Title: American Epilepsy Society Plenary II
1American Epilepsy Society Plenary II
Treatment of Epilepsy Improving Outcomes with
Innovative Surgical Techniques
2Plenary II
- The Overview
- The theme of the symposium is innovative surgical
techniques for epilepsy. Three topics
(hemispheric syndromes, temporal lobe epilepsy,
and tuberous sclerosis) will each include two
subtopics addressed by a neurologist and a
neurosurgeon. The talks will address 1)
selection of candidates for hemispherectomy, 2)
experience related to seizure outcome and
complications of hemispherectomies performed in
different clinical settings, and the strategy for
choosing the best surgical approach, 3)
challenges related to offering temporal
resection, 4) current available data from
surgical trials that may have bearing on this
issue, 5) the available data concerning the roles
of conventional MRI, scalp EEG, PET (FDG,
flumazenil, and AMT), ictal SPECT, and
diffusion-weighted MRI in identifying the
epileptogenic tuber(s) for resection, and 6) the
overall surgical strategy for patients with
tuberous sclerosis.
3Plenary II
- Learning Objectives
- At the conclusion of this activity, participants
should be able to - Identify favorable candidates for hemispherectomy
for refractory epilepsy, and understand the
issues related to selection of operative
technique - Recognize the issues related to surgical planning
in temporal lobe epilepsy, to obtain the best
seizure outcome with the least risk for
postoperative memory deficit - Appreciate strategies for developing a surgical
plan for patients with focal epilepsy due to
tuberous sclerosis.
4Plenary II
- It is the policy of the American Epilepsy Society
that all faculty participating in continuing
medical education activities are expected to
disclose to the audience any real or apparent
conflicts of interest related to the content of
the activity. Faculty disclosure has been made
in writing and can be found in the Annual Meeting
program book. - Each speaker has been asked to disclose to you if
and when unapproved products and/or unapproved
indications will occur in his or her
presentation.
5Plenary II
- AES now has the Medical Education Evaluator, an
online system to obtain CME and Pharmacy credit.
The Evaluator will be used to verify course
attendance, enter pre- tests and post-tests and
complete course and activity evaluations. You use
the pre-assigned numbers printed on your badge to
gain access to the activity and course
evaluations. A booklet containing paper copies of
test and evaluation forms are available in the
AES conference bag and will allow for note taking
before completing the tests and evaluations
online.
6Plenary II
- After logging in at AESnet.org with your badge
number, you must enter the time spent in each
Annual Meeting educational session, complete any
required pre/post-tests and then complete an
evaluation on each session you attend. The system
will allow you to enter your information while at
the Annual Meeting, through the Cyber Cafes or
with a personal laptop through the wireless
network, or at your leisure back at your office.
When complete, the system will format a PDF
certificate for you to download and print.
7Evolving ConceptsIn Selection Of Hemispherectomy
Candidates Plenary II SessionAmerican Epilepsy
Society MeetingDecember 7, 2004
- Ajay Gupta, M.D.
- Cleveland Clinic Foundation
- Cleveland Ohio
8What have we learnt so far from the published
literature on selection of candidates for
hemispherectomy?
950-70 Patients Who Had Hemispherectomy Are
Seizure Free
- Intractable (catastrophic) partial epilepsy
- Unilateral focal/multifocal EEG discharges
- Unilateral hemispheric abnormality
- Cortical dysplasia, Hemimegalencephaly, Stroke,
Rasmussens encephalitis - Low risk of new post-operative deficits
- Pre-existing hemiparesis, visual field deficit,
cognitive delay
Kossoff EH et al. Neurology 2003 Jonas R et al.
Neurology 2004 Devlin AM et al. Brain 2003
Boongird A et al. J Neurosurg 2005 (abstract)
10 Evolving Concepts Selection of Hemispherectomy
Candidates
- Could more children benefit from hemispherectomy?
11Children With Exclusively Generalized Scalp EEG
Discharges And Hemispheric/Focal Brain
Abnormalities Could They Be Surgical Candidates?
- Ajay Gupta, MD Elaine Wyllie, MD
- Deepak Lachhwani, MD Prakash Kotagal, MD
- William Bingaman, MD
- Cleveland Clinic Foundation
- Cleveland OH
Platform presentation at the American Academy of
Neurology, 2004 (Abstract)
12Limitations To Localize Epileptogenic Zone In
Children
- Semiology is of limited use under 2 years
- Acharya et al, Neurology, 1997 Nordli et al,
Epilepsia, 1997 - Scalp EEG could be non-localizing
- Infants with hypsarrhythmia and non-localizable
ictal scalp EEG during spasms became seizure free
after resection of congenital lesion seen on PET
and MRI - Chugani et al., Annals of Neurology, 1990
13The Question
- If infants with generalized EEG pattern like
hypsarrhythmia and a brain lesion could be
surgical candidates, - then why may not children with generalized
epileptic discharges and a brain lesion be
candidates for surgery?
