epilepsy surgery: an under-utilized treatment modality - … surgery.pdf · epilepsy surgery: an...

Epilepsy surgery: an under-utilized

treatment modalityDipika Aggarwal, MD

Clinical Neurophysiology Fellow

Background

• Epilepsy is among the most serious primary disorders of the

brain, accounting for 1% of the global burden of disease

• Second most common cause of mental health disability,

particularly among young adults

• World wide burden of illness similar to breast cancer in

women and lung cancer in men

• Prevalence : 5 to 10 per 1,000 population in the US

• Pharmacotherapy is unsuccessful in controlling seizures in 20-

40% of patients

• Medically intractable epilepsy patients account for 80% of the

cost of epilepsy in the US

Background

• Temporal lobe epilepsy (TLE) is the most common cause of pharmaco-resistant seizures

• Most easily and effectively treated with surgery, 60-80% of patients become free of disabling seizures

• More than 100,000 patients, while fewer than 2000 received surgical treatment (Engel and Shewmon, 1993)

• Average duration of 22 years between onset of epilepsy and referral (Berg et al., 2003)

• Reason - Absence of a randomized control trial (RCT) to demonstrate the superiority of surgical intervention over continued pharmacotherapy

Objective

• Who is a surgical candidate?

• Types of surgical treatments

• Pre surgical evaluation in adults: non invasive

and invasive

• Risks and outcome

Failure of adequate trials of two well tolerated and appropriately chosen

and used AEDs to achieve sustained seizure freedom for a sufficiently long

period of time.

A sufficiently long period of time is defined for an individual patient as

three times the longest inter seizure interval for that patient, or 1 year,

whichever is longer.

www.epilepsycases.com

When to refer children for

comprehensive epilepsy evaluation

• All children

– Persistent generalized or partial seizures after failure of 2 or 3 AEDs, or

unacceptable side effects

– Urgent if more than one seizure per day

• Children under age 2 years

– Urgent referral to prevent developmental delay and epileptic

encephalopathy esp. if daily seizures

• Special circumstances

– TLE, cortical dysplasia, hemi-megalencephaly, Rasmussen’s

encephalitis, tumors, prior ischemic brain injury, tuberous sclerosis,

hypothalamic hamartomas

Common misconceptions and pitfalls

• Lesions in the dominant hemisphere, bilateral interictal

epileptiform discharges, a normal MRI brain, or memory

deficits are contraindications for surgery

• Patients who may not seem to meet surgical criteria at a non

specialized center may be deemed surgical candidates after

expert assessment

• Patients with psychiatric conditions, cognitive disabilities, and

the elderly can often benefit from surgical procedures

Objective




and invasive


Types of surgical treatments

Standardized resections

• Anterior temporal resections

• Amygdalohippocampectomy

• Hemispherectomy

Tailored resections

• Localized cortical resections

• Lesionectomies

• Multilobar resections

Disconnections

• Corpus callosotomy

• Multiple subpial resections

Other

• Gamma knife

• Deep brain stimulation

• Response stimulation

• Early Randomization Surgical Epilepsy Trial (ERSET), 2012

• Multicenter, 16 US epilepsy surgery centers

• 38 participants – MTLE and disabling seizures for no more than 2

years following adequate trials of 2 appropriately chosen AEDs

• 23 continued AED, 15 standardized AMTR plus AED

• Primary outcome: seizure freedom during 2 year follow up period

• Secondary outcome: measure of quality of life (QOLIE-89), cognitive

function and social adaptation

• Results: • 0/23 in the medical group and 11/15 patients in the surgical group

were seizure free during 2 years

• QOLIE-89 score was higher in surgical group

Objective




and invasive


Pre surgical evaluation

• Goal of epilepsy surgery:

– Complete removal of epileptic tissue

– No neurological or neuropsychological deficits

• These goals can be achieved only by a thorough pre surgical

evaluation during which the epileptic tissue and essential

brain regions are localized as accurately as possible

Cortical zones• Irritative zone: brain region where inter ictal spikes can be recorded

• Seizure-onset zone: brain region where seizures originate (where ictal

epileptiform discharges begin)

• Ictal symptomatogenic zone: brain region responsible for the generation of the

first clinical symptoms during a seizure

• Functional deficit zone: brain region which is affected by non epileptic

functional disturbances (NP, EEG, SPECT, PET and WADA)

