CASE REPORTS

PERFUSION AND DIFFUSION TENSOR IMAGING IN A PATIENT
WITH LOCKED-IN SYNDROME AFTER NEUROSURGICAL
VASCULAR BYPASS AND ENDOVASCULAR EMBOLIZATION OF A
BASILAR ARTERY ANEURYSM: CASE REPORT
Yvonne W. Lui, M.D.
Department of Radiology,
New York University
Medical Center,
New York, New York

Meng Law, M.D.
Departments of Radiology
and Neurosurgery,
New York University
Medical Center,
New York, New York

Jafar J. Jafar, M.D.
Department of Neurosurgery,
New York University
Medical Center,
New York, New York

Andrea Douglas, M.D.
Department of Neurosurgery,
New York University
Medical Center,
New York, New York

Peter Kim Nelson, M.D.
Department of Radiology,
New York University
Medical Center,
New York, New York
Reprint requests:
Yvonne W. Lui, M.D.,
NYU Medical Center,
Department of Radiology,
Section of Neuroradiology,
530 First Avenue,
New York, NY 10016.
Email: luiy01@med.nyu.edu

OBJECTIVE AND IMPORTANCE: Locked-in syndrome is a state of preserved consciousness
in the setting of quadriplegia, anarthria, and usually also includes lateral gaze palsy. It is most
commonly associated with upper brainstem infarction variably sparing the third cranial nerve
nucleus. There are likely many etiologies that contribute to this clinical syndrome. These are
incompletely understood, and the syndrome remains a rare but devastating complication that
can occur after neurosurgical and neurovascular interventions. Advanced magnetic resonance
imaging techniques such as perfusion and diffusion tensor imaging may help to elucidate the
mechanism behind locked-in syndrome. To the authors’ knowledge, there are no reports in the
literature of perfusion and diffusion tensor findings in patients with this syndrome. A postprocedural case of locked-in syndrome is described with abnormalities on perfusion and diffusion
tensor imaging in the absence of any changes in conventional magnetic resonance imaging.
CLINICAL PRESENTATION: A 57-year-old man who presented with acute onset
headache, ataxia, and other nonspecific symptoms was found on imaging to have a
giant fusiform basilar artery aneurysm.
INTERVENTION: A saphenous vein graft bypass between the proximal right external
carotid artery and P2 segment of the right posterior cerebral artery followed immediately by endovascular embolization of the aneurysm sac and distal left vertebral artery
was performed.
CONCLUSION: Postprocedural angiography demonstrated patency of the bypass
graft, and diffusion weighted imaging showed no evidence for acute brainstem infarction. Nevertheless, despite technically successful procedures and the absence of
abnormalities on conventional magnetic resonance imaging, the patient developed
quadriplegia and anarthria and remained in a locked-in state until he expired. Abnormalities were, however, seen on both perfusion and diffusion tensor imaging, where
hypoperfusion, increased mean diffusivity, and decreased fractional anisotropy were
observed in the ventral brainstem. The findings suggested a disruption of pontine white
matter tracts. Advanced imaging techniques may allow us to image important microstructural changes that were previously not discernable and assist in the evaluation of
patients with complex neurological sequelae such as locked-in syndrome.
KEY WORDS: Basilar artery aneurysm, Diffusion tensor imaging, Locked-in syndrome, Perfusion
Neurosurgery 58:794-795, 2006

DOI: 10.1227/01.NEU.0000204893.07192.1F

www.neurosurgery-online.com

Received, June 17, 2005.
Accepted, November 19, 2005.

