Transcript here - University of Kansas Medical Center

Minimally Invasive Epilepsy Surgery
Is it better?
Patrick Landazuri, M.D.
Epilepsy Division
August 5, 2016
Disclosures
 None
Overview
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What is refractory epilepsy?
Why should we do epilepsy surgery?
Barriers to epilepsy surgery
Minimally invasive techniques
Refractory epilepsy
 Failure of two tolerated,
appropriately chosen,
and adequately dosed
anti-epileptic medications
 There can be limited 1-2
year periods of seizure
remittance in refractory
epilepsy
Kwan P, Schachter SC, Brodie MJ. “Drug-Resistant Epilepsy”. NEJM. 2011
Callaghan B, et al. “Remission and relapse in a drug-resistant epilepsy population followed prospectively”. Epilepsia. 2011
AED effectiveness
Stein MA and Kanner AM. “Management of Newly Diagnosed Epilepsy”. Drugs 2009
Isn’t there just another medicine?
Wang SP, et al. “Seizure recurrence and remission after switching AEDs”. Epilepsia 2013
First RCT for temporal lobe epilepsy (2001)
Wiebe S, et al. “A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy”. NEJM 2001
Guidelines
Engel Jr. J, et al. “Practice parameter: Temporal lobe and localized neocortical resections for epilepsy”. Neurology 2003
ERSET (2012)
Engel Jr. J, et al. “Early Surgical Therapy for Drug-Resistant Temporal Lobe Epilepsy”. JAMA 2012
Mortality benefits
Sperling MR, Barshow S, Nei M, Asadi-Pooya AA. “A reappraisal of mortality after epilepsy surgery”. Neurology. 2016
Employment benefits
Edelvik A, Flink R, Malmgren K. “Prospective and longitudinal long-term employment outcomes after resective epilepsy surgery”. Neurology. 2015
IQ benefits
Boshuisen K, et al. “Intelligence Quotient Improves after Antiepileptic Drug Withdrawal following Pediatric Epilepsy Surgery”. Ann Neurol. 2015
Healthcare savings
Langfitt JT, et al. “Health care costs decliene after successful epilepsy surgery”. Neurology. 2007
Benefits of successful epilepsy surgery
 Seizure freedom
 Increased quality of life
 Able to decrease or titrate off AEDs
 IQ increase secondary to AED withdrawal
 Increased likelihood to return to work
 Decreased healthcare costs (in the long run)
Continued referral difficulty
Burneo JG, et al. “Disparities in surgery among patients with intractable epilepsy in a universal health system”. Neurology 2016
Barriers
 Physician
 Educational
 Patient
Canadian neurologist survey part 1
 56% did not believe lack of seizure freedom was reason for
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referral
48% did not realize that failing 2 AEDs constituted drug
resistant epilepsy
45% are not aware of the AAN clinical practice guidelines for
epilepsy surgery
46% believe patients must be refractory for >1 year to warrant
epilepsy surgery referral
20% have never referred a patient for surgical evaluation
Roberts JI, et al. “Neurologists’ knowledge of and attitudes towards epilepsy surgery”. Neurology. 2015
Canadian neurologist survey part 2
 Neurologist concerns with referring patients
 34% report long wait times
 14% limited resources and access issues
 7% report distance concerns for their patients
Roberts JI, et al. “Neurologists’ knowledge of and attitudes towards epilepsy surgery”. Neurology. 2015
Educational barriers
 Suboptimal clinical exposure for neurology (and
neurosurgery) residents
 Relatively few didactics focused on non-AED
treatment of refractory epilepsy
 Better outreach to non-neurologists?
