key: cord-0907077-uk8czn60
authors: Sanghvi, D.; Kale, H.
title: Imaging of COVID-19-associated craniofacial mucormycosis: a black and white review of the “black fungus”
date: 2021-07-28
journal: Clin Radiol
DOI: 10.1016/j.crad.2021.07.004
sha: 2968f8feefdcc7e0aa521b7ed5a45dc9502d5994
doc_id: 907077
cord_uid: uk8czn60

A subset of diabetic COVID-19 patients treated with steroids, oxygen, and/or prolonged intensive care admission develop rhino-orbito-cerebral mucormycosis. Radiologists must have a high index of suspicion for early diagnosis, which prompts immediate institution of antifungal therapy that limits morbidity and mortality. Assessment of disease extent by imaging is crucial for planning surgical debridement. Complete debridement of necrotic tissue improves survival. Imaging features reflect the angioinvasive behaviour of fungal hyphae from the Mucoraceae family, which cause necrotising vasculitis and thrombosis resulting in extensive tissue infarction. Contrast-enhanced magnetic resonance imaging (MRI) is the imaging technique of choice. The classic “black turbinate” on contrast-enhanced imaging represents localised invasive fungal rhinosinusitis (IFRS). A striking radiological feature of disseminated craniofacial disease is non-enhancing devitalised and necrotic soft tissue at the orbits and central skull base. Sinonasal and extrasinonasal non-enhancing lesions in IFRS are secondary to coagulative necrosis induced by fungal elements. Multicompartmental and extrasinonasal tissue infarction is possible without overt bone involvement and caused by the propensity of fungal elements to disseminate from the nasal cavity via perineural and perivascular routes. Fungal vasculitis can result in internal carotid artery occlusion and cerebral infarction. Remnant non-enhancing lesions after surgical debridement portend a poor prognosis. Assessment for the non-enhancing MRI lesion is crucial, as it is a sole independent prognostic factor for IFRS-specific mortality. In this review, we describe common and uncommon imaging presentations of biopsy-proven rhino-orbito-cerebral mucormycosis in a cohort of nearly 40 COVID-19 patients.

imaging represents localised invasive fungal rhinosinusitis (IFRS). A striking radiological feature of disseminated craniofacial disease is non-enhancing devitalised and necrotic soft tissue at the orbits and central skull base. Sinonasal and extrasinonasal non-enhancing lesions in IFRS are secondary to coagulative necrosis induced by fungal elements. Multicompartmental and extrasinonasal tissue infarction is possible without overt bone involvement and caused by the propensity of fungal elements to disseminate from the nasal cavity via perineural and perivascular routes.

Fungal vasculitis can result in internal carotid artery occlusion and cerebral infarction. Remnant non-enhancing lesions after surgical debridement portend a poor prognosis. Assessment for the non-enhancing MRI lesion is crucial, as it is a sole independent prognostic factor for IFRS-specific mortality. In this review, we describe common and uncommon imaging presentations of biopsy-proven rhino-orbitocerebral mucormycosis in a cohort of nearly 40 COVID-19 patients.

India is witnessing a devastating outbreak of opportunistic rhino-orbito-cerebral

Since the primary site of inoculation of fungus is the nose and paranasal sinuses, clinical presentation in early disease is with facial numbness, pain, or swelling, dark coloured nasal discharge and/or nasal stuffiness. Some patients present with predominant dental symptoms such as jaw pain or loosening of teeth. Clinical features of disseminated disease include blurred vision, proptosis, ptosis, ophthalmoplegia, facial paresis, altered sensorium, and stroke. Unfortunately, many patients from remote areas present late and require debilitating craniofacial resections and orbital exenteration.

Imaging features of mucormycosis closely reflect the angioinvasive behaviour of fungal hyphae from the Mucoraceae family, which invade blood vessels, cause necrotising vasculitis and thrombosis resulting in extensive tissue infarction. The radiological appearances of COVID-19-associated rhino-orbito-cerebral mucormycosis are similar to invasive fungal rhinosinusitis (IFRS) historically identified in immunocompromised individuals with poorly controlled diabetes mellitus, haematological malignancies, and following transplantation or chemotherapy.