14Hypotheses
- Developmental evolution of scalp EEG patterns in
the presence of a focal lesion in a developing
brain is unknown - Generalized scalp EEG discharges may represent
progressive abnormal networking in the presence
of a lesion acquired during perinatal or early
postnatal life
15Methods Pediatric Series Cleveland Clinic
2001-04
- 8 children
- Exclusively generalized or multiregional scalp
epileptiform discharges - No predominant epileptogenic region defined on
neurophysiology - Unilateral hemispheric or focal brain lesion on
brain MRI - Pre-surgical evaluation and surgery at Cleveland
Clinic
16Methods Patient Population
- Sick children with dead end
- Multiple daily seizures, status epilepticus
- Not candidates for surgery at other centers or at
CCF during previous evaluations - Consideration for no new post-operative deficits
- Parental understanding, informed consent
- Approved by patient management committee
- Independent evaluation by bio-ethicist
17Katie Lennox Gestaut Syndrome
- 8 years-old, onset at 18 months
- Seizure types (no focal semiology)
- Abrupt drop attacks with injury, 10-20/day
- Slumping over, bobbing, clonic jerking of the
head and upper body for 10-30 sec, 50-100/day - Exam
- Severe cognitive impairment (20-40 words), left
hemiparesis - Failed medications
- FBM, VPA, CBZ, LTG, TPM, ZON, LEV, ESM, MSM,
Clonazepam, Chlorazepate, B6, Ketogenic diet, VNS
18(No Transcript)
19Interictal EEG
20Seizure Head nod, Fall
21Seizure, continued
22Katies Brain MRI
23Katie Now 10 Years Old
- Right functional hemispherectomy (Nov 2002)
- No seizures since surgery
- On reduced antiepileptic medications
- EEG 6 months after surgery
- Diminished right hemisphere background
- Left Hemiparesis unchanged
- Parents report brighter affect
24Results
- Age of children 2 - 24 (mean 8) years
- Seizure onset 1 day 4 (mean 2) years
- Mean sz. (loss of awareness/fall) 32/day
- Current medications 2 - 5 (mean 3.5)
- Failed meds 4 - 9 (mean 5), 4 had VNS
- Neurological Exam
- Cognitive delay All
- Hemiparesis 4
- Hemianopsia 3
- Spastic quadriparesis (asymmetric) 1
25Results - Pre-surgical Evaluation
- Semiology Lateralization in 3 (focal motor
component) - EEG
- Exclusively generalized interictal and ictal
- Slow spike and wave pattern in 5
- Brain PET
- Correlated with MRI 6
- Poorly localized in 1
- SPECT Not done
26Results
- Surgery
- Hemispherectomy 4
- Temporo-occipital/parietal resections 3
- Frontal lobe resection 1
- Etiology
- Malformations of Cortical Development 4
- Trauma (Perinatal, non-accidental) 2
- Encephalomalacia after febrile status 1
- Perinatal ischemic stroke 1
27Results (N8)
- Mean follow up after surgery
- 16 months (11 22 months)
- Seizure outcome
- No seizures 7
- 1 patient had 2 surgeries (within 6 weeks with
extension of posterior temporal resection) - gt75 reduction in 1 (most disabling type)
28Results
- Complications
- No deaths
- No new post-operative motor deficits
- Chemical meningitis and VP shunt 1
- Cognition
- Remain delayed
- Parents report developmental gains
- Improved affect and behavior
29How could a focal or hemispheric epileptogenic
lesion give rise to exclusively generalized
epileptic discharges or slow spike and wave
patterns?
- Progressive phenomena
- Early focal EEG ictal onset Generalized
scalp EEG patterns - This has been shown in infants where very early
seizures with focal EEG onset are later replaced
by hypsarrhythmia (Chugani et al, Epilepsia 1993
Wyllie et al, Ann Neurol 1998)
30Discussion cont.
- Could this be an extralesional phenomenon or a
form of Secondary epileptogenesis in a developing
brain? - Hypothalamic Hamartoma
- A model of progressive symptomatic generalized
epilepsy with focal lesion where not all seizures
originate from the hamartoma (invasive studies)
yet patients may become seizure free after
surgery (Freeman JL et al., Neurology 2003)
31Conditions with exclusively generalized
progressive EEG findings in the presence of focal
lesions where seizure freedom is possible after
surgery
- Infants with hypsarrhythmia
- Hypothalamic hamartoma
- ..? Some older children with brain lesions
(extensive) that are congenital or acquired
during early brain development
32Conclusions
- Our observational series suggests that even older
children (beyond infancy) with focal or
hemispheric brain lesions may be surgical
candidates in the presence of exclusively
generalized interictal and ictal epileptiform
discharges on scalp EEG.
33Conclusions
- Careful consideration to several complicating
factors is required in surgical decision and is
best done at a specialized and experienced
Pediatric epilepsy center - More data are required before the results of this
small observational series are validated
34Thank You
35Tailoring the Hemispherectomy Improving Surgical
Outcomes
- William E. Bingaman, MD
- Cleveland Clinic Comprehensive Epilepsy Center
- Cleveland, Ohio
36Theory
- Theoretical chance of seizure freedom for
unilateral hemispheric epilepsy after
hemispherectomy is 100.
37Seizure-Free Outcomes All Etiologies
- UCLA series (2004) 71 at 2 years.
- Baltimore series (2003) 65 at 4.5 years.
- Bonn series (2002) 63 at 26 months.
- Multicenter study (1995) 70 seizure free at 6
months. - Personal series (2004) 76 at 33 months.
38Reasons for Failure
- Bilateral disease (patient selection)
- Malformations of cortical development.
- Rasmussen's encephalitis.
- Peri-natal infarction (esp. IVH).
- Incomplete disconnection
- Likely most important cause of failure.
- Technical issues.
- Pathology related?
39Hemispherectomy Techniques
- Surgical terminology is confusing.
- Basic categories include anatomic removal of
hemisphere, functional hemispherectomy,
hemispherotomy and variants, hemidecortication. - Trend to smaller craniotomies and less cortical
resection to improve peri-operative course and
avoid long-term complications.
40Are techniques equal?
