Anesthesia for Intraoperative Brain Mapping and Deep Brain
Stimulation in Children
Nicholas Carling, M.D.
Houston, Texas
Introduction to Brain Mapping
Intraoperative brain mapping is an essential tool for neurosurgical
procedures that involve lesions near functional or “eloquent” cortex. Eloquent areas
include primary motor cortex, primary somatosensory cortex, language areas such
as Broca and Wernicke’s, primary visual areas, angular gyrus, and mesial temporal
regions for memory. When tumors or epileptic foci are located adjacent to these
areas of functional cortex, both intraoperative electrophysiological monitoring and
neurocognitive testing aid in aggressive resection of the pathological lesion while
attempting to minimize neurological deficits.
The demands of electrophysiological monitoring have a profound effect on
the anesthetic technique and agents that can be used during the procedure. In some
instances the patient must be awake, such as when language testing is being
performed. Electrocorticography and motor mapping can be performed under
general anesthesia. Anesthetic goals include providing adequate surgical conditions,
minimizing interference on intraoperative brain mapping, and maintaining patient
comfort and safety throughout the procedure1.
Any procedure involving brain mapping requires constant communication
between the anesthesia team and surgeon. Preoperatively, this ensures that the
entire team understands the surgical and anesthetic plan; and intraoperatively,
neurophysiologic monitoring may require adjustments of anesthetic depth and
anesthetic agents.
Adding to the difficulty of providing anesthesia to these patients is the lack of
prospective, randomized trials comparing anesthetic techniques. Most evidence
involves case-series or retrospective analysis. These studies can be confusing to an
anesthesiologist naïve to the technical neurophysiology language, and the available
studies form conclusions that are sometimes contradictory and inconsistent. This
has resulted in protocols that vary by institution, and there is no consensus as to the
optimal anesthetic technique for mapping procedures.
Brain Mapping Techniques and Anesthetic Issues
Electrocorticography
Electrocorticography is utilized during epilepsy surgeries to help identify
abnormal EEG patterns that result from epileptogenic foci. These spike waves
identify the seizure focus and allow precise resection. After resection, ECoG
recordings can be performed again to ensure there is no further spike activity.
Most anesthetics affect intraoperative ECoG recordings, yet ECoG has
successfully been performed with local anesthetic only, monitored anesthetic care,
and general anesthesia. The commonly used agents, including volatile anesthetics,
nitrous oxide, propofol, dexmedetomidine, and opioids will now be discussed in
greater detail.
Volatile Agents
Volatile agents are commonly used for maintenance of general anesthesia
when patients are not candidates for an awake craniotomy. However, their use still
varies between institutions,. For instance, sevoflurane has been shown to
significantly reduce spike activity in epileptic patients at 1.5 MAC2. However, this
study was performed with patients under the effects of a fentanyl-based anesthetic.
Fentanyl, like many opioids, has been shown to induce spike wave activity especially
at high doses and may have increased spike activity at the baseline recordings for
this study3. Other studies have shown that sevoflurane can increase spike activity at
higher concentrations, just prior to causing burst suppression4,5,6. One can see the
confusion as one agent, sevoflurane, has both epileptic and antiepileptic properties.
Indeed, some institutions’ protocols avoid volatile agents altogether for fear that
they may make reliable ECoG impossible, while others have attempted to use the
epileptogenic properties of higher dose sevoflurane to localize seizure foci.
As shown by Kurita et al7, sevolfurane’s ability to increase epileptiform
activity may help in accurate resection of seizure foci. This study showed that ECoG
at 0.5MAC sevoflurane were similar to recordings at ictal onset in the awake state,
whereas at 1.5 MAC the ECoG recordings were more similar to the interictal period
in the awake state. These interictal spikes correspond to “irritative” zones, whereas
the ictal onset zone is the area where a seizure originates, and is the gold standard
for localizing the epileptogenic zone, the smallest area needed to be resected to
prevent further seizures. Higher sevoflurane levels may increase the “volume” of
the recordings; however, may not increase the specificity of recordings which allow
for resection of the smallest area necessary. Isoflurane, like sevoflurane, does
appear to have the some epileptogenic potential, but not to the same degree6. When
used to maintain general anesthesia during ECoG monitoring, low levels of
volatile anesthetic combined with higher dose opioid administration should
not interfere with electrocorticography7,8. At our institution, a dexmedetomidine
infusion is commonly added to further lower the volatile agent needed to maintain
an adequate level of anesthesia.
