CLINICAL REPORT

Locked-In Syndrome Due to Invasive Fungal Rhinosinusitis
in an Immunosuppressed Patient
Nathan P. Young, DO, P. James B. Dyck, MD, and Eelco F. M. Wijdicks, MD

Background: The locked-in syndrome is typically caused by basilar
artery thrombosis, resulting in ventral pontine infarction. Infectious
basilar arteritis is a rare alternative etiology.
Case Summary: We present a 24-year-old female with a prodrome
of facial pain without fever or meningismus, who developed a
locked-in syndrome due to an invasive fungal infection after bone
marrow transplantation. The clinical course and neuroimaging demonstrating sinusitis with adjacent pontine infarction but without basilar
artery thrombosis are presented. The infectious differential diagnosis
and management of invasive fungal infection are discussed.
Conclusion: Facial pain without fever or meningismus may be an
early symptom of invasive fungal rhinosinusitis, which may involve
small basilar pontine perforating arteries, leading to a locked-in
syndrome in immunosuppressed patients. Early recognition and
treatment may prevent life-threatening neurologic complications.
Key Words: locked-in syndrome, invasive fungal rhinosinusitis
(The Neurologist 2007;13: 158 –160)

T

he locked-in syndrome classically localizes to the ventral
pons, where a lesion disrupts the corticospinal and bulbar
fibers serving voluntary movement but spares the dorsal
nuclei of the ascending reticular activation system, permitting
consciousness.1 The most common cause of the locked-in
syndrome is an embolus to the basilar artery.2 Infectious
causes are very uncommon but may lead to basilar arteritis
and secondary infarction. We present a fulminant course of
fungal rhinosinusitis encroaching on the basilar artery in an
immunosuppressed patient.

CASE REPORT
A 24-year-old female presented to the hematology
clinic with diplopia 107 days after a mismatched, unrelated
bone marrow transplantation for acute myelogenous leukemia
in remission. She was admitted to the hospital for further
evaluation.

From the Mayo Clinic College of Medicine, Department of Neurology,
Rochester, MN.
Reprints: Eelco F. M. Wijdicks, MD, Mayo Clinic College of Medicine,
Division of Critical Care Neurology, Department of Neurology, W8B,
200 First Street SW, Rochester, MN 55905. E-mail: wijde@mayo.edu.
Copyright © 2007 by Lippincott Williams & Wilkins
ISSN: 1074-7931/07/1303-0158
DOI: 10.1097/01.nrl.0000263701.15487.97

158

Two weeks prior to presentation, she reported a constant right anterior facial pain, without numbness or paresthesia. This aching pain was worse when lying supine and
became bilateral 2 days prior to admission.
Her posttransplantation course was complicated by
CMV viremia, with no detectable serum CMV DNA on
valganciclovir. She required tacrolimus and prednisone to
control graft-versus-host disease of the skin and intestinal
tract. She was compliant with prophylactic voriconazole and
pentamidine.
A contrasted CT scan of the head demonstrated an
opacified right sphenoid sinus without enhancement. On
admission the leukocyte count was 1.7 ⫻ 10(9)/L without
neutropenia, with a platelet count of 26 ⫻ 10(9)/L and
hemoglobin 12.9 g/dL. A tacrolimus level was 21.3 ng/mL.
After platelet transfusion, a lumbar puncture was performed,
and then empiric intravenous amphotericin B, acyclovir, and
meropenem were initiated. The CSF showed 14 polymorphonuclear cells, protein 56 mg/dL, and glucose 56 mg/dL, with
normal gram stain, cytology, and flow cytometry. CSF
VRDL, cryptococcal antigen, and PCR studies for CMV,
HSV, VZV, and EBV were negative. There was no growth of
CSF or blood bacterial, fungal, viral, and mycobacterial
cultures after 1 month.
She developed progressive cranial neuropathies and
quadriparesis. Brain and neck CT angiogram was negative for
basilar artery narrowing or thrombosis. Sixteen hours after
the onset of diplopia, she was intubated, breathing above the
ventilator, and awake. She followed commands to blink her
eyelids and look vertically but was unable to look horizontally. She blinked to threat bilaterally. She had partial bilateral ptosis, with normal pupils. Third cranial nerve function
was relatively preserved, with passive head turning. Corneal
responses were absent. A weak gag response was present to
deep suctioning. She was unable to move her face or limbs.
There was symmetric extensor posturing to pain. Reflexes
were normal in the upper extremities, reduced at the patellae,
and absent at the ankles. There was no response to plantar
stimulation bilaterally.
Brain MRI revealed a ventral pontine infarction with
adjacent sinusitis (Fig. 1). The basilar artery appeared irregular but remained without focal narrowing or thrombosis.
Sphenoidotomies with biopsy revealed pathologic evidence
of invasive fungus, likely mucormycosis; however, the organism eluded precise identification. Intravenous and intrasinus amphotericin B were continued.
The Neurologist • Volume 13, Number 3, May 2007

The Neurologist • Volume 13, Number 3, May 2007

Locked-In Syndrome Due to Invasive Fungal Rhinosinusitis

the patient, support was withdrawn, and she died 20 days
after admission.