- Anatomic
- Functional hemispherectomy
- Hemispherotomy
- Delalande
- Villemure Mascott
- Schramm
- Shimizu
- Mathern
- Decortication
41Outcome
- Efficacy of all hemispherectomy variants reported
to be similar (Rasmussen, UCLA, Schramm,
Kossoff). - Decision regarding which technique used appears
to be surgeons training, intraoperative
concerns, and avoidance of stormy post-operative
course. - No prospective, randomized comparisons exist.
42UCLA Series
- N115
- Anatomic, Rasmussen functional hemispherectomy,
modified lateral hemispherotomy (resect
BG/thalamus). - 48 cases MCD 40 received modified lateral
hemispherotomy. - No statistical difference in outcome based on
technique or substrate.
- Cook S., et al. J Neurosurg 100 125-141, 2004.
43Multicenter Review (Holthausen)
- 333 patients retrospectively studied from ten
centers. - Surgical technique matters with respect to
outcome Adams modification and hemispherotomy
associated with better outcomes over functional,
anatomic, hemidecortication. - 56 patients with MCD seizure free versus 82 of
SWD. - Seizure free outcome after hemispherotomy for
SWD, Rasmussens encephalitis, perinatal infarct
was 95. - Problems with study retrospective, multiple
centers, human factor not considered.
Holthausen et al. Seizures Post Hemispherectomy.
In Tuxhorn I, Holthausen H, Boenigk H (eds)
Pediatric Epilepsy Syndromes and Their Surgical
Treatment. 1997, pp 749-773.
44Are there differences in outcome according to
etiology?
- Dysplasia hemimegalencephaly with worst outcome
- Holthausen, Multicenter review, 1997
- Schramm, Neurosurgery Clin NA 37 113-133, 2002.
- Carreno et al, Neurology 2001 57 331-333.
- Jonas et al., Neurology 2004 62 1712-1721.
- Kossoff et al, Neurology 2003 61 887-890.
- Maehara et al, No To Hattatsu 32 395-400, 2000.
- Dysplasia hemimegalencephaly with better
outcomes - Shimizu et al, Neurosurgery 47 367-373, 2000.
(14 mcd,12 hm) 67 seizure free with
hemispherotomy. - DiRocco et al, Pediatr Neurosurg 2000 33
198-207. 14/15 HM seizure free (11 anatomic
technique).
45Malformations of Cortical Development
- Variable presentation of dysplasia from HM to
regional MCD. - Each malformation individual but share certain
surgical issues - Involvement of subcortical tissue with absence of
normal white matter tracts. - Enlarged hemisphere.
- Ventricular abnormalities.
- Possibility of imaging invisible disease.
46Hemimegalencephaly
- Enlarged hemisphere, hemiparesis, epilepsy,
severe psychomotor delay. - Cortical dysplasia.
- Worst developmental outcome of all children
undergoing hemispherectomy. - Suspected to be secondary to abnormal
contralateral hemisphere (Rintahaka et al,
Pediatric Neurol 921-8, 1993). - Jahan (1997) Bilateral neuropathology in HM.
- Robain (1988) 2/4 bilateral neuropathologic
changes.
47Posterior frontal lobe deep subcortical
involvement
T2 hyperintensity gross architectural
distortion with relative sparing of
parietal/occipital region
Hemimegalencephaly
JM
48Disordered Cortical/Subcortical Anatomy with HM
Patient DW
Patient JC
Patient JM
49Hemispheric Dysplasia
- Mild or no enlargement of affected brain.
- Minimal T2 signal change.
- Minimal (no) mass effect on other hemisphere.
- Multi-lobar or holohemispheric.
- Sometimes subtle on neuroimaging.
- Less developmental delay.
50Hemispheric Dysplasia
Patient EF
Patient ZN
Patient AH
51Personal Experience
- 102 patients undergoing hemispherectomy January,
1997 through October, 2004. - Technique used initially Rasmussen functional
hemispherectomy. - Anatomic hemispherectomy applied later.
- Finally, tailored combinations of anatomic
removal of most affected tissue with
disconnection of less affected tissue.
n102, overall seizure free rate 76 at mean 33
month f/u.
52Outcome versus Technique
- Functional 53/75 (71) seizure free.
- Anatomic 22/27 (82) seizure free.
- Majority of all patients are dramatically
improved (Engel I,II) 86/102 (84).
53Outcome versus Etiology
- Hemispheric dysplasia 22/30 seizure free (73).
- Hemimegalencephaly 14/17 seizure free (82).
- Rasmussens encephalitis 6/9 seizure free (67).
- Sturge Weber disease 4/4 seizure free (100).
- Perinatal Stroke 29/40 seizure free (73).
- Miscellaneous 0/2 seizure free.
54Hemimegalencephaly
- First four cases treated with FH all with
improved but persistent epilepsy and residual
frontal tissue (One converted to AH with
cessation of seizures). - 9/13 subsequent cases treated with modified
anatomic approach and 4 with functional technique
(One FH underwent reop to AH with cessation of
seizures). - 11/17 treated with anatomic technique and all are
seizure free. 6/17 treated with FH 50 sz free. - Re-operated FH cases converted to AH 2/2 seizure
free. - Overall, 14/17 (82) seizure free with 3 off
AEDs and 7 on monotherapy.
55Hemimegalencephaly
Sylvian fissure
Dural opening with exposure cerebral hemisphere
56Post resection cavity
57Hemimegalencephaly
58My First Hemispherectomy
DW Pre-operative MRI. R hemimegalencephaly.
59DW Post-op MRI after functional hemispherectomy
with residual dysplastic frontal tissue.
Underwent VPS and redo x2.
60DW Post-operative anatomic hemispherectomy. VPS
removed at last surgery.