The classic imaging sign of the "black turbinate" (BT; Fig. 1 ) refers to lack of contrast enhancement of invaded mucosa secondary to occlusion of small vessels. 4 Caution is warranted while reporting BT as diagnostic of invasive fungal rhinosinusitis (IFRS), as up to 30% of patients without IFRS may have heterogeneous enhancement or even lack of enhancement (particularly in the posterior part of the turbinate). 5 The lack of enhancement in the posterior aspect of the turbinates in patients without IFRS improves temporally if delayed imaging after contrast medium administration is J o u r n a l P r e -p r o o f obtained and has been referred to as "benign BT". 5 In contradistinction, in IFRS, lack of enhancement of the BT persists until the delayed phase of contrast-enhanced imaging. The most common site of involvement of IFRS is the middle turbinate, which filters the major volume of the nasal airflow explaining the penchant for fungal seeding in this region. 6 A similar lack of enhancement is seen in the involved mucosa of the paranasal sinuses ( Fig. 2 ) and sometimes referred to as sinonasal lack of contrast enhancement (LoCE) lesion. 7 A diagnostic pitfall is obscuration of normal enhancement in the sinus by susceptibility artefacts at the air-mucosa interface and adjacent to metallic dental implants. On unenhanced MRI, the fungus has variable signal; however, low T2 signal is characteristic with occasional cases showing restricted diffusion in the invaded mucosa 4 Prior studies have shown contrast-enhanced MRI to demonstrate mucormycosis at considerable distance from the primary focus of infection by perineural spread in addition to perivascular spread. The fungi invade the perineural connective tissue of the cranial nerves and their branches. 13 Perineural spread is known along the trigeminal nerve 14, 15 and rarely along the labyrinthine segment of the facial nerve and geniculate ganglion with retrograde extension into the internal auditory canal (IAC) (Fig. 3a) . Involvement of the pterygopalatine fossa ( Fig. 4) ipsilateral to the diseased nasal cavity in the absence of bone destruction is explained by perineural spread along the superior nasal nerves and sphenopalatine artery. 11 Similarly, involvement of the periantral fat is common without intervening bone destruction. Thus, although J o u r n a l P r e -p r o o f bone dehiscence is a specific marker for IFRS, due to low sensitivity it is not a useful exclusion criterion. 11 In the present epidemic, bone necrosis of the facial skeleton indicating an advanced stage is often seen at presentation 16 A striking feature of skull-base osteomyelitis (SBO) in mucormycosis is extensive soft-tissue infarction and necrosis, which appears as large areas of non-enhancing profoundly low signal devitalised soft tissue in and around the bony central skull base (Fig. 3a) and along the nasopharynx. 19 This is sometimes referred to as extrasinonasal LoCE lesion 7 and not encountered in bacterial SBO. 20 Abscess formation seen in bacterial SBO is not a feature of fungal SBO. Thus, necrosis or J o u r n a l P r e -p r o o f tissue infarction are features of fungal SBO contrasting with suppuration, which is the hallmark of bacterial/pyogenic SBO. 21 Although fungal SBO originates from fungal inoculation in the nasal cavities, bacterial SBO is usually otogenic in origin; however, enhancement patterns of IFRS are known to be diverse. 22 Occasionally, infected soft tissue in maxillofacial or skull base fungal disease may show an alternative contrast enhancement pattern; presenting as variable signal mass, such as soft-tissue thickening, that enhances avidly and also displays restricted diffusion (Fig. 10) .

On postoperative MRI obtained after surgical exenteration, any residual LoCE lesions are associated with a higher mortality and merit further debridement (Fig.   11 ). When infarcted soft tissue cannot be completely eradicated by surgery due to poor access (pterygopalatine fossa) or possibility of complications (cavernous sinus), the prognosis is grim; however, residual contrast-enhancing lesions (including in the orbits and brain) may be conserved with antifungal medication. 7

Large-vessel vasculitis is another distinct feature of rhino-cerebral mucormycosis, seen as mural thickening and enhancement of the intracranial internal carotid artery (ICA) (Fig. 3a) , sometimes leading to ICA occlusion (Fig. 3b) and cerebral infarction.

The vasculitis is secondary to direct invasion of the vessel wall by fungal elements.

The infarcts from fungal vasculitis may be either bland or laden with fungal elements.

Intracranial extension with pachymeningitis, dural-based mass-like lesions (Fig. 12) and cerebritis in the frontal or temporal lobes is also encountered. Vascular invasion and neurotropism are established pathological attributes of invasive mucormycosis. 23 

In clinically or radiologically suspected cases, diagnosis is validated by potassium hydroxide (KOH) wet-mount preparation and histopathology of specimens obtained  In May 2021, the central government in India directs all states to notify "black fungus" or mucormycosis cases under the Epidemic Diseases Act (1897). 2 

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