Abstract

Background: Cerebral aspergillosis (CA) is a rare fungal infection and life-threatening disease often associated with immunocompromised patients but can occasionally be present in immunocompetent individuals, mimicking an intracranial neoplasm. CA is highly linked to reduced immunity and is commonly seen in patients with background immunodeficiency, such as acquired immunodeficiency syndrome, chemotherapy, organ transplant patients on immunosuppressive therapy, and those with long-term steroid use. Diagnosis and management of CA can be quite challenging in immunocompetent individuals due to its unusual presentation, non-specific symptoms, and resemblance to tumors in imaging, the necessity of invasive procedures for diagnosis confirmation, complex surgical management, and the need for prolonged antifungal treatment with possible side effects.

Case Description: The case of a 36-year-old immunocompetent male who presented with a 2-year history of recurrent headaches, vomiting, seizures, inability to walk, and altered sensorium, with no history of immunosuppression. Clinical examination revealed a chronically ill patient with multiple cranial nerve palsies, and magnetic resonance imaging revealed a fourth ventricular mass with pan ventriculomegaly causing obstructive hydrocephalus. Initial management of the patient included a ventriculoperitoneal shunt followed by a midline suboccipital craniectomy and excision of the mass lesion 5 days later. Histopathology confirmed CA diagnosis, and the patient was treated with intravenous voriconazole, after which improvement in his clinical status was observed.

Conclusion: This case emphasizes the importance of early detection of unusual CA in immunocompetent individuals and the importance of combining surgical intervention with antifungal therapy. The patient presented with a rare form of CA as an intracranial mass causing obstructive hydrocephalus, which initially mimicked a tumor. Early diagnosis and effective management, including surgery and antifungal treatment with voriconazole, led to significant improvement despite incomplete mass removal. Multidisciplinary care and long-term monitoring are crucial for managing such complex cases.

Keywords: Aspergillosis, Hydrocephalus, Magnetic resonance imaging

INTRODUCTION

Cerebral aspergillosis (CA) is a fungal infection commonly seen in patients with depressed immune systems.[ 3 , 7 ] It can be life-threatening and, in rare cases, mimic an intracranial neoplasm, which has been reported in immunocompetent individuals.[ 3 - 5 ] CA is usually linked to reduced immunity and is commonly seen in patients with background immunodeficiency, such as acquired immunodeficiency syndrome, chemotherapy, organ transplant patients on immunosuppressive therapy, and those with long-term steroid use.[ 10 ] Diagnosis and management of CA can be quite challenging in immunocompetent individuals due to its unusual presentation,[ 1 ] non-specific symptoms,[ 16 ] resemblance to tumors in imaging,[ 8 ] complex surgical management,[ 13 ] and the need for prolonged antifungal treatment with possible side effects.[ 14 ] It can manifest as meningitis, cerebritis, or abscess [ 8 ], although it is presented in this case as an obstructive hydrocephalus.[ 6 , 15 ]

This case study aims to create awareness of CA in immunocompetent hosts and emphasize the importance of early diagnosis and intervention along with the necessity for clinicians to maintain a high index of suspicion for fungal pathogenesis in patients presenting with unexplained neurological symptoms. The Table 1 compared the age of the patients at presentation,the gender, the presenting complaints and the treatment given in previously reported cases in comparison to the present case report.

Table 1:

Similar reported cases, age, sex, symptoms, and intervention provided.

CASE REPORT

The patient is a 36-year-old male who presented with a 2-year history of recurrent headaches, a 2-month history of recurrent vomiting, a 2-week history of multiple episodes of seizures and inability to walk, and a 1-week history of altered sensorium. He also had urinary and fecal incontinence. There was no history of steroid or immunosuppressive medications, organ transplant, chronic or malignant cough, hypertension, or diabetes. General examination revealed a young man who was confused and lethargic, slightly dehydrated but not febrile and had marked right-sided temporalis and masseter muscle wasting [ Figure 1 ]. The vital signs at presentation were within normal limits except for the elevated blood pressure of 150/94 mmHg.

