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Surgical Resection of Cavernous Malformations of the Brainstem: Evolution ofa Minimally Invasive Technique

Jeffrey C. Mai, Dinesh Ramanathan, Louis J. Kim, Laligam N. Sekhar

INTRODUCTION

Cavernous malformations (cavernomas)

have an estimated prevalence of approxi-

mately 0.4% to 0.8% in the population (4,

25, 29, 37, 38, 40, 43), with approximately

40% discovered incidentally(28). Prospec-

tive observation has indicated an overall

symptomatic rate of hemorrhage of 0.22%

to 0.7% per year for these lesions (15, 26,

37). Nevertheless, data from cavernous

malformations situatedin thebrainstem sug-

gest a markedly greater propensity for bleed-

ing.In retrospective analyses of patientswith

such lesions, a calculated annual average

symptomatic hemorrhage rate of 2.7% to 5%and re-hemorrhage rate of 21% to 60% per

year and per lesion was discovered (1, 14, 23,

25,27, 33). In accordance withtheir location,

hemorrhages of brainstemcavernousmalfor-

mationscarriedwiththemahighlevelofmor-

bidity and mortality(14,23).

Given the significant risk of death and

disability presented by expectant manage-

ment of cavernous malformations of the

brainstem (CMBs), surgical resection has

been increasingly advocated for therapy(2,

13, 14, 16, 33, 39, 42). Over this timeframe,

imaging technologies have significantly

improved (5, 10-12, 43), and surgical tech-

niques have been refined for approaching

lesions of the brainstem (6, 13, 14, 24, 25,

32, 35, 39, 42). Here, we report our case

series of 22 surgically treated brainstem

cavernomas, their presentation, and out-

comes, as well as describe the general prin-

ciples guiding surgical resection.

PATIENTS AND METHODSFrom 2005 to 2010, 22 consecutive patients

underwent 27 procedures for resections of

brainstem cavernous malformations. Of

these patients, 7 were men and 15 women,

with a mean age of 43 years (SD 15 years;

range, 8-69 years). Patients were drawn

fromHarborview Medical Center at the Uni-

versity of Washington in Seattle. Patient re-

cords wereretrospectivelyreviewed, includ-

ing outpatient, clinical, and surgicalrecords and radiologic imaging.

Diagnostic workup for all patients in-

cluded magnetic resonance (MR) studies,

usually with computed tomography scans

at the time of initial presentation as well as

Table 1. Deficits at Time ofPresentation

Deficit %

CN deficit 77

Ataxia 59

Headache 55

Diplopia 41

Weakness 27

Sensory changes 27

Vertigo or dizziness 23

Dysphagia 14

CN, cranial nerve.

OBJECTIVE: The purpose of this study is to provide an institutional retrospec-tive review of surgically treated brainstem cavernous malformations.

METHODS: Between 2005 and 2010, 22 consecutive patients with brainstemcavernous malformations (15 female and 7 male) with a mean age of 43 yearsunderwent surgical treatment. Mean volume of the resected cavernous malfor-mations was 0.65 cm3. A minimally invasive resection technique was used forthese cases, in conjunction with skull base approaches.

RESULTS: The mean follow-up period was 26.6 months (range, 4-68 months). Ofthe 22 patients, 9% did not have clear evidence of hemorrhage at the time of

presentation. Of the remainder, 22% had two or more instances of hemorrhagedocumented by magnetic resonance imaging. After resection and during follow-up,54% of patients had an improvement in their modified Rankin scale, whereas 14%were worse compared with their preoperative presentation; 32% were unchangedand 9% of patients were found to have residual cavernoma post-surgery.

CONCLUSION: Our longitudinal experience has guided us to emphasizeminimally invasive approaches during resection of the brainstem cavernousmalformations, occasionally at the expense of achieving a complete resection, toimprove patient outcomes.

Key words Brainstem

Cavernoma

Cavernous malformation

Skull base

Abbreviations and AcronymsCMB: Cavernous malformation of the brainstemGd: GadoliniummRS: Modified Rankin scaleMR: Magnetic resonance

Department of Neurosurgery, University of

Washington School of Medicine, Seattle,Washington, USA

To whom correspondence should be addressed:

Laligam N. Sekhar, M.D.

[E-mail: [email protected]]

Citation: World Neurosurg. (2013) 79, 5/6:691-703.

http://dx.doi.org/10.1016/j.wneu.2012.04.030

Supplementary digital content available online.

Journal homepage: www.WORLDNEUROSURGERY.org

Available online: www.sciencedirect.com

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Elsevier Inc.