L

cate only via blinking and most frequently
preserves vertical movements of the eyes. The
most common etiology is stroke, with 75 to
85% of cases attributable to upper brainstem
infarction (5, 9). Other etiologies include pontine hemorrhage, trauma (5), tumor (6), central
pontine myelinolysis (10), and infection (7). It

E794 | VOLUME 58 | NUMBER 4 | APRIL 2006

www.neurosurgery-online.com

ocked-in syndrome, a term coined by
Plum and Posner (11) in 1966, is a clinical
diagnosis made by the presence of upper
motor neuron quadriplegia and lower cranial
nerve dysfunction most commonly with preservation of the oculomotor nucleus that leaves
the patient conscious and able to communi-

TENSOR IMAGING IN A PATIENT WITH LOCKED-IN SYNDROME

has been described as a rare complication of surgery in which
the underlying etiology was also most frequently ischemic (1).
Despite new surgical and endovascular techniques, giant
fusiform basilar artery aneurysms present a therapeutic challenge because of their location at the cranial base, adjacent to
critical brainstem structures (2). We describe diffusion tensor
and perfusion magnetic resonance imaging (MRI) findings in
a case of locked-in syndrome after neurovascular bypass and
embolization of a giant basilar artery aneurysm and discuss
the potential role of advanced MRI techniques in the evaluation of such patients.

CASE REPORT
Clinical History
A 57-year-old man with past medical history of peripheral
neuropathy, presumptively diagnosed as Charcot Marie Tooth
Syndrome, was referred for treatment of a giant fusiform
aneurysm of the proximal basilar artery. Three months earlier,
he was hospitalized with acute onset of crushing headache
accompanied by dizziness, unsteady gait, blurred vision, and
nausea. The diagnostic workup, including head computed
tomography, brain MRI, intracranial computed tomographic
angiography, and conventional cerebral angiography, was significant for a partially thrombosed giant fusiform aneurysm
with evidence of acute intramural hemorrhage involving the
distal left vertebral, vertebrobasilar junction, and basilar artery
proximal to the anterior inferior cerebellar artery segment.
There was considerable mass effect on the ventral pons and
medulla (Fig. 1). His diplopia and ataxia gradually resolved;
however, he continued to experience severe headaches daily,
and, on admission for treatment, his neurological examination
was significant for spastic myelopathy and unsteady gait.
After consideration of the risks and benefits of surgical and
neurointerventional therapies versus conservative management, the patient was admitted for combined surgical/
endovascular treatment and subsequently underwent surgical
establishment of a saphenous vein graft bypass between the
proximal right external carotid artery and P2 segment of the
right posterior cerebral artery followed immediately by endovascular occlusion of the aneurysm sac and distal left vertebral
artery with combination Guglielmi detachable and platinum
fiber coils. Posttreatment angiography demonstrated occlusion of the aneurysm with collateral reconstitution of the distal
basilar artery and anterior inferior cerebellar arteries through
the surgical graft (Fig. 2).
Although able to move all extremities to command after his
emergence from generalized anesthesia, within 4 hours, the
patient became unresponsive with a flaccid quadriparesis.
Over the next 2 hours, his neurological examination evolved
with recovery of bilateral eye opening and an improved level
of consciousness with brisk responses to yes and no questions
via eye-blinking. His examination, however, was otherwise
significant for a left lateral gaze preference, decerebrate pos-

NEUROSURGERY

FIGURE 1. Midline sagittal T1
weighted MRI (A), axial source
image from computed tomography
angiogram (B), and surface rendered three-dimensional reconstruction from computed tomography angiogram (C) demonstrate
partially thrombosed, giant, fusiform vertebrobasilar aneurysm
(arrow) compressing and deforming brainstem. Incidental note is
made on MRI of heterogeneous
sellar mass compatible with a pituitary macroadenoma (arrowhead).

FIGURE 2. Images from postprocedure digital subtraction angiogram. A,
selected injection into right vertebral artery demonstrates opacification of
anterior spinal artery (black arrow) and right posterior inferior cerebellar
artery (black arrowhead). Subtraction artifact from coil mass seen within
thrombosed aneurysm. B, selected injection into bypass graft demonstrates
patency of graph (arrowhead) with good opacification of posterior cerebral
arteries and retrograde flow into distal basilar artery. Left anterior inferior
cerebellar artery is well demonstrated (white arrow).

turing to noxious stimuli, and the inability to voluntarily
move his head or mouth.
Conventional postoperative MRI demonstrated no brainstem infarction. Brainstem auditory evoked potentials were
performed and were normal; however, somatosensory evoked
potentials, and motor evoked potentials were absent. Over the
following weeks, his examination gradually deteriorated.
MRI, brainstem auditory evoked potentials, somatosensory
evoked potentials, and motor evoked potentials were repeated

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LUI ET AL.