Figure 1:

(a) Anterior and (b) right-sided view of the patient highlighting right-sided temporalis and masseter muscle wasting with zygomatic arch prominence.

He was confused with a Glasgow coma score (GCS) of 14, and the pupils were 4 mm bilaterally and briskly reactive to light. The cranial nerve examination revealed left 3^rd, 6^th, 7^th, 8^th, and 12^th cranial nerve palsies. The long tract examination showed exaggerated deep tendon reflexes and florid cerebellar signs.The results of the laboratory investigations at the presentation were all within the limit of normal. The human immunodeficiency virus I and II screening, hepatitis B surface antigen, and hepatitis C virus antibody were non-reactive. The Mantoux and sputum gene Xpert tests were negative for tuberculosis. The brain magnetic resonance imaging (MRI) revealed a mixed consistency space-occupying lesion in the fourth ventricle with obstructive hydrocephalus. A solid mass measuring 1.8 × 0.6 cm was noted within the posterior fossa at the foramen of Magendie, with resulting cystic dilatation of the 4^th ventricle measuring 1.9 × 9 × 1.6 cm. The lesion was iso-intense on T1-weighted imaging with irregular enhancement on T1 contrast and irregular hyper-intense on T2-weighted imaging [ Figure 2 ]. He was worked up for an urgent cerebrospinal fluid (CSF) diversion through ventriculoperitoneal (VP) shunt placement. He had a right occipital VP shunt placement on the 3^rd day of admission, and the procedure was well tolerated, as evidenced by improvement of the GCS on postoperative day 3. The CSF sample revealed a slightly reduced CSF glucose while the CSF protein was within the limit of normal, no organism was cultured; however, no fungal study was requested. He then subsequently had a midline suboccipital craniectomy with a telovelar approach and excision of the 4^th ventricular outlet lesion 4 days after the VP shunt placement under general anesthesia. The intra-operative findings were mixed cystic and solid lesions, with the appropriate plastered to the floor of the 4^th ventricle near the exit [ Figure 3 ].

Figure 2:

Preoperative brain magnetic resonance imaging showing a mixed consistency space-occupying lesion at the exit of the 4^th ventricle (blue arrow) (which histology later confirmed to be a fungal mass)with obstructive hydrocephalus (red arrow), (Green arrow - 4^th ventricle; yellow arrow - Lesion), (a-T1, b-T1 with contrast, c-T2, d-flair).

Figure 3:

Intraoperative pictures. Residual lesion plastered to the floor of the 4^th ventricle (arrow).

The tissue sample from the solid component was sent for histology; complete resection was not possible due to the extent of adhesion to the brainstem.

The histology confirmed CA [ Figures 4 and 5 ], on account of which intravenous (IV) Voriconazole was commenced on the 27^th postoperative day. The chest computed tomography (CT) scan ruled out the chest focus of the fungal infection.

Figure 4:

Immediate postoperative brain magnetic resonance imaging (Green arrow-4^th ventricle; yellow arrow-residual lesion).

Figure 5:

Histological section of the tissue biopsied from the 4^th ventricular exit lesion showing exudates comprised predominantly of neutrophilic infiltrates. Note the (a) elongated structures present within the exudate (yellow arrow) (b) (Hematoxylin and Eosin, ×400).

The course of IV Voriconazole was completed on the 42^nd postoperative day. The brain MRI, which was done at 6 weeks postoperatively, showed some reduction in the size of the 4^th ventricular lesion and hydrocephalus [ Figures 6 - 8 ]. The patient made some clinical improvement became self-ambulant, and was discharged home on oral Voriconazole at 100 mg bd.

Figure 6:

Histological section showing a mass of hyphal structures within the lesion, some of which demonstrate acute angle branching (red arrows) (Gomori Methenamine Silver, ×400) (Red arrow with blue outline-Fungal hyphae).

Figure 7:

Magnetic resonance imaging (MRI) done before initiation of intravenous voriconazole (Green arrow-4^th ventricle; yellow arrow-residual lesion). Description: (a and b) T1- and (c and d) T2-weighted images from cranial MRI (axial and sagittal views) showing fourth ventricular mass lesion and obstructive hydrocephalus.