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Table 2. Surgical Approaches to Brain Stem Cavernous Malformations

Sex Age Location Approach

Volume,

cm3 Depth Entry Corridor

Intraoperative

Neurophysiology

Preoperative

Symptoms

Postope

Sympto

F 23 Mesencephalothalamic Orbitozygomatic 1.2 At pial

surface

Lateral midbrain SEPs, MEPs, BAEPs

unchanged

Left hemiparesis, left

hyperreflexia.

Left hemipare

improvement

F 50 Mesencephalic Lateralsupracerebellar

0.05 Justbeneath

pial

surface

Dorsal lateralmidbrain

SEPs, MEPs, BAEPsunchanged

Headache, ataxia,diplopia.

Headaches pDiplopia on e

lateral gaze w

functional im

M 58 Mesencephalic Lateral

supracerebellar

1 .1 At pial

surface

Lateral midbrain SEPs, MEPs, BAEPs

unchanged

Multiple hemorrhages in

past with rebleed and

worsening of diplopia,

gait ataxia, and right

hemibody numbness.

Diplopia reso

Right hemibo

numbness sli

worse than p

now stable. N

impairment in

M 8 Mesencephalic Occipital

transtentorial

0.08 At pial

surface

Tectal plate; inferior

to superior colliculus

SEPs, MEPs, BAEPs

unchanged

Vertigo, diplopia,

headaches, nausea,

emesis, syncopal

events.

Diplopia reso

minor headac

F 60 Mesencephalic Transpetrosal 1.3 Justbeneath

pial

surface

Lateral midbrain Left tibial and left mediannerve SSEP responses

showed a marked decline.

No change in MEPs or

BAEPs.

Somnolence, gait ataxia,left arm weakness and

left hemibody numbness.

Postoperativehydrocephalu

requiring shu

placement. A

pneumonia. P

left hemipare

to ambulate w

assistance. R

nursing home

M 3 7 Mesence phalic Orb itozygomatic 0 .2 Be neath

the pial

surface

Medial crus cerebri SEPs, MEPs, BAEPs

unchanged

Mild left limb numbness.

Partial right CN III and

CN VI palsy.

Post-operativ

infection. Rig

and diplopia

on follow-up.

F 6 0 Mesen ce phalic Orbitozygomatic 0.85 5 mm Ante rolatera l

midbrain

SEPs, MEPs, BAEPs

unchanged

Diplopia, gait ataxia,

headache, right

hemiparesis.

Right hemipa

improved, dip

resolved.

M 57 Mesen ce phalic Orbitozygomatic 0.48 At pial

surface

Anterolateral

midbrain

Right MEPs transiently

decreased. SEPs and

BAEPs unchanged.

Headache, dizziness,

impaired tandem gait.

Post-operativ

malocclusion

managed

conservativel

F 38 Mesencephalic Orbitozygomatic 1.3 At pial

surface

Anterolateral

midbrain

SEPs, MEPs, BAEPs

unchanged

Severe headache,

tremors, dysphagia.

Mild right CN

palsy. Tremo

dysphagia re

R

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F 40 Pontome se ncephal ic Suboccipital 0. 44 At pial

surface

Posterolateral

midbrain

Right SEPs declined to

40% of baseline. MEPs

and BAEPs unchanged.

Left hemibody numbness,

diplopia, headaches.

Hydrocephalu

requiring shu

venous throm

aspiration pn

Feeding tube

placement. P

diplopia. Nur

home for car

F 2 4 Pon tome sencepha lic Subte mporal 0 .84 Justbeneath

pial

surface

Superior andanterior to

trigeminal root entry

zone

SEPs, MEPs, BAEPsunchanged

Severe headaches, leftdysmetria, gait ataxia.

Left CN V numbness.

Post-operativinfection. Imp

baseline.

M 39 Pontomesencephalic Combined

transtemporal,

transpetrosal

2 .0 At pial

surface

Posterior to

trigeminal root entry

zone

Poor to absent cortical

SEPs on left consistent

with pre-operative left

hemibody numbness.

MEPs unchanged from

baselines.

Two previous

hemorrhages with left

facial and hemibody

numbness, now

progressively worsening.

Left numbnes

unchanged. N

weakness an

left dysmetria

F 45 Pontine Combined

transtemporal,

transpetrosal

0.56 Just

beneath

pial

surface

Pontomesencephalic

junction

SEPs, MEPs, BAEPs

unchanged

Dysarthria, diplopia, left

hemipareis, gait ataxia,

severe headaches.

