Minimally invasive

strategies for epilepsy

surgery in children

PrasannaPrasannaPrasannaPrasanna JayakarJayakarJayakarJayakar MD., PhDMD., PhDMD., PhDMD., PhD

Goals

Tests Techniques

Epileptogenic region

Conventional Surgery

Conventional Surgery

Minimally / NonInvasive

“Less is More”

Strategy

CriticalCortex

Pediatric Epilepsy Surgery

Goals of epilepsy surgery Goals of epilepsy surgery

�� Curative Curative –– Resection /ablation of Resection /ablation of

epileptogenicepileptogenic zone [EZ] to achieve seizure zone [EZ] to achieve seizure

freedomfreedom

�� Palliative Palliative –– Disconnection or Disconnection or neuromodulationneuromodulation

to reduce seizure burdento reduce seizure burden

Curative Resection strategies Curative Resection strategies

Smaller incompleteSmaller incomplete

Resections of EZ Resections of EZ

>> lesser chances>> lesser chances

of seizure freedomof seizure freedom

>> better >> better preservation of preservation of functionfunction

Larger complete

Resection of EZ

>> Enhance chances

of seizure freedom

>> increased risk

of neurological

deficit “LESS “LESS

ISIS

MORE”MORE”

Less is more strategyLess is more strategy

EZ

Epicenter

Critical Cortex

�� Discrete Discrete epileptogenicepileptogenic MRI lesionMRI lesion

Defining the EpicenterDefining the Epicenter-- II

�� Multimodal Convergence of functional abnormalitiesMultimodal Convergence of functional abnormalities

Defining the EpicenterDefining the Epicenter-- II II

�� EEG EEG

�� 3D EEG source/MEG3D EEG source/MEG

�� EEGEEG--fMRIfMRI

�� PETPET-- Hypo or HyperHypo or Hyper

�� SPECT/SISCOMSPECT/SISCOM

�� OthersOthers

Lee et al. 2005 ; Seo et al., 2011Thivard et al. (2011)

Kalamangalam et al. (2013)

Kudr et al., 2013; Widjaja et al. (2013)

�� Specific patterns on Invasive EEG:Specific patterns on Invasive EEG:�� IctalIctal onsets onsets

�� Discrete burst suppression or attenuationDiscrete burst suppression or attenuation

�� Continuous epileptic discharges [CEDs]Continuous epileptic discharges [CEDs]

Defining the EpicenterDefining the Epicenter-- IIIIII

IEEG postIEEG post--processing to define the Epicenterprocessing to define the Epicenter

�� Weiss et al. A Weiss et al. A practical, efficient practical, efficient

method to identify method to identify

thethe smallsmall ictalictal core core regions. Brain.2013 regions. Brain.2013

Dec;136(Pt 12):3796Dec;136(Pt 12):3796

� Cabrerizo et al. A new parametric feature description for the classification epileptic

EEG records in pediatric population. International J Neural syst. 22 [2] : 2012

Brain Mapping of Critical Function Brain Mapping of Critical Function

Why? How?

�� RETAIN: Disturbances of cortical organization RETAIN: Disturbances of cortical organization ((polymicrogyriapolymicrogyria, , schizencephalyschizencephaly, and mild, and mild--type FCD)type FCD)

�� REORGANIZE: REORGANIZE:

�� Disturbances of abnormal neuronal or Disturbances of abnormal neuronal or glialglial proliferation proliferation ((hemimegalencephalyhemimegalencephaly, Taylor, Taylor--type FCD, and type FCD, and heterotopiaheterotopia) )

�� Destructive or sclerotic lesionsDestructive or sclerotic lesions

Janszky et al. Ann Neurol; 2003 Jun;53(6):759-67.

Lesions may retain or reorganize function

Schizencephaly Transmantle FCD

Burneo et al. Neurology. 2004 ; 63(10):1818-24.

Brain Mapping TestsBrain Mapping Tests

Critical Cortex:Critical Cortex:

��fMRIfMRI

��MEGMEG

��TMSTMS

��ECS mappingECS mapping

Critical PathwaysCritical Pathways

��DTI DTI TractographyTractography

No SilverNo Silver

Bullet testBullet test

Example- False negative lateralization of language (Jayakar et al., 2001)

12 hrs post-ictal

2 wks post-ictal

Rt handed

Lt TLE

fMRIfMRI showed preserved motor on the left in ¾ subjectsshowed preserved motor on the left in ¾ subjects

TMSTMS-- no response from left & bilateral response from rightno response from left & bilateral response from right

No deficit following No deficit following hemispherectomyhemispherectomy

Zsoter et al. Epilepsia, 2012 ;53(6):1528-1167.