• Epileptogenic lesion: structural lesion causative for the patient’s seizure

• Epileptogenic zone: brain region whose removal is necessary and sufficient to

achieve a seizure free outcome

Pre-surgical evaluation

• Phase 1: Non-invasive tests

– Video EEG monitoring

– MRI

– Neuropsychological testing

– SPECT, PET, functional MRI, MR Spectroscopy, magneto-

encephalography, Wada test

• Phase 2: Invasive tests

Video-EEG Monitoring

• Cornerstone of non invasive evaluation

• Continuous EEG and video for at least 5 days

• Goals

– Documentation of seizure semiology

– Sampling of inter ictal EEG

– Documentation of ictal changes and their correlation with

clinical seizure semiology

Intensive Video-EEG Monitoring

• So why is clinical seizure semiology so important??

– Epileptic versus non-epileptic and their frequencies

– Single or multiple different seizure types indicating

multiple seizure onset zones

– Lateralization and localization of seizure onset zone

Lateralizing signs

• Ipsilateral signs

– unilateral hand

automatism

– non versive (early) head

turning

– postictal nose wiping

– peri-ictal headache

– unilateral eye blinking

– lateral tongue biting

• Contralateral signs

– unilateral dystonic/ tonic

posturing

– unilateral mouth deviation

– unilateral clonic

movements

– figure of 4 sign

– ictal hemiparesis

– postictal hemiparesis

Lateralizing signs

• Dominant Hemisphere

– postictal aphasia

– ictal vocalization

• Non-dominant Hemisphere

– preserved ictal language

– automatism with preserved

responsiveness

– ictal retching/vomiting

– ictal spitting

– peri-ictal urinary urge

– peri-ictal water drinking

Sensitivity of scalp EEG

• First EEG is abnormal in only 30-50% of seizure patients

• Serial EEG (by the 3rd) raise the sensitivity to 80-90%

• Sensitivity can be increased by:

– Slow-wave sleep activates IED (inter ictal epileptiform

discharges)

– IED are activated after seizure

– Anterior temporal electrodes, sphenoidal electrodes or closely

placed electrodes

– Longer duration of scalp EEG

Magnetic resonance imaging

• Major breakthrough in pre surgical evaluation

• Post op seizure control is significantly increased if an

epileptogenic lesion can be identified on pre-op scans

• With improvement in MRI hardware (3T), acquisition, and

post processing methods, relevant structural abnormalities

can now be identified in 10-30% of patients with previously

unremarkable scans

Neuropsychological (NP) testing

• Mandatory for localization of epileptogenic zone and

functional deficit zone and to assess the NP risks for surgery

• TLE – memory and language

• Dominant TLE – verbal memory deficits

• Non dominant TLE – visuospatial memory deficits

• Memory decline – most common deficit after TLE surgery

• Patients with average or above average memory and language

function are at higher risk for developing postoperative

deficits

SPECT• 99mTc-HMPAO (hexamethyl-propyleneamine) and 99mTc-ECD

(ethyl cysteinate dimer)

• Regional blood flow (rCBF) markers

• Marked increase in rCBF can be seen within the seizure onset zone during ictal SPECT

• In TLE, inter ictal SPECT shows regional temporal hypo-perfusion in 40-50% of patients ipsilateral to epileptogenic zone

• Sensitivity of ictal SPECT can be significantly increased by the co-registration of ictal SPECT with inter ictal SPECT and MRI –subtraction ictal SPECT co-registered to MRI (SISCOM)

PET

• [18F]FDG (fluorodeoxyglucose)

• Inter ictal glucose hypometabolism

• In TLE sensitivity is 65-90%, less in patients with normal

MRI

• PET is generally utilized in evaluation of cryptogenic cases

and for identifying seizure spread patterns

Other ancillary tests

Functional MRI (fMRI)