Left hemibod

neuropathic p

Headaches re

F 69 Pontine Transmaxillary-transclival

0.38 Justbeneath

pial

surface

Mid-ventral pons SEPs, MEPs, BAEPsunchanged

Headaches, lefthemibody numbness and

hemiparesis. Gait ataxia,

dysphagia, vertigo.

Resolution ofoperative sym

M 35 Pontine 1) Retrosigmoid

2) Presigmoid,

Transsigmoid

0.07 6 mm 1) Lateral pons,

anterior to CN VII/

VIII root entry zone

2) More posterior

and inferior

approach to same

region

1) SEPs, MEPs, BAEPs

unchanged 2) Transient

changes in the left BAEP

and right thenar MEP

with recovery at closing.

Lightheadedness,

dizziness, diplopia,

headaches. Left CN VI

palsy.

Cerebrospina

leak requiring

drain. Left he

loss. Persiste

CN VI palsy.

F 42 Pontine Suboccipital 0.13 At pial

surface

Floor of the fourth

ventricle, superior to

facial colliculus

SEPs, MEPs, BAEPs

unchanged

Left torsional nystagmus,

gait ataxia.

Right CN VI a

palsy, requiri

gold weight.

hyperacusis alimb coordina

problems.

F 43 Pontine Transpetrosal 0.32 Just

beneath

pial

surface

Posterior and inferior

to trigeminal root

entry zone

SEPs, MEPs, BAEPs

unchanged

Numbness of the right

face, dizziness, ataxia,

diplopia and weakness.

Right CN V1

decreased se

and diminish

corneal reflex

Diplopia reso

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cerebral angiography. Episodes of hemor-

rhage related to the cavernomas were con-

firmed by an acute change in neurologic ex-

amination in correspondence with MR

findings suggestive of acute bleeding (T2

hypointensity) (39). Suspected episodes of

bleeding in the past not confirmed by MR

imaging were excluded from the calcula-

tions. The volume of the lesions was calcu-

lated by estimating the volume of an ellip-soid (4/3 1/2 sagittal diameter 1/2

axial diameter 1/2 coronal diameter) as

determined by MR measurements.

Follow-up information included outpa-

tient neurologic examinations and calls to

patients and their relatives. A mean fol-

low-uptimeof 26.6months (SD18 months;

range, 4-68 months) was obtained. Patient

outcomes pre- and postsurgery and during

long-term follow-up were assessed by use

of the modified Rankinscale (mRS) (8,34).

RESULTS

Preoperative History

Allpatientswho were included in this study

were symptomatic from their brainstemcavernomas; only three patients did not

have an overt hemorrhage beforecomingto

medical attention (Table 1). The three pa-tients who did not have a clearly docu-

mented recent hemorrhage with acute

neurologic deterioration were offered

surgery because their lesions appeared to

come to the surface of the brain stem on

MR imaging. The vast majority presented

with cranial nerve deficits (77%), many of

which associated with diplopia (41%). A

total of 55% of patients presented with

headache.Thesenumbers aregenerallyin

keeping with other previously published

data (2, 39, 42).

On the basis of MR findings in conjunc-tionwith patient reports of neurologic dete-

rioration, 64% of the patients had a single

bleed at the time of presentation, and 22%

hadsustained twoor more hemorrhages by

the time they were taken to the operating

room. In this series, 31% of cavernomas

were located in the midbrain, 35% in the

pons,and19%inthemedulla(Table2).Theremainder of lesions spanned multiple

brainstem regions. The mean volume of

these lesions was0.65 cm3, with a standard

deviationof 0.69 cm3. Multiple cavernomas

were found in six patients (27%), with one

of these individuals undergoing separate

surgical procedures for their CMBs.

Surgical Approaches

A broad range of approaches was used dur-

ing surgical resection of brainstem caver-

nomas, as shown in Table 2. The primaryaim of surgery was to provide safe resec-

tion of the lesion through as small an

access point through the brainstem as

possible, that is, the minimal access

technique. Approaches were chosen to

maximize exposure with as little brain re-traction as possible as well as facilitate

ready entry through brainstem safeentry

zones (6, 7, 21, 24, 35). Developmental

venous anomalies associated with these

cavernomas, identified either on preoper-

ative workup or intraoperatively, were left

extant during surgery(2).

All lesions wereresected under frameless

stereotaxy, with coregistration to the oper-

ating microscope used whenever possible.

Intraoperative bilateral somatosensory and

motor-evoked potentials were combined

with cranial nerve monitoring, including

brainstem auditory evoked responses, aswell as direct stimulation (44).