Figure 8:

Magnetic resonance imaging (MRI) done after completion of 15-day course initiation of intravenous Voriconazole (Green arrow-4^th ventricle; yellow arrow-residual lesion). Description: (a and b) T1 and (c and d) T2-weighted images from cranial MRI (axial and sagittal views) show a reduction in the size of the fourth ventricular mass lesion and hydrocephalus.

DISCUSSION

Aspergillosis is caused by the species of the fungi Aspergillus, which is ubiquitous in the environment and is usually found in soil, decaying leaves, and growing as mold.[ 9 , 12 , 18 ] The spores of the fungi are commonly inhaled into the respiratory tract but can also invade and colonize the external auditory canal. About 90% of infections in humans are caused by the species Aspergillus fumigatus. CA is highly lethal and predominantly seen in patients who are immunocompromised. Over the past few years, there has been an increase incidence of this condition presenting as an intracranial mass in immunocompetent patients.[ 11 ] This is in keeping with similar findings in our above patient, who is a 36-year-old male with no evidence of depressed immunity, as all relevant investigations to assess immune status were performed. The chest CT scan showed no evidence of lung involvement. CA commonly presents with symptoms of raised intracranial pressure such as headaches, seizures, and vomiting[ 3 ], and this is similar to the patient who had presented with the above symptoms in addition to altered sensorium, multiple cranial nerve palsies, and inability to walk. A particularly unusual presentation of the patient is the marked wasting of the temporalis and masseter muscles with zygomatic prominence which was indicative of extensive fungal infiltration of the 5^th cranial nerve. This is similar to a finding in a 2012 study.[ 17 ]

MRI showed a mass in the fourth ventricle, which was iso-intense on T1 and hyper-intense on T2. This is partly in contrast with other studies that have reported T2 hypointensity instead but the same T1 iso-intensity.[ 3 ] A 2020 case report of MRI revealed T2 hyperintensity which is in keeping with our findings.[ 7 ]

Surgical intervention in combination with antifungal therapy is the mainstay of treatment for CA no matter the immune status.[ 2 ] The patient presented with obstructive hydrocephalus due to the mass being located at the exit of the fourth ventricle, so he initially had CSF diversion through VP shunt insertion. This was effective in reducing the intracranial pressure and led to an increase in his GCS from 14 to 15, complete resolution of vomiting, and partial resolution of headache at postoperative day 4. Complete resection of the associated mass has been advocated for in all cases except where access is difficult, and the patient is at risk of multiple neurological complications,[ 2 ] as seen in the index case in which the mass was plastered to the floor of the 4^th ventricle. Radical resection was sought 5 days after VP shunt insertion but this was impossible due to the adherence of the mass to the floor of the brainstem.Voriconazole has been favored as the main therapeutic agent due to its ability to penetrate the central nervous system and better outcomes with therapy.[ 5 ] It is, however, hepatotoxic; therefore, pre- and post-treatment liver function tests are recommended.[ 5 ] Our patient had a 14 U/L and 9 U/L in alanine aminotransferase and aspartate aminotransferase values after 15 days of IV Voriconazole. He had a high pre-treatment gamma glutamyl transferase of 130.1 U/L, which increased by 12.91 U/L after 15 days of IV therapy.

Post-treatment MRI showed a reduction in the size of the fourth ventricular mass and hydrocephalus. The pre-excision insertion of a VP shunt could have contributed to the reduction in hydrocephalus. We also had a longer duration of therapy (15 days) than the median duration of 10 days, as advised by our infectious diseases specialist. This highlights the importance of multi-disciplinary specialist care.

CONCLUSION

This case emphasizes the importance of early detection of unusual presentations of CA in immunocompetent individuals and a combination of surgical intervention with antifungal therapy for optimal outcomes. This case that presented as an intracranial mass in an immunocompetent adult, leading to obstructive hydrocephalus, is a rare form of CA that posed diagnosis and management challenges as the patient’s initial presentation mimicked a tumor. Early diagnosis and successful management were achieved through surgical intervention for the hydrocephalus and antifungal treatment with voriconazole. Although complete removal of the mass was not possible due to its attachment to vital brain structures, the combination of partial resection and prolonged antifungal therapy led to significant clinical improvement. Multidisciplinary management and long-term monitoring of such complex cases like this are essential.