Nitrous Oxide
Nitrous oxide is often used in neurosurgical procedures. It has been shown
to attenuation spike activity on ECoG especially when combined with volatile
anesthetics9,10. Despite this, nitrous oxide is a key part of many successful
anesthetic protocols for epilepsy surgery. If used, it should not be combined with
additional volatile agent, but rather with a liberal opioid administration. Opioid
and nitrous oxide alone should not interfere with ECoG8.
Of note, when patients already have an ECoG grid in place and are returning
for resection, one should avoid using nitrous oxide until the dura is open to prevent
pneumocephalus11.
Propofol
As with sevoflurane, propofol has been shown to have both epileptic and
antiepileptic properties that appear to be dose dependent. In low doses, propofol
causes activation of EEG activity12,13. It may even cause background activity, which
may resemble epileptiform spiking14. Larger doses lead to slowing and attenuation
of spike activity, and at sufficient doses may lead to burst suppression and
isoelectricity.
Both Herrick14 and Soriano15 showed that propofol did not affect the
ability to obtain ECoG recordings if terminated at least 20 minutes prior to the
start of ECoG. In light of the evidence, propofol should be discontinued prior
the start of ECoG.
Dexmedetomidine
Dexmedetomidine has minimal effect on ECoG and can be continued
during recordings at low infusion rates16. Because of its minimal respiratory
depression, titratability, and ability to provide a cooperative, relaxed patient,
dexmedetomidine is an excellent anesthetic for procedures that require a patient to
be awake during a portion of the procedure. In addition, dexmedetomidine has
been shown to provide hemodynamic stability during neurosurgical procedures17.
Modest reductions in blood pressure and heart rate are secondary to alpha-2
mediated adrenoreceptor activity. Reductions in circulating catecholamines result
in a decreased incidence of tachycardia and hypertension during the perioperative
period18.
When used for maintenance of general anesthesia in combination with
sufentanil, dexmedetomidine did suppress epileptiform activity19. However, at
Texas Children’s Hospital high infusion rates of dexmedetomidine are typically used
throughout brain mapping procedures with adequate ECoG recordings. We perform
almost all these procedures under general anesthesia, and volatile agents and/or
propofol are discontinued prior to ECoG. During the time of very “light” anesthesia,
we supplement an opioid infusion with a dexmedetomidine infusion up to 1
mcg/kg/hr during electrocorticography, and have experienced no difficulty with
neurophysiologic monitoring.
Opioids
Opioids are a mainstay of neuroanesthesia, and this is particular true
with brain mapping procedures performed under general anesthesia.
Because both volatile agents and propofol are discontinued or used in very
low doses during brain mapping, there is potential for patient awareness,
discomfort, and movement. Using large doses of short-acting opioids, one can
maintain patient comfort, minimize the chance of patient movement, and not
affect brain mapping. During awake craniotomies, opioids help manage pain and
discomfort that may occur despite an adequate scalp block with local anesthesia.
Opiates do not alter seizure threshold or interictal spike activity. Moderate
doses may result in muscle rigidity without EEG spiking, and extremely high doses
will induce seizures20,21,22. Patients with partial complex epilepsy given moderate
doses of fentanyl, may experience increases in IIS that is not confined to the
previously identified seizure foci23. Alfentanil, an opioid with a shorter terminal
half-life than fentanyl, has been used in bolus dosage to increase IIS activity for
mapping foci24. Remifentanil has a similar effect on IIS but its duration of action is
much shorter than fentanyl, making it a better choice during awake craniotomy
when ventilation cannot be mechanically supported25.