Minimal Access Technique

The entry to the brainstem cavernoma is

made through a pial opening if the lesion

points to the surface through a defined

safe entry zone (24, 35). The approach is

Figure 1. Case 1: CMB situated in the right midbrain peduncle. Axial T2-weighted (A), sagittal (B), and

coronal (C) T1-weighted, post-gadolinium (Gd) enhancement views demonstrate the location of thelesion. Red overlay depicts the operative corridor available for resection of the lesion via a right

orbitozygomatic osteotomy approach. Three-month postoperative axial T2-weighted image

demonstrating gross total resection (D).

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JEFFREY C. MAI ET AL. RESECTION OF CAVERNOUS MALFORMATIONS OF THE BRAINSTEM



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best determined with careful consideration

of the anatomy and any available additional

imaginginformation,such as diffusionten-

sor imaging. Intraoperative neuronaviga-

tion is indispensable in delineating the

entry approach, in conjunction with neuro-

anatomical landmarks. The incision into

the brainstem and the tract are kept as nar-

row as possible until the cavernoma is

reached. Once inside the cavernoma, any

liquefied hematoma is drained. Solid por-

tions of the cavernoma are removed piece-

meal, starting centrally, and gradually pro-

gressing to the margins, until the lesion is

completely removed (Video 1). Most caver-nomas are removed in three to five pieces,

depending on their size and consistency.

Care is taken toremove allof thecavernoma

elements while preserving any major veins

or en passage arteries. Vigorous removal of

the gliotic, hemosiderin-stained margin of

the cavernoma is not attempted, especially

with large lesions, because the risk of sei-

zures triggered by these residual tissues is

nonexistent.

Operative ResultsA total of 27 operative procedures were per-

formed for the 22 patients in the series for

their brainstem cavernomas; 31% of the

cavernomas weremesencephalic, 35%were

pontine, and 19% were located in the me-

dulla (Table 2). Four lesions were largeenough to span adjoining domains, includ-

ing one mesencephalothalamic and three

Figure 2. Case 2: left tectal plate cavernous malformation. Sagittal T1-weighted post-Gd (A) and axial T2-weighted preoperative (B) and

postoperative scans at 2 months (C). Red overlay depicts the operative

approach via a left occipital transtentorial approach.

Figure 3. Case 3: left lateral supracerebellar infratentorial approach (red transparent overlay) to dorsalmidbrain cavernoma. Sagittal (A), coronal (B), and axial (C) T2-weighted images and axial T2-

weighted image 14 months postoperatively (D) demonstrating no obvious residual cavernoma.

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pontomesencephalic cavernomas. A 91%

gross total resection rate was achieved, as

assessed by serial MR imaging. In 9% of

patients, residual cavernoma was identified

on post-operative imaging. No postopera-

tive mortality was observed in

this series, andno further sur-

geries were required in these

patients.

Midbrain. Case 1. This 23-

year-old woman developed

left hemiparesis with distal weakness

greater than proximal in the arms in legs

(graded 4/5) and hyperreflexia on the ipsi-

lateral side. As her cavernoma was situated

in the right peduncle, a right frontotempo-

ral orbitozygomatic approach was under-

taken (Figure 1). She developed transientleft facial weakness and worsening of her

left hemiparesis postoperatively. At 20

months after the procedure, she has pro-

gressed from an mRS 4 to an

mRS2 with persistence of her

mild left-sided weakness.

Case 2. An 8-year-old boypre-sented with vertigo, head-

aches, nausea, and vomiting

and was found to have at least

seven supra- and infratentorial cavernous

malformations, including the largest in the

tectum, which had evidence of recent hem-

orrhage on MR imaging, andanotherin the

medulla. The tectal plate cavernoma was

approached via a left occipital, transtento-

rial approach using frameless stereotaxy

(Figure2). Asthe lesioncameto thesurface,

gross totalresection was possible,with new

postoperative diplopia noted at 2 months

follow-up, and at 1 year, he was asymptom-

atic, mRS 0.

Case 3. A 58-year-old man with known his-

toryof CMBand multiple hemorrhages pre-

sented with rebleed accompanied by diplo-

pia, right hemibody numbness, and gait

ataxia, mRS 2. The cavernoma was located

on the left dorsal mesencephalon (Fig-

ure3). Weapproachedthe lesionby a lateral

supracerebellar infratentorial approach. At

25 months follow-up, patient has resolu-

tion of diplopia but slight worsening of

right body numbness, mRS 1.

