Extensive Brainstem Ischemia on Neuroimaging Does Not
Preclude Meaningful Recovery from Locked-In Syndrome:
Two Cases of Endovascularly Managed Basilar Thrombosis
Nestor D. Tomycz, MD, Margo B. Holm, PhD, OTR/L, FAOTA, ABDA, Michael B. Horowitz, MD,
Lawrence R. Wechsler, MD, Ketki Raina, PhD, OTR/L, Rishi Gupta, MD, Tudor G. Jovin, MD
From the Department of Occupational Therapy, School of Health and Rehabilitation Services, University of Pittsburgh, Pittsburgh, Pennsylvania (MBH, KR); Department
of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (NDT, MBH); Department of Neurology, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania (LRW, TGJ); Department of Neurology, Michigan State University, Lansing, Michigan (RG).

ABSTRACT
We report 2 patients with angiographically demonstrated basilar artery thrombosis who
received emergent intra-arterial thrombolysis with successful recanalization of the basilar
artery. In the ensuing weeks after the procedure, both patients were in a locked-in state
and had sustained large bilateral regions of pontine ischemia on brain imaging. Following
aggressive supportive care and rehabilitation, outcomes obtained prospectively revealed
that both patients made a remarkable recovery, becoming fully independent with Barthel
scores of 20 and modified Rankin scores of 2.

Key words: Locked-in syndrome, basilar
thrombosis, thrombolysis, ischemia.
Acceptance: Received June 26, 2006,
and in revised form January 28, 2007.
Accepted for publication March 5, 2007.
Correspondence: Address correspondence to Tudor G. Jovin, MD, University of Pittsburgh Medical Center, Center
for Neuroendovascular Therapy, UPMC
Stroke Institute, 200 Lothrop Street,
Suite C-424, Pittsburgh, PA 15213-2582.
E-mail: jovintg@upmc.edu.
J Neuroimaging 2008;18:15-17.
DOI: 10.1111/j.1552-6569.2007.00147.x

Background and Significance
Locked-in syndrome is the neurologic constellation of anarthria,
quadriplegia, horizontal gaze paresis, and preserved consciousness usually engendered by a ventral pontine lesion. The most
common cause of locked-in syndrome is pontine infarction secondary to basilar artery thrombosis.1 Patients with the classic
form of locked-in syndrome can communicate solely through
vertical eye movements and blinking. Mortality reported from
one of the largest series of locked-in patients was 60%,2 but more
recently, 10-year survival rates of 80% have been achieved with
early, intensive rehabilitation.1 It therefore behooves physicians
to make this diagnosis and therefore to distinguish the patient’s
condition from other prognostically distinct states of diminished
responsiveness.
Case series of patients with locked-in syndrome have
reported motor recovery rates ranging from 55% to 91%
in addition to less frequent improvements in respiration,
bladder/bowel continence, swallowing, and verbal communication.3 Moreover, although the mortality of patients with lockedin syndrome has proved highest when the etiology is vascular,
ie, secondary to basilar artery thrombosis, complete or nearcomplete recovery has been reported in patients locked-in following several hours of basilar artery thrombosis.4-7 However,
in these few published reports of vascular locked-in syndrome
reversibility, the extent of brain ischemia is poorly documented
and it is unclear if recovery was associated with rapid (spontaneous or therapeutic) basilar artery recanalization that preserved large brainstem regions or occurred despite severe brainstem ischemia. We present 2 cases of meaningful neurological
recovery in patients who had evidence of extensive bilateral is-

chemic insult to the brainstem and an initial locked-in syndrome
examination after endovascular basilar artery thrombolysis.

Methods
This case series was performed with Institutional Review Board
approval. Patients with locked-in syndrome were retrospectively identified from a prospectively acquired database composed of patients with acute ischemic stroke admitted to the
University of Pittsburgh Medical Center Presbyterian Hospital
stroke service between 2000 and 2003 who were enrolled in the
prospective “stroke outcome study” ongoing at our institution
during that period. Outcomes at 3, 6, 9, and 12 months were
obtained independently from caretakers by a group of nurses
and occupational therapists trained in performing neurological
outcome scales. Clinical and radiological data were obtained
retrospectively through chart review.

