studies and 2,250 patients showed
that 63% of patients remained seizure free after 2-5
years of follow-up .
 Tellez-Zenteno and colleagues, in a meta-analysis of
40 studies that included 3,895 patients, showed that
long term follow-up of more than 5 years was 66%.

42.  Lesional - In adult patients with a well-circumscribed
lesion, such as a developmental tumor (ganglioglioma,
dysembryoplastic neuroepithelial tumor [DNET], or
pleomorphic xanthoastrocytoma [PXA]) or a cavernous
malformation, seizure-free outcome rates are in the range
of 60-80%.
 Usually, seizure-free outcome is related to complete
lesion resection.

43.  In nonlesional - only 20-25% of patients have a seizure-
free outcome, with an additional 25% of patients having
worthwhile improvement.
 However, this outcome can be improved to 45% seizure
free and 21% with rare disabling seizures with the use of
functional imaging data (PET scanning, SPECT scanning )
and scalp EEG.

44.  Typically, dual pathology is more commonly seen in children
than in adults.
 Li et al found that seizure freedom was attained in 73%
patients with a lesionectomy and a medial temporal
resection ,
 seizure-free outcome was only 20% in patients with medial
temporal resection alone and
 only 12.5% with lesionectomy alone.

45.  Surgical outcome in children with focal resections is similar to
adults, with seizure-free rates in the range of 75-80%,
particularly in patients with hippocampal sclerosis or tumors .
 MCD (malformation of cortical development ) and low-grade
tumors, are the most frequent causes of intractable epilepsy in
childhood.
 In which outcomes after resection of MCDs are less favorable
than resection of wellcircumscribed lesions, with only 50% of
pediatric patients attaining freedom from seizures after MCD
resection.

46.  It is a palliative disconnection procedure in which the corpus
callosum is sectioned to prevent the Inter hemispheric
propagation of seizures .
 It involves disconnection of the anterior two thirds of the
corpus callosum or complete callosal resection.
 It is recommended for children and adults with symptomatic
generalized epilepsies, such as Lennox-Gastaut syndrome,
who have disabling atonic and/or tonic seizures .

47.  It results in an 80% average reduction in tonic/atonic
seizures resulting in falls, a 50% reduction in generalized
tonic and tonic-clonic seizures, and 50% atypical absence
seizures .
 Overall, success rates are similar between children and
adults and the effects are usually sustained long term.
 After corpus callosotomy, most patients have significant
improvement in cognitive function, activities of daily living,
and behavior.

48.  Outcome is better with a complete callosotomy than
with an anterior two-thirds callosotomy.
 But complications are more common with complete
callosal resection, including disconnection syndrome
(mutism ,hemiataxia, alexia).
 Typically, an anterior two-thirds callosotomy is
performed, with complete callosotomy reserved as a
second procedure.

49.  It is reserved for infants and children with catastrophic epilepsy,
developmental regression, and a unilateral useless hand.
 The pathologic substrates include hemi megalencephaly,
perinatal infarction, diffuse MCDs, Sturge-Weber syndrome, and
Rasmussen encephalitis.
 Multiple single-center series from the Cleveland Clinic, Johns
Hopkins Hospital, and Miami Children's Hospital reported
seizure-free outcome rates in the range of 53-67%.
 Overall, their seizure surgery outcomes were better in patients
with non-MCD pathologies than in those with MCD.

50. Memory outcome :-
 anterior temporal resections have a potential risk of producing
a memory deficit.
 Bilateral injury to the hippocampi is known to produce long-
lasting, profound, anterograde amnesia.
 Long-term studies with more than 5 years follow-up suggest
that the memory deficit appears early after surgery and that
the rate of decline stabilizes after 1-2 years.

51.  Dominant-hemisphere ATL has a selective risk of
postoperative decline in visual confrontation naming.
 Numerous studies have demonstrated that patients
with a high preoperative score on the Boston Naming
Test (BNT) and a later age of onset (>10 y) are at
greatest risk of a postoperative decline in naming .