Pons. Case 4. A 43-year-old woman pre-

sented with right V1-V3 facial numbness,diplopia, ataxia, and weakness with two

symptomatic hemorrhages from a right

middle cerebellar peduncle cavernous mal-

formation(Figure4). Given thelocation,we

opted for a right transpetrosal approachfor

the lesion. In thisinstance, diffusion tensor

imaging was used during preoperative

planning to map the direction of displaced

tracts in a rostral-caudal axis.In comparing

the side of the brainstem with the caver-

noma to the contralateral unaffected side,

we found these fibers to be medially dis-

placed, confirming that entry from a lateral

approach would be safest. At 27 months

postoperatively, her diplopia had resolved,

but she has developed a right diminished

corneal reflex and slightly worsened V1-V3

numbness. Nevertheless, she is able to

drive a vehicle, and hermRS improved from

a 2 to a 1.

Case 5. A 69-year-old woman presented

with acute onset of headache,left hemibody

numbness and weakness (4/5), left dysme-

tria, ataxia, dysphagia, and vertigo with a

central pontine hemorrhage secondary to a

cavernoma (Figure 5). Because the lesion

was located in the midline and did notclearly reach the surface, we opted for a

transmaxillarytransclival approach, as il-

lustrated in Figure 5. In this case, a transfa-

cial LeFort I maxillotomy was used, with a

clivectomy performed with neuronaviga-

tion used to guide the trajectory directly to

the lesion. This approach, although techni-

cally demanding, affords an excellent work-

Figure 4. Case 4: CMB located in the right cerebellar peduncle. T2-weighted sagittal (A) and axial (B)images. Three-dimensional diffusion tensor imaging demonstrates medial displacement of rostral-

caudal fibers with cavernoma coming to surface of the lateral pons (C). Red overlay illustrates a right

transpetrosal approach. (D) Axial T2-weighted image at 10-month postoperative follow-up.

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ing view of the ventral pontine surface, in-

cluding the basilar artery and its associated

paramedian perforators, thereby facilitat-

ing their preservation. In addition, it repre-

sents the most direct pathway to the lesion,

without the need to traverse normal brains-

tem tissue to reach the lesion. Here, the

basilar artery was moved gently aside, ex-

posing a small area of discoloration in the

midline representing the cavernomas

emergence at the surface of the pons. Afterresection, the defect in the clival dura was

repaired with placement of two pieces of

abdominal fascia beneath the inner surface

of dura,followed by application of DuraSeal

(Confluent Surgical Inc., Waltham, Massa-

chusetts, USA). An additional two layers of

fascia were applied to the outside, secured

again with a layer of DuraSeal and Gelfoam

(Pfizer, NewYork,New York, USA), and the

sphenoid rostrum was covered with a mu-

cosal flap. A right frontal externalventriculo-

stomydrainwas placedat thetime of surgery

to minimize risk of CSFleak and wasweaned

by postoperative day 9. Her mRS improved

from 2 to 1 at 44 months follow-up.Case 6. A 57-year-old man who developed

sudden onset of headache, dizziness, and

gait disturbance was found to have a left

lateral pontine hemorrhage as the result ofunderlying cavernoma (Figure 6). A leftsubtemporal approach with zygomatic os-

teotomy was used to gain access to the lat-

eral pons, where the cavernous malforma-

tion wasobserved to come to thesurface.At

22 months follow up, the patient had im-

proved from an mRS score of 2 to an mRS

of 1.

Case 7. A 39-year-old man with two previ-

ous hemorrhages of a right dorsal lateral

pontine cavernoma re-presented with pro-

gressive left facial droop, left hemibody

numbness, and truncal ataxia. As shown in

Figure 7, a right transpetrosal and presig-moid approach was used for extirpation of

thelesion. At 7 months postoperatively, thepatient had improved from an mRS of 3 to

an mRSof 1 andreported improvingnumb-

ness onthe left side and mild left dysmetria.

Medulla. Case 8. A 37-year-old woman pre-

sented with baseline disequilibrium and

previous subtotal resection of dorsal med-

ullary brainstem cavernoma by another

neurosurgeon. She represented with sud-

den deterioration, including numbness in

her right arm, intermittent dysphagia, and

difficulty breathing. A far lateral retrosig-

moid approach was used, and gross total

resection was achieved (Figure 8). At 42months follow-up, she has now made a

complete recovery (mRS 0).

Long-Term Outcomes

During the course of follow-up, 54% of pa-

tients were noted to improve compared

with their preoperative status, whereas 32%

remained generally unchanged from a neu-

rologic standpoint. During this time, 14%

of patients had declined compared with

their preoperative status. The distribution

of preoperative mRS and long-term mRS is

shown in Figure 9. Of the 9% of patientswith residual brainstem cavernomas, no in-

stances of rehemorrhage were recorded. At

present, both of these patients have de-

clined reoperation.