FIGURE 3. Axial T2 weighted image (A) demonstrates postsurgical
changes in right middle cranial fossa
and small amount of T2 hyperintensity at right lateral aspect of the pons.
Diffusion weighted image at b value
of 1000 (B) and corresponding apparent diffusion coefficient map (C)
through level of pons demonstrates no
restricted diffusion to suggest acute
brainstem infarction.

and were unchanged in comparison with the initial evaluation.
After 4 weeks, the patient was returned to the operating
room for resection of the aneurysm sac in an effort to relieve
presumptive brainstem compression. The patient tolerated
this procedure well but remained locked-in with no change in
evoked potentials and expired approximately 6 weeks after
his initial procedure.

MRI
On postprocedure day 1, MRI was performed on a 1.5 Tesla
system (Siemens Sonata or Symphony, Siemens AG, Erlangen,
Germany). A localizing sagittal T1-weighted image was obtained followed by nonenhanced axial T1-weighted spin echo
(repetition time/echo time, 600/14 ms), axial fluid-attenuated
inversion recovery (fluid attenuated inversion recovery, 9000/
110/inversion time 2500), and T2-weighted (3400/119) images). Diffusion weighted imaging and diffusion tensor imaging were also performed.
Conventional MRIs demonstrated expected postoperative
and postprocedural changes. There remained mass effect on
the brainstem from the aneurysm sac. Diffusion weighted
images acquired in the axial plane using an echo-planar imaging sequence with b values of 0, 500, and 1000 seconds mm-2
demonstrated no restricted diffusion within the brainstem to
suggest acute infarction (Fig. 3).

E794 | VOLUME 58 | NUMBER 4 | APRIL 2006

FIGURE 4. A and B, fractional anisotropy directional color map (A) and
fractional anisotropy map (B) demonstrating poor visualization of corticospinal tracts at level of mid pons. There is decreased FA and increased
mean diffusivity in brainstem, more on B side than A. C and D, normal
control is provided for comparison, demonstrating corticospinal tracts
encoded blue in superior-inferior direction in anterior pons (arrows).

Diffusion tensor imaging using echo planar technique imaging (repetition time/echo time, 5300/74; 128 ⫻ 128 matrix;
220 ⫻ 220 mm field of view; 45 3 mm contiguous slices; b ⫽
1000 s/mm2) was also performed using six gradient directions. Mean diffusivity, fractional anisotropy (FA), and colorcoded direction of maximum anisotropy maps were then generated. There was an abnormal appearance to the brainstem
white matter tracts. In particular, at the level of the mid pons,
the corticospinal tracts were poorly visualized on the FA color
maps (Fig. 4) and region of interest FA measures in the corticospinal tracts were low, measuring 0.526 and 0.343, respectively, on the right and left at the level of the pons. The
corresponding mean diffusivity measures at this level were
high, measuring 0.888 and 1.478 (Table 1). Seed areas placed in
the expected location of the corticospinal tracts at the level of
the mid pons demonstrated decreased number and extent of
fiber tracts (Fig. 5) compared with a normal control.
Follow-up MRI 3 days later showed no change on conventional images. Once again, there was no restricted diffusion in the
brainstem. Perfusion imaging using dynamic susceptibility contrast MRI was performed and showed diminished cerebral blood
flow, cerebral blood volume, and prolonged mean transit time in
the brainstem, particularly in the pons and medulla (Table 1) (Fig.
6). Diffusion tensor imaging was repeated as well on postproce-

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TENSOR IMAGING IN A PATIENT WITH LOCKED-IN SYNDROME

dure day 4. There was no
change in the FA measures
within the corticospinal tracts
or in the overall appearance of
the FA color maps and tractography.

