Neurocrit Care
https://doi.org/10.1007/s12028-020-00934-2

NEURO-IMAGES

Another Pitfall in Brain Death Diagnosis:
Return of Cerebral Function After Determination
of Brain Death by Both Clinical and Radionuclide
Cerebral Perfusion Imaging
Julius Gene S. Latorre1* , Elena B. Schmidt1 and David M. Greer2
© 2020 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society

Introduction
Brain single-photon emission computed tomography
(SPECT) is a noninvasive ancillary test used in selected
patients in the determination of brain death (BD) with
reported 100% specificity [1]. We report a case of falsepositive brain SPECT imaging in a patient who fulfilled
clinical criteria (minus apnea testing) for BD but who
subsequently regained some cerebral function.
Case Report
A 59-year-old man suffered catastrophic brain injury due
to a spontaneous intracerebral hemorrhage likely secondary to uncontrolled hypertension (See Fig. 1). CT angiography revealed no aneurysm or vascular malformation.
Repeat head CT the next day (See Fig. 2) showed worsening cerebral edema, herniation and mass effect. The
patient remained unresponsive off all sedation except for
right lower extremity withdrawal to stimulation. The next
day, this movement was no longer observed.
Clinical Neurological Examination
Clinical BD testing was performed based on our institutional protocol (See Appendix 1), adapted from the 2010
American Academy of Neurology guidelines [2].

*Correspondence: latorrej@upstate.edu
1
Department of Neurology and Neurosurgery (UH‑7134), SUNY Upstate
Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
Full list of author information is available at the end of the article

A board certified neurointensivist performed the
neurologic examination. Otoscopic examination
showed normal tympanic membranes bilaterally. Cranial nerve examination showed fixed dilated pupils at
6 mm bilaterally using bright LED light, absent corneal reflexes using a sterile cotton swab, absent oculocephalic and oculovestibular reflexes, absent cough
and gag reflexes, absent spontaneous respirations,
absent grimace to supraorbital pressure, absent motor
response to central and peripheral noxious stimulation. Apnea testing was deemed unsafe due to hemodynamic instability requiring multiple vasopressors
(norepinephrine and vasopressin). Therefore, a brain
SPECT was obtained within 1 h of completing the clinical examination, with no alterations in his management in that intervening time.

Nuclear Medicine Procedure
Radiopharmaceutical preparation The Tc-99mBicisate (Neurolite, Du Pont Merck Pharmaceutical
Company, Billerica, MA, USA) was prepared and
stabilized according to manufacturer specification,
and 1.1038 Gbq (27.4 mCi) of Tc-99m Bicisate was
used.
Study acquisition Scintigraphy was performed according to the Practice Parameters and Technical Stand-

Fig. 1 CT scan on admission (2 h after event) A noncontrast CT brain obtained 2 h from last known well showing a large intraparenchymal
hematoma measuring 6.4 × 4.5 cm centered in the right basal ganglia extending into the right temporal lobe into the middle cranial fossa. There
was a separate focus of intraparenchymal hemorrhage just medial to this large hematoma measuring 9.3 × 1.1 cm. There were bilateral subdural
hematomas, right greater than left, with the right measuring 5 mm in greatest thickness and the left measuring 2 mm in greatest thickness. Scat‑
tered areas of subarachnoid hemorrhage were identified overlying the right cerebral hemisphere. There was significant mass effect on the adjacent
brain parenchyma in the right lateral ventricle, which was partially effaced. There was approximately 1.1 cm midline shift to the left of the level of
the lateral ventricles. Right uncal herniation was noted

ards for the performance of SPECT imaging as recommended by the American College of Radiology (ACR)
[3], 51 h from symptom onset with the patient supine,
including the head and neck in the gamma camera’s

field of view. For additional details of the study acquisition, please refer to “Appendix 2”.

Fig. 2 Follow-up CT scan (17 h after event) A noncontrast CT brain obtained 17 h from last known well showing the large intraparenchymal hema‑
toma along the right temporal and insular region, with compression of the lateral ventricle, midline shift causing leftward subfalcine herniation.
Both transtentorial and tonsillar herniations were present

Fig. 3 Cerebral perfusion scintigraphy performed 51 h after event (A-coronal, B-axial, C-sagittal view). The absence of Tc-99m Bicisate uptake in the
cerebral hemispheres and posterior fossa on static images was interpreted as consistent with BD. A nuclear medicine attending physician evalu‑
ated and interpreted the study. The images were reviewed independently and in a blinded fashion in a separate academic institution by attending
nuclear medicine physicians

BD Determination and Hospital Course
The patient was declared dead after the brain SPECT
result was finalized documenting the absence of

radionuclide uptake intracranially (See Fig. 3), and the
family subsequently consented to organ donation. The
following morning, the nurse reported a cough response.

Repeat assessment confirmed the presence of cough,
intermittent spontaneous respirations and extensor posturing of the right arm and leg to noxious stimulation.
The family was informed of the new findings, but before
any further decisions could be made, the patient developed a generalized seizure followed by ventricular tachycardia and cardiac arrest. No autopsy was performed.