61JC Pre-operative MRI demonstrating R
hemimegalencephaly. Note involvement of entire
hemisphere including subcortical structures.
62JC Post-operative Anatomic Hemispherectomy
63Hemispheric Dysplasia
- Diffuse or multi-lobar dysplasia with pre-op
hemiparesis, /- hemianopsia. - 22/30 (73) seizure free overall.
- 12/15 (80) seizure free with functional
technique. - 10/15 (67) seizure free with anatomic technique.
- 5 re-ops with only 1 seizure free.
64Perinatal Infarction
- All treated with functional technique.
- 29/40 (73) seizure free.
- No re-ops.
- Of 11 failures, 6 with b/l MRI findings and 4
with b/l ictal onset. - Patient selection and informed consent important
in this population.
65Rasmussens Encephalitis
- All nine treated with functional technique.
- One converted to anatomic after seizure
recurrence (became seizure free). - 6/9 (67) seizure free.
- 4/9 (44) with residual FL 2 with persistent
seizures. - 2/9 (22) with residual insula both seizure
free. - 2/3 failures with contralateral EEG onset
post-op (only one known pre-op).
66Re-operations
- Nine patients (8.8) re-operated for persistent
seizures and residual tissue (8 FH, 1 AH). - 7/9 re-ops in MCD/HM group
- Two HMs converted from functional to anatomic
(residual tissue) with relief of seizures. - Five patients with hemispheric dysplasia only 1
seizure free from re-operation.
67Re-operations
- One patient with Rasmussens encephalitis
converted from functional to anatomic with
cessation of seizures (additional insula
resected). - One patient with SWD and incomplete callosal
sectioning (immediate post op recurrence of
seizures) seizure free after completed
callosotomy.
68Historical Re-operation Rate
- Greatest with FH technique and dysplastic
etiology - UCLA (2004) 14 re-ops (12) highest in FH and
dysplasia. None in anatomic group. - Germany (2002) too anteriorly placed
disconnection lines were seen. - Mittal S. et al (2001) failure of FH due to
residual FL dysplastic tissue. After re-op,
patient seizure free. - Carreno M. et al (2001) 3/13 re-ops for residual
tissue in MCD population. - Shimizu H. (2000) 3/34 patients (26 MCD) with
re-op following hemispherotomy. - Kossoff E. (2003) 5/105 re-operated for residual
tissue. Four others with persistent seizures and
residual tissue.
69Success of Reoperation
- UCLA (2004) 7/14 (50) re-ops seizure free
- Cleveland (2004) 5/9 (56) re-op's seizure free
- Baltimore (2003) 1/5 (20) re-ops seizure free
- Montreal (2001) case report with MCD seizure
free after basal FL resected.
70Examples of Re-operations
- Splenial remnant
- Value of post-op MRI scan.
- Small amount of callosal tissue intact can lead
to persistence of seizures. - Frontal lobe remnant (easy to identify unclear
significance?)
71Incomplete Disconnection
Re-operation with splenial section seizure free
x 7 years.
72Disconnective Hemispherectomy Frontal Lobe
Surgical landmarks during disconnection crucial.
Steep learning curve to become familiar with this
area, especially via limited exposure technique.
73Residual FL Tissue MRI Analysis
- Arbitrarily defined as greater than 1cm of tissue
anterior to carotid bifurcation on sagittal MRI. - Identify whether MRI abnormality present.
74Residual Dysplastic FL in HM
75Tailored Hemispherectomy without Residual FL
76Residual FL
- 18/47 (38) of MCD/HM group with gt1cm residual
FL. - 5/18 (28) persist with seizures 4/5 had pre-op
dysplasia in area of residual tissue. - 13/18 were seizure free 11/13 had no pre-op
dysplasia in area of residual tissue.
77Residual FL without dysplasia
78Morbidity and Mortality
- No mortality
- Infection 3
- Hydrocephalus
- Pre-op shunts 12
- Post-op shunts (new) 9 (8.8)
- Post-op ventriculomegaly- 1
- Hemorrhagic 34 coagulopathic, 1 post-op
hemorrhage requiring evacuation, 1
intraventricular hemorrhage treated medically. - Ischemic 1 return to OR for temporal lobectomy
- Aseptic meningitis 25
79Anatomical
- Blood loss
- UCLA 688 cc average
- CCF 559 cc average
- Italy not reported
- VP shunts
- UCLA 29/37 (78)
- CCF 5/27 (19)
- Italy 4/11 (36)
- Reoperation for seizure control
- UCLA 0/37
- CCF 1/27 (4)
- Italy 0/11
80Functional hemispherectomy
- Blood loss
- UCLA 547 cc average
- CCF 330 cc average
- VP shunts
- UCLA 3/32 (9.4)
- CCF 4/75 (5)
- Reoperation for seizure control
- UCLA 8/32 (25)
- CCF 8/75 (11)
81Hemispherotomy
- Blood loss
- UCLA ave. 288cc
- Japan ave. 359cc (79 transfused).
- Germany 3/20 transfused
- VP shunts
- UCLA 22 new shunt rate
- Japan 15 new shunt rate
- Germany no new shunts
- Reoperation for seizure control
- UCLA 4/46 (9).
- Japan 3/34 (9)
- Germany 0/20
82Factors in Tailoring Surgical Treatment
- Anatomy of hemisphere to be disconnected
- Presence of gray-white anomalies (distortion of
normal anatomy) - Hemispheric size
- Ventricular size
- Posterior basal frontal lobe dysplasia
- Corpus Callosum
- Etiology
- MCD/HM most challenging
- Body weight/age of patient
83Modified Anatomic Hemispherectomy
Frontal/parietal dysplasia greater than posterior
quadrant, enlarged hemisphere, small ventricles,
MCD/HM etiology
Removal of Frontal-parietal-temporal lobes with
disconnection of posterior parietal-occipital
lobes
84Summary
- Surgeon experience with steep learning curve.