DISCUSSION

Indications for Removal

The vast majority of brainstem cavernous

malformations come to attention after a

hemorrhage. In general, we are willing to

delay surgical management of these lesions

after a single bleeding ictus unless the pa-tients cardiac or neurologic instability ne-

cessitatesemergent evacuation or thelesion

clearly abuts the pial or ependymal surface

on T1-weighted MRimaging(18, 39, 42). For

deeper seated lesions, a second bleed or pro-

gressiveneurologic deficit necessitatessurgi-

cal extirpation of the brainstem cavernoma

because it suggests the propensity of the

Figure 5. Case 5: Midline, ventral pontine cavernoma approached via a transmaxillary-transclivalapproach (red transparent overlay). T1-weighted post-Gd sagittal (A), coronal (B), and axial (C)

images. (D) T2-weighted axial scan at 3-year follow-up.

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lesion to rebleed in the future. In these in-

stances, carefully weighingthe risk of mor-

bidity from surgery compared with that of

future re-hemorrhage, on the basis of the

natural history of these lesions, tips thebal-

ance in favor of surgical intervention (18).

This is especially true if deep-seated lesions

can be approached through safe entry

corridors.

The use of radiosurgery for cavernous

malformations has been reported, withmixed results (27, 30). As such, the use of

radiosurgery as a primary treatment modal-

ity for cavernous malformations, including

those of the brainstem, remains controver-

sial. At present, we advocate surgical resec-

tion as the primary means for treatment for

high-risk cavernomas of the brainstem.

With regard to timing of surgery after a

hemorrhage, although some surgeons ad-

vocate delaying surgery until the subacute

phase, when the blood products will un-

dergo liquefaction (13, 18, 39); waiting

much beyond the first several weeks risks

development of gliosis, which may hinder

complete resection.

Approaches to the Brainstem

Unlike with supratentorial cavernous mal-formations, those associated with CMBs

present a special challenge to the surgeon

due to the presence of surrounding brains-

temnuclei andtracts (7, 17, 24, 35). As with

others, we advocate carefully tailoring the

surgical approach to each individuals le-

sion. It is incumbent upon the surgeon to

recognize the normal anatomy of the region

surrounding the cavernomas, as well as

take into careful consideration the distor-

tionin surroundinganatomy thatcan arise as

a result of the lesion as well as associated

hemorrhage. Unless the cavernoma comes

clearly to the pial surface,the direction of ap-

proach may not always be optimally defined

as the shortest path from the surface to thelesion.Given the eloquence of the brainstem,

even a thin parenchymal layer overlying the

cavernoma canharbor criticaltracts.Compli-

cating this situation is the paucity of widely

used and reliable intraoperative methods to

identify these displaced and distorted struc-

tures. Broadly, we have subcategorized ap-

proaches to the brainstem with respect to the

midbrain, pons, and medulla.

Midbrain. The midbrain is subdivided into

three general approaches: anteromedial,

lateral, and posterior. In the anteromedial

approach for interpeduncular lesions, anextended transsylvian corridor is used,with

the assistance of an orbitozygomatic crani-

otomy (18). Slightly more laterally, a sub-

temporal approach can be used, or in com-

bination with a transsylvian route (31).

Laterally, a supracerebellar-infratentorial

or petrosal approach can be used to reach

mesencephalic cavernomas. Posteriorly, a

suboccipital or occipital transtentorial ap-

proach can be used to reach lesions cen-

tered near the posterior midbrain, includ-

ing the tectal plate. From a posterior

approach, dependingon the location of the

cavernomas, entry at the lateral mesen-

cephalic sulcus may be used to avoid injur-

ing oculomotor and trochlear nuclei and

the medial longitudinal fasciculus situated

more medially (17, 21, 35). The supracol-

licular and infracollicular lines that delin-

eate therostralandcaudal extentof thelam-

ina quadrigemina represent other potential

corridors of entry along the midline (9, 17).

Otherwise, midline approaches through

the tectal plate should be avoided whenever

possible given their postoperative morbid-

ity.Throughexperience,we andothers have

learned that avoidance of injury to the cen-

tral tegmentum and adjacent medial longi-

tudinal fasciculus is vital, as the resultant

postoperative complications of nystagmus

and internuclear ophthalmoplegia, respec-

tively, are particularly debilitating during

recovery(17).

Pons. The pons is the largest region of the

brainstem andthe most commonlocation for

Figure 6. Case 6: Left, lateral pontine cavernoma with a left subtemporal approach with zygomatic

osteotomy depicted with the red overlay. Fluid-attenuated inversion recovery sagittal (A), T1-weighted post-Gd coronal (B), and T2-weighted axial preoperative (C) and 22 months postoperative

(D) images.