TABLE 1. Brainstem diffusion tensor and perfusion metrics in a patient with locked-in syndromea
DTI
Location
Midbrain

DSC MRI

FA

MD

CBF

CBV

MTT

R

0.529 (0.774)

0.71 (0.861)

9.3 (43.3)

0.48 (2.01)

3.11 (2.79)

L

0.778 (0.747)

0.639 (.753)

14.1 (44.2)

0.73 (2.26)

3.11 (3.07)

R

0.526 (0.588)

0.888 (0.715)

17.5 (42.5)

0.99 (2.25)

3.4 (3.17)

DISCUSSION

Despite the postoperative
development of a clinically apparent locked-in state in our
patient, supported by disrupL
0.343 (0.606)
1.478 (0.858)
10.8 (36.3)
0.58 (1.93)
3.22 (3.18)
tions in motor and somatosensory evoked potentials, conMedulla b
R
0.320 (0.455)
0.875 (1.216)
16.9 (46.7)
1.02 (1.90)
3.63 (3.13)
ventional spin-echo and
diffusion MRI sequences were
L
0.366 (0.508)
0.799 (1.053)
noncontributory, failing to
confirm the anticipated braina
DTI, diffusion tensor imaging; DSC MRI, dynamic susceptibility contrast perfusion magnetic resonance imaging; FA,
stem stroke. Perfusion and diffractional anisotropy; MD, mean diffusivity, these measures were taken in the region of the corticospinal tracts at the
fusion tensor imaging, howlevels noted; CBF, cerebral blood flow (ml/100g/min); CBV, cerebral blood volume (ml/100g); MTT, mean transit time(s);
ever, demonstrated clear
R, right; L, left. Numbers in parentheses indicate normal values from an age/sex match control.
b
Data obtained in the lower brainstem may not be as reliable because of susceptibility artifact. Perfusion data in the
abnormalities within the
medulla were obtained from a region of interest placed in the midline.
brainstem. This suggests that
advanced MRI techniques can
detect critical microstructural
changes that are not visible on conventional MRIs.
In our patient, the diffusion tensor metrics and MRI tractography suggested a profound disruption of ventral fibers at
the pontomesencephalic junction, which corresponded to the
clinical manifestations evident on neurological examination.
The etiology of this disruption, unfortunately, is less clear.
Two possible mechanisms might include chronic subinfarct
brainstem ischemia versus a critical exacerbation of aneurysmal mass effect.
In terms of brainstem ischemia, imaging obtained during the
course of the patient’s hospitalization is conflicted. Angiography
repeated 2 weeks after symptom onset confirmed maintained
bypass support of the distal basilar artery and anterior inferior
cerebellar arteries and diffusion weighted imaging showed no
acute brainstem infarction. On the other hand, MRI perfusion
demonstrated a slight prolongation in the mean transit time with
decreased blood flow and decreased blood volume compared
with published data from normal subjects (3). Global brainstem
vascular compromise may have been present because of a number of different reasons: 1) insufficient arterial collaterals, 2) a
transient critical thrombotic event involving the distal basilar
artery, the vascular stigmata of which resolved by the time of
subsequent angiographic imaging, 3) the effect of acute venous
congestion, 4) local vascular insufficiency related to worsening
FIGURE 5. A, tractography sagittal projection (A) superimposed on corbrainstem compression, perhaps related to brief upward herniaresponding sagittal T1 weighted image and three-dimensional anteriortion, or 5) injury or thrombosis of small basilar arterial perforaposterior projection (B) with seeds placed within expected location of cortitors.
cospinal tracts bilaterally in mid pons. Sagittal projection demonstrates
Of note, it is possible that hypoperfusion as demonstrated
relationship of fiber tracts to aneurysm with no fibers tracked inferior to
by perfusion MRI may have been present before intervention
mid pontine level. C and D, normal control is provided for comparison,
and be a result of longstanding mass effect within the postedemonstrating normal number and course of corticospinal tracts.
Pons

NEUROSURGERY

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LUI ET AL.