Case Report 1
A 46-year-old man with no significant past medical history
developed severe headache and slurred speech. He became
unresponsive and was taken to a local hospital where his neurological exam showed extensor posturing and an absent left
corneal reflex. The patient was transferred to our facility where
he exhibited unresposiveness, abnormal eye movements, and
quadriparesis. Noncontrast head computed tomography (CT)
demonstrated a hyperdense basilar artery. Emergent cerebral
angiography revealed thrombus in the distal two-thirds of the
basilar artery just above the AICA origin (Fig 1), high-grade
stenosis of the right vertebral artery (VA) origin with an occlusive thrombus from approximately the C2-C5 vertebral levels,

◦

Copyright C 2008 by the American Society of Neuroimaging

15

Fig 1. Cerebral angiography (A, B, E, F) diffusion weighted MRI (C, G), and axial FLAIR sequence MRI images (D, H) of patient 1 (A, B, C,
D) and patient 2 (E, F, G, H) showing basilar artery thrombosis, recanalization, and extensive pontine infarctions.

and moderate stenosis of the left VA origin. Approximately
11 hours after ictus, defined as the sudden onset of unresponsiveness, his basilar artery was recanalized to thrombolysis in
myocardial ischemia (TIMI) grade 2 flow (minimal residual
thrombus with brisk antegrade flow) via the administration
of 32 mg tissue plasminogen activator (t-PA) into the occlusive thrombus. Brain magnetic resonance imaging (MRI) obtained 2 days after ictus demonstrated ischemia within large
areas of the pons and extending into the cerebral peduncles
(Fig 1). Magnetic resonance angiogram showed a patent basilar
artery. The patient’s neurological examination confirmed by
several neurologists revealed a locked-in state with preserved
blinking and vertical eye movement superimposed on a background of quadriplegia, anarthria, and horizontal gaze paresis.
The patient was discharged to a standard rehabilitation program after a 3-week hospitalization during which his condition
had not changed significantly. Following discharge he started
to steadily improve and at 6 months after hospitalization, his
Barthel score and modified Rankin scores obtained independently from physician caretakers were 20 and 2, respectively.
Today the patient is fully independent, walks with a cane, and
continues to enjoy activities including hunting, lake fishing, and
woodwork.

Case Report 2
A 27-year-old woman presented to her local hospital with a
2-day history of intermittent vertigo, neck pain, nausea, and
vomiting. Her only medication was an oral contraceptive and
she had no significant past medical history. While being evaluated at the hospital, the patient developed sudden anarthria,
urinary incontinence, and left hemiparesis followed rapidly by
unresponsiveness and decerebrate posturing. Noncontrast head

16

Journal of Neuroimaging Vol 18 No 1 January 2008

CT showed hyperdensity in the lower basilar artery and distal
right vertebral artery. Cerebral angiography showed dissection
of the right VA at the C1-C2 level, a patent left VA, and complete occlusion of the proximal basilar artery (Fig 1). Approximately 7 hours after ictus, the basilar artery was recanalized to
a TIMI grade 2 flow with 22 mg intra-arterial t-PA. Brain MRI
obtained 4 days after ictus showed substantial bilateral pontine as well as cerebellar ischemic lesions (Fig 1). On examination performed by several neurologists, she was locked-in with
preserved vertical eye movements and appropriate blinking
to different commands. Eight days after admission the patient
regained some lateral gaze capability but remained otherwise
unchanged. The patient was discharged to a standard rehabilitation program and eventually became fully independent. Her
recovery was quantified independently of physician caretakers
at 6 months as a Barthel score of 20 and modified Rankin score
of 2. The patient became fully independent and returned to
work as a software instructor. She currently drives a car, walks
with a cane, and is able to engage in about 50% of previous
leisure activities.

Discussion
Although the reversibility of locked-in syndrome has been described, this is the first report of patients achieving functional
recovery from vascular locked-in syndrome in the context
of near-complete pontine ischemic insult on neuroimaging.
Understanding that diffusion weighted imaging hyperintensity
in the setting of acute ischemic stroke may be a reversible
imaging finding, which overestimates final histological infarct
volume, we confirm the impressive magnitude of irreversible
brainstem ischemic damage in these 2 patients by displaying
corresponding regions of hyperintensity on brain MRI FLAIR

(Fluid-attenuated inversion recovery) sequences.8-11 Diffusionperfusion MRI of patients with acute basilar artery occlusion
has revealed that intra-arterial thrombolytic recanalization of
the basilar artery can salvage substantial volumes of hypoperfused brain tissue, preventing the lethality of total basilar artery
territory infarction.12 Our report suggests that early revascularization of basilar artery thrombosis may not spare patients
the morbidity of locked-in state, which may be only temporary,
but may permit them to sustain a recoverable type of basilar
artery stroke limited primarily to paramedian ventral pontine
perforator territory.13
Given the known poor natural history of basilar thrombosis,
the outcomes observed in these 2 cases lends credence to the expectation that the mortality and morbidity of vascular locked-in
syndrome may decline in parallel with technological advances
that enable rapid revascularization of the posterior circulation.
The time window during which recanalization of the basilar
artery remains beneficial is poorly defined. Yet, it is likely that
the time windows for thrombolytic therapy in the basilar circulation are significantly longer than most anterior circulation occlusions. While recent studies have suggested beneficial effects
of recanalization even after 79 hours of basilar thrombosis, our
patients were revascularized relatively early.14 Our study adds
meaningful prospective outcomes to a list of vascular lockedin patients that have been aggressively revascularized. Similar
to patients with intracerebral hemorrhage in whom withdrawal
of care ensures dismal self-fulfilling prophecies,15 it is possible
that the poor outcomes in locked-in patients may in part derive
from a reluctance to provide aggressive care.
Locked-in syndrome is a devastating condition in which
consciousness is preserved despite complete deprivation of
voluntary activity. This report establishes the counterintuitive
potential for good recovery in locked-in patients with earlyrevascularized basilar thrombosis even when MRI shows large
brainstem strokes. Physicians treating this heterogeneous patient population must remain wary of allowing the magnitude
of brainstem ischemia on modern neuroimaging to influence estimates of prognosis and the supportive effort. Identifying those
patients who are most likely to recover and in whom aggressive
and sustained rehabilitative efforts are justified remains a great
challenge.

