Keywords
neuroaspergillosis - brain abscess - COVID-19 - aspergillosis
Palavras-chave
neuroaspergilose - abscesso Encefálico - COVID-19 - aspergilose
Introduction
Cerebral aspergillosis is a rare infectious condition that accounts for ∼ 5% to 10%
of all fungal infections of the central nervous system (CNS).[1]
The incidence of patients diagnosed with this pathology has increased in recent years
due to the rise in the number of solid organ and bone marrow transplants, consequently
increasing the immunosuppressed population.[2] Other immunosuppressive states that present the risk of developing the disease are
AIDS, alcohol abuse, diabetes, and hematologic diseases with neutropenia.[3]
[4]
The reports of patients with an intact immune system who manifest this infection in
the brain are rare. However, when reviewing in detail the history of these patients,
it is possible to identify that there was some factor promoting transient immunosuppression,
such as the use of chemotherapy, high doses of corticosteroids or poor glycemic control.[5]
In the present paper, we report the case of a man with no previous comorbidities whose
only immunosuppression factor in his history was the use of corticosteroids for the
treatment of coronavirus disease 2019 (COVID-19).
Case Report
A 64-year-old male rural worker, previously healthy, started to experience changes
in his mental state with bradypsychism and ideomotor apraxia. He had a history of
infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for ∼ 2
months, with hospitalization in another service. According to the discharge report,
he did not need ventilatory support but received a course of corticosteroid therapy
with dexamethasone during the 7-day period he was hospitalized and for another 12
days after discharge. Since then, he started to have a lack of glycemic control, and
treatment with metformin was started.
Due to the progression of the neurological condition, he was admitted to a local hospital,
and underwent an investigation with brain magnetic resonance imaging (MRI) scans that
showed multiple lesions in both cerebral hemispheres, characterized by annular contrast
enhancement and diffusion restriction, suggesting brain abscesses ([Fig. 1]). Empirical treatment was started with vancomycin, ceftriaxone, metronizadole, and
dexamethasone 4 mg 4 times a day for the vasogenic edema caused by the lesions.
Fig. 1 Brain magnetic resonance imaging (MRI) scan showing\ multiple hypointense brain lesions
with a halo of enhancement and surrounding edema on a T1-weighted image (above). Diffusion-weighted
imaging (DWI) (below) showing hyperintense lesions.
He was transferred to the neurosurgery service of our hospital with a proposal for
a surgical approach to the brain injuries. The antibiotic therapy regimen was expanded
to meropenem and vancomycin. We performed a complementary investigation with serology
for HIV, hepatitis B, and C, all of which were negative. Chest X-ray ([Fig. 2]) and transthoracic echocardiography did not identify abnormalities. A stereotaxic
biopsy of one of the lesions was then performed with the aspiration of purulent content
([Fig. 3]).
Fig. 2 Chest X-ray without visible changes suggestive of aspergillus pneumonia.
Fig. 3 Intraoperative macroscopic aspect of the aspirate of one of the brain lesions.
He remained hospitalized in the Intensive Care Unit (ICU) postoperatively, receiving
empirical antibiotic therapy until we received the results of the cultures. He was
discharged to the ward on the second postoperative day, in good clinical condition.
The results of the pathological examination and cultures were available on the fifth
day after surgery, and were compatible with a fungal infection, and Aspergillus fumigatus was identified as the etiological agent ([Fig. 4]). Endovenous voriconazole was indicated.
Fig. 4 Microscopic analysis sowing inflammatory infiltrate permeated by multiple neutrophils
in hematoxylin and eosin (H&E) staining (above). Below we can see Aspergillus fumigatus hyphae in Grocott silver stain.
On the seventh day after surgery, his neurological condition worsened, and he experienced
sudden sensorium alteration. An emergency cranial computed tomography (CT) scan was
performed, which showed recurrence of the lesion that had been surgically aspirated
and important cerebral edema with midline deviation ([Fig. 5]). As the patient's score on the Glasgow Coma Scale (GCS) was of 3 and bilateral
mydriasis had no reactivity, we did not indicate a new surgical approach. After two
days of hospitalization in the ICU, the criteria to determine brain death were met.
