23 February 2023: Articles
Fungal Brain Abscess In Early Post-Renal Transplant: A Rare, Unexpected, Mysterious Pathogen
Challenging differential diagnosis, Unusual or unexpected effect of treatment, Rare disease, Rare coexistence of disease or pathologyShreya Jayaram1ABCDEF*, Shankar Prasad2A
Am J Case Rep 2023; 24:e939241
BACKGROUND: Central nervous system fungal infections are rarely encountered in current medicine, with fungal abscesses even less commonly seen. Clinical entities and their development largely depend on the interplay between the host’s immune system and fungal virulence factors. Due to the large size of fungal organisms, they are prevented from entering the meningeal circulation. Hence, they cause focal diseases like cerebritis, abscesses, vasculitis of larger vessels, vascular occlusion, cerebral infarcts, and aneurysms.
CASE REPORT: A 34-year-old male patient of Indian descent diagnosed with stage 5 chronic kidney disease, bilaterally small kidneys, and hypertension underwent cadaveric renal transplantation and subsequent immunosuppression. Three months later, he returned with complaints of high-grade fever with chills and rigor, along with massive headaches. Plain brain computed tomography showed an intra-axial heterogeneously hypodense area with a hyperdense rim in the right temporal lobe. MRI revealed a well-defined enhancing lesion with irregular crenated margins and satellite lesions. Abscess wall biopsy showed fragments of hyaline septate filamentous fungal hyphae. Craniotomy with excision and drainage of the abscess was done and sent for histopathological examination along with culture. The results showed the growth of Nodulisporium fungus. The patient was then managed on amphotericin B and voriconazole for completion of treatment.
CONCLUSIONS: This is the first case reported of a Nodulisporium species fungal abscess developing in the brain after cadaveric kidney transplantation. Urgent evaluation via imaging and biopsy is crucial in determining the exact causal organism of brain abscesses, which can lead to better patient outcomes.
Keywords: brain abscess, Kidney Transplantation, Meningitis, Fungal
Organ transplantation has always been a standard therapeutic intervention in patients with end-stage organ failure. Renal transplants are widely carried out around the globe with high success rates. A major challenge faced by medical practitioners is overcoming post-transplant infections, which tend to occur due to the highly immunosuppressed state of the patient. Various regimens consisting of various drug combinations are accepted as standard practice. Infections developing in such patients tend to have a high overall mortality rate.
Fungi are ubiquitous organisms that tend to drastically alter the post-transplant patient status . Overall mortality due to invasive fungal infections (IFIs) in solid-organ transplant recipients varies and depends on individual patient profiles. The risk of such infections following renal transplant is related to the dosage of immunosuppressive agents, environmental factors, and post-transplant duration. Most fungal infections occur in the first 6 months after transplant due to the use of numerous immunosuppressors.
Brain-specific fungal infections are rarely seen, and when they do occur, the larger morphology of fungal organisms precludes their entry into the meningeal microcirculation. This results in a more focal disease when fungi are seen in the central nervous system (CNS), leading to cerebritis, abscess formation, or involvement of larger vessels resulting in vasculitis, vascular occlusion, cerebral infarctions, or mycotic aneurysms.
The CNS may be invaded by some pathogenic fungi that show neurotropism and ability to invade to establish an infection. The etiological agent described in our case is
A 34-year-old male patient with comorbid hypertension was diagnosed with stage 5 chronic kidney disease. He had bilaterally small kidneys on imaging. A cadaveric renal transplantation was carried out, and he was subsequently put under anti-thymocyte globulin (ATG) and triple immunosuppression therapy consisting of low-dose cyclosporine, azathioprine, and prednisone. Three months after the transplant, he returned and presented with complaints of a high-grade fever associated with chills and rigor and a holocranial headache for the previous 2 days. There was no history of nausea/vomiting, blurring of vision, seizures, bowel/bladder dysfunction, or behavioral changes. Physical examination was otherwise unremarkable. No overt signs of meningeal irritation and no focal neurological deficits were seen in the patient. Fundoscopic examination also revealed no papilledema. All his vital signs were stable. Initial radiological tests, including chest X-ray and echocardiography, were normal. A routine blood and biochemistry panel consisting of elements including basic liver and kidney function tests showed no abnormal values.