Example- fMRI false positive

Jayakar et al.Epilepsia.2014; 55

(4): 507-18

Special ReportSpecial ReportDiagnostic test Diagnostic test

utilization in evaluation utilization in evaluation

for for resectiveresective epilepsy epilepsy

surgery in childrensurgery in children

Goals

Tests Techniques

Epileptogenic region

Conventional Surgery

Conventional Surgery

Minimally / NonInvasive

“Less is More”

Strategy

CriticalCortex

Pediatric Epilepsy Surgery

MCH series of Epicenter resection MCH series of Epicenter resection –– conventional surgeryconventional surgeryHyslopHyslop et al., 2014et al., 2014-- submitted submitted

�� 25 pts aged 0.525 pts aged 0.5--19.9 yrs [mean 11.8] who underwent 19.9 yrs [mean 11.8] who underwent focal focal corticectomycorticectomy involving one aspect of a single lobe involving one aspect of a single lobe

preserving all functionpreserving all function

Engel I II III IV

N=25 15[60%]

3[12%]

2 5

Case example- Rt parietal ictal onset

PETPET-- rtrt posterior quadrantposterior quadrant

IEEG: wide ictal onset zone

1 2 3 4

Calculation

Motor

Wide “EZ” encroaching/involving critical cortex

ECoGECoG using multiple using multiple SD+depthsSD+depths –– discrete CEDsdiscrete CEDs

1 2 3 4

Wernickes

Calculation

Motor

Engel I outcome

Minimally

Invasive

Non

Invasive

Epicenter

Unclear

Stereo-EEG guided Radiofrequency Ablation

Epicenter

Clear

MR guided Thermal Laser Ablation

- MR Guided laser insterstitial thermal therapy (MRgLITT)- MR guided Focused Ultrasound

Minimal/ Non invasive surgical techniquesMinimal/ Non invasive surgical techniques

Stereo-EEG guided radio frequency thermocoagulation

Cossu et al. Neurol Neurosurg Psychiatry.2014 Jun;85(6):611-7.

Guénot et al., Adv Tech Stand Neurosurg 2011; 36:61-78.

RF thermocoagulation of nodular heterotopia

Outcome of RF Outcome of RF thermocoagulationthermocoagulation of nodulesof nodules

Cossu et al. Neurol Neurosurg Psychiatry.2014 Jun;85(6):611-7.

MR guided thermal laser ablationMR guided thermal laser ablation

Thermal Laser ExampleThermal Laser Example–– MTLE MTLE

MesialMesial Temporal Thermal Laser seriesTemporal Thermal Laser series

Willie et Willie et al., Neurosurgery al., Neurosurgery 2014 Jun;74(6):5692014 Jun;74(6):569--8484

�� 13 adults. A mean 60% volume of the 13 adults. A mean 60% volume of the amygdalohippocampalamygdalohippocampalcomplex was ablated complex was ablated

�� 1 visual field deficit from deviated insertion 1 visual field deficit from deviated insertion

�� Variances in ablation volume and length did not correlate with Variances in ablation volume and length did not correlate with outcomesoutcomes

�� At followAt follow--up from 5 to 26 months (median, 14 months):up from 5 to 26 months (median, 14 months):

I II III-IV

N=13 7[54%]

3[23%]

3[23%]

WilfongWilfong & Curry. & Curry.

Epilepsia,54(Suppl.):10Epilepsia,54(Suppl.):10

99––114,2013114,2013

SF SF 12 (86%) of 14 cases12 (86%) of 14 cases

Hypothalamic Hypothalamic HamartomaHamartoma --Thermal Laser seriesThermal Laser series

MCH MCH -- Thermal laser seriesThermal laser seriesMiller et al., 2014 AESMiller et al., 2014 AES

�� 1717 patients mean age 15.3 years (range: 5.9 patients mean age 15.3 years (range: 5.9 -- 20.6 years).20.6 years).

�� Varied substrates including FCD, Tuberous Sclerosis, Varied substrates including FCD, Tuberous Sclerosis, Hypothalamic Hypothalamic HamartomaHamartoma, HS, HS

�� No major or permanent complicationsNo major or permanent complications

�� At 2 yr follow up At 2 yr follow up

I II III IV

N=17 7[41%]

1[6%]

3[18%]

6[35%]

Example Thermal laser Example Thermal laser ––

MesialMesial occipital occipital

Miller et al., 2014

Seizure free after two treatmentsNo Visual field deficit

� Preoperative FLAIR and T2-weighted MRI

�Ictal SPECT

�T1 with gadolinium and T2- MRI postoperative day 1

�5 months postoperatively

Example Thermal laser Example Thermal laser ––

Left Left InsulaInsula

Thermal Laser – Low neuropsychologic

deficits and complications

�� Willie et al. , Neurosurgery. 2014 Jun;74(6):569Willie et al. , Neurosurgery. 2014 Jun;74(6):569--8484

�� Curry et al. Epilepsy Curry et al. Epilepsy BehavBehav.. 2012 Aug;24(4):4082012 Aug;24(4):408--14. 14.

