Clinical and Neuroimaging Characteristics of Ischemic Stroke in Rhino-Orbito-Cerebral Mucormycosis Associated with COVID-19.

PURPOSE: The aim of this study was to compare clinical, neuroimaging, and laboratory features of rhino-orbito-cerebral mucormycosis (ROCM) in COVID-19 patients with and without ischemic stroke complications. METHODS: This observational study was conducted between August and December 2021 and 48 patients who had confirmed ROCM due to COVID-19, according to neuroimaging and histopathology/mycology evidence were included. Brain, orbit and paranasal sinus imaging was performed in all included patients. Data pertaining to clinical, neuroimaging, and laboratory characteristics and risk factors were collected and compared between patients with and without ischemic stroke complications. RESULTS: Of the patients 17 were diagnosed with ischemic stroke. Watershed infarction was the most common pattern (N = 13, 76.4%). Prevalence of conventional risk factors of stroke showed no significant differences between groups (patients with stroke vs. without stroke). Cavernous sinus (p = 0.001, odds ratio, OR = 12.8, 95% confidence interval, CI: 2.3-72) and ICA (p < 0.001, OR = 16.31, 95%CI: 2.91-91.14) involvement was more common in patients with stroke. Internal carotid artery (ICA) size (on the affected side) in patients with ischemic stroke was significantly smaller than in patients without stroke (median = 2.4 mm, interquartile range, IQR: 1.3-4 vs. 3.8 mm, IQR: 3.2-4.3, p = 0.004). Superior ophthalmic vein (SOV) size (on the affected side) in patients with stroke was significantly larger than patients without stroke (2.2 mm, IQR: 1.5-2.5 vs. 1.45 mm IQR: 1.1-1.8, p = 0.019). Involvement of the ethmoid and frontal sinuses were higher in patients with stroke (p = 0.007, OR = 1.85, 95% CI: 1.37-2.49 and p = 0.011, OR = 5, 95% CI: 1.4-18.2, respectively). Patients with stroke had higher D­dimer levels, WBC counts, neutrophil/lymphocyte ratios, and BUN/Cr ratio (all p < 0.05). CONCLUSION: Stroke-related ROCM was not associated with conventional ischemic stroke risk factors. Neuroimaging investigations including qualitative and quantitative parameters of cavernous sinus, ICA and SOV are useful to better understand the mechanism of stroke-related ROCM in COVID-19 patients.

MR imaging spectrum in COVID associated Rhino-Orbito-Cerebral mucormycosis with special emphasis on intracranial disease and impact on patient prognosis.

In the wake of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, a new epidemic of COVID associated mucormycosis (CAM) emerged in India. Early diagnosis and prompt treatment of this deadly disease are of paramount importance in improving patient survival. MRI is the cornerstone of diagnosis of early extrasinus disease, particularly intracranial complications which have traditionally been associated with a high mortality rate. In this review, we depict the sinonasal, perisinus, orbital and intracranial involvement in CAM. Special emphasis is laid on intracranial disease which is categorized into vascular, parenchymal, meningeal, bony involvement and perineural spread. Vascular complications are the most common form of intracranial involvement. Some unusual yet interesting imaging findings such as nerve abscesses involving the optic, trigeminal and mandibular nerves and long segment vasculitis of the internal carotid artery extending till its cervical segment are also illustrated. In our experience, patient outcome in CAM (survival rate of 88.5%) was better compared to the pre-pandemic era. Presence of intracranial disease also did not affect prognosis as poorly as traditionally expected (survival rate of 82.8%). Involvement of brain parenchyma was the only subset of intracranial involvement that was associated with higher mortality (p value 0.016). The aim of this review is to familiarise the reader with the MR imaging spectrum of CAM with special focus on intracranial complications and a brief account of their impact on patient prognosis in our experience.

Coronavirus Disease 2019 (COVID-19)-Associated Rhino-Orbito-Cerebral Mucormycosis: A Multi-Institutional Retrospective Study of Imaging Patterns.

