Surgery for Epilepsy surgery and anaesthesia in epileptic patients.

1. Epilepsy and Anaesthesia
Presented by – Dr. Dhritiman Chakrabarti
Moderated by – Dr. Gopala Krishna K N

2. Basic Definitions
• Seizure (from the Latin sacire—to take
possession of) is the clinical manifestation of
an abnormal, excessive, hypersynchronous
discharge of a population of cortical neurons.
• Epilepsy is a disorder of the central nervous
system characterized by recurrent seizures
unprovoked by an acute systemic or neurologic
insult.

3. Mechanisms of Neuronal
Excitability
• Intrinsic Factors:
1. The type, number and distribution of voltage- and
ligand-gated channels.
2. Biochemical modification of receptors
3. Activation of second-messenger systems
4. Modulating gene expression, as by RNA editing
• Extrinsic Factors:
1. Changes in extracellular ion concentration
2. Remodeling of synaptic contacts and neuronal network
3. Modulating transmitter metabolism by glial cells

4. Seizure Initiation
Seizure initiation is characterized by two concurrent
events:
1) High-frequency bursts of action potentials
(paroxysmal depolarization shift)
2) Hypersynchronization of a neuronal population (local
spread).
3) Distal Seizure propagation (loss of surround
inhibition)
Epileptogenesis
1) Neuronal network reorganization.
2) Kindling.

5. Antiepileptic Drug Interactions
• Induction and inhibition of the cytochrome
P450 isoenzymes.
• Inducers – CBZ, Phenytoin, Phenobarbital,
Topiramate
• Inhibitors – Valproate
• No effect - Gabapentin, lamotrigine,
levetiracetam, tiagabine, and vigabatrin
Drugs to be careful about – Antibiotics,
Amiodarone, β-Blockers, CCB, NMBA, Opioids.
Carbepenems induce Valproate metabolism.

6. Effect of Anaesthetic agents
on Epilepsy
• Inhalational Agents:
1) N2O – Proconvulsant in animal models; Suppresses
Ecog epileptiform potentials intraoperatively;
Myoclonus observed in humans at hyperbaric doses
and along with other inhaled agents.
2) Sevoflurane – Well known proconvulasant activity in
children and when combined with hypocapnea.
Widespread EEG activation.
3) Isoflurane & Desflurane – Well known anticonvulsant
properties, even used in SE.

7. • Opioids (Proconvulsant):
1) Pethidine – Association with myoclonus and tonic clonic
seizure activity.
2) Alfentanyl and Remifent – Used to induce spike activity
and help in localization of epileptogenic zones
intraoperatively.
3) GTCS in low to moderate doses – Fent, alfent, sufent and
morphine.
• IV Anaesthetic agents:
1) Propofol, thiopentone, methohexital, etomidate, ketamine
all have proconvulsant effects (myoclonus, ophistotonus,
GTCS) in low doses and anticonvulsant at high doses.
2) Benzodiazepines – always anticonvulsant.
3) LA – GTCS at high plasma levels. Lignocaine used to treat
SE in children in small case series.
4) NMBA – Laudanosine.

8. • Perioperative AEDs: -
1. IV is better than oral (doses are equal)
2. Continue AEDs perioperatively, without missing out a
single dose.
3. ICU stay with changes in pH and S. Albumin levels
and other drug interactions warrant serum drug
level measurements (esp. Phenytoin).

9. STATUS EPILEPTICUS
• Status epilepticus is defined as 5 min or more of
(i) continuous clinical and/or electrographic seizure activity or
(ii) recurrent seizure activity without recovery (returning to
baseline) between seizures.
• Refractory status epilepticus (RSE) is defined as SE that fails
to respond to first- and any two drugs in the second-line
therapy and it is observed in 9% to 31% of patients with SE .
• Most convulsive seizures abate within 2–3 min and a seizure that
continues for more than 5 min has a low chance of terminating
spontaneously, so should be treated with emergency
antiepileptic medications.
• The traditional definition of 30 min for SE definition has been
revised to 5 min because permanent neuronal injury and
pharmacoresistance may occur before deadline of 30 min
(Brophy 2012).

10. PhysiologyofStatusEpileticus

11. Stages of SE:
1) Pre-monitory stage (out of hospital) – Nasal/buccal
Midazolam, rectal diazepam
2)Early stage (first 5 min) – IV benzodiazepines
3)Established CSE (>5 min) – Phenytoin,
phenobarbital, valproate, levetiracetam,
topiramate, lacosamide.
4)Refractory status – Midazolam, Thiopentone,
Propofol, Ketamine, Isoflurane, Desflurane
5)Non-convulsive status epilepticus

13. Status Epilepticus Treatment
Refractory SE Treatment

14. Alternative therapies for RSE

15. Epilepsy Surgery -
Identifying Surgical Candidates
1) Medical intractability:
–Two appropriately chosen, well-tolerated first line
antiepileptic drug regimens have failed due to lack of
efficacy.
2) Sufficient Disability
3) Minimum duration from diagnosis – 2 yrs (Adults)
4) Difference between Adults and Paediatric
population.
• Plasticity phenomenon: Early surgical intervention can
maximize efficacy, recovery, and cognitive potential.
• No defining concept of disability.