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brainstemcavernomas (13,18, 33, 42). Given

its size, a variety of surgical approaches are

available to the surgeon, depending on the

precise location of the cavernous malforma-

tion(Table2). Wehavedefinedapproachesto

the pons intofour categories: dorsal, central,

anterolateral, and lateral.

From a dorsal approach, a midline sub-

occipital approach can be used. In such

cases,it is paramountto minimize dividing

the vermis given associated complications,

including truncal ataxia (44). Alternately, a

subtonsillar-transcerebellomedullary (te-

lovelar) approach can be used (13, 44),

which involves dividing the cerebellomed-

ullary fissure. This approach is useful in ac-

cessing pontomedullary and medullary le-

sions. Unfortunately, unless the cavernoma

clearly emerges at thesurface of thefloor of

the fourth ventricle, injury to the medial

longitudinal fasciculus, facial, and abdu-cens nerve are common when operating

along thisregion (3,44). As withothers (13,

17, 18, 33), we view the floor of the fourth

ventricle with great caution when ap-

proaching CMBs, despite the published

morphometric descriptions of safe entry

zones in the infra- and supra-abducental or

facial regions (6, 7, 24). These lesions can

be approached if the locations of the facial,

vagal, and hypoglossal nuclei are carefully

established intraoperatively by direct stim-

ulation. Nevertheless, it may be difficult to

avoidthe intrinsicportionof thefacial nerve

tract or the abducens nucleus when resect-ing cavernomas in immediate vicinity. Post-

surgical brainstem tract and nucleus-re-

lated complications have been reduced as

we have shifted away from posterior ap-

proaches to the pons over time.

We prefer more lateral or anterolateral

approaches to the brainstem, particularly

when dealing with deep-seated lesions of

the pons. The anterior and anterolateral

brainstem tracts are generally more resil-

ient to surgical manipulation than the dor-

sal pontineand medullarysurfaces. A trans-

petrosal (19, 22, 31, 45) or retrosigmoid

approach will enable accessto themore an-teriorsurface of the pons (16, 31). A presig-

moid approach will yield a more lateral, al-

beit more direct, view of the pons (20).

From any of these approaches, the peritri-

geminal area, a safe entry zone, can be

accessed and safely traversed horizontally,

followingalong theplane of thefibers. This

triangular region is bound medially by the

Figure 7. Case 7: Right transpetrosal and presigmoid approach (red overlay) to a right dorsal lateralpontine cavernoma. T1-weighted post-Gd axial (A), T2-weighted axial (B), T1-weighted post-Gd

sagittal (C), and postoperative 3-month T2-weighted axial image (D). Intraoperative image

demonstrating bimanual removal of cavernoma through a small portal in the brainstem (E) and image

after gross total resection (F).

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pyramidal tract, inferiorly by the pon-

tomedullary sulcus out to the flocculus,and

laterallyjustmedial tothe root entry zone of

cranial nerve V (35).

Cavernomas situated directly on the ven-

tral midline surface of the pons require a

central approach. For these difficult, but

fortunately rare, lesions, we advocate a

transmaxillary-transclival approach, which

we used during the resection of one of our

pontine cavernomas in ourseries (Table 2).

Medulla. The medulla can be approached

from the following routes: dorsal, anterior,

and anterolateral corridors. As with the

pons, a midline suboccipital craniotomy

with a telovelar approach can be used to

reach the dorsal medullary surface (17, 31).

In theupper dorsalmedulla,alongthe infe-

rior floor of the fourth ventricle, risk of in-

jury to the nucleus of XII medially and the

nucleus X laterally with resultant ipsilateraltongue weakness and cardiac/respiratory

instability, respectively, makes entry from

thisdirection generallycontraindicated (13,

17, 18, 33). Furthermore, the medial longi-

tudinal fasciculus underlies these struc-

tures medially. For the lower dorsal me-

dulla, safe entry zones are defined by

Bricolo as the posterior median fissure and

the posterior intermediate and posterior

lateral sulci (9, 17).

Generally, a far lateral retrosigmoid ap-

proach will suffice for reaching pontomed-

ullary lesions (13). An extreme far lateral

approach with the resection of the jugular

tubercle (thetranstubercular approach) will

enable access to the anterolateral lesionsoriginating in the medulla down to the up-

per cervical spinal cord(18, 31). Fromeither

approach, safe medullary access is realized

by way of entry through the retro-olivary

sulcus, which does not result in clinically

evidence deficits (35). Finally, strictly ante-

rior cavernomas of the ventral medulla can

be reached via a transoral route (36, 44).