BACKGROUND: Mucormycosis infection of the maxillofacial region and brain has been associated with coronavirus disease 2019 (COVID-19) infection. Mucormycosis was relatively a rare infection before COVID-19, and imaging findings are not very well described. MATERIALS AND METHODS: A retrospective imaging study of 101 patients diagnosed with COVID-19-associated mucormycosis by histopathology and/or culture was performed. All patients underwent computed tomography and/or magnetic resonance imaging based on the clinical condition of the patient and on consensus decision by the team of treating physicians. A simple 3-stage classification system based on imaging findings was adopted. RESULTS: One hundred one cases were included in the final analysis (mean age = 55.1 years; male/female ratio = 67:34). The affected patients had diabetes in 94% of the instances (n = 95), 80.1% (n = 81) received steroids), whereas 59.4% (n = 60) patients received supplemental oxygen. The majority underwent surgical intervention, whereas in 6 cases, patients were treated with antibiotic regimens. Sixty subjects improved following therapy, whereas 18 eventually succumbed to the illness. We noted a significant positive correlation between the imaging stage and outcomes. No association was seen between other clinical parameters and final clinical outcomes. Salient imaging findings include lack of normal sinonasal mucosal enhancement, perisinus inflammation, ischemic optic neuropathy, perineural spread, pachymeningeal enhancement, and presence of strokes. CONCLUSIONS: We describe the imaging findings in the largest cohort of patients with rhino-orbito-cerebral mucormycosis in the context of the current COVID-19 pandemic. A simplified staging system described here is helpful for standardized reporting and carries prognostic information.

COVID-19-Related Rhino-Orbital-Cerebral Mucormycosis in a Renal Transplant Recipient.

Coronavirus disease 2019 increases transplant recipients' susceptibility to rare opportunistic infections as a consequence of the impairment that COVID-19 can cause in the immune system. Mucormycosis is a rare complication but has a high risk of fatal outcome. A 50-year-old woman who received a kidney transplant 10 years previously was admitted to the hospital with COVID-19. During follow-up by the inpatient service, the patient developed pain, edema, and proptosis in the right eye. She was diagnosed with rhino-orbitalcerebral mucormycosis. This is the first reported case of rhino-orbital-cerebral mucormycosis in a renal transplant recipient with COVID-19 infection.

Magnetic Resonance Imaging in Coronavirus Disease - 2019 Associated Rhino-Orbital-Cerebral Mucormycosis (CA-ROCM) - Imaging Analysis of 50 Consecutive Patients.

BACKGROUND AND PURPOSE: Rhino-orbital-cerebral mucormycosis has emerged as a major opportunistic infection in patients with COVID-19. High clinical suspicion and prompt imaging are crucial for early diagnosis and management. Our study evaluates imaging characteristics of patients with COVID-19 associated Rhino-orbital-cerebral Mucormycosis (CA-ROCM) in a tertiary care hospital in India. MATERIALS AND METHODS: A retrospective analysis of clinical and imaging data of patients with CA-ROCM who presented between December 2020 to June 2021 was performed. All patients had microbiologically or histologically proven sino-nasal mucormycosis along with documented SARS-CoV-2 positive RT-PCR test and/or classical lung imaging features of COVID-19 infection. The extent of sinus involvement, bony erosions, extra-sinus soft tissue extension, orbital-intracranial invasion, perineural spread, and vascular complications were assessed. RESULTS: Fifty patients were included for the final analysis. Diabetes was the most common associated comorbidity. Seven patients presented with stage I disease, 18 patients with stage II, and 25 patients with stage III disease. The stage of disease showed a positive statistical correlation with HbA1c levels using Pearson's correlation. The common imaging features were "Black turbinate sign" and nonenhancing sino-nasal mucosa (82%), orbital involvement (76%), and diffusion restriction in the optic nerve (24%). Intracranial involvement was seen as perineural extension into the brain (42%), cerebritis (30%), and internal carotid artery involvement (16%). CONCLUSIONS: CA-ROCM is an acute invasive fungal sinusitis with an aggressive clinical course. Black-turbinate sign and peri-antral soft tissue infiltration are early features, whereas extra-nasal tissue infarction, optic nerve diffusion restriction, and vascular invasion are seen with advanced disease.

CT and MRI Findings of Invasive Mucormycosis in the Setting of COVID-19: Experience From a Single Center in India.

