Abstract

Background: Central nervous system involvement due to aspergillosis is an extremely serious entity, particularly in patients with severe neutropenia, hematological diseases, or post-transplant cases. Immunocompetent patients can be infected by intense exposure, particularly iatrogenic after invasive procedures.

Case Description: We present the case of a 26-year-old male with a 1 year appendectomy background, which required epidural anesthesia. After that surgery, insidious headache presented, requiring mild analgesics for adequate control. In the following weeks, headaches increased and tomographic imaging revealed hydrocephalus. A ventriculoperitoneal shunt was placed, and empirical treatment for neurocysticercosis was established, but diagnosis was never confirmed. Sequentially, shunt dysfunction occurred twice, for which shunt replacement was performed. Cerebrospinal fluid and shunt’s catheter were cultured. Some days later, a filamentous fungus was isolated and finally identified as Aspergillus sp. Intravenous amphotericin B and fluconazole at therapeutic dosage were administered; however, a torpid clinical evolution was observed. After a 2-week antifungal scheme, the fungus was identified as Aspergillus terreus. The patient developed sudden rostrocaudal deterioration. Computed tomography imaging was done, revealing a 70 cc hematoma in the right operculoinsular region, midline shift, and a 9 mm saccular aneurysm at the bifurcation of the middle cerebral artery.

Conclusion: Cerebral aspergillosis is a serious disease with high mortality in patients, particularly those without identifiable risk factors. The iatrogenic forms are serious, due to the delay of clinical diagnosis. It is important to have a high index of suspicion in patients with a history of invasive procedures such as epidural anesthesia or surgery, and who develop a persistent chronic headache or chronic meningitis.

Keywords: Aneurysm, Aspergillus terreus, Mycotic

INTRODUCTION

In 1885, William Osler was the first to describe an aortic aneurysm secondary to infectious endocarditis.[ 21 ] Since then, infectious, or so-called “mycotic,” cerebral aneurysms are uncommon and represent around 1% of all intracranial aneurysms.[ 2 , 12 ] Although the term mycotic refers to fungal infections, most of these aneurysms are caused by bacterial agents, being viridans group streptococci and Staphylococcus aureus, the two most common pathogens, secondary to infectious endocarditis that causes septic embolism. Fungal agents that can cause mycotic aneurysms (MA) include Candida species and Aspergillus species, and even specific organisms such as Mycobacterium tuberculosis can become a causal agent.[ 22 ] Aspergillus species excels as the most common fungal agents in MA, and it was Oppe,[ 20 ] in 1897, who reported the first case of cerebral aspergillosis in humans. Multiple cases of cerebral aspergillosis with aneurysm formation have been reported since, in which, a lethal outcome occurred in most of them [ Table 1 ][ 1 , 5 , 7 , 8 , 9 , 18 , 19 , 26 , 27 ].

Table 1:

Reported cases of Aspergillus species mycotic aneurysms.

CASE DESCRIPTION

We present the case of a 26-year-old non-HIV male with a 1-year background appendectomy, which required epidural anesthesia. After surgery, he presented an insidious headache, requiring mild analgesics for adequate control. In the following weeks, headaches increased and tomographic imaging revealed hydrocephalus. A ventriculoperitoneal shunt was installed for suspicion of neurocysticercosis. Even though treatment was initiated, there was no clinical improvement. Sequentially, during hospital stay, shunt dysfunction occurred twice, for which shunt replacement was performed. Cerebrospinal fluid (CSF) and shunt’s catheter were cultured, identifying a filamentous fungus. CSF and serum galactomannan tests were positive for Aspergillus spp.: 9.4 ng/dl and 5.8 ng/dL, respectively. Intravenous amphotericin B and fluconazole were administered; however, a torpid clinical evolution was observed. The filamentous fungus was finally sequenced as Aspergillus terreus. After a 2-week antifungal scheme, sudden rostrocaudal deterioration appeared. Computed tomography imaging was done, revealing a 70 cc hematoma in the right operculoinsular region, midline shift [ Figure 1a - c ], and maximum intensity projections revealed a 9 mm saccular aneurysm at the bifurcation of the middle cerebral artery [ Figure 2a and b ]. Due to bad prognosis, hematoma evacuation surgery was not performed, and the patient died from intracranial hypertension 5 days after diagnosis. No evidence of immunocompromise was evidenced during hospital stay.