What do patients think of epilepsy surgery
 Considered dangerous with 56% saying it’s very dangerous
 Concern for adverse events
 47% say paralysis is possible
 61% say brain damage is possible
 45% say concern for loss of independence
 Almost 30% of patients had pre-existing negative attitudes
 Over half of that 30% were completely opposed
 73% think surgery should be the last resort
 56% would not undergo surgery unless a 100% success rate
Erba G, et al. “Acceptance of epilepsy surgery among adults with epilepsy – What do patients think?”. Epilepsy Behav. 2012
Patient characteristics and response to
epilepsy surgery conversations
 In favor of surgery
 Adequately informed of risks and benefits (OR 2)
 Higher level of education (OR 5)
 High degree of trust with neurologist (OR 4)
 Against surgery
 The opposite of the above statements as well
 Existing disability (OR 3)
 Thus, educating patients does help
 Did not sway many that were completely opposed though
Erba G, et al. “Acceptance of epilepsy surgery among adults with epilepsy – What do patients think?”. Epilepsy Behav. 2012
Standard anterior temporal lobe resection
Wiebe S, et al. “A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy”. NEJM 2001
Actual pictures from Google search
“anterior temporal lobectomy”
Untitled image. Retrieved July 30, 2016 from http://www.augusta.edu/mcg/neurosurgery/clinicalprograms/esphoto_gallery.php
“Scar over left temporal lobe after surgery”. Retrieved July 30, 2016 from https://oneintwentysix.files.wordpress.com/2014/11/lobectomy.jpg
Minimally invasive techniques
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Selective amygdalohippocampectomy
Stereotactic radiosurgery
Stereotactic radiofrequency ablation
Laser thermal ablation
Focused ultrasound ablation
Neurostimulation
Selective amygdalohippocampectomy
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Multiple different surgical approaches
Removes only the mesial structures
Developed as a way to preserve lateral neocortex
End goal to improve neuropsychological
outcomes while maintaining seizure outcomes
Josephson CB, et al. “Systematic review and meta-analysis of standard vs selective temporal lobe epilepsy surgery”. Neurology. 2013
Hoyt AT and Smith KA. “Selective amygodalohippocampectomy”. Neurosurg Clin Am. 2016
Selective amygadolohippocampectomy
Seizure and neuropsychology outcomes
• Neuropsychology results varied
• At worst, the results are no worse compared to ATL
• Barrow Neurological Institute’s cohort showed:
• 1/3 of LEFT surgeries have decrease in memory, verbal intellect, and naming
Josephson CB, et al. “Systematic review and meta-analysis of standard vs selective temporal lobe epilepsy surgery”. Neurology. 2013
Gleissner U, Helmstaedter C, Schramm J, and Elger CE. “Memory Outcomes after Selective Amygdalohippocampectomy in Patients with Temporal Lobe Epilepsy: One-year Follow-up”. Epilepsia
2004
Hill SW, Gale SD, Pearson C, Smith K. “Neuropsychological outcome following minimal access subtemporal selective amygalohippocampectomy”. Seizure 2012
Stereotactic radiosurgery
 Stereotactic delivery of ionized radiation
 200 separate sources are delivered at various vectors by
linear accelerators to a focus point within the calculated
center
 Has been used for multiple lesion types as well as
physiologically defined epilepsies
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Tumors – high volume > low volume more likely to be seizure free
AVMs – make sure to get the AVM nidus
Cavernomas – perilesional tissue is epileptogenic too
Hypothalamic hamartoma – only 27% seizure free, but improved
behaviors
Quigg M and Harden C. “Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies”. J Neurosurg. 2014
Stereotactic radiosurgery
MTLE
 Prospective, randomized 20 vs 24 Gy
 30 patients (13 high dose)
 The above study led to the ROSE trial
 RCT for radiosurgery vs ATL
 Closed early due to poor enrollment, but now awaiting results
Barbaro NM, et al. “A Multicenter, Prospective Pilot Study of Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy: Seizure
Response, Adverse Evetns, and Verbal Memory”. Ann Neurol. 2009
Radiographic progression of SRS
Barbaro NM, et al. “A Multicenter, Prospective Pilot Study of Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy: Seizure