� Malikova et al.l. Epilepsy Res.2013 Oct;106(3):423-32.

�� WilfongWilfong ,, Curry DJ. Curry DJ. EpilepsiaEpilepsia.. 2013 Dec;54 2013 Dec;54 SupplSuppl 9:1099:109--14. 14.

�� Wagner et al., EpilepsyWagner et al., Epilepsy BehavBehav.. 2014 Jul 2014 Jul

22;37C:20422;37C:204--209. 209.

�� Chen et al. J Chen et al. J ClinClin NeurosciNeurosci.. 2014 2014

Sep;21(9):1525Sep;21(9):1525--8. 8.

�� Problem in childrenProblem in children--

Radiation/radiation/radiation !!Radiation/radiation/radiation !!

MRMR--guided Laser Interstitial guided Laser Interstitial

Thermal Therapy (Thermal Therapy (MRgLITTMRgLITT))

MR guided Focused Ultrasound System

FUS Device

1024 phased array transducers

Benefits compared to MRgLITT:- No radiation- Immediate result that can be controlled and monitored by thermal MR imaging.

Limitations:- Mainly effective towards the center of the skull- Not FDA approved

� Clinical Trials in adults� Movement disorders: 175 patients with essential tremor >

no safety concerns > being submitted to FDA

� Tumor ablations [3 patients]

� Experimental data� Epilepsy targets [starting 2015]

� Anterior Cingulotomy, Septum Pellucidotomy, Third ventriculostomy for hydrocephalus, Cyst Fenestration, Trigeminal Neuralgia,

Thrombolysis

MRgFUS –

Scope of clinical applications

Example of Pallidotomy for essential tremors

Highly precise ablations

T1w Diffusion

T2w T1w

Treatment Day

Follow-up

Before After

1 Month2 Days 3 Months

T1w

MRgFUS Cadaveric Ablation

Summary of techniquesSummary of techniques

Feature Radio

Frequency

Thermal

Laser

MRgLITT MRg

FUS

Invasive Min Min Non Non

Radiation +++

ALOS 7-10 d 2 OP OP

IEEG ++++ + - -

# of Surgeries

2 1 1 1

Effect Immediate Immediate Delayed Immediate

Monitored No Yes No Yes

�� Access to deep seated lesions, prior operated Access to deep seated lesions, prior operated cases or cases or surgically inoperable regions. surgically inoperable regions.

�� SafetySafety-- Low risk to surround grey and white Low risk to surround grey and white matter > better functional outcome matter > better functional outcome

�� Recovery times and hospital stays reduced Recovery times and hospital stays reduced --usually OP or 1 day stayusually OP or 1 day stay

�� Procedure can be repeated multiple timesProcedure can be repeated multiple times

�� Family Preference Family Preference

Advantages compared to conventional surgery Advantages compared to conventional surgery

Limitations compared to conventional surgery Limitations compared to conventional surgery

� Concern for swelling limit the size of ablation in one session> Large lesions are not suited

� Ablation of irregular lesions or functional abnormal zones is difficult especially near critical cortex

� Intracranial EEG tailored resection is not feasible

Conclusions Conclusions

�� “Less is More” “Less is More” –– ablation of the Epicenter is an ablation of the Epicenter is an effective treatment strategy in effective treatment strategy in select epilepsy select epilepsy

casescases..

�� Minimally or Non Invasive techniques offer an Minimally or Non Invasive techniques offer an

attractive alternative to conventional surgery and attractive alternative to conventional surgery and

enhance safety and comfortenhance safety and comfort

�� Comparable efficacy for discrete deep seated targets Comparable efficacy for discrete deep seated targets -- HS, HH, TS, or periventricular nodule.HS, HH, TS, or periventricular nodule.

�� Less efficacious for irregular or illLess efficacious for irregular or ill--defined targetsdefined targets--Complex FCD or TS.Complex FCD or TS.

Thank YouEpilepsy Program Team• Epileptology/Neurophysiology:

� Ian Miller MD

� Michael Duchowny MD

� Trevor Resnick MD

� Catalina Dunoyer MD

• Neurosurgery� John Ragheb MD

� Sanjiv Bhatia MD

� Toba Niazi MD

• Neuroradiology� Nolan Altman MD

� Santiago Medina MD

� Esperanza Pacheco MD

� Martha Ballesteros

� Byron Bernal MD

• Neuropsychology� Brandon Korman PhD

• Nursing specialist� Pat Dean

� Aileen Rodriguez

• Neurointensivists

• NeuroAnesthesiologists• NeuroPathologist

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“ Less is More”