- Pay attention to anatomy
- Small ventricular size, subcortical dysplasia,
loss of white matter tracts - Tailor the operation to accomplish the goal
- More tissue removal for HM, MCD
- Remove insula?
- Pay special attention to posterior basal frontal
lobe particularly when dysplastic!
85Pediatric Epilepsy Surgery Team
- William Bingaman, MD
- Atthaporn Boongird, MD
- Joann Palmer, RN
- Ann Warbel, RN
86Pediatric Epilepsy Team
- Adina Chirla, RN
- Ajay Gupta, MD
- Prakash Kotagal, MD
- Deepak Lachhwani, MD
- Kathy Powaski, RN
- Elaine Wyllie, MD
87Used with parental permission
88Striking a Balance Between Memory and Seizure
Outcome
- Frank Gilliam, MD, MPH
- Professor of Neurology
- Columbia University
- New York, NY
89(No Transcript)
90Memory vs Seizure Outcomes
- Measures for Evaluation?
- Objective memory change
- Subjective memory change
- Function (employment, education achievement)
- Criteria for Clinical Decisions?
- Risk for objective memory change
- Risk for subjective memory change
- Risk for functional change
- Patient preference
91Memory vs Seizure Outcomes
- Classic Problem of Statistical versus Clinical
Significance
92Lateral Temporal EEG and Memory
Ojemann et al. Nat Neurosci. 564-7, 2002
93Predictors of Postsurgical Memory
- Lower Baseline Memory Scores
- MRI- Mesial Temporal Sclerosis
- WADA Memory Scores
- FDG-PET Hypometabolism
Better Memory Outcome
94Martin et al, Arch Neurol. 591895-901, 2002.
95Cognition in Temporal Lobe Epilepsy
Helmstaedter et al. Ann Neurol. 54425-32, 2003
96Outcomes Research
1) The study of the results of health
services that takes patients experiences,
preferences, and values into account. 2)
Outcomes research is intended to provide
scientific evidence relating to decisions made by
all who participate in health care.
-Clancy and Eisenberg, Science, 1998
97Subjective vs Objective Memory
Sawrie et al. Neurology. 1999 Oct
2253(7)1511-7.
98Subjective vs Objective Memory
Table 2. Base rates of significant change on
measures of subjective and objective memory
Sawrie et al. Neurology. 531511-7, 1999.
99Patient Preference
Memory Risk
Probability of Seizure Freedom
100Memory vs Seizure Outcomes
Memory Change
Seizure Control
101Standard vs. Selective Resectionvs.
RadiosurgeryWhat have we learned from
comparative trials?
- Nicholas M. Barbaro, MD
- University of California at San Francisco
102Three measures of outcome
- Seizure outcome
- Neuropsychological outcome
- Language
- Memory
- Quality of life
103Goals of Epilepsy Surgery
- Seizure-free
- Remove sufficient amount of functionally-irrelevan
t tissue - No reduction in neurological function
- Memory
- Language
- Motor, sensory, visual
- Improve QOL
- Correlates directly with seizure-free state
104Techniques of Temporal Resection
- Temporal lobectomy
- Anatomical (standard, en bloc)
- Tailored (ECoG with or without speech mapping)
- Selective medial resection
- Amygdalohippocampectomy
- Transcortical, trans-sylvian
105A Randomized, Controlled Trial of Surgery for
Temporal-Lobe EpilepsyNEJM 345311-318August
2, 2001 Number 5Wiebe S, Blume WT, John P.
Girvin JP, Eliasziw M Temporal Lobe Epilepsy
Study Group for the Effectiveness and Efficiency
of Surgery
106Determinants of outcome in temporal resection
- Mesial temporal sclerosis
- MRI is best predictor
- PET
- MRS
- Normal MRI
- Best case for tailored approach
107Outcome for Temporal Lobectomy
- Seizure-free outcome 60-90
- Improved performance IQ for non-dominant
- Significant (gt30) reduction in verbal memory
(Boston naming) for dominant resections - Unproven benefit of speech mapping
- Possible benefit of sparing superior temporal
gyrus - Smaller reduction in oral fluency (5)
- Quality of life determined by seizure outcome
108Results of Selective Temporal Resections
- Seizure-free rates 60-85
- Disagreement on neuropsychological advantage
(verbal memory) - Most large series fail to show difference between
selective and standard resection - Possible disadvantage in pediatric cases
- Vasospasm increased in trans-sylvian approach
- QOL varies with seizure outcome
109(No Transcript)
110Why radiosurgery?