Direct Cortical Stimulation
Direct cortical stimulation is the process of applying direct electrical
stimulation to the cortex to help map eloquent areas responsible for motor function,
language, vision, or sensation. Of these, only motor mapping may be performed
under general anesthesia, as all other forms of mapping inherently require the
patient to be awake to participate in testing and provide feedback while testing is
being performed.
Motor mapping has few limitations on anesthetic agents, the main
limitation being that cortical motor evoked potential (cMEPs), just like
transcranial motor evoked potentials, are especially sensitive to volatile
agents. Concentrations as low as 0.2-0.4 MAC have been shown to interfere with the
ability to obtain adequate recordings. Intravenous agents and an awake anesthetic
technique have less interference with motor mapping than the use of volatile agents
and general anesthesia28,29.
Motor mapping may be performed by the surgeon stimulating the cortex, and
either the anesthesiologist or another member of the operating team assessing
whether there is a visually observed motor response to a particular area, such as
hand, foot, or face. This allows for mapping of the functional motor cortex during
the operation so that it may be spared during resection.
For motor mapping to be performed, the patient cannot receive
neuromuscular blocking agents.
Protocols for Brain Mapping Procedures
Awake or Asleep
The decision to perform either a general anesthetic or an awake craniotomy
is complex, dependent on patient factors, institutional culture, surgeon preference,
and anesthesia provider’s familiarity and comfort with various techniques. Some
basic rules are evident that may make this decision a little more simple.
1. Language/Sensory testing can only be performed in an awake patient.
2. General anesthesia can be performed during ECoG and motor mapping
3. Less anesthetic=less interference with neurophysiologic monitoring. So,
if a patient is a candidate for an awake craniotomy, one should strongly
consider it.
4. Do not perform an awake anesthetic on a patient that cannot be expected
to cooperate.
This puts the anesthesiologist in a unique situation. On the one hand, what might be
best for the surgical excision of the lesion (awake patient minimizing the chance of
interference with neuromonitoring or neurological deficit), might not be best for the
patient (traumatic experience from awake craniotomy or risks from lack of
cooperation/movement).
While these rules are helpful, they ignore the complexity of the challenges
involved in patient selection and the risk/benefit ratio inherent to the decision to
perform an awake craniotomy or general anesthetic.
Patient Selection
Some institutions have absolute age cut-offs for performing an awake
craniotomy. At our institution this does not exist and each case is taken on a case-by
case-basis. Ideally, this decision involves many team members including surgeon,
patient and parents, anesthesiologist, neurologist, and if possible someone with
expertise in helping ascertain whether a patient is mature and capable of dealing
with the procedure, such as a child psychiatrist. The importance of a thorough
preoperative assessment and communication with the child cannot be
overemphasized. The patient should have a clear understanding of what will be
done, what he/she will experience, and reassured that they will be kept comfortable
and safe. Other issues which can make the decision more clear cut include
comorbidities such as anxiety disorder, developmental delay, obesity,
obstructive sleep apnea, and anything that would make conversion to general
anesthesia challenging(difficult airway). Such comorbidities are strong
contraindications for performing an awake craniotomy.
Risk/Benefit Ratio
Adding to the difficult decision as to whether an awake or general anesthetic
is more appropriate are the opposing risks and benefits of both techniques. To
simplify, an awake anesthetic will benefit aggressive surgical excision of the tumor
or seizure focus and allow for neurocognitive assessment to look for neurological
deficits during resection. However, inherent to this technique is a certain loss of
control of parameters that as anesthesiologists we are accustomed to maintaining.