Fig. 5 Head computed tomography scan performed on an urgent basis after the patient's neurological
worsening. We can see the permanence of hypodense content with annular contrast uptake,
perilesional edema, and midline shift.
Discussion
After the respiratory tract, the brain is the site most affected by invasive aspergillosis.[4] The main etiological agent is A. fumigatus, with cases of infection by A. nidulans, A. terreus, or A. flavus
[3]
[4] Presentations in the CNS can be due to meningitis, granulomatous reaction with abscess,
or vasculopathy.[1] Aspergillus hyphae have tropism for vessels and can produce thrombosis, infarction,
hemorrhagic changes, or mycotic aneurysms.[3]
[6] Meningeal lesions usually represent contamination by contiguity after infection
of the paranasal sinuses, mastoiditis, trauma, or neurosurgery.[2] Parenchymal abscesses are most commonly located in the cerebral hemispheres; however,
they may also present in the basal ganglia, corpus callosum, thalamus, or perforating
artery territory, suggesting hematogenous dissemination.[2]
[3]
The clinical presentation is variable, and localized neurological manifestations may
be observed. Ruhnke et al.[3] reviewed the results of 4 studies on clinical manifestations of cerebral aspergillosis,[7]
[8]
[9]
[10] totaling 90 patients. The most common symptoms were persistent fever, changes in
mental status, and seizures.[3] Headache, vomiting, and papilledema with signs of intracranial hypertension may
also be observed.
The MRI findings are similar to a common pyogenic abscess, with a hypodense lesion
on T1, hyperdense on T2, ring contrast-enhancing, surrounding cerebral edema, and
with diffusion restriction. The analysis of the cerebrospinal fluid (CSF) usually
shows pleocytosis with a slight increase in protein, and the aspergillus antigen,
galactomannan, can be found.[1]
[11]
The definitive diagnosis is histopathological; however, it is usually not possible
to perform a surgical approach to obtain material for analysis, given the severity
that many patients present.[3]
The treatment commonly employed involves a combined approach of surgical evacuation
and prolonged antifungal administration.[4]
[12]
[13]
[14] There is no consensus regarding the best surgical strategy, since most studies[2]
[4]
[6]
[7] [superscript] are small retrospective series. However, the most adopted approach
in cases of location in an eloquent area is minimally-invasive aspiration by the stereotaxic
method or by neuronavigation. In cases in which resection is feasible, a more extensive
surgery should be performed.[1]
The first-line antifungal therapy consists of voriconazole; however, there are reports[1]
[4]
[15] of successful treatments with new-generation azole agents, liposomal amphotericin
B, caspofungin, or micafungin. The proposed duration of the treatment varies in the
literature and can be influenced by the type of surgery performed. Shorter treatment
regimens are employed in cases in which total lesion resection has been performed,
with some institutions describing 6 months of therapy with satisfactory results. In
cases of subtotal resection, a regimen of 12 to 18 months is advocated.[1]
Despite the appropriate therapy, the disease has an unfavorable prognosis, with reported
mortality rates of 10% to 20% in immunocompetent patients, and of 85% to 100% in immunosuppressed
patients.[2]
Conclusion
In the case herein reported, an important factor in the previous pathological history
was the recent infection by COVID-19. Despite being a disease that has emerged recently,
there are already several studies on the manifestations of the virus in the CNS. Neurological
involvement may be secondary to the systemic proinflammatory state that may develop
in some infected patients, with a predisposition to endothelial dysfunction and prothrombotic
events.[16] There are also changes directly caused by the presence of the virus in the nervous
system, explained by the binding of viral proteins to neuronal and glial receptors,
leading to viral encephalitis, meningoencephalitis, Guillain-Barré syndrome, and seizures.[17]
Fungal brain abscess in an immunocompetent patient was probably a consequence of a
combination of factors such as hospitalization, microvascular alterations caused by
the virus, and prolonged use of corticosteroids. We found sparse similar reports in
our research,[18]
[19] which enabled us to raise the hypothesis that despite being a rare condition, it
can also be a poorly-recognized change, due to the severity that many patients evolve
with the need for ventilatory support and high doses of sedatives, making it difficult
to diagnose neurological changes.
A postmortem study would enable a better understanding of the pathophysiological mechanisms
responsible for brain involvement; however, this was not an option accepted by the
patient's family.