16. Surgical candidacy to be determined on a case by case basis
using data from an extensive multimodality assessment.
• Timing of Surgery - People suffering from epileptic
syndromes with a high probability of medical intractability
and a favourable surgical prognosis should be considered
for surgery early.
• Presurgical Evaluation:-
1) Medical History with ictal and interictal symptoms.
2) High resolution Neuroimaging.
3) Identifying Epileptogenic Zone – EEG, Neurophysiological
evaluation, Video EEG..
4) Invasive intracranial recordings.
5) Other ancillary neurophysiologic techniques - evoked
potential studies, cerebral functional mapping, MEG and
magnetic stimulation.
6) Identifying Functional deficit zone and lateralization of
eloquent cortex - interictal SPECT and/or PET, and the
intracarotid sodium amytal (Wada) test, fMRI

17. Zones of the Epileptic Cortex

18. EEG for Diagnosis and Localization
• Interictal sharp or spike wave is cornerstone for
epilepsy diagnosis.
• Represents cortical hyperexcitability and
hypersynchrony, which may persists in the “normal”
interictal state.
• Montage specificity of EEG abnormality helps localize
epileptogenic zone.
• Chowdhary et al (2013) found overall sensitivity of
EEG in yielding abnormal interictal epileptiform
discharges was 62.7% in epilepsy patients.

19. Right posterior temporal spike. This EEG is from a 15-year-old boy with a history of complex
partial seizures. The spike phase reverses at T6. The field of the discharge extends into the
parietal and occipital regions.

20. Interictal generalized spike-wave complexes - Idiopathic eneralized epilepsy

21. Ictal EEG recording of right temporal lobe epilepsy

22. Video EEG
Useful to diagnose distinguish Psychogenic seizures, Syncope, Parasomnias,
Hemifacial spasms from actual epilepsy.
Interictal EEG findings – Sharp waves, Spike & wave complexes, Polyspikes,
TIRDA, Continuous Polymorphic Delta etc.
Ictal EEG findings – Generalized, Lateralized or Focal spikes accompanied with
clinical seizure in patients. There may be post-ictal slowing of EEG.

23. Electrocorticography
Case of refractory
seizure disorder with
frontal gliosis and
mesial temporal
sclerosis

24. Advantages:
1) Recordings that can be done before as well as after the
resection, to estimate the potential residual epileptic activity in
the neighbouring of the resection zone,
2) Intraoperative electrical stimulation to map cortical functions
Disadvantages:
1) Llimited placement of the electrodes to the craniotomy,
2) Limited sampling time,
3) Recording almost exclusively of spontaneous interictal epileptic
activity and very rarely epileptic seizures,
4) Difficulty to differentiate between primary epileptic discharges
from secondarily propagated discharges from a distant
epileptic zone,
5) Alterations by anaesthetics and analgesics as well as the
surgery, of both the background activity as well as the epileptic
discharges,
6) Ambient artefacts in the operating room.

25. fMRI
• Functional MRI (fMRI) methods use currently
standard MRI scanning hardware to detect changes in
regional blood flow and metabolism that accompany
regional brain activation.
• Major applications of fMRI in epilepsy include the
localization of task-correlated language and memory
function, and the localization of ictal and paroxysmal
phenomena.
• Language lateralization by fMRI provides comparable
results to intracarotid amobarbital testing.

27. SPECT
• Ictal SPECT is of great value.
• I-123 & Tec 99
• Due to low temporal resolution, both ictal onset zone
and propagation pathways get delineated.

28. PET
• PET with fluorine-18
fluorodeoxyglucose
([18F]FDG) localizes
areas of glucose
hypometabolism in
epileptogenic zone.
• Interictal PET has
sensitivity of 75-
80% in TLE and 30-
40% in no TLE.
• Ictal PET not
logistically possible.

29. Neuropsychologic evaluation &
WADA Test
• For improvement of QoL:
1. Optimum resection of Seizure focus.
2. Minimal post operative neurological deficits.
Factors predicting good seizure outcome - presence of
MRI abnormalities, extent of resection and the
Wada Memory Asymmetry (WMA) score
Factors predicting post op cognitive decline - age at
onset of seizures, side of surgery, preoperative
neuropsychological test performance, presence or
absence of MRI abnormalities, and the WMA.