A plain computed tomography (CT) scan of the brain was conducted, which showed an intra-axial heterogeneously hypodense area with a hyperdense rim in the right temporal lobe measuring around 3×2×2 cm with surrounding perilesional edema. A mass effect was noted in the form of effacement of adjacent sulci and compression of bilateral third and lateral ventricles. MRI (plain and contrast) revealed a well-defined enhancing lesion with irregular crenated margins in the right temporal lobe, along with satellite lesions showing blooming foci and a mass effect. This was associated with ventriculitis and meningitis. Magnetic resonance spectroscopy showed a lipid lactate peak with N-acetyl aspartate (NAA) level reduction (Figures 1, 2).
A decision was made to biopsy the lesion, and microscopy of the abscess wall showed areas of necrotic cell debris, granulation tissue, lymphoplasmacytic infiltrate, and fragments of hyaline septate filamentous fungal hyphae that were periodic acid-Schiff (PAS) and Gomori’s methenamine silver (GMS) positive. Also present in the biopsy sample were foreign body giant cells, congested blood vessels, reactive gliosis, and hemorrhage.
A right temporal craniotomy with excision and drainage of the abscess was carried out, and the specimen was sent for histopathological examination along with culture (Figures 3, 4). This was suggestive of a fungal brain abscess. Mycological culture of the abscess fluid showed growth of
A brain abscess is a focal suppurative process of variable size that develops within the brain parenchyma and is surrounded by an inflammatory exudate. In the immunocompetent host, brain abscesses are usually bacterial. They consist of a central area of necrotic debris and leukocytes with a fibroblastic capsule surrounded by cerebritis and perivascular infiltrates. In the immunocompromised host, however, fungal brain abscesses predominate and usually originate via hematogenous spread from a primary invasion site. Under a microscope, the picture resembles arteritis with vessel thrombosis and obliteration leading to ischemic/hemorrhagic infarct .
A CT scan usually reveals multiple low-density, non-enhancing lesions most frequently located in the CNS regions of the basal ganglia and cerebral hemispheres. In our case, the lesion was restricted to the right temporal lobe with surrounding tissue changes like edema and vasculitis. The criterion standard for reliable diagnosis is a biopsy with histopathological and tissue analysis. Due to the high virulence of fungal CNS-targeting organisms, complete and successful treatment remains a challenge. The tendency to occlude blood vessels, leading to difficulty delivering antifungal agents to infected brain tissue, adds to morbidity and the risk of mortality. Established CNS fungal abscesses are therefore considered a surgical emergency and end up being fatal in most cases. In those who survive, there may be a high risk of neurological sequelae .
Host and environmental factors are critically essential determinants in the epidemiology of fungal infections following transplantation. The highest risk is in small bowel (11.6%) and lung (8.6%) transplants, followed by liver (4.7%), heart (4.0%), pancreas (3.4%), and kidney (1.3%) transplants . Drug-induced immunosuppression given post-kidney transplantation is a well-known risk factor for fungal infections.
Lungs are the most common primary site of infection in cases of fungal spread to the brain via blood route transportation . Principal pathogens causing these infections are
Patients who have undergone kidney transplantation under immunosuppression must be kept under close followup and be advised to return immediately at signs of any symptoms like fevers, headaches, or seizures. If an abscess is suspected on imaging, surgery plays a crucial role in obtaining tissue for histopathology and culture. Based on laboratory reports, appropriate therapeutic treatment may be started that targets the causative organism. Therapy should be continued until complete radiographic resolution occurs or there is evidence of halted progression on repeat MRI scans spanning a significant time period.
Interesting to note is the fact that the treatment of a fungal brain abscess tends to differ from that of a bacterial brain abscess. Surgical excision, which is usually performed for a bacterial abscess, may prove less effective for fungi since fungal hyphae are known to penetrate and extend beyond the fibrous capsule, making surgical resection complicated .
In our case, the
FiguresFigure 1.. Brain MRI scan report. The red arrow points to a right-sided temporal lobe lesion (abscess). MRI – magnetic resonance imaging. Figure 2.. Brain CT scan report. The yellow arrow points to a right temporal lobe lesion. CT – computed tomography. Figure 3.. Histopathology slide with GMS staining. The orange arrow points to the hyaline septate filamentous fungus. The blue arrow points to foreign body giant cells in the background with granulation tissue and necrotic cell debris. GMS – Gomori’s methenamine silver. Figure 4.. Nodulisporium species grown on Sabouraud dextrose agar after 7 days incubation at 28°C.
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