Discussion
This is the first report of a false-positive brain SPECT in
a BD patient who subsequently exhibited indisputable
brainstem function (cough reflex, spontaneous respirations, extensor motor response). Although the reported
generalized seizure could have represented cortical activity, convulsive-like movement due to brainstem irritation
was another possibility.
Until now, there have been no reports of false-positive
brain SPECT using diffusible radiopharmaceutical tracers [4] in a patient who did meet the clinical criteria for
BD when strict procedural parameters for radionuclide
scanning as recommended by ACR were performed.
Appropriate quality measures in the preparation of
the radiopharmaceutical agent were an issue with Tc99m-HMPAO [5], but not with the more stable Tc99m
Bicisate. Five cases of false positive radionuclide blood
flow studies using nondiffusable radiopharmaceutical tracers were reported [6], and another was retracted
due to inappropriate interpretation [7]. Several erroneous reports of false-positive brain SPECT using diffusible radiopharmaceutical tracers were likely due to the
absence of a lateral view to examine the posterior fossa
and brainstem [4, 8], or due to misinterpretation of a spinal reflex [9].
It is unclear what mechanism was in our patient to
explain the return of brainstem function. The patient
was examined for BD approximately 10 h after the
last remaining brainstem reflex disappeared. Arrest of
cerebral blood flow occurs when the intracranial pressure rises to or above the mean arterial pressure. This
process likely follows a continuum with progressive
rostrocaudal brain herniation. Although unlikely, the
intracranial pressure in our patient may have decreased
with continued management for organ donation purposes, allowing return of intracranial flow and regaining
of brainstem function. Alternatively, the cerebral perfusion scan may not have detected residual brainstem viability. We performed our radionuclide scan following
the ACR recommendations using diffusible tracers and
obtained both planar and SPECT images to better view
the brainstem. Another potential confounder was the

possibility of nonconvulsive status epilepticus masking clinically observable brain function. Our patient did
not have any electroencephalogram. However, ictal foci
would generally appear hypervascular on brain SPECT
imaging [10]. The possibility of residual sedative effect
seems unlikely as well since the patient had small doses
of sedating drugs during the initial management on
the field (2 mg lorazepam, 2 mg IV midazolam, 30 mg
etomidate, 100 mcg fentanyl, and 200 mg succinylcholine for intubation, and infusion of propofol at rate of
25 mcg/kg/min for 60 min), with no additional doses
from admission to the time of BD testing, an interval of
50 h. Unfortunately, the BD testing done on this patient
was limited by the absence of apnea testing due to the
persistent hemodynamic instability and requirement
for multiple vasopressors.
In conclusion, we reaffirm that BD should remain a
clinical diagnosis performed by experienced providers. We also reaffirm the importance of performing the
apnea test if the patient can be hemodynamically stabilized using vasopressors and/or fluids. However, when
the clinical assessment for BD cannot be completed
due to inability to perform an apnea test or other key
aspects of the clinical examination, an additional waiting period from the time of loss of brainstem function to the initiation of BD testing may be warranted
prior to doing ancillary testing, unless demonstration
of intracranial pressure greater than or equal to mean
arterial pressure for an extended period of time can be
done. Moreover, if using nuclear imaging, SPECT imaging in addition to planar imaging is recommended.
Author details
1
Department of Neurology and Neurosurgery (UH‑7134), SUNY Upstate Medi‑
cal University, 750 East Adams Street, Syracuse, NY 13210, USA. 2 Department
of Neurology, BU School of Medicine, Boston, MA, USA.
Author Contributions
JGSL, EBS, and DMG were involved in conception and design of the study.
JGSL and EBS were involved in acquisition and analysis of data. JGSL, EBS,
and DMG were involved in drafting a significant portion of the manuscript
and figures. JGSL, EBS, and DMG were involved in revising the manuscript for
important intellectual content.
Source of Support
No financial support was obtained for this manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors do not have any conflict of interest to disclose.
Ethical approval
This article does not contain any studies with human participants performed
by any of the authors.

Appendix 1: SUNY Upstate Brain Death Checklist

Appendix 2: SPECT Technical Detail

The data were acquired using a triple head gamma camera (Trionix, Triad XLT) equipped with low-energy
high-resolution parallel beam collimators in a 128 × 128
detector element matrix over 360 degree orbits, with
120 views obtained at 3-degree intervals for 30 s per
view following a circular orbit with a radius of 218 mm.
The photopeak energy setting was at 140 keV with an
18% window. Transaxial images were reconstructed in
a 128 × 128 matrix with attenuation correction and collimator modeling and 3.2-mm cubic voxels using the
OSEM algorithm in ten iterations, OS = 30, a Butterworth post-filter (order = 5, cutoff = 1.0 cycle/cm). The
reconstructed system resolution was approximately
12 mm full width at half maximum (FWHM). The images
were viewed in the usual three orthogonal planes (coronal, sagittal, and transaxial) and as maximum intensity
projection objects. Special care was taken to obtain good
visualization of the posterior fossa and brainstem.

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