30. Aims of Neuropsychological Testing:
1) Identify any pre-existing cognitive deficits.
2) Whether the deficits are concordant with the
suspected epileptogenic focus.
3) If the suspected epileptogenic focus subserves
important skill with no apparent deficits.
WADA Test:- Developed by Juhn Wada to establish
speech dominance prior to temporal lobe resection .
Test extended to evaluate memory function also.
Modification – Usage of other agents Lignocaine,
Etomidate instead of or along with amobarbital.
WMA – WADA Memory Assymetry.

31. Key Considerations for Surgery
1. Is a structural lesion identified? (MRI)
2. Is an epileptogenic zone identified? (EEG,
functional imaging)
3. Are the lesion and epileptogenic zone
concordant?
4. Location? Relationship to eloquent cortex?
(MR landmarks, functional imaging,
Neuropsychologic evaluation, WADA)
5. Focal or extensive? Single or multiple?
Unilateral or bilateral?

32. Common Types of Epilepsy Surgery
Goals of surgery:
• To resect the epileptogenic zone, OR
• To disconnect avenues of seizure spread
Types of surgery
• Lesionectomy
• Temporal Lobectomy
• Hemispherectomy
• Corpus Callosotomy
• Multiple Subpial Transections
• Radiosurgery
• Vagal nerve stimulators

33. Lesionectomy
Lesions:
1) FCD
2)Tumors
3)Vascular malformations

34. Temporal Lobectomy
Selective Amygdalohippocampectomy Anterior Temporal Lobectomy

35. Hemispherectomy
Indications: Secondary generalized seizures where focus is large or
multifocal involving only one hemisphere
• Anatomical Hemispherectomy :- Epileptogenic hemisphere is
usually severely dysfunctional with Hemiparesis & Language
mediated by the contralateral hemisphere
•Therefore extensive resection may be justified.
Anatomic Hemispherectomy Functional Hemispherectomy

36. • Functional Hemispherectomy:- A “window” of cortex
may be removed to then make the appropriate white
matter transections.
White matter tracts that are disconnected
–Corpus Callosum
–Coronal radiata/internal capsule
–Fornix
–Anterior Commisure
–Outflow tracts of the amygdala

37. Corpus Callosotomy
Typical Indications:
–Intractable seizures
without resectable
focus or when only
incomplete resection is
possible
–Patients may have
multiple epileptogenic
zones

38. Multiple Subpial Transections
Typical Indications:
Epileptogenic zone in
dominant eloquent
cortex
A “disconnection” type
procedure to avoid
resecting eloquent
structures:

40. Vagal Nerve Stimulation
• Simple device with two electrodes anchored and
looped around the mid-cervical portion of left vagus
nerve.
• Causes on demand summation to abort or deintensify
oncoming seizures.
• Indications: Medically intractable seizures in >12 yrs
old patient who is not suitable or willing for surgical
management.
• Adverse effects: Laryngeal irritation; Hoarseness;
Cough; SOB in COPD; Change in voice quality;
Bradycardia; Periodic apnoea; Cardiac arrest
• To be careful in MRI, Monopolar diathermy.

41. Anaesthetic Considerations
• Anaesthesia for ECog Monitoring:
1) Effect of Anaesthetic agents on Ecog output.
2) Usage of agents and techniques to increase
epileptiform activity (Opioids, Hyperventilation, low
dose Methohexital)
3) Awake craniotomy is the best option.
• Anaesthesia for Surgeries near eloquent cortex:
1. Anaesthetic technique – Awake craniotomy with
conscious sedation or asleep-awake-asleep
technique with intraop neuropsychological monitoring
of the patient.
2. General Anaesthesia with traditional anaesthesia
practice.

42. • Common Anaesthetic regimens for Awake
craniotomy:-
1) Scalp block and Incision area field block + Propofol/
Opioid/ Dexmedetomidine infusion for sedation.
2) Scalp block + Asleep –awake-asleep technique using
LMA as airway control.

43. Awake Craniotomy vs. GA
• Gupta et al (2007) studied 53 patients with intrinsic eloquent
cortex lesions and compared Awake craniotomy vs GA for
excision of such lesions (with electrophysiologic guidance).
• They found:
1) More than 90% tumor excision was observed in 57% patients in
awake group versus 73.7% in GA group
2) Mean operative time, blood loss was found to be was found to
be less in GA group patients than in awake group.
3) Better tumor cytoreduction, neurological improvement was
seen in GA group (motor improvement in 35.7%, speech
improvement in 62.5%) than in awake group patients (motor
improvement in 18.7%, speech improvement in 14.3%) – in
immediate postop, with no difference at 3 mths.
However only significant difference was for duration of surgery
parameter.

44. Thank You