Ethical approval:

The Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

References

1. Agrati C, Bartolini B, Bordoni V, Locatelli F, Capobianchi MR, Di Caro A. Emerging viral infections in immunocompromised patients: A great challenge to better define the role of immune response. Front Immunol. 2023. 14: 1147871

2. Beraldo D, Guerra R, Alvarenga V, Crepaldi L. Surgical treatment alone of cerebral aspergillosis in immunocompetent patient. J Neurol Surg A Cent Eur Neurosurg. 2016. 77: 452-6

3. Bokhari R, Baeesa S, Al-Maghrabi J, Madani T. Isolated cerebral aspergillosis in immunocompetent patients. World Neurosurg. 2014. 82: e325-33

4. El Hasbani G, Chirayil J, Nithisoontorn S, Antezana AA, El Husseini I, Landaeta M. Cerebral aspergillosis presenting as a space occupying lesion in an immunocompetent individual. Med Mycol Case Rep. 2019. 25: 45-8

5. Ellenbogen JR, Waqar M, Cooke RP, Javadpour M. Management of granulomatous cerebral aspergillosis in immunocompetent adult patients: A review. Br J Neurosurg. 2016. 30: 280-5

6. Fasciano JW, Ripple MG, Suarez JI, Bhardwaj A. Central nervous system aspergillosis: A case report and literature review. Hosp Phys. 1999. 35: 63-70

7. Finelli PF. MR target sign in cerebral aspergillosis. Neurohospitalist. 2020. 10: 287-90

8. Godkhindi VM, Monappa V, Kairanna NV, Sharma S, Vasudevan G, Hebbar KD. Brain infections that mimic malignancy. Diagn Histopathol. 2022. 28: 456-66

9. Leroy J, Vuotto F, Le V, Cornu M, François N, Marceau L. Invasive rhino-orbital-cerebral aspergillosis in an immunocompetent patient. J Mycol Med. 2020. 30: 101002

10. Nemade SV, Shinde KJ, editors. Aspergillosis. Granulomatous diseases in otorhinolaryngology, head neck. Berlin: Springer Nature; 2021. p. 101-15

11. Neyaz Z, Singh V, Mehrotra A, Jain M. Cerebral aspergillosis mimicking a neoplasm in an immunocompetent patient. Int J Appl Basic Med Res. 2018. 8: 269-71

12. Nyga R, Delette C, Mabille C, Bennis Y, Chouaki T, Boone M. Ibrutinib related cerebral aspergillosis successfully treated with isavuconazole: A case report. Leuk Lymphoma. 2020. 61: 1760-2

13. Ruhnke M, Kofla G, Otto K, Schwartz S. CNS aspergillosis: Recognition, diagnosis and management. CNS Drugs. 2007. 21: 659-76

14. Shariati A, Didehdar M, Rajaeih S, Moradabadi A, Ghorbani M, Falahati V. Aspergillosis of central nervous system in patients with leukemia and stem cell transplantation: A systematic review of case reports. Ann Clin Microbiol Antimicrob. 2021. 20: 44

15. Wang RX, Zhang JT, Chen Y, Huang XS, Jia WQ, Yu SY. Cerebral aspergillosis: A retrospective analysis of eight cases. Int J Neurosci. 2017. 127: 339-43

16. Więsik-Szewczyk E, Jahnz-Różyk K. From infections to autoimmunity: Diagnostic challenges in common variable immunodeficiency. World J Clin Cases. 2020. 8: 3942-55

17. Xiao A, Jiang S, Liu Y, Deng K, You C. Invasive intracranial aspergillosis spread by the pterygopalatine fossa in an immunocompetent patient. Braz J Infect Dis. 2012. 16: 192-5

18. Zhang S, Fu Q, Chen Q, Liang TB. Isolated cerebral aspergillosis in an immunocompetent woman on treatment for bacterial infected necrotizing pancreatitis: A case report. Medicine (Baltimore). 2017. 96: e8908