- Selective temporal resections are effective
- Morbidity is low, but not zero
- Infection
- Neuropsychological change
- Blood loss (intra-operative, post-operative)
- Other focal neurological deficits
- Medical contraindications of open surgery
- Some patients are afraid of surgery
111Indirect evidence for efficacy
- Tumors
- Radiation and radiosurgery reduces seizures
- Hypothalamic hamartomas
- AVMs
- Standard AVM
- Cavernous malformations (Regis et al)
112Pre-clinical Evidence
- Kainic acid University of Pittsburgh
(Kondziolka) - Spontaneous Limbic Epilepsy University of
Virginia (Lee)
113Direct evidence for efficacy
- Barcia Salorio et al 1994
- 11 patients treated with 10-20 Gy
- 4/11 Seizure free, 5/11 reduced, 2/11 no response
- Radiosurgical treatment in Marseille (Regis)
- Radiosurgical treatment of patients with temporal
lobe epilepsy (24 Gy) - European Multi-center Trial
- 65 seizure-free
114U.S. Multi-center Trial
- Pilot Trial designed to gain preliminary evidence
that Gamma Knife radiosurgery is safe and
effective in reducing or eliminating seizures in
patients with temporal lobe epilepsy - Dose comparison in advance of Phase 3
multi-center trial
115U.S. Multi-center Trial
- Study Center UCSF
- Centers with at least one patient treated
- UCSF (Laxer, Garcia)
- University of Pittsburgh (Kondziolka)
- University of Virginia (Quigg)
- Columbia University (Goodman)
- Indiana University (Witt)
- University of Southern California (Heck)
- SUNY Syracuse (Beach)
- NINDS PSMB
- Dennis O. Dixon, Ph.D, chair
- Margaret Jacobs
- Ruben Kuzniecky, MD
- Quynh-Thu Xuan Le, MD
- Allen R. Wyler, MD
- Neuropathology
- Yale (de Lanerolle
116Treatment Protocol
- Select patients with medically refractory
temporal lobe epilepsy (best surgical treatment
group) - Randomize patients into 2 groups
- High dose 24Gy to 50 isodose line
- Low dose 20Gy to 50 isodose line
- Medical follow-up for 3 years
117(No Transcript)
118Radiosurgical Treatment
- Conformal radiation directed at temporal portion
of the amygdala, the anterior 2cm of the
hippocampus and adjacent parahippocampal gyrus - Total volume within 50 isodose line between 5.5
and 7.5cc - Treatment isocenters 2-6
119Radiosurgical Treatment
- Brainstem dose below 10Gy
- Optic nerve dose below 8Gy
- Shielding techniques used to achieve optimum fit
and remain below safety limits - All treatment plans monitored by Study Center on
day of treatment
120(No Transcript)
121Preliminary Results
- Patients treated 30
- Patients at gt18 month follow-up 18
- Patients at gt12 months 29 (1 lost to f/u)
122Typical Clinical Response
- Initial increase in auras with simultaneous
decrease in complex partial seizures - Headaches
- Radiological changes
123Pre- and post-treatment(1 year) FLAIR
124One year post radiosurgery
125Two years post radiosurgery
126(No Transcript)
127(No Transcript)
128(No Transcript)
129(No Transcript)
130Radiosurgery Adverse Events
131Preliminary Neuropsychological Analysis
- Performance IQ
- improvement in non
- dominant hemisphere
- cases
132Preliminary Neuropsychological Analysis
- No verbal memory
- decline in dominant
- hemisphere patients
133Preliminary Neuropsychological Analysis
- No short-term affective changes
- Improved quality of life in seizure-free patients
134Lessons from Temporal Lobe Surgery Trials
- Its the seizures, stupid
- Patients will accept mild reduction in function
in exchange for a seizure-free state - Verbal memory deficits are likely caused by
surgical access route - Radiosurgical treatment results in reduction in
seizures in well-defined cases
135Well-designed surgical trials are needed
- Is there a neuropsychological advantage of open
selective resections? - Is radiosurgery a reasonable alternative for some
patients with temporal lobe epilepsy? - Is there an advantage in the dominant temporal
lobe?
136Surgical trials continued
- Radiosurgery Phase 3 trial
- Direct comparison with temporal resection
- Attention to neuropsychological aspects
- Verbal function
- Post-operative mood changes
- Investigators meeting
- 430-600pm December 7th Sheraton Hotel
- Grand Chenier room
137Tuberous Sclerosisidentifying epileptogenic
tubers by noninvasive techniques
- J Helen Cross
- Institute of Child Health Great Ormond Street
Hospital for Children NHS Trust, London, UK
138Tuberous sclerosis
- Epilepsy
- 78 in population based study
- Age dependence, first seizure
- lt12m 69 IS in one third
- 1-16 27
- gt16 4
- Cognitive outcome dependent on
- h/o seizures
- age of onset
- seizure type (IS)
Webb, Fryer Osborne 1996
139Tuberous sclerosis
- Surgical management
- Evidence stereotyped seizure, localised focus
from likely tuber - Guerreiro et al Neurology 1998 51 1263-1269
- 12/18 patients focal resection 5 SF, 2 gt75
improved - F/up 1m-47 yrs
- Koh et al Epilepsia 2000 41 1206-1213
- 13/21 patients focal resection 9/13 seizure
free, 1gt75 improved F/up 6-82m - Karenfort et al Neuropediatrics 2002 33255-261
- 8/9 patients, 2 hemispherectomy, 2 SF, 5gt75
improved - F/up 6-52m
-
140Questions
- Is there evidence of seizures arising from a
single focus? - Can a single tuber be determined to be
responsible? - Can the tuber be removed without a functional
deficit?
141Noninvasive evaluation
- Localisation of area responsible for seizure
onset - Clinical evaluation
- Interictal EEG
- Ictal EEG
- how many seizures?
