Keywords
Brain - COVID-19 - ECD - severe acute respiratory syndrome coronavirus-2 - transient
antiphospholipid
Introduction
COVID-19 is a viral respiratory disease caused by severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2). Most patients are either asymptomatic or show mild respiratory
symptomatology, however, a minority can present acute respiratory distress syndrome
and cardiovascular and neurologic manifestations including loss of smell and taste.[[1]]
Neurologic manifestations associated with COVID-19 encompass a wide variety of symptoms
with different proposed etiologies. The most common manifestations are headache and
anosmia but, less commonly, patients may also present seizures,[[2]] ischemic stroke,[[3]] and GuillainBarre syndrome.[[4]],[[5]]
Determining the etiology of serious neurologic manifestations, such as seizures, in
patients with COVID-19 can be a challenging undertaking as their pathophysiologic
mechanisms are often unclear. Some authors have proposed different mechanisms for
seizures including cytokine storm, breakdown of bloodbrain barrier, electrolyte imbalance,
and abnormal coagulation, among others,[[2]] suggesting their manifestation may be multifactorial.
We present a case of a patient with recurrent self-resolving episodes of seizures
and left hemiplegia, where the brain of 99mTc-bicisate (ECD)-single-photon emission computerized tomography/computerized tomography
(SPECT/CT) was successfully utilized for diagnosis and management guidance of COVID-associated
ischemia secondary to flare antiphospholipid syndrome.
Case Report
A 35-year-old male patient without major cardiovascular risk factors presented after
eight days of recurrent episodes of left hemiplegia, facial droop, and dysarthria.
Each spell was sudden, not associated with aura- or interictal-like symptomatology
and self-resolved within 10–20 min of onset. Initial diagnostic work up including
electroencephalogram and CT brain perfusion scan was unremarkable for epileptogenic
foci. Magnetic resonance angiography (MRA) [[Figure 1]] of the brain revealed an equivocal irregularity in the M1 segment of the right
middle cerebral artery, that was favored to be artifactual in an otherwise normal
scan.
Figure 1 (a) brain CT perfusion scan was unremarkable for epileptogenic foci. (b) Magnetic
resonance angiography of the brain revealed an equivocal irregularity in the M1 segment
of the right middle cerebral artery, as shown on axial view (b) and maximum intensity
projection (c), which was favored to be artifactual in etiology in an otherwise-normal
magnetic resonance angiography
Following consultation with the nuclear medicine department, an “intra-ictal” ECD
Brain SPECT/CT was requested for evaluation of a suspected epileptogenic focus [[Figure 2]]. Approximately 1-minute following initiation of left hemiplegia, the patient received
approximately 1,110 MBq of ECD intravenously. Attenuation-corrected SPECT/CT was acquired
approximately 45 minutes following administration of ECD, which revealed relatively
decreased perfusion in the distribution of the right middle cerebral artery. Retrospectively,
the M1 irregularity seen in the right middle cerebral artery on MRA was believed to
correspond to a real lesion.
Figure 2 Transaxial fused single-photon emission computerized tomography/computerized tomography
(a) and single-photon emission computerized tomography (b), and transcoronal single-photon
emission computerized tomography (c), showed relatively decreased perfusion in the
distribution of the right middle cerebral artery
The patient underwent additional work up with beta-2 glycoprotein and cardiolipin
antibodies which were positive. Additional testing revealed positive IgG and IgM antibodies
for SARS-CoV2 indicating convalescent stage of COVID-19,[[6]] although the patient denied any recent respiratory or other COVID-related symptomatology.
The patient was treated with a course of corticosteroids leading to complete resolution
of symptoms and progressive decrease of antiphospholipid antibodies and has remained
asymptomatic for several months after this episode.
Discussion
Prior case series have shown an increased incidence of stroke[[3]] and deep venous thromboembolism, including younger patients,[[7]] suggesting an increased risk for hypercoagulable states such as antiphospholipid
syndrome. In the case presented, brain perfusion ECD-SPECT/CT evaluation supported
a diagnosis of cerebral ischemia rather than epilepsy in a patient with nonspecific
neurologic manifestations and largely negative neurologic work up – in the setting
COVID-19 and newly-elevated antiphospholipid markers.
Antiphospholipid syndrome has been associated with viral infections,[[8]] including COVID-19.[[9]],[[10]],[[11]] A case series of 86 critically-ill patients with COVID-19 reported a 65% incidence
of neurologic manifestations and a higher prevalence of antiphospholipid antibodies
in those with ischemic stroke.[[12]] Other authors have suggested various pathophysiologic mechanisms leading to stroke
in patients with COVID-19 including coagulation pathway activation, virus-induced
vascular inflammation, and myocardial injury.[[13]]
A case series could be useful to determine the role of brain ECD SPECT/CT in the evaluation
of COVID-19 associated with nonspecific neurologic manifestations. As in this case,
the use of brain perfusion scintigraphy may be individualized and particularly considered
in patients with equivocal diagnostic work up.
Declaration of patient consent
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understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.