Figure 1:

Simple computed tomography scan: (a) axial, (b) coronal, and (c) sagittal reconstructions, in which a right operculoinsular hematoma is observed. Due to the location of the hematoma, it can be suspected that the origin is from the middle cerebral artery.

Figure 2:

Contrast-enhanced computed angiotomography scan: (a) axial and (b) coronal reconstructions of maximum intensity projection images showing a saccular 9 mm aneurysm located in the right middle cerebral artery bifurcation.

DISCUSSION

Fungal cerebral MAs are most commonly seen in patients with immunocompromised states, such as AIDS or complicated diabetes mellitus.[ 3 ] Historically, infectious endocarditis has been considered as the main origin of septic emboli.[ 25 ] However, there are multiple other origin sites that should be considered when facing these cases such as cavernous sinus thrombophlebitis,[ 24 ] paranasal sinus infections,[ 4 ] and, as in our case, following spinal anesthesia.[ 6 , 23 ] Diagnosis still remains a challenge for most physicians, as the distinctive pathological process can only be evidenced through autopsy material study. The causal organism can only be identified in 30–50% of cases when cultures from blood or CSF are taken.[ 17 ] In 2008, Kannoth et al.[ 14 ] proposed diagnostic criteria for the diagnosis of MAs, which showed a sensitivity of 96% and a specificity of 100% when all the criteria are met [ Table 2 ]. According to these criteria, our patient could be included in the “probable diagnosis” group, reaching a sensitivity of 100% and specificity of 87.4%.

Table 2:

Diagnostic criteria for mycotic aneurysms.

Iatrogenic fungal infections of the central nervous system must be suspected in patients with meningitis and a background of epidural invasive procedures such as anesthesia or any drug administration.[ 15 ] Kainer et al.[ 11 ] reported a series of 66 patients, in which central nervous system fungal infections were evidenced following contaminated methylprednisolone epidural administration. All the patients presented with one of these syndromes: meningitis, cauda equina syndrome, focal infection, or stroke. CSF analysis is a useful, but not definite, diagnostic study, as the only constant variable observed in multiple studies is a white cell count above normal (>5 cells/mm³), as glucose and protein values tend to vary greatly, and it is suggested that antifungal treatment must be initiated as soon as pleocytosis is detected.[ 13 ] Galactomannan detection in CSF is highly useful in Aspergillus detection with a sensitivity of 80% and specificity of 100%.[ 16 ] Specific antifungal treatment must be always initiated as soon as diagnosis is suspected. Combined antifungal therapy is recommended for central nervous system infections, being caspofungin plus voriconazole the first option.[ 10 ]

CONCLUSION

We present the first case report of a fungal MA of the middle cerebral artery bifurcation caused by A. terreus, a fungus found worldwide in soil. It has been reported to cause pathologic states in immunocompromised patients; however, our patient showed no evidence of immunocompromise whatsoever. Intrathecal inoculation following epidural anesthesia represents the form of transmission, which should be always taken into account with patients presenting this background history. The lethal outcome observed, depicts the intrinsic resistance this pathogen presents for amphotericin, which has been administered to the patient. Even though the wide range of diagnostic studies and treatment strategies, fungal central nervous system infections remain a diagnosis challenge which requires high suspicion and continues to be have one of the highest mortality rates among neurological diseases.

Declaration of patient consent

Patient’s consent is not required as identity is not disclosed or compromised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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