- MRI including FLAIR
- ?CT
- Other SPECT, PET,
142(No Transcript)
143(No Transcript)
144F8-F4
F4-Fz
Fz-F3
F3-F7
100 µV
0.5 sec
T10-C6
C6-C4
C4-Cz
Cz-C3
C3-C5
C5-T9
P8-P4
P4-Pz
Pz-P3
P3-P7
ECG
145(No Transcript)
146 147Other techniques
SPECT
- Koh et al 1999
- 15 patients TSC, age 3m-15yrs
- EEG
localised 10 5 focal ictal SPECT unlocalised 5
1 focal ictal SPECT
148Other techniques
AMT PET
Chugani et al 1998 9 children, 1-9yrs,
increase AMT uptake in 1-4 tubers in 8/9
children
Fedi et al 2003 8 patients TSC, increase uptake
in epileptogenic tuber in 4, multifocal 2
correlation with interictal spike activity
149Other techniques
150 The role of invasive monitoring?
151Noninvasive evaluation
- Discussion about outcome imperative
- What is the likely longterm outcome for
- Seizure control?
- Cognitive outcome?
- Behaviour?
- What are the outcome aims for the family?
-
152Outcome
Lachhwani et al 2004 17 patients, 1981-2003,
f/up 12m-15 yr Localised EEG concordant MRI
(9) 8 SF (89) Localised EEG multituber MRI
(6) 2SF Non-localised EEG predominant tuber
(2) 1SF
Jarrar et al 2004 22 patients, 1986-2002, f/up
1-14 yrs 12m 5yrs Seizure
free 13/22 (59) 9/21 (42) III/IV 9/22
(41) 12/21 (57)
153GOSH
11 children 12m 15yrs, 12m-10 yrs follow-up 8
noninvasive evaluation all EEG, MRI, 4 ictal
SPECT Outcome 12m 5/8 SF 3yrs 0/7 SF 4gt75
improved 3 invasive evaluation (for proximity to
motor cortex) Outcome 12m 2/3 SF 3 yrs 1/3
SF
154Tuberous sclerosisnoninvasive evaluation
- Noninvasive evaluation is possible in children
with TS - Caution accumulation of evidence for single
seizure type - Invasive evaluation may still be required where
functional concern, or uncertainty of responsible
tuber - Outcome aims for child will be individual and
family should be counselled accordingly
155Surgery in Tuberous Sclerosisthe role of
invasive monitoring in the identification of
epileptogenic tubers
- Howard L. Weiner, MD, FACS, FAAP
- Associate Professor of Neurosurgery Pediatrics
- NYU Comprehensive Epilepsy Center
- Division of Pediatric Neurosurgery
- NYU School of Medicine
156NYU Comprehensive Epilepsy Center
- Neurology
- Orrin Devinsky, MD, Director
- Ruben Kuzniecky, MD, Co-Director
- Daniel Miles, MD
- Josiane LaJoie, MD
- Blanca Vazquez, MD
- Steven Pacia, MD
- Daniel Luciano, MD
- Catherine Schevon, MD, PhD
- Anuradha Singh, MD
- Rolando Sousa, MD
- Nandor Ludvig, MD, PhD
- Siddhu Nadkarni, MD
- Sathyashanka Subbana, MD
- Ravi Tikoo, MD
- Neurosurgery
- Werner Doyle, MD
- Neuropsychology
- Charles Zaroff, PhD
- William Barr, PhD
- Chris Morrison, PhD
- Neuro-Psychiatry
- Kenneth Alper, MD
- Melanie Shulman, MD
- Oliver Sacks, MD
- Collaborators
- Peter Crino, MD, PhD (UPenn)
- Guy McKhann II, MD (Columbia)
157Surgery is effective in Tuberous Sclerosis
- What is the traditional approach ?
- The NYU experience with invasive
- monitoring
1581966
- The first report of epilepsy surgery for Tuberous
Sclerosis - Montreal Neurological Institute
- Perot P, Weir B, Rasmussen T Arch Neurol
159- What can we learn from the literature about the
traditional surgical approach in Tuberous
Sclerosis ?
160Epilepsy Surgery for TSThe Literature
- Individual studies have shown surgery to be safe
and effective in TS patients - Older children/adolescents
- Single tuber/epileptogenic region
- Little reliance on invasive monitoring
161Epilepsy Surgery for TSThe Literature
- Does the literature have an inherent bias ?
- Outcome is good if single primary focus can be
identified and resected - Outcome is not good if this is not the case
- (ie. any pt without single primary focus offered
palliation, such as callosotomy)
Can one consider a different approach for TS
pts with more than one primary seizure focus ?
162The traditional approach in TS (1)
- Operate approximately at age 10 (based on 81
patients reported in 9 papers since 1989)
163The traditional approach in TS (1)
- Operate approximately at age 10 (based on 81
patients reported in 9 papers since 1989) - Limitation Much of development occurs before
this age - ARE WE UNDERESTIMATING THE POTENTIAL BENEFIT OF
SURGERY IF IT IS NOT PERFORMED AT AN EARLY AGE ?
164The traditional approach in TS (1)
- Take Home Point 1 Identify potential surgical
candidates at an early age
165The traditional approach in TS (2)
- Identify single epileptogenic focus based on
correlation between EEG and imaging
166The traditional approach in TS (2)
- Identify single epileptogenic focus based on
correlation between EEG and imaging - Limitation this is often very difficult in TS
patients - DO WE EXCLUDE CHILDREN WHO DO NOT MEET THIS
CRITERIA ?
167Multiple bilateral tubers
168The NYU approach in TS (2)
- Take Home Point 2 identify potential surgical
candidates with bilateral electrode survey
169The traditional approach in TS (3)
- Resect primary tuber plus surrounding
epileptogenic zone
Pre-op
Post-op
170The traditional approach in TS (3)
- Resect primary tuber plus surrounding
epileptogenic zone - Limitation defining the margins of the
epileptogenic zone is often difficult in TS
patients - WILL SURGERY FAIL DUE TO AN ADJACENT OR DISTANT
TUBER/EPILEPTOGENIC ZONE ?