References
1. Casanova E, Lazzari RE, Lotta S, Mazzucchi A. Locked-in syndrome: improvement in the prognosis after an early intensive mul-

tidisciplinary rehabilitation. Arch Phys Med Rehabil 2003;84:862867.
2. Patterson JR, Grabois M. Locked-in syndrome: a review of 139
cases. Stroke 1986;17(4):758-764.
3. Smith E, Delargy M. Locked-in syndrome. BMJ 2005;330:406409.
4. Mellado P, Sandoval P, Tevah J, Huete I, Castillo L. Intra-arterial
thrombolysis in basilar artery thrombosis. Recovery of two patients with locked-in syndrome. Rev Med Chil 2004;132(3):357360.
5. McCusker EA, Rudick RA, Honch GW, Griggs RC. Recovery from
‘locked-in’ syndrome. Arch Neurol 1982;39(3):145-147.
6. Cabezudo JM, Olabe J, Lopez-Anguera A, Bacci F. Recovery from
locked-in syndrome after posttraumatic bilateral distal vertebral
artery occlusion. Surg Neurol 1986;25(2):185-190.
7. Wijdicks EFM, Nichols DA, Thielen K, Fulgham JR, Brown RD Jr,
Meissner I, Meyer FB, Piepgras DG. Intra-arterial thrombolysis in
acute basilar artery thromboembolism: the initial Mayo experience.
Mayo Clinic Proceedings 1997;72:1005-1013.
8. Guadagno JV, Warburton EA, Aigbirhio FI, Smielewski P, Fryer
TD, Harding S, Price CJ, Gillard JH, Carpenter TA, Baron
JC. Does the acute diffusion-weighted imaging lesion represent
penumbra as well as core? A combined quantitative PET/MRI
voxel-based study. J Cereb Blood Flow Metab 2004;24(11):12491254.
9. Noguchi K, Ogawa T, Inugami A, Fugita H, Hatazawa J, Shimosegawa E, Okudera T, Uemura K, Seto H. MRI of acute cerebral
infarction: a comparison of FLAIR and T2-weighted fast spin-echo
imaging. Neuroradiol 1997;39:406-410.
10. Ritzl A, Meisel S, Wittsack H, Fink GR, Siebler M, Modder U, Seitz
R. Development of brain infarct volume as assessed by magnetic
resonance imaging (MRI): follow-up of diffusion-weighted MRI lesions. J Magn Reson Imaging 2004:20:201-207.
11. Kidwell CS, Saver JL, Starkman S, Duckwiler G, Jahan R, Vespa
P, Villablanca JP, Liebeskind DS, Gobin YP, Vinuela F, Alger JR.
Late secondary ischemic injury in patients receiving intra-arterial
thrombolysis. Ann Neurol 2002;52:698-703.
12. Thajeb P, Lie LK, Chang TR. Types of basilar artery syndrome:
clinicoradiologic correlation. Angiology 1993;44:368-375.
13. Cross DT, Moran CJ, Akins PT, Angtuaco EE, Diringer MN. Relationship between clot location and outcome after basilar artery
thrombolysis. Am J Neuroradiol 1997;18:1221-1228.
14. Ostrem JL, Saver JL, Alger JR, Starkman S, Leary MC, Duckwiler G, Jahan R, Vespa P, Villablanca JP, Gobin YP, Vinuela F, Kidwell CS. Acute basilar artery occlusion: diffusionperfusion MRI characterization of tissue salvage in patients
receiving intra-arterial stroke therapies. Stroke 2004;35:e30e34.
15. Becker KJ, Baxter AB, Cohen WA, Bybee HM, Tirschwell DL,
Newell DW, Winn HR, Longstreth WT Jr. Withdrawal of support
in intracerebral hemorrhage may lead to self-fulfilling prophecies.
Neurology 2001;56(6):766-772.

Tomycz et al: Brainstem Ischemia Does Not Preclude Meaningful Recovery from Locked-In Syndrome

17