FIGURE 6. A, dynamic
susceptibility contrast perfusion MRI signal intensity
curves show diminished perfusion to brainstem in comparison with supratentorial
white matter (region of interest placed in left occipital
white matter). B, cerebral
blood volume (CBV) map
demonstrates decreased perfusion within brainstem (see
also Table 1).

rior fossa. Unfortunately, preoperative baseline perfusion values for the patient were not available for comparison.
Alternatively, critical mass effect on the brainstem without
ischemia may have contributed to this patient’s clinical decline. A
transient or sustained compressive event related to the aneurysmal mass effect could be postulated to result in mechanical
disruption of brainstem white matter tracts as supported by the
low FA in the corticospinal tracts. Recent work using diffusion
tensor imaging has demonstrated that in the normal control,
brainstem white matter tracts can be visualized on FA color maps
as well as using tractography as robust bilateral tracts running in
a superior-inferior direction within the ventral pons (8, 12). We
have been able to reproduce this in normal controls at our institution. The exact pathological correlate and clinical significance
of abnormal or poorly visualized tracts are unclear. Axonal disruption and white matter edema are among the mechanisms that
have been suggested (4).
In view of the potential reversibility of symptoms attributable to persistent mass effect, a decision was made to surgically resect the thrombosed aneurysm sac through a midline
posterior suboccipital craniotomy to correct any possible
brainstem compressive effect. Although the surgery was technically successful, the patient’s clinical status did not improve.
Further follow-up imaging continued to demonstrate no

E794 | VOLUME 58 | NUMBER 4 | APRIL 2006

brainstem infarction. Repeat diffusion tensor imaging was not
interpretable because of susceptibility artifact from surgical
hardware relating to the craniotomy.
In this vein, a potential limitation of our report is the fact
that minor susceptibility effects attributed to the endovascular
coils theoretically could have affected the tractography and
tensor metrics obtained during the initial imaging of our patient. We believe that the diffusion tensor imaging performed
is reliable as tensor metrics, and tractography of the transverse
pontine fibers adjacent to the corticospinal tracts at the same
brainstem level were preserved.
The overall prognosis of locked-in syndrome caused by basilar
artery occlusion is poor, with clinical recovery occurring rarely,
particularly when a vascular etiology is implicated. For patients
with locked-in syndrome, conventional CT and MRI are instrumental in determining the presence and extent of brainstem infarction;
however, as demonstrated by this case (which was diagnostically
confounded by the absence of brainstem diffusion abnormalities as
well as the clinical history of Charcot Marie Tooth Syndrome),
perfusion and diffusion tensor imaging may have an additional role
in confirming an anatomic substrate for the suspected clinical phenomenon and clarifying the pathogenesis and prognosis of patients
with cryptic forms of locked-in syndrome.

REFERENCES
1. Breen P, Hannon V: Locked-in syndrome: A catastrophic complication after
surgery. Br J Anaesth 92:286–288, 2004.
2. Drake CG, Peerless SJ: Giant fusiform intracranial aneurysms: Review of 120
patients treated surgically from 1965 to 1992. J Neurosurg 87:141–162, 1997.
3. Helenius J, Perkio J, Soinne L, Ostergaard L, Carano RA, Salonen O,
Savolainen S, Kaste M, Aronen HJ, Tatlisumak T: Cerebral hemodynamics in
a healthy population measured by dynamic susceptibility contrast MR
imaging. Acta Radiol 44:538–546, 2003.
4. Jellison BJ, Field AS, Medow J, Lazar M, Salamat MS, Alexander AL:
Diffusion tensor imaging of cerebral white matter: A pictorial review of
physics, fiber tract anatomy, and tumor imaging patterns. AJNR
Am J Neuroradiol 25:356–369, 2004.
5. Leon-Carrion J, van Eeckhout P, Dominguez-Morales MR, Perez-Santamaria
FJ: The locked-in syndrome: A syndrome looking for a therapy. Brain Inj
16:571–582,2002.
6. Masuzawa H, Sato J, Kamitani H, Kamikura T, Aoki N: Pontine gliomas
causing locked-in syndrome. Childs Nerv Syst 9:256–259, 1993.
7. Murphy MJ, Brenton DW, Aschenbrener CA, Van Gilder JC: Locked-in
syndrome caused by a solitary pontine abscess. J Neurol Neurosurg Psychiatry 42:1062–1065, 1979.
8. Nagae-Poetscher LM, Jiang H, Wakana S, Golay X, van Zijl PC, Mori S:
High-resolution diffusion tensor imaging of the brain stem at 3 T. AJNR
Am J Neuroradiol 25:1325–1330, 2004.
9. Patterson JR, Grabois M: Locked-in syndrome: A review of 139 cases. Stroke
17:758–764, 1986.
10. Pirzada NA, Ali II: Central pontine myelinolysis. Mayo Clin Proc 76:559–
562, 2001.
11. Plum F, Posner JB: The Diagnosis of Stupor and Coma. Philadelphia, F. A.
Davis Co., 1966.
12. Stieltjes B, Kaufmann WE, van Zijl PC, Fredericksen K, Pearlson GD,
Solaiyappan M, Mori S: Diffusion tensor imaging and axonal tracking in the
human brainstem. Neuroimage 14:723–735, 2001.