171The Challenge of Localization in Tuberous
Sclerosis
172The NYU approach in TS (3)
- Take Home Point 3 Identify unrecognized adjacent
or distant tuber/epileptogenic zones with
multi-stage surgery
173The Challenge of Localization in Tuberous
Sclerosis
174Epilepsy Surgery for Children with Tuberous
Sclerosis
- We have utilized a novel surgical approach using
invasive monitoring, which is frequently
multi-staged and bilateral
175 What is the traditional epilepsy surgery
approach ?
- Operation 1 Grid/strip/depth electrode
placement - Operation 2 Resection of seizure focus/lesion
176Multi-stage approach
- Operation 1 Grid/strip/depth electrode
placement - Operation 2 Resection of seizure
focus/lesion/ REPLACE grid/strip - Operation 3 Resection of seizure focus/lesion
177Multi-stage Epilepsy Surgery
- Multi-stage invasive monitoring can detect
residual adjacent or distal epileptogenesis, and
is especially useful when pre-surgical data
suggest eloquent cortex or bi-hemispheric
involvement - Bauman, Feoli, Romanelli, Doyle, Devinsky,
Weiner, in press, Neurosurgery
1785 year old boy with TS
- Onset of seizures age 2 months
- Infantile spasms age 9 months
- Multiple seizures daily- CP, T, GTC
- Significant developmental delay with subsequent
regression
179Previous treatment and evaluation
- Failed 10 AEDs, VNS and ketogenic diet
- MRI, EEG and VEEG multi-focal
- Not considered a surgical candidate
- Developmental delay with regression
- Poor quality of life for child and family
- NYU Plan a bilateral strip survey to identify
one or two predominant seizure foci that could be
further studied with grid/strip coverage.
180Multiple bilateral tubers
181Bilateral Strip StudyVertex Craniotomy
182Stage I
183(No Transcript)
184(No Transcript)
185(No Transcript)
186(No Transcript)
187Stage I
8 days of monitoring
Interictal
Seizure Onset
Seizure Spread
- Seizures with right hemisphere onset 77
- Seizures with left hemisphere onset 17
188Resection of right frontal tuber/seizure focus
189Replacement of electrodes after resection at 2nd
stage
190MRI scan after 2nd stage
Pre-op
191Stage II
Interictal
Seizure Onset
Seizure Spread
192Surgical Outcome over 1 Year
The surgery has changed our lives. Thank
you!!! Glad we could make your day. You've made
our lives!(And if things start up again, we
know we have options...) Is he benefiting from
surgery????? His life--our lives--have completely
changed!! Every single day we think of you and
your team and think how thankful and lucky we
are.Since his surgery, he's had a handful of
very mild seizures--nothing like he had
before--when he was having an average of 6 huge
seizures a day. (At times he would have stretches
of 14 strong seizures a day. Diastat daily. The
works.) Never in his life has he had such relief!
193Surgical Outcome
- I just wanted to let you know that he is
still doing really well. - No seizures and he's happy, happy. As you can
see in this picture.
194NYU TS Epilepsy Surgery in Children
- 21 children
- 7 boys
- 14 girls
- Mean age 3.6 yrs
- range 7 months - 16 years
- 66 total operations
- 3-Stage18 pts
- 2-Stage 3 pts
- 3-Stage at re-op 2 pts
- Mean follow-up 24 months
- range 3 months - 6 years
195NYU TS Epilepsy Surgery
- 6 children prior surgery
- 1 resection
- 5 VNS
- 12 children had bilateral electrode studies
- 5 bilateral strips
- 7 gridcontralateral strips
196NYU TS Epilepsy Surgery
2 pts not improved at initial follow-up?
underwent re-operation one year later and now
Engel I outcomes
197NYU TS Epilepsy Surgery
- 5 pts whose seizures could not be lateralized
were found to have unilateral primary focus on
bilateral strip survey - 4 are seizure free
- 18/21 pts underwent resections of 2 or more
tubers - 15/21 pts underwent multi-lobar resections
- 2 pts underwent bilateral resections
198Re-operation in 2 children
- 5-year-old girl seizure-free x 3 months
- 4-year-old girl not improved after surgery
- Both are now seizure free after extension of
original resections
199Complications
- 1 pt infection (2-stage)
- 5 pts transient hemiparesis
- recovery within 2 months time
- 3 partial bone flap resorption
- 2 required repair
200What are we learning about surgery for TS ?
- Take Home Point 1 Identify potential surgical
candidates at an early age - Take Home Point 2 Identify potential surgical
candidates with bilateral electrode survey - Take Home Point 3 Identify unrecognized adjacent
or distant tuber/epileptogenic zones with
multi-stage surgery
201Surgery in Tuberous Sclerosis
- Multiple or bilateral epileptogenic foci are not
necessarily a contraindication to surgery in
selected patients. - The multi-stage surgical approach has been useful
in identifying both primary and secondary
epileptogenic zones in TS patients with multiple
tubers. - Invasive EEG may reveal epileptogenic zones that
are more extensive than the radiographic lesions. - Selected children with TS may benefit from a more
aggressive surgical approach. - Long-term follow-up will determine whether this
approach has durable effects. - Better methods for identifying the epileptogenic
zone, both non-invasive and invasive, are needed.
202Surgery in Tuberous Sclerosis
- How does removal of the primary seizure focus
alter the remaining network ? - What can our observations about surgery in TS
teach us about epilepsy surgery in general ? - Is TS really a model system for lesional epilepsy
?
203Special Thanks to
- Dr. Chad Carlson
- Fellow
- NYU Comprehensive Epilepsy Center