Madurella mycetoma—a rare case with cranial extension

1. Introduction 

Madurella species of fungus more frequently causes chronic subcutaneous infection of the lower extremities, and such infections are commonly labeled as Madura foot. Fungal infections related to Madurella species has been relatively infrequently identified in several other locations in the body. We present a case of Madurella infection of the paranasal sinuses that extended into the intracranial compartment. We could not locate any case of intracranial involvement of Madurella fungal infection in the literature.

2. Case report 

A 31-year-old male, an Ayurvedic doctor by profession, hailing from a village in the state of Rajasthan in India, presented with complaints of intermittent extrusion of blackish “tea leaves-like” granules from his left nostril for about 2 years. The patient was investigated for the same and found to have Madurella fungal sinusitis and was started on antifungal drug treatment (ketoconazole, 200 mg BD). Despite the ongoing drug therapy, the nasal discharge continued for about 1 year. The patient had left hemifacial pain for about 1 year and diplopia on left lateral gaze for about 2 weeks. The patient was of generally thin build. Neurologic examination revealed left sixth nerve paresis and no other deficit. The routine blood investigations and chest x-ray were normal. There was no evidence of immunocompromise of any kind. The MRI scan showed a large lesion involving the paranasal air sinus that extended into the left cavernous sinus. It was a mixed attenuation lesion with areas of hyperintensity and hypointensity on T1-weighted images (Fig. 1) and hypointensity on T2-weighted images (Fig. 2). The lesion enhanced on contrast administration (Fig. 3). A left basal temporal craniotomy was carried out. After retracting the temporal lobe, the lateral wall of the cavernous sinus was seen to be bulging laterally. The lesion was entirely within the confines of the cavernous sinus. It was exposed between the laterally stretched fibers of the fifth cranial nerve. The lesion was firm, granulomatous, and only moderately vascular and had dense adhesions to the adjoining structures. Black granular mass could be identified interspersed in the lesion. The lesion was radically but incompletely resected. The lesion was found to extend into the paranasal air sinus during the surgery. The patient had immediate postoperative relief in facial pain, and the sixth nerve paresis and related diplopia completely recovered. Histopathologic examination showed black-colored grains found amid neutrophilic abscesses (Fig. 4). The abscess showed brown cement matrix and embedded chlamydospores and septate hyphae (Fig. 5). These features confirmed that the infection was due to fungus Madurella mycetomi. The patient was now placed on liposomal-amphotericin B antifungal drug treatment. The patient took this drug treatment for a period of 2 months. The cumulative dose was 3 g. There were no adverse effects related to the drug. He was followed up 7 months after surgery with recurrence of diplopia. Examination revealed left sixth nerve palsy, and investigations showed a large recurrence of the lesion. In addition, enhancement of the tentorium could be observed suggesting the intracranial spread of the lesion. In addition, there were several other abscesses in the paranasal sinuses and in the infratemporal fossa. No further surgical treatment was advocated, and the drug treatment was continued. At a follow-up of 18 months, the patient is still having diplopia and nasal discharge of black granules but is free of facial pain.

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Fig. 1. T1-weighted MRI shows a mixed attenuation tumor in the region of the cavernous sinus, encasing the internal carotid artery. Extension of the tumor into the paranasal air sinus can be observed.

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Fig. 2. T2-weighted MRI showing the largely hypointense lesion involving the cavernous sinus.

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Fig. 3. Contrast MRI shows the enhancement in the tumor.

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Fig. 4. Chlamydospores and hyphae in brown cementlike matrix (hematoxylin and eosin, original magnification ×200).

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Fig. 5. Pigmented granule surrounded by neutrophils and granulation tissue (hematoxylin and eosin, original magnification ×100).

3. Discussion 

Fungi are ubiquitous in nature; they find a nidus in human body and adopt to its metabolism either in symbiosis or become pathogenic [8]. Fungal infection of brain and of the cranial cavity is a rare and challenging therapeutic problem [2], [5], [8]. Of late, the frequency of fungal infection appears to be on the rise, probably due to increase in number of cases with immunocompromised state such as HIV/AIDS and increased frequency of organ transplantation [2], [8]. The pathologic examination of CNS fungal infection is largely dictated by the size of the fungus—the small size yeast forms enter the microcirculation to cause microabscess and meningitis, whereas the larger hyphal forms invade the vasculature and manifest as infarcts [3], [7], [8].

Aspergilloma and zygomycosis (mucormycosis) are 2 most common fungal infections that involve the cranial cavity and cerebral parenchyma [4], [5], [7], [8]. Mycetoma is chronic subcutaneous infection induced by traumatic inoculation with saprophytic species of fungi or actinomycetes bacteria found in soil. Fungal agents of mycetoma include Pseudoallescheria boydii, Madurella mycetomi, Madurella grisea, Exophiala jeanselmei, and Acremonium falciforme.

The 2 forms of mycetoma are bacterial mycetoma and fungal mycetoma; bacterial mycetoma is known as actinomycetoma, whereas the fungal form is called eumycetoma. The true incidence and the geographical distribution of mycetoma throughout the world is not exactly known due to the nature of the disease that is usually painless, slowly progressive that may lead to the late presentation of most patients. Mycetoma has a worldwide distribution, but this is extremely uneven. It is endemic in tropical and subtropical regions. The African continent seems to have the highest prevalence. It prevails in what is known as the mycetoma belt stretching between the latitudes of 15° south and 30° north. The belt includes Sudan, Somalia, Senegal, India, Yemen, Mexico, Venezuela, Colombia, Argentina, and others. In India, its high prevalence is seen in states of Rajasthan, Tamil Nadu, and Andhra Pradesh. Actinomycotic mycetoma is prevalent in South India, south east Rajasthan, and Chandigarh, whereas eumycetoma, which constitutes one third of total cases, is mainly reported from North India and central Rajasthan [1], [6], [9].

The generally exposed areas of the body that include hands and feet are more frequently involved with mycetoma. Lesions are usually characterized by suppuration, abscess formation, granulomas, and formation of draining sinuses that contains granules. These granules may range up to 2 mm, are hard, and contain intertwined septate hyphae that are typically distorted and enlarged at the periphery of the granule. These granules help in the diagnosis of the fungal species [2], [8].

Madurella mycetoma usually involves the lower extremities, and intracranial spread of the infection has not been reported before in the literature. The organisms may reach the brain via traumatic inoculation or spread from the surrounding infected structures. In the presented case, there was evidence of paranasal infection [8]. The typical histopathologic picture seen in the lower limb Madurella mycetoma was seen in this patient. The black grains of Madurella mycetoma found amid neutrophilic abscesses, contain uniform rust brown cement, chlamydospores, and septate hyphae with expanded terminal ends [2], [8].

Surgical debridement followed by treatment with itraconazole, ketoconazole, or amphotericin B are found to be effective in mycetoma of the lower limb [2].