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TENSOR IMAGING IN A PATIENT WITH LOCKED-IN SYNDROME

COMMENTS

clinical problems. The authors are encouraged to pursue these studies
in a larger series.

T

he authors describe a patient harboring a difficult fusiform posterior circulation aneurysm that developed a post-procedure,
locked-in syndrome following revascularization and aneurysm/
parent vessel occlusion. Traditional magnetic resonance imaging
(MRI) did not fully explain the patient’s neurological condition, although perfusion and diffusion tensor imaging demonstrated clear
abnormalities in the brainstem.
Fusiform aneurysms of the posterior circulation resulting in brainstem compression unfortunately remain formidable lesions to treat.
The neuroanatomical basis for a locked-in syndrome remains elusive and may be multifactorial. The fact that perfusion and diffusion
tensor imaging may identify anatomical abnormalities not delineated
by conventional magnetic resonance sequences is interesting. The
relative contributions of true ischemic versus non-ischemic events to
fiber disruption is meritorious of further study.
The authors have highlighted the potential importance of advanced
imaging techniques to help explain clinical symptomatology when
conventional methods falter and have highlighted the need for future
investigation in this area.
Aaron S. Dumont
Sagi Harnof
Neal F. Kassell
Charlottesville, Virginia

I

n this case report, the authors describe a 57-year-old male who
developed a locked-in syndrome after treatment of a basilar artery
aneurysm. Conventional MRI techniques were not helpful in explaining the clinical condition. By contrast, imaging abnormalities were
seen on perfusion and diffusion tensor imaging. These techniques can
be used to examine white matter structure and help understand
anatomic organization and neural connection in human brain. This
case report illustrates how advanced neuro-imaging can be applied to

NEUROSURGERY

Peter D. Le Roux
Philadelphia, Pennsylvania

I

n this article, the authors describe a case report of a “locked-in”
patient after an attempt to treat a fusiform basilar aneurysm. During
this period, multiple diagnostic studies were undertaken and MRI
findings, including diffusion tensor imaging and perfusion abnormalities, are described. The paper primarily expresses three major points.
One is that we continue to have great difficulty in effectively treating
these giant fusiform basilar aneurysms with compression of the brainstem. Multiple theories have been espoused and consistent success is
not achieved. In this case, the authors make two attempts to decrease
mass effect but still had progressive fatal dysfunction of the brainstem. Second, the syndrome of “locked-in” described by Plum and
Posner (1), may have multiple etiologies. In this case, the authors
suggest that straightforward ischemia may be augmented by the
presence of mass effect or axonal dysfunction. Finally, the authors
show magnetic resonance perfusion and diffusion tensor imaging to
suggest that there is a differential, at least in this patient, between true
infarct and axonal disruption.
The authors emphasize the finding of disruption of white matter
tracks without diffusion weighted imaging evidence for acute infarction. Such findings would suggest that the multiple etiologies may
lead to the same clinical syndrome. This should encourage clinicians
to attempt to define new treatments for those components that may be
reversible.
Robert J. Dempsey
Madison, Wisconsin

1. Plum F, Posner JB: The Diagnosis of Stupor and Coma. Philadelphia, F. A.
Davis Co., 1966, ed 2, p 24.

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