These include the ability to precisely control hemodynamics and ventilatory status
(blood pressure control, secure airway, adjustment of CO2). These parameters not
only allow us to feel more comfortable, but they benefit surgical conditions by
preventing a “tight brain” and ensuring patient cooperation. By performing a
general anesthetic, the risk of interference with mapping techniques and neural
deficits postoperatively may be increased. As one can see, the decision as to
anesthetic choice can be quite complex, and requires communication between
surgeon, anesthesiologist, and patient.
General Anesthesia
These are some examples of protocols for epilepsy surgery involving brain
mapping with electrocorticography and cortical mapping under general anesthesia.
The basic premise is to minimize anesthetic agents that may interfere with mapping
procedures (volatile agents, propofol, benzodiazepines), yet still ensure patient
safety and comfort. To do this, one should consider opioid administration as the
backbone of the anesthetic technique.
Protocol
1. Minimal or no benzodiazepines for premedication
2. Opioid Infusion: Sufentanil 0.3-1mcg/kg/hr or
Remifentanil 0.1-0.5mcg/kg/min
(higher end of dose range during ECoG if volatile agent is turned off)
3. Volatile Agent <0.5 MAC. (At our institution, we attempt to
completely discontinue volatile agent during ECoG)
OR
N2O substituted for volatile agent
OR
Propofol infusion 100-250 mcg/kg/min (turn of prior 20-30 min
prior to ECoG
4. Motor mapping: no neuromuscular blockade, low volatile agent
(0.2-0.4MAC) but may still attenuate cortical MEPs
5. Consider adding Dexmedetomidine 0.2-0.7 mcg/kg/hr for all
variations of this protocol. This has minimal effect on ECoG
recordings while helping deepen the anesthetic while other agents are
discontinued.
6. Local Anesthetic: as general anesthesia during ECoG is a time when
the patient may be “light” one should consider the scalp block just as
important as during an awake craniotomy. This may lower the chance
of patient discomfort or movement during this time.
Methods to Improve ECoG
Despite strict attention to anesthetic technique, sometimes poor signals are
still present. The following are some drugs that have been used to increase
epileptiform activity.
1.Methohexital 0.3-0.5 mg/kg30
2.Etomidate 0.1-0.2 mg/kg31
3.Alfentanil 50 mcg/kg 32,33
4.Remifentanil 2.5 mcg/kg34
Awake Craniotomy
Two common methods for “awake craniotomy” include local with conscious
sedation and the Asleep/Awake/Asleep (AAA) technique whereby general
anesthesia is induced and then completely stopped during the time of mapping.
The benefits of the AAA include shortened time needed for patient cooperation,
increased depth of anesthesia during stimulating portions of the procedure
(craniotomy), and more control of ventilation if an airway is in place. The
disadvantages include the need to remove an airway during the procedure with
limited access to reacquire it and the chance of patient bucking or delirium on
awakening.
All combinations of anesthetic agents have been used successfully for all
anesthetic techniques during awake craniotomy. The most popular agents for
sedation include propofol and dexmedetomidine. These agents have been used
alone or in combination with an opioid, with both fentanyl and remifentanil being
the most popular. Volatile agents have also been used during the asleep portion of
AAA techniques. When deciding on which agents to choose the following should be
considered:
1. Dexmedetomidine causes minimal respiratory depression and has been
shown to provide stable hemodynamics during craniotomy17. It also
allows for smooth emergence from anesthesia and provides a cooperative
patient that is easily arousable. Typical infusion rates during the asleep
portion range from 0.5-1 mcg/kg/hr and during the awake portion from
0.1-0.5 mcg/kg/hr16.
2. Propofol is widely used during awake craniotomies because of its easy
titratability. Its antiemetic properties are also beneficial for an awake
patient. It does cause dose dependent ventilatory depression, and should
be terminated 20-30 min prior to ECoG to prevent attenuation of spike
activity15.
3. Remifentanil is easily titratable, allowing for rapid emergence from
anesthesia. In this author’s opinion, these characteristics make it an ideal
opioid for an AAA technique.