DISCUSSION
This case of a locked-in syndrome secondary to invasive fungal rhinosinusitis serves as a reminder of the angioinvasive nature of this infection, for which a high level of
suspicion is required for early diagnosis.3,4 In this case, the
fungal infection likely involved the small pontine perforating
arteries, leading to ventral pontine infarction. We are not
aware of another case evolving to a locked-in syndrome.

The fungal infection likely involved the small
pontine perforating arteries, leading to ventral
pontine infarction.

FIGURE 1. Locked-in syndrome 1 day after admission. Axialdiffusion-weighted MRI shows restricted diffusion in the ventral pons. The corresponding ADC signal was decreased.

Over several days, the neurologic examination remained unchanged. However, serial brain MRI demonstrated
progression of sinus and brainstem disease (Fig. 2). Communication with the patient through eye blinking became unreliable because of delirium. Based on prior conversations with

This case also highlights the importance of recognizing
the locked-in syndrome in which a patient may appear comatose but is actually cognitively spared but unable to move
or verbally communicate. If possible, communication with
the patient through eye movements should be attempted.
Various infectious causes of basilar arteritis and secondary infarction are documented mainly in case reports. In
addition to mucormycosis,5 other fungal infections presenting
similarly include aspergillosis, candidosis, coccidioidomycosis, actinomycosis, and cryptococcosis. Nonfungal organisms
reported include Mycobacterium tuberculosis, Treponema
pallidum, Borrelia burgdorferi, Streptococcus milleri, Streptococcus anginosis, Streptococcus pneumoniae, Neisseria
meningitides, and varicella zoster virus. Most cases of fungal
infection report associated fever and meningismus, features
notably absent in our case.
In this case and others,3,6 facial pain was a harbinger of
cerebral involvement. Our patient presented with normal
facial sensation and corneal reflexes, suggesting the pain was
due to sinusitis and not trigeminal neuropathy. Clinicians
therefore should consider such a nonneurologic cause in the
immunosuppressed patient with facial pain.

Once an invasive fungal infection is suspected,
empiric intravenous antifungal therapy and
early sinus debridement with diagnostic biopsy
are indicated.
FIGURE 2. Locked-in syndrome 10 days after admission. Axial FLAIR MRI shows increased signal in the sinuses with adjacent pontine infarction and now involvement of the right
temporal lobe.
© 2007 Lippincott Williams & Wilkins

Once an invasive fungal infection is suspected, empiric
intravenous antifungal therapy and early sinus debridement
with diagnostic biopsy are indicated.3 Amphotericin B is the

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Young et al

empiric treatment of choice as voriconazole-resistant zygomycosis is well recognized.7 In this case, MR imaging with
gadolinium was most sensitive for documenting the precise
location and extent of disease. Early recognition and treatment of invasive rhinosinusitis may halt or prevent fatal CNS
complications.3,4,6,7
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Davis; 1966.
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3. Pagano L, Offidani M, Fianchi L, et al. Mucormycosis in hematologic
patients. Haematologica. 2004;89:207–214.
4. Sundaram C, Mahadevan A, Laxmi V, et al. Cerebral zygomycosis.
Mycoses. 2005;48:396 – 407.
5. Calli C, Savas R, Parildar M, et al. Isolated pontine infarction due to
rhinocerebral mucormycosis. Neuroradiology. 1999;41:179 –181.
6. Drakos PE, Nagler A, Or R, et al. Invasive fungal sinusitis in patients
undergoing bone marrow transplantation. Bone Marrow Transplant.
1993;12:203–208.
7. Kontoyiannis DP, Lionakis MS, Lewis RE, et al. Zygomycosis in a
tertiary-care cancer center in the era of Aspergillus-active antifungal
therapy: a case-control observational study of 27 recent cases. J Infect
Dis. 2005;191:1350 –1360.

© 2007 Lippincott Williams & Wilkins