An increasing incidence of rhinoorbitocerebral mucormycosis (ROCM) among patients with COVID-19 has recently been reported in India. We report the imaging findings for 25 patients with COVID-19 and invasive ROCM at a single hospital in India. Findings included sinus wall erosions (n = 20), air within bony sinus structures (n = 11), and focal mucosal nonenhancement (n = 8). Orbital, vascular, and intracranial complications were also observed. Radiologists should recognize the increasing incidence of ROCM among patients with COVID-19 to facilitate early diagnosis.

COVID-19 associated Rhino-Orbito-Cerebral Mucormycosis: Imaging spectrum and Clinico-radiological correlation- a single Centre experience.

PURPOSE: The study aims to depict the radiological features of Cov-ROCM, depict the common routes of spread to orbits and intracranial compartment and look for an association of the risk factors with radiological severity of the disease. METHODS: 96 patients who had COVID-19 infection in the past 3 months and were diagnosed with ROCM underwent CECT PNS examinations which were assessed by two experienced radiologists. They were divided into three groups based on the intraorbital and intracranial involvement and were correlated with various risk factors. RESULTS: The incidence of bony erosions which was the commonest finding (75%) was double in Cov-ROCM than the ROCM cases of pre COVID era (33-40%). The most common route of spread to orbit was through angioinvasion(52%) with intact orbital walls; and intracranial extension was via erosion of the cribriform plate(52%). Sphenoid sinus involvement is strongly associated with intracranial and intraorbital involvement.(p-value = .0004). History of longer ICU stays and being on mechanical ventilation as a part of COVID management is associated with aggressive disease pattern(p-value = .002). Similarly, poor glycaemic control signified by raised HbA1c levels showed statistically significant correlation with severe Cov-ROCM(intraorbital/intracranial extension) (p-value = .040). CONCLUSION: Amidst the COVID pandemic, it is pertinent to look at bony erosions in case of any sinusitis, especially bony maxillary walls and the turbinates. The intraorbital compartment must be viewed thoroughly even in the absence of bony erosions due to the angioinvasive nature of these fungi. Aggressive follow-up for patients with ICU stays for COVID and for glycaemic control would help reduce the morbidity.

Imaging findings using a combined MRI/CT protocol to identify the "entire iceberg" in post-COVID-19 mucormycosis presenting clinically as only "the tip".

AIM: To analyse combined computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of invasive rhino-orbital mucormycosis (IROM) in post-COVID-19 infection patients for accurate diagnosis and delineation of the extent of involvement. MATERIALS AND METHODS: A retrospective analysis was undertaken of 50 patients who developed IROM post-COVID-19 infection who underwent combined CT/MRI evaluation. RESULTS: The age range of the 50 affected patients was 23-73 years. Out of these, 41 were diabetic. CT/MRI showed predominant involvement of the maxillary (n=26) and ethmoid (n=19) sinuses. Extension of disease to the orbit (n=35), cavernous sinus (n=18), hard palate (n=15), skull base (n=8), and intracranial involvement (n=3) was seen. Perineural spread of the disease was analysed along all divisions of the trigeminal nerve and its branches. MRI showed T2-hypointense soft-tissue thickening with heterogeneous contrast enhancement with corresponding hyperdensities on CT diagnosing the presence of fungal elements. CONCLUSION: Clinicians should be aware of the possibility of IROM post-COVID-19 infection. Conjunctive use of CT, which depicts bone destruction and other reactive bony changes along with MRI, which reveals characteristic findings of soft-tissue thickening of the involved sinuses with extension of disease to the orbits, cavernous sinus, dura, hard palate, skull base, and intracranial structures. Accurate diagnosis and early recognition of the disease and its extension with appropriate use of these techniques helps to initiate appropriate and timely treatment, which is vital to prevent a fatal outcome.

Imaging of COVID-19-associated craniofacial mucormycosis: a black and white review of the "black fungus".

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.

Increased incidence of rhino-orbital mucormycosis in an educational therapeutic hospital during the COVID-19 pandemic in western Iran: An observational study.