Tips for Awake Craniotomy
The success or failure of an awake craniotomy is dependent on many
variables. However, with attention to detail and proper planning, most patients
tolerate the procedure very well.
1. Local Anesthetic for scalp block is essential for patient comfort
2. Antiemetic: nausea from opioids, hypotension, hypovolemia, or from
pulling on the dura may occur.
3. LMA for less straining/bucking on emergence
4. If endotracheal intubation, local anesthetic to trachea may prevent
bucking/straining
5. BIS monitor may help with timing of removal of airway
6. Patient padding and positioning are crucial to patient comfort while
awake
Anesthetic Issues with Deep Brain Stimulation (DBS)
An excellent review of the issues associated with DBS was written by
Venkatraghavan36. The most common indications for DBS in the pediatric
population include movement disorders such as dystonia and Tourette’s. The
challenge with DBS procedures concerns balancing the desire for an awake patient
with a patient population that, because of their disease process, can be difficult to
manage with an awake technique. Additionally, microelectrode recordings place
many limitations on anesthetic agents.
Surgical Procedure
DBS involves the placement of electrodes into deep nuclei of the brain, with
common targets including the globus pallidus internus (GPi) and subthalamic nuclei
(STN). The procedure has two parts; the insertion of electrodes, and then
internalization of the connecting wires and pacemaker. These can be done on the
same day of surgery are separated into a two part procedure.
The first step is placement of the head frame, which in pediatric patients is
usually done after induction of anesthesia. An MRI or CT is then performed, and for
the initial surgery burr hole(s) are placed. If DBS insertion is bilateral, then bilateral
burr holes are made. After that, electrode placement begins. There are three
methods by which proper electrode placement in the target nuclei is achieved. First
is the frame-based imaging, which calculates depth and trajectory to get electrodes
close to the target nuclei. Second, neurophysiological monitoring via microelectrode
recordings further guides electrodes to the proper placement, and third is
macrostimulation. Microelectrode recordings (MER) record electrical activity of
individual neurons, and can distinguish between such tissue as globus pallidus
externa, interna, and even the border between the two. MER is started about 10mm
away from the target, and then the probe is inserting millimeter by millimeter as
recordings are taken. This is a painstaking process, and may take hours. After this,
macrostimulation of an awake patient occurs. The patient needs to be awake in
order to express if there is alleviation of his/her symptoms and if there are any side
effects during stimulation of the electrodes.
After the electrode is in place, the rest of the procedure involves placement of
the wires and pacemaker (usually subclavicular) and this portion can be performed
under any anesthetic technique.
With newer technology, some DBS insertions are being performed with just
MRI based imaging. This cuts out the need for MER and an awake patient, and
relieves many of the limitations on anesthetic agents.
Anesthetic Agents and MER
Anesthetic agents have a profound effect on MER, although the mechanisms
by which are not completely understood. The effects appear dependent on both the
target nuclei (GPi vs STN) and disease process37,38,39. MER is less affected in
dystonia than in Parkinson’s disease, and the GPi is more sensitive to anesthetic
agents than the STN. This may be due in part to higher GABA input to the GPi.
All GABA agents affect MER, despite this, propofol is the most widely
used agent for these procedures. Agents with the least effect include the
opioids remifentanil and fentanyl, as well as dexmedetomidine and ketamine,
likely due to their non-GABAergic action40,41.
Volatile agents have also been used for DBS, yet most success has been
shown in procedures where the STN was the target42-44. Unfortunately for the
pediatric anesthesiologist, the primary target of dystonia patients is the GPi.
Information as to acceptable concentrations of volatile agents, or whether one agent
is preferable over another, is lacking.
MER have been successfully recorded with commonly used anesthetic agents
such as propofol, volatile agents, opioids, ketamine, and dexmedetomidine.
However, any agent with GABA agonism may attenuate MER. Benzodiazepines have
been shown to abolish MER and propofol may attenuate MER. As such, our protocol
for DBS relies heavily on combinations of dexmedetomidine, remifentanil, and
ketamine. In our experience, these agents cause minimal interference with MER,
and allow for an awake and comfortable patient during macrostimulation.