• Assessment of functional deficit

zone

• Language lateralization

• Concordance: 90-100 % in left

dominant, 67-100% in right

dominant and 50-75% bilateral

dominant patients

Magnetoencephalography

• Measures brain’s weak magnetic

field

• MEG is more sensitive than EEG

in neocortical epilepsy

• Can be useful in non lesional

cases

• Can localize the eloquent cortex-

sensorimotor cortex, language

mapping

Wada test

• Intracarotid amobarbital procedure

• Language and memory lateralization

• Atypical language lateralization is more likely in epilepsy patients

• Rationale – anesthetize mesial temporal structures to simulate

potential effects of the proposed surgery

• Patients with impaired memory ipsilateral to the epileptogenic

focus and intact memory contralaterally are at lowest risk for

postoperative memory decline

• Despite of high accuracy, it is associated with false negatives and

false positives

Invasive Phase 2 evaluation

• Scalp EEGs are unable to lateralize in up to one-third of patients

with TLE

• Up to 10% of lateralizing non invasive tests could be falsely

localizing

• Indications

– Discordance amongst non invasive test results

– Multifocal / bitemporal epilepsy

– MRI negative TLE

– MRI with questionable / widely extended lesion

– Epileptogenic lesion is close to, or overlaps with eloquent areas

– Extra temporal lobe epilepsy syndromes


• Intra cerebral “depth” electrodes, subdural strips, subdural

grid recordings

• Each technique has specific advantages and limitations

• Intracerebral “depth” electrodes:

– Penetrate brain tissue directly

– Recording from deep structures such as

amygdala, hippocampus, insula or sulcal cortex

– Target lesions in deep cerebral locations such as

heterotopic gray matter abnormalities,

hypothalamic hamartomas etc


• Subdural electrodes:

– overlie the surface of the brain

– localization of epileptogenic regions on

the cortical surface

– Inter hemispheric locations

– inaccurate for defining EEG patterns

arising from deep generators

• Subdural grids:

– ideal for functional mapping of cortex

• Often used together

Risks associated with surgery for TLE

• Motor deficits: – Contralateral hemiplegia

– 2% of the cases, majority patients improve over months to a year

• Cranial nerve deficits:– Oculomotor nerve (CNIII) and trochlear nerve (CNIV)

– 1.5-3%, transient, traction injury

• Visual field deficits:– Superior quadrantanopsia

– Damage to lateral aspect of Meyer’s loops (optic radiations)

– ~ 55% of patients

– Most cases patients are unaware, diagnosed on formal visual field testing


• Language deficits:

– Dominant TLE surgery

– Most common - transient anomia

• Memory deficits:

– Patients may still suffer significant memory deficits following TLE

surgery despite of favorable WADA testing and results

– High ipsilateral memory function - greater degree of post operative

memory decline


• Psychiatric risks:

– TLE associated with depression ~ 50%

– Preoperative history of depression

– Suicide rates greater than 5 times general population

– Rare – psychotic type illness , schizophrenia

– Low threshold for psychiatric assessment

66% seizure

freedom at 5 yrs

7.6 years seizure

freedom

62% - adults

50% - children

Seizure freedom (%): no.

of yrs

75% : 2 years

67% : 5 years

51%: 10 years

When to withdraw AEDs?

• AED withdrawal uncovers the natural history of epilepsy, or

the success of a surgical procedure, without influencing the

long-term seizure outcomes

• No RCT in post surgical patients

• Previous studies: in medically treated patients, the risk of

seizure recurrence is high until 2 years after AED withdrawal

• It has been recommended to continue AEDs for at least 2

years after surgery in seizure free patients, largely based on

AED withdrawal policies in nonsurgical cohorts

KU Case

• 49 year old right handed female with medically intractable epilepsy with complex partial seizures at least 1-2 per day since age 30

• She has been on several name brand AEDs with no improvement

• EEG: epileptogenic tissue in the right temporal and left frontal lobes

• VEEG: typical seizures captured, lateralizing to the left hemisphere

• MRI: normal hippocampi bilaterally

• fMRI: right hemispheric dominance

• PET: moderate to marked decreased activity in the left mesial and anterior temporal lobe

Case (contd.)

• Neuropsych testing: dominant (probably left) hemisphere involvement

• WADA test: right hemispheric language dominance and adequate memory function from right hemisphere

• Phase II evaluation localized seizures to left anterolateral temporal lobe and left hippocampus

• Left anterior temporal lobectomy (4cm) and hippocampectomy in May 2014

• Seizure free since then and counting days when she would be able to drive

How are we doing?

• Since 2013, 9 patients with medically intractable epilepsy

were evaluated for surgery

• 6 underwent surgery and are seizure free and doing well thus

far

• 1 ATL resection earlier this week

• More cases to go!!

Questions

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