Response, Adverse Evetns, and Verbal Memory”. Ann Neurol. 2009
SRS benefits/drawbacks
 Biggest positive is this is truly non-invasive
 Several drawbacks
 Delayed development of radiosurgical lesion
 Seizure reduction take between 9-15 months to manifest
 Seizure frequency can acutely worsen during acute swelling
 Risk of radiation induced tumor is small (0.64%)
Quigg M and Harden C. “Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies”. J Neurosurg. 2014
Stereotactic radiofrequency ablation
MTLE
 Under MRI guidance, current at
high frequency is applied to an
electrode
 Can be done during invasive
monitoring if proper electrodes
are used
 Recently championed by one
group in the Czech Rep
 Report nearly 80% seizure
freedom in 51 patient cohort
 No MRI diagnoses or path
reported
 Good neuropsych outcomes
Liscak R, et al. “Sterotactic radiofrequency amygdalohippocampectomy in the treatment of mesial temporal lobe epilepsy”. Acta Neurochir. 2010
Malikova H, Kramska L, Vojtech Z, Lukavsky J, Liscak R. “Stereotactic radiofrequency amygdalohippocampaectomy: two years of good neuropsychological
outcomes”. Epilepsy Res. 2013
Stereotactic radiofrequency ablation
Hypothalamic hamartoma
 100 patient cohort from
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Japan
71% total seizure freedom
rate
86% gelastic seizure
freedom
Behavioral problems
resolved if seizure free
Behavioral improvement
seen even with continued
seizures
Kameyama S, et al. “MRI-guided steretactic radiofrequency thermocoagulation for 1000 hypothalamic hamartomas?”. J Neurosurg. 2016
Stereotactic radiofrequency ablation
Palliative approaches
 Due to the possibility of
making small lesions,
treatment consideration in
eloquent locations
 One small 7 patient series
from Germany
 Mostly palliative results
 One with post operative
aphasia that patient knew was a
possibility
 One case report from China
of bilateral mesial
radiofrequency ablations
Wellmer J, et al. “Lesion guided stereotactic radiofrequency thermocoagulation for palliative, in selected cases curative epilepsy surgery”. Epilepsy Res. 2016
Luo H, et al. “Bilateral stereotactic radiofrequency amygdalohippocampectomy for a patient with bilateral temporal lobe epilepsy”. Epilepsia. 2013
Laser thermal ablation
 Delivery of energy with rapid and localized heating
of tissue with sharp boundaries
 Can monitor heat real time via MRI
 Initially used for brain tumors
 Rapidly being adopted for epilepsy
Willie JT, et al. “Real-Time Magnetic Resonance-Guided Stereotactic Laser Amygadalohippocampotomy for Mesial Temporal Lobe
Epilepsy”. Neurosurgery. 2014
Laser thermal ablation for MTLE
 Emory cohort (2013)
 13 patients (9 with HS)
 6/9 seizure free in HS group
 1/4 seizure free in non-HS group
 Thomas Jefferson cohort (2015)
 12/20 seizure free (almost all had HS)
 3/4 non-responders seizure free after ATL
Willie JT, et al. “Real-Time Magnetic Resonance-Guided Stereotactic Laser Amygadalohippocampotomy for Mesial Temporal Lobe Epilepsy”.
Neurosurgery. 2014
Kang JY, et al. “Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy”. Epilepsia 2015
Laser thermal ablation of other etiologies
 Miami Children’s
cohort
 7/17 seizure free in total
(heterogenous pathology)
 8/17 had previous resection
 4/8 showed improvement
 Focal cortical dysplasia - 2/7
seizure free
 Cavernomas
 Periventricular nodular
heterotopia
 2 patients – both seizure free
after subsequent clinical care
 Completion of corpus
callosotomy
 50% seizure reduction in
palliative procedure
 4/5 Engel class I (5th seizure
free with resection)
Lewis EC, et al. “MR-guided laser interstitial thermal therapy for pediatric drug-resistant lesinoal epilepsy.” Epilepsia. 2015
McCracken DJ, et al. “Magnetic Resonance Thermometry-Guided Stereotactic Laser Ablation of Cavernous Malformations in Drug-Resistant Epilepsy: Imaging and Clinical Results”. Neurosurgery. 2015
Ho AL, et al. “Stereotactic laser ablation of the splenium for intractable epilepsy”. Epilepsy Behav Case Rep 2016
Esquenazi Y, et al. “Stereotactic laser ablation of epileptogenic periventricular nodular heterotopia”. Epilepsy Res. 2014
Practice effect and/or improved patient
selection with laser thermal ablation
Willie JT, et al. “Real-Time Magnetic Resonance-Guided Stereotactic Laser Amygadalohippocampotomy for Mesial Temporal Lobe Epilepsy”.