Macrostimulation
Macrostimulation involves an awake and cooperative patient. The benefit of
performing macrostimulation is that it allows for confirmation of correct placement
of electrodes by relief of symptoms and assessment of side-effects such as rigidity,
nausea, pain, and parasthesia.
Example of Protocol for DBS
1. Dexmedetomidine: Bolus 1mcg/kg over 20-30 minutes
Continuous infusion 4 mcg/cc, @ 0.1- 2mcg/kg/hour)
2. Ketamine: Infusion @ 5 – 30 mcg/kg/min. 1-2 mg/kg/hr
3. Remifentanil: Continuous infusion , 50 mcg/cc, @ 0.05 – 0.1 mcg/kg/min asleep
0.005 – 0.01 mcg/kg/min awake.
4. Nicardipine: 0.1 mg/cc @ 0.5 – 5.5 mcg/kg/min ( systolic BP < 140, risk of
parenchymal hemorrhage during insertion of electrodes).
5. Decadron
6. Antiemetics
7. Avoid all drugs that affect the GABA–receptor activity. AVOID Propofol,
benzodiazepines, barbiturates and etomidate.
DBS can be a long, tedious procedure with a long period where the patient must be
awake if macrostimulation must be performed. An asleep/awake/asleep technique is
employed at our institution, but DBS has been performed under conscious sedation in
pediatric patients with success using combinations of dexmedetomidine/propofol45.
REFERENCES
1. Herrick IA, Gelb AW. Anesthesia for temporal lobe epilepsy surgery. Can J
Neurol Sci. 2000;27(suppl 1):S64–S67.
2. Endo T et al. Effects of sevoflurane on electrocorticography in patients with
intractable epilepsy. J Neursurg Anesth 2002;14:59-62.
3. Templehoff R, Modica PA, Bernardo KL, Edwards I. Fentanyl induced
electrocorticographic seizures in patients with complex partial epilepsy. J
Neurosurg 1992;77:201-208.
4. Iijima et al. The epileptogenic properties of volatile anesthetics sevoflurane
and isoflurane in patients with epilepsy. Anesth Analg 2000;91:989-95
5. Hisada K, Morioka T, Fukui K, et al. Effects of sevoflurane and isoflurane on
electrocorticographic activities in patients with temporal lobe epilepsy. J
Neurosurg Anesth 2001;13:333-337.
6. Watts AD, Herrick IA, McLachlan RS, et al. The effects of sevoflurane and
isoflurane anesthesia on interictal spike activity among patients with
refractory epilepsy. Anesth Analg 1999;89:1275-81.
7. Kurita N, et al. The Effects of Sevoflurane and Hyperventilation on
Electrocorticogram Spike Activity in Patients with Refractory Epilepsy.
Anesth Analg 2005;101:517-23.
8. Soriano S. Anesthesia for Epilepsy in Children. Childs Nerv Syst (2006)
22:834-843
9. Kurita N, Kawaguchi M, Hoshida T, et al. Effects of Nitrous Oxide on Spike
Activity on Electrocorticogram Under Sevoflurane Anesthesia in Epileptic
Patients. J Neurosurg Anesthesiol. 2005 Oct;17(4):199-202).
10. Iijima et al. The epileptogenic properties of volatile anesthetics sevoflurane
and isoflurane in patients with epilepsy. Anesth Analg 2000;91:989-95
11. Reasoner DK, Todd MM, Scamman FL, Warner DS (1994) The incidence of
pneumocephalus after supratentorial craniotomy. Observations on the
disappearance of intracranial air. Anesthesiology 80(5):1008–1012
12. Seifert HA, Blouin RT, Conard PF, Gross JB. Sedative doses of propofol
increase beta activity of the processed electroencephalogram. Anesth Analg.
1993 May;76(5):976-8.
46.
