|Year : 2016 | Volume
| Issue : 4 | Page : 550-553
Successful treatment of primary cerebral mucormycosis: Role of microbiologist
KK Benachinmardi1, P Rajalakshmi2, HB Veenakumari1, RD Bharath3, V Vikas4, A Mahadevan2, S Nagarathna1
1 Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3 Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
4 Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
|Date of Submission||15-Jul-2016|
|Date of Acceptance||29-Sep-2016|
|Date of Web Publication||8-Dec-2016|
Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Fungal brain abscess is rare with a rapidly progressive disease with fulminant course and invariably fatal outcome, unless diagnosed early and treated rapidly. We report a 56-year-old woman diagnosed to have fungal abscess who recovered completely following amphotericin B treatment. She presented with weakness of the right hand, deviation of mouth to left and aphasia for 2 days. Computed tomography of the brain revealed a left frontal capsuloganglionic hypodense lesion. Stereotactic biopsy was performed, and microbiological confirmation of non-septate fungal hyphae from pus from aspirate within 2 h helped initiate timely and appropriate treatment leading to cure. Histopathology and culture later confirmed mucormycosis.
Keywords: Angioinvasion, brain abscess, mucormycosis
|How to cite this article:|
Benachinmardi K K, Rajalakshmi P, Veenakumari H B, Bharath R D, Vikas V, Mahadevan A, Nagarathna S. Successful treatment of primary cerebral mucormycosis: Role of microbiologist. Indian J Med Microbiol 2016;34:550-3
|How to cite this URL:|
Benachinmardi K K, Rajalakshmi P, Veenakumari H B, Bharath R D, Vikas V, Mahadevan A, Nagarathna S. Successful treatment of primary cerebral mucormycosis: Role of microbiologist. Indian J Med Microbiol [serial online] 2016 [cited 2017 Nov 22];34:550-3. Available from: http://www.ijmm.org/text.asp?2016/34/4/550/195373
| ~ Introduction|| |
Brain abscess is a focal, intracerebral infection that begins as a localised area of cerebritis and develops into a collection of pus surrounded by a well-vascularised capsule. It accounts for approximately 8% of intracranial masses in developing countries and 1%–2% in the Western countries. Most of the brain abscesses are either pyogenic or tubercular in origin. Fungal brain abscess is very rare, among which mucormycosis (MM) as an etiological agent is exceptional.
Common fungal agents causing brain abscess include Aspergillus spp., Candida spp. and zygomycetes. MM is an infection caused by fungi of the order Mucorales in the phylum Zygomycota. Mucorales is saprophytic fungi commonly found in the upper respiratory tract and is non-pathogenic in otherwise healthy adults. However, it is highly pathogenic in immunocompromised patients and invariably results in death or permanent central nervous system sequelae. It most commonly affects diabetic and immunocompromised patients. However, isolated cerebral MM is seen mainly in IV drug abusers and is invariably life threatening, with high mortality rate. The incidence of MM is approximately 1.7 cases/10 lakh population/year. Different forms of MM have been described which includes rhinocerebral, pulmonary, gastrointestinal, cutaneous and disseminated forms. Among these, rhinocerebral MM is the most common one.
Most common mode of entry of Mucorales to the brain is rhinocerebral in which infection ascends from nasal or paranasal sinuses to orbit and then to the brain. Direct implantation of this fungus into the brain can also occur by open head injury.
Here, we are reporting a case of isolated cerebral MM (brain abscess) in a diabetic patient, etiological agent of which was identified within ½ h of the cerebral exploration resulting in successful treatment.
| ~ Case Report|| |
A 56-year-old woman, a homemaker, presented with weakness of the right hand, deviation of mouth to left side and aphasia for 2 days. She had headache and fever, on and off since the last 2 months. On examination at admission, she was conscious, obeying commands but disoriented. Neurological examination revealed right hemiparesis with facial weakness. She was not a known diabetic, but on admission, the random blood glucose was 292 mg/dl. The patient was seronegative for human immunodeficiency virus-1 (HIV-1). Her haemoglobin level was 13.5 g/dl, and all other haematological parameters were within normal limits. Liver and renal function tests were within normal range except alkaline phosphatase which was raised (186 U/L). Cranial magnetic resonance imaging (MRI) revealed a left frontal capsuloganglionic hypodense lesion with ring enhancement on contrast and perilesional oedema [Figure 1]. Clinical diagnosis considered was metastatic lesion or chronic abscess.