Neurosurgery. 2014
Kang JY, et al. “Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy”. Epilepsia 2015
Focused ultrasound ablation
Monteith S, et al. “Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study”. J Neurosurg. 2016
Low-intensity Focused Ultrasound Pulsation (LIFUP) for Treatment of Temporal Lobe Epilepsy retrieved from https://clinicaltrials.gov/ct2/show/NCT02151175
Neurostimulation
 Vagus nerve stimulation
 Responsive neurostimulation
 Deep brain stimulatoin
Vagus nerve stimulation (VNS)
 51% reduction in seizures after one year
Englot DJ, Chang EF, Auguste KI. “Drug-Resistant Epilepsy”. J Neurosurg. 2011
Reponsive neurostimulation (Neuropace)
 Implantable depth or
strip electrodes that
record real time
electrocorticography
 Deliver an electrical
stimulus when it sees the
Ecog seizure pattern
 Ideal candidates
 Multifocal epilepsy
 Epileptogenic zone in eloquent
 Efficacy
 44% seizure reduction at year
one
 53% seizure reduction at year
two
 “12.9% had at least 1 seizurefree period of 1 year or longer”
 Implant site infections
(9%)
 5.5% had device removal
cortex
Bergey G, et al. “Long-term treatment with responsive brain stimulation in adults with refractory partial seizures”. Neurology 2015
Deep brain stimulation
 5 patient case series from
Colombia in HH
 3 patient case series from
China in BTLE
 91%, 92%, and 95% seizure
reduction
Fisher R, et al. “Electrical stimulation of the anteriori nucleus of thalamus for treatment of refractory epilepsy”. Epilepsia. 2010
Benedetti-Isaac JC, et al. “Seizure frequency reduction after posteriomedial hypothalamus deep brain stimulation in drug-resistant epilepsy associated with intractable aggressive behavior”. Epilepsia.
2015
Jin H, et al. “Hippocampal deep brain stimulation in nonlesional refractory mesial temporal lobe epilepsy”. Seizure 2016
Where are minimally invasive techniques
useful?
 Small lesions
 Radiographic
 Electrophysiological
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Multifocal
Deep structures
High medical risk patients?
Patient preference
How does this fit in at KU?
 From Jan 2012 – May 2016
 23 surgeries, with 14 being seizure free
 8/11 ATL seizure free
 3/5 neocortical seizure free
 3/7 ablations seizure free
 3/5 MTS seizure free
 2 palliative cases (one seizure free after ATL)
 Stereoencephalography techniques
 RNS implantation site
 Selected as a site for prospective trial for laser ablation of mesial
temporal lobe epilepsy
 In consideration for a neocortical epilepsy RCT
Munyon C, Sweet J, Luders H, Lhatoo S, Miller J. “The 3-Dimensional Grid: A Novel Approach to Stereoelectroencephalography”. J
Neurosurg. 2015
Take home
 Resection remains the gold standard
 Data remains limited for all minimally invasive modalities
 Use of minimally invasive techniques completely hinges on
adequate localization of the epileptogenic zone
 No significant neuropsychological benefit has been
demonstrated yet
 Minimally invasive treatment options may open up avenues for
some patients who would otherwise be resistant to epilepsy
surgery
Thank you