52.  Psychiatric disorders, particularly depression and anxiety are
seen in up to 50% of patients with epilepsy.
 In fact, in patients with medically intractable epilepsy,
depression predicts worse QOL ( quality of life ) whereas seizure
frequency has no predictive value.
 The psychosocial outcome after epilepsy surgery appears to be
intrinsically linked to a change in self and to difficulties , patients
may have in adjusting to freedom from seizures.

53.  Used for the adjunctive treatment of refractory partial-onset
seizures in adults and adolescents aged 12 years or older. ( for
chronic or recurrent depression )
 studies that demonstrated 24.5% to 28% short-term reduction in
seizure frequency.
 VNS is usually programmed to stimulate for 30 seconds
alternating with 5 minutes of rest, but the duration of stimulation
time on and off can be changed.

55.  Advantages are :
 Does not have the AED adverse effects of sleepiness, tiredness,
dizziness, or cognitive dysfunction.
 It may improve mood and promote alertness
 on-demand stimulation to abort seizures.
 compliance does not require patient effort.
 Adverse effect :
 Hoarseness of voice
 Infection
 dyspnoea , chest pain

56.  It is a non invasive cortical stimulation method .
 investigated as a treatment for drug-resistant epilepsy .
 It modulates cortical excitability with high and low frequency .
 In which low-frequency rTMS Is moderately beneficial, with more
improvement in cortical dysplasia or neocortical epilepsy
patients.
 it’s due to greater and more precise access of rTMS therapy to
the more superficial seizure foci.

57.  It is a suitable treatment option for patients with bilateral
independent seizure foci or with an
 epileptogenic zone in eloquent cortex not suitable for surgical
resection.
 May be closed loop or open loop .
 Advantage - it is reversible and adjustable, unlike resective
surgery.
 But the optimal stimulation parameters are not generally well
defined, so predominantly palliative.

58.  A safe and efficacious treatment for drug-resistant epilepsy.
 It is effective in reducing seizure frequency in patients who otherwise have no
other treatment options.
 The targets includes the ANT, the CMT and the hippocampus.
 Partial seizures or secondarily generalized seizures benefit - from ANT DBS,
 Generalized epilepsy such as in Lennox-Gastaut syndrome - from CMT DBS.
 Mesial TLE - from hippocampal DBS.
 The most common adverse event - implantation site pain (23.6%) and
Paresthesias ( 22.7% )
 Additional large randomized double-blind trials will help to solidify the efficacy
of DBS and increase its utilization.

59.  seizure control within the first year after surgery also predicts
more favorable longer-term seizure outcomes.
 The rationale for reducing antiseizure drugs includes
avoidance of drug interactions and dose-related adverse
effects as well as concerns regarding teratogenesis .
 There are no prospective, randomized data evaluating
discontinuation of antiseizure drugs following epilepsy.

60.  In practice, most individuals are not considered for
antiseizure drug withdrawal unless they are seizure free
for at least one year following surgery.
 Those with auras or seizure activity following surgery
should probably remain on antiseizure drug therapy
unless they are seizure free for two to five years.

61.  Patients with drug-resistant focal epilepsy should be referred to a
comprehensive epilepsy center to confirm the diagnosis,
categorize the epilepsy syndrome, and evaluate all possible
treatment options, including surgery.
 Surgical evaluation is recommended for patients with refractory
focal seizures.
 The goals of the surgical evaluation are to identify the
epileptogenic zone fully and avoid operative morbidity associated
with a focal cortical resection.

62.  In adult patients, mesial temporal lobe epilepsy secondary to
mesial temporal sclerosis is the most frequently encountered
surgically remediable epileptic syndrome.
 Outcomes are typically better for patients with tumors and
vascular malformations than Malformation of cortical
development (MCD).
 Epilepsy surgery is associated with low rates of morbidity and
mortality when performed at specialized centers.

63.  Kerr MP, Mensah S, Besag F, et al. International consensus clinical practice
statements for the treatment of neuropsychiatric conditio associated with
epilepsy.
 Jones AL, Cascino GD. Evidence on Use of Neuroimaging for Surgical
Treatment of Temporal Lobe Epilepsy: A Systematic Review. JAMA Neurol
2016; 73:464.
 Bradley’s Neurology
 Up To Date
 emedicine.medscape.com

64. THANK YOU