BACKGROUND: COVID-19 patients, especially the patients requiring hospitalisation, have a high risk of several complications such as opportunistic bacterial and fungal infections. Mucormycosis is a rare and opportunistic fungal infection that mainly affects diabetic and immunocompromised patients. An increase has been observed in the number of rhino-orbital mucormycosis in patients with COVID-19 admitted to Imam Khomeini Hospital, Kermanshah, Iran, since October 2020. This is a report of the frequency, risk factors, clinical manifestations, treatment and prognosis of COVID-19 associated with mucormycosis infection. METHODS: The medical records of COVID-19 patients with rhino-orbital mucormycosis who were diagnosed in an educational therapeutic hospital in Kermanshah, west of Iran were surveyed. Several parameters were analysed including demographic, clinical, therapeutic and laboratory characteristics. RESULTS: Twelve patients with COVID-19-associated rhino-orbital mucormycosis were identified from 12 October to 18 November 2020. All cases reported as proven mucormycosis had a history of hospitalisation due to COVID-19. Comorbidities mainly included diabetes mellitus (83.33%) and hypertension (58.33%). Seventy-five per cent of patients received corticosteroids for COVID- 19 treatment. The sites of involvement were rhino-sino-orbital (83%) and rhino-sino (17%). Amphotericin B/liposomal amphotericin B alone or in combination with surgical debridement or orbital exenteration was used as the first-line therapy. The overall mortality rate was 66.7% (8/12). CONCLUSIONS: We found a high incidence of mucormycosis among COVID-19 patients. Diabetes mellitus and corticosteroid use were the dominant predisposing factor of mucormycosis. Mucormycosis is a life-threatening and opportunistic infection; therefore, physicians should know the signs and symptoms of the disease so that a timely diagnosis and therapy can be performed.

Magnetic resonance imaging in rhino-orbital-cerebral mucormycosis.

Coronavirus disease-associated mucormycosis (CAM) is an established clinical entity in India. In the past 4 months, there has been a sharp upsurge in the number of CAM cases in most parts of the country. Early diagnosis can be lifesaving. Magnetic resonance imaging (MRI) imaging remains the corner stone of management in patients with ROCM. This review discussed the utility of MRI imaging in ROCM with an emphasis on the ideal MRI protocol in a suspected case of ROCM, the pathways of spread of infection, the classic diagnostic features, MRI for staging of the disease, MRI for prognostication, MRI for follow up, and imaging features of common differentials in ROCM. The pit falls of MRI imaging and a comparison of CT and MRI imaging in ROCM are discussed. The clinical interpretation of areas of contrast uptake and those of necrosis and its relevance to treatment are discussed. This review aims to familiarize every member of the multidisciplinary team involved in managing these patients to be able to interpret the findings on MRI in ROCM.

COVID-19 triggering mucormycosis in a susceptible patient: a new phenomenon in the developing world?

A middle-aged woman with diabetes presented with left-sided facial pain, complete ptosis and fever of short duration. On presentation, she had hyperglycaemia without ketosis. There was total ophthalmoplegia of the left eye with a visual acuity of 6/36. She incidentally tested positive for COVID-19. CT paranasal sinus and MRI brain revealed left-sided pansinusitis with acute infarct in the left parieto-occipital region without angioinvasion. An emergency functional endoscopic sinus procedure was done, which confirmed mucormycosis on histopathological examination. After 1 week of conventional amphotericin B and antibiotics, repeat CT brain showed improvement in mucosal thickening and sinusitis. This case is a rare presentation of mucormycosis associated with rapid progression to orbital apex syndrome with brain infarction in a patient with non-ketotic diabetes and COVID-19. Early diagnosis and treatment are essential to prevent further end-organ damage. It is also interesting that there was no angioinvasion and transient periarterial inflammation was attributed to brain infarction.

Secondary infection with rhino-orbital cerebral mucormycosis associated with COVID-19.

We report two fatal cases of rhino-orbital-cerebral mucormycosis associated with COVID-19 infection. Both patients had pre-existing diabetes mellitus type 2, were treated with corticosteroids, and developed ketoacidosis. Both patients rapidly declined owing to rapid extension of the infection into the intracranial cavity. We postulate that additional risk factors for opportunistic fungal infection exist in COVID-19 patients including mechanical ventilation and Sars-CoV-2 induced immunosuppression. The ophthalmologist's role is particularly important in the early diagnosis of mucormycosis associated with COVID-19.