This was not used in our series due to the

absence of any cases requiringit. Because of

the concern for CSF leak and associated in-

fection, an alternative is the subtemporal

infratemporal approach for these lesions

(41).In each case, the guiding principle is to

avoid breaching major brainstem tracts or

nuclei. If there is no option, then traversing

the most accessible route to the brainstem

cavernoma must then be chosen on a case-

by-case basis.

Evolution of a Minimally Invasive

Resection Technique

Once the decision has been made to pro-

ceed with resection, careful preoperative

planning is essential. When possible, we

have useddiffusiontensor imaging to studythe distortion of the underlying white mat-

ter tracts surrounding the lesion (11). It is

performed when lesions do not appear to

cometo the pial surface onMR imaging,so

that the corridor for entry through the

brainstem maynot be as apparent.The util-

ity of such imaging can be limited by sus-

ceptibility artifact when one is resecting a

relatively fresh hemorrhage, which pre-

vents adequate tractography. Nevertheless,

in such cases, comparing the contralateral

side tractsas a pointof reference and com-

pensating for anticipated displacementof

the tracts on the ipsilateral side can behelpful.

Intraoperative cranial nerve monitoring

is generally more important for dorsal ap-

proaches. For anterior and lateral ap-

proaches to the brainstem, motor-evoked

potentials are obligatory. Intraoperatively,

real-time guidance with frameless stereo-

taxy registered to the operating microscope

Figure 8. Case 8: Suboccipital approach (red transparent overlay) to cavernous malformation of thedorsal medulla previously with subtotal resection. T2-weighted sagittal (A), coronal (B), and axial

preoperative (C), and 3 year postoperative (D) images shown.

Figure 9. Bar graph showing the distributionof the preoperative mRS scores for the 22

patients compared with the distribution at

last follow-up. Mean follow-up time was 26.6

months with a range of 2-68 months, SD of

17.7 months.

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field of view is ofparticular importance dur-

ing resection of small cavernomas.

In the senior authors experience

(L.N.S.), a general approach to brainstem

cavernous malformations is to create as

small a portal for access to the lesion asfeasible, a minimal access technique.

Through this window, the cavernoma is re-

sected as much as possible, given the con-

straints of the surrounding anatomic struc-

tures. In these cases, the cavernoma

generally is internally debulked to decom-

press the lesion, and the wall is then gently

taken down from the surrounding brains-

tem and disconnected with the use of a bi-

manual technique (Figure 10). Any associ-ated developmental venous anomalies,

which are commonly associated with these

lesions (1, 3, 32), or hemosiderin-stained

tissue is preserved.This method has been able to yield gen-

erally favorable results in the majority of

brainstem cavernomas, with the drawback

that given the small surgical window, a

gross total resection may be impossible to

achieve. Reviewing the retrospective data

shown above, there have been two recur-

rences after surgery: both were managed

conservativelywith monitoring by serial im-

aging. These recurrences are tempered

against the reduction of expected post-op-

erative complications. We have generally

opted for repeated resections, if indicated,

for residual brainstem cavernomas, as they

do present a risk of rehemorrhage.

Future Developments

As technology advances, we anticipate the

development of specialized microsurgical

instrumentation, including flexible endo-

scopes and other articulated devices that

will facilitate working through highly con-

strained operative corridors, thereby mini-

mizing damage to the surrounding brains-

temtracts andnuclei.The useof thecarbon

dioxide laser hasalready been employed for

selected cavernomas in the brainstem (G.

Steinberg, personalcommunication, 2010),

and we are presently exploring the utility ofthe flexible CO

2laser (OmniGuide, Cam-

bridge, Massachusetts, USA) at our institu-

tion.

CONCLUSION

Our approach to cavernous malformations

of the brainstem represents a progressive

and iterative refinement of surgical tech-

niques during the past two decades. We

have sought to incorporate new technolo-

gies, such as image guidance and diffusion

tensor imaging, wherever practical. Fromexperience, we have opted to eschew mid-

line approaches to the dorsal midbrain and

to the floor of the fourth ventricle, instead

selecting operative corridors that are di-

rected more laterally and anteriorly to the

brainstem. Finally, we recommend a mini-

mal access technique, wherever possible,

which reduces the likelihood of postopera-

tive morbiditydue to brainstemnuclear and

tractinjuryat theexpenseof achievinggross

total resection.

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Conflict of interest statement: The authors declare that the

article content was composed in the absence of any

commercial or financial relationships that could be

construed as a potential conflict of interest.

Received 12 September 2011; accepted 14 April 2012

Citation: World Neurosurg. (2013) 79, 5/6:691-703.


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Available online: www.sciencedirect.com

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