13. Veselis RA, Reinsel RA, Wronski M, Marino P, Tong WP, Bedford RF. EEG and
memory effects of low-dose infusions of propofol. Br J Anaesth. 1992
Sep;69(3):246-54.
47.
14. Herrick IA, Craen RA, Gelb AW, McLachlan RS, Girvin JP, Parrent AG, et al.
Propofol sedation during awake craniotomy for seizures:
electrocorticographic and epileptogenic effects. Anesth Analg. 1997
Jun;84(6):1280-4
15. Soriano SG, Eldredge EA, Wang FK, Kull L, Madsen JR, Black PM, et al. The
effect of propofol on intraoperative electrocorticography and cortical
stimulation during awake craniotomies in children. Paediatr Anaesth.
2000;10(1):29-34.
16. Souter MJ, Rozet I, Ojemann, J et al. Dexmedetomidine during awake
craniotomy for seizure resection: effects on electrocorticography. J
Neurosurg Anesthesiol 2007;19:38-44.
17. Bekker A, Sturaitis MK. Dexmedetomidine for neurological
surgery. Neurosurgery 2005; 57:1-10.
56.
18. Talke P, Chen R, Thomas B., et al. The hemodynamic and adrenergic effects of
perioperative dexmedetomidine infusion after vascular surgery. Anesth
Analg. 2000; 90:834-839.
19. Sturaitis MK, Ford EW, Palac S et al: Effect of Dexmedetomidine on operative
conditions and electrocorticographic responses during asleep craniotomy for
seizure focus resection. Anesthesiology 99:A290, 2003
20. de Castro J, Van de Water A, Wouters L, Xhonneux R, Reneman R, Kay B.
Comparative study of cardiovascular, neurological and metabolic side effects
of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine,
fentanyl, R 39 209, sufentanil, R 34 995. II. Comparative study on the
epileptoid activity of the narcotics used in high and massive doses in
curarised and mechanically ventilated dogs. Acta Anaesthesiol Belg. 1979
Mar;30(1):55-69. 21. Scott JC, Sarnquist FH. Seizure-like movements during a fentanyl infusion
with absence of seizure activity in a simultaneous EEG recording.
Anesthesiology. 1985 Jun;62(6):812-4. 22. Benthuysen JL, Smith NT, Sanford TJ, Head N, Dec-Silver H. Physiology of
alfentanil-induced rigidity. Anesthesiology. 1986 Apr;64(4):440-6. 23. Tempelhoff R, Modica PA, Bernardo KL, Edwards I. Fentanyl-induced
electrocorticographic seizures in patients with complex partial epilepsy. J
Neurosurg. 1992 Aug;77(2):201-8. 24. Cascino GD, So EL, Sharbrough FW, Strelow D, Lagerlund TD, Milde LN, et al.
Alfentanil-induced epileptiform activity in patients with partial epilepsy. J
Clin Neurophysiol. 1993 Oct;10(4):520-5. 25. Wass CT, Grady RE, Fessler AJ, Cascino GD, Lozada L, Bechtle PS, et al. The
effects of remifentanil on epileptiform discharges during intraoperative
electrocorticography in patients undergoing epilepsy surgery. Epilepsia.
2001 Oct;42(10):1340-4. 26. Vinik HR, Kissin I. Rapid development of tolerance to analgesia during
remifentanil infusion in humans. Anesth Analg. 1998 Jun;86(6):1307-11. 27. Stricker PA, Kraemer FW, Ganesh A. Severe remifentanil-induced acute
opioid tolerance following awake craniotomy in an adolescent. J Clin Anesth.