|Figure 1: Magnetic resonance imaging axial sections reveal multiple ring-enhancing lesions (a) in the left frontal lobe (an inset) and basal ganglia with a heterogenous appearance on T2-weighted imaging (b). The bright signal on diffusion-weighted image (c) suggesting restricted diffusion with additional evidence of discrete hypointense specks on the wall on susceptibility weighted imaging (d) are consistent with the imaging diagnosis of a fungal abscess|
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The patient underwent stereotactic biopsy and aspiration. Thick yellowish pus of 6–7 ml was aspirated and sent to neuromicrobiology laboratory. Immediate wet mount preparation revealed numerous ribbon-like, broad aseptate fungal hyphae and few polymorphonuclear cells. The fungal hyphae were Gram-positive. Bacterial culture both aerobic and anaerobic was sterile. Fungal culture yielded greyish-white fluffy or cottony mould with black dots on the surface. Lactophenol cotton blue preparation showed long, ribbon-like non-septate hyphae with terminal globular sporangia supported by columella, and rhizoids were absent [Figure 2]a and [Figure 2]b. Slide culture confirmed the above findings. Based on these features, etiological agent of brain abscess was confirmed to be Mucor species. The patient was started on amphotericin B 1 mg/kg body weight/day on the day of exploration itself based on the wet mount and Gram-staining result. Histopathological examination of biopsy from the lesion confirmed the diagnosis. Biopsy revealed a necrotic lesion with several thrombosed vessels, occluded by fibrin thrombi and polymorphs [Figure 2]c. The vessel walls were invaded by broad, aseptate fungal hyphae [Figure 2]d. The patient stayed for 15 days in the hospital, and hyperglycaemia was managed with insulin. The patient was continued on amphotericin B 2.5–3 g/day for 6 weeks after discharge with alternate day renal parameters check at a local hospital and laboratory with a telephonic follow-up with the neurosurgeon. On follow-up, the patient improved clinically without any sequelae and went back to normal life.
|Figure 2: (a) Mucor growth on Sabouraud's dextrose agar. (b) Lactophenol cotton blue preparation from fungal culture. (c and d) Stereotactic biopsy of the lesion revealed necrosis with inflamed thrombosed vessel (c) shows infiltration of vessel wall by numerous broad aseptate branching fungal hyphae. (d) Gomori methenamine silver stain; magnification = scale bar (=50 μ) (H and E)|
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| ~ Discussion|| |
Despite diagnostic advancements with introduction of computed tomography, MRI as well as better antimicrobial agents and neurosurgical procedures, brain abscess continues to be a serious, life-threatening condition. Although intracranial abscesses are rare in developed countries, it still remains a significant health-care problem in developing countries. Most infections occur in adults with the youngest patient reported being 15-day-old child and the oldest being 79 years. Males are frequently involved. This patient came to us after 2-month history of vague symptoms. Some patients can present as early as 3 days or as late as more than 200 days. Frontal lobe is commonly involved as seen in our case.
Frequently described risk factors for fungal brain infections are HIV/AIDS, haematopoietic stem cell transplant, lymphoid malignancies, neutropenia, hereditary immune defects, immunosuppressive medications, diabetes mellitus, intravenous drug abuse and mechanical breakdown of the blood brain barrier through surgery or trauma. The most common pre-disposing condition is diabetic ketoacidosis accounting for 70% of abscesses. In our case, diabetes was undetected until the present admission. In diabetic ketoacidosis, there is substantially reduced binding of iron to transferrin, leading to freely available iron promoting the growth of Mucorales. However, the mechanism of susceptibility to MM in patients with other pre-disposing factors is not clear though enhanced metabolism, acidosis and neoglucogenesis could be contributing.
MM is a rare fulminating opportunistic fungal infection caused by fungus of the order Mucorales. It is a rapidly progressive disease with fulminant course and fatal outcome, unless diagnosed early and treated rapidly. MM is caused by several genera belonging to the family Mucoraceae such as Rhizopus, Mucor and Absidia. Rhizopus is the common organism in 95% of cases (Rhizopus arrhizus and Rhizopus oryzae). MM is usually acquired by airborne fungal spores, contamination of traumatised tissue, ingestion or by direct inoculation as in IV drug abusers. In immunocompromised patients, when spores get converted into hyphae, they become invasive and may spread to paranasal sinus, orbit and brain. However, direct soft-tissue invasion and formation of abscess are also been described.Mucor is known for its angioinvasion particularly arteries. The fungus proliferates in the internal elastic lamina dissecting away from the media with hyphae penetrating the endothelium. Thrombotic arteritis, infarction, haemorrhage and extensive necrosis follows.
Identification of the causative pathogen is important for appropriate management. It is clearly evident that if neurosurgeon uses the expert opinion of microbiologist, simple techniques such as wet mount, Gram-staining and Z-N stain would help in the selecting proper therapy. This is very true especially in cases of tuberculosis and fungal brain abscess which are difficult to distinguish clinically and radiologically from pyogenic ones.
In our case, we could not find the underlying primary lesion from where the infection could have spread. Cryptogenic brain abscess incidence ranges from 15% to 22% according to several studies. It is possible that few of the isolated CNS MM develops from unrecognised indolent infections, probably extending from paranasal sinuses.
Medical management alone is not sufficient because of poor drug delivery to infection site due to extensive vascular thrombosis as seen in our case. Systemic antifungal therapy includes a high dose of amphotericin B following which, survival rate is about 72%. It is intravenously administered at a dose of 1–1.5 mg/kg/day. Since Amphotericin B is associated with renal toxicity, careful monitoring of renal parameters including potassium levels is an essential.
The survival rate in cerebral MM was 9.4% before 2000; however, it has improved to more than 50% at present due to early diagnosis, surgical resection, timely and appropriate treatment and most importantly, recognising and correcting the pre-disposing condition, especially diabetes.
| ~ Conclusion|| |
Isolated cerebral MM with no evidence of underlying regional or systemic disease is a very rare and uncommon clinical entity. Microbiologist plays a critical role in providing early diagnosis and facilitates initiation of life-saving treatment of an otherwise fatal condition.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]