2009 Mar;21(2):124-6.
28. Neuloh G, Pechstein U, Cedzich C: Motor evoked potential monitoring with
supratentorial surgery. Neurosurgery 54:1061-1072, 2004
29. Vitaz TW, Marx W, Victor JD et al: Comparison of conscious sedation and
general anesthesia for motor mapping and resection of tumors localized near
motor cortex. Neurosurg Focus 15:E8, 2003
30. Wyler Ar, Richey ET, Atkinson RA, Hermann BP. Methohexital activation of
epileptogenic foci during acute electrocorticography. Epilepsia 1987; 28:
490-4
31. Gancher S, Laxer KD, Krieger W. Activation of epileptogenic activity by
etomidate. Anesthesiology 1984; 61:616-8
32. Keene DL, Roberts D, Splinter WM, et al. Alfentanil mediated activation of
epileptiform activity in the electrocorticogram during resection of
epileptogenic foci. Can J Neurol Sci 1997; 24: 37-9
33. Cascino GD, So EL, Sharbrough FW, Strelow D, Lagerlund TD, Milde LN, et al.
Alfentanil-induced epileptiform activity in patients with partial epilepsy. J
Clin Neurophysiol. 1993 Oct;10(4):520-5. 34. Wass CT, Grady RE, Fessler AJ, Cascino GD, Lozada L, Bechtle PS, et al. The
effects of remifentanil on epileptiform discharges during intraoperative
electrocorticography in patients undergoing epilepsy surgery. Epilepsia.
2001 Oct;42(10):1340-4.
35. Skucas AP, Artru AA. Anesthetic complications of awake craniotomies for
epilepsy surgery. Anesth Analg 2006;102(3):882–7
36. Venkatraghavan L, Luciano M, Manninen P. Anesthetic management of
patients undergoing deep brain stimulation insertion. Anesth Analg 2010;
110:1138–1145
37. Hutchison WD, Lang AE, Dostrovsky JO, Lozano AM. Pallidal neuronal
activity: implications for models of dystonia. Ann Neurol 2003;53:480–8
38. Peduto VA, Concas A, Santoro G, Biggio G, Gessa GL. Biochemical and
electrophysiologic evidence that propofol enhances GABAergic transmission
in the rat brain. Anesthesiology 1991;75:1000 –9
39. Steigerwald F, Hinz L, Pinsker MO, Herzog J, Stiller RU, Kopper F, Mehdorn
HM, Deuschl G, Volkmann J. Effects of propofol anesthesia on pallidal
neuronal discharges in generalized dystonia. Neurosci Lett 2005;386:156–
40. Rozet I, Muangman S, Vavilala MS, Lee LA, Souter MJ, Domino KJ, Slimp JC,
Goodkin R, Lam AM. Clinical experience with dexmedetomidine for
implantation of deep brain stimulators in Parkinson’s disease. Anesth Analg
2006;103:1224 – 8
41. Elias WJ, Durieux ME, Huss D, Frysinger RC. Dexmedetomidine and arousal
affect of subthalamic neurons. Mov Disord 2008;23:1317–20
42. Yamada K, Goto S, Kuratsu J, Matsuzaki K, Tamura T, Naga- hiro S, Murase N,
Shimazu H, Kaji R. Stereotactic surgery for subthalamic nucleus stimulation
under general anesthesia: a retrospective evaluation of Japanese patients
with Parkinson’s disease. Parkinsonism Relat Disord 2007;13:101–7
43. Hertel F, Zu ̈chner M, Weimar I, Gemmar P, Noll B, Bettag M, Decker C.
Implantation of electrodes for deep brain stimulation of the subthalamic
nucleus in advanced Parkinson’s disease with the aid of intraoperative
microrecording under general anesthesia. Neurosurgery 2006;59:1138–45
44. Lin SH, Chen TY, Lin SZ, Shyr MH, Chou YC, Hsieh WA, Tsai ST, Chen SY.
Subthalamic deep brain stimulation after anesthetic inhalation in Parkinson
disease: a preliminary study. J Neurosurg 2008;109:238–44
45. Sebeo J, S,Deiner SG, Alterman R, Osborn IP. Anesthesia for Pediatric Deep
Brain Stimulation. Anesthesiol Res Pract 2010; 2010