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MRI Evaluation of Rhino-orbito-cerebral Mucormycosis in Post COVID-19 Patients: A Cross-sectional Study |
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Siddappa Ramappa Shirahatti, KS Prashanth, Eranna Palled, RC Sudhakar 1. Assistant Professor, Department of Radiodiagnosis, Belagavi Institute of Medical Sciences, Belagavi, Karanataka, India. 2. Senior Resident, Department of Radiodiagnosis, Belagavi Institute of Medical Sciences, Belagavi, Karanataka, India. 3. Professor and Head, Department of Radiodiagnosis, Belagavi Institute of Medical Sciences, Belagavi, Karanataka, India. 4. Senior Resident, Department of Radiodiagnosis, Belagavi Institute of Medical Sciences, Belagavi, Karanataka, India. |
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Correspondence Address : Siddappa Ramappa Shirahatti, Department of Radiodiagnosis BIMS Belagavi, Karanataka, India. E-mail: shirahattisiddu@gmail.com |
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| ABSTRACT |  | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
: Introduction: Mucormycosis is the common cause of invasive fungal sinusitis in post Coronavirus Disease-2019 (COVID-19) patient. Mucormycosis is a life-threatening infection with a death rate of >50%. Early detection is critical for determining the amount of infection dissemination, as medical and surgical intervention can reduce death and morbidity. Aim: To evaluate the Magnetic Resonance Imaging (MRI) findings of Rhino-Orbito-Cerebral Mucormycosis (ROCM) in the post COVID-19 patients to detect the extent of the disease and complications. Materials and Methods: This was the retrospective cross-sectional analysis of medical records of 93 patients admitted from 1st June 2021 to 31st July 2021 in tertiary care centre with documented history of COVID-19 infection with clinically suspected and histopathologically confirmed ROCM retrieved for the study. Radiological findings such as involvement of Paranasal Sinus (PNS), intracranial extension, extrasinus extension, orbit, brain parenchyma, perineural extension in ROCM were recorded. Results: Records of total 93 patients (65 males and 28 females; aged between 20-80 years) were studied. The MRI findings revealed, the most common sinus involved was ethmoid sinus (n=92, 98.92%) followed by maxillary (n=90, 96.77%), sphenoid (n=76, 81.72%) and frontal sinus (n=61, 65.59%). There was an involvement of infratemporal and pterygopalatine fossa (n=73, 78.49%), orbit (n=58, 62.36%), cavernous sinus (n=22, 23.65%), Internal Carotid Artery (ICA) (n=12, 12.90%), cranial nerves (n=6, 6.45%), brain parenchyma (n=22, 23.65%) and skull base (n=1, 1.07%). MRI showed T2 isointense to hypointense mucosal thickening and heterogeneous postcontrast enhancement as the most common finding. The mucosa was hypointense on T1W images in all cases (100%). Hypo to isointense components in thickened hyperintense mucosa on T2W images was seen in 77 cases (82.79%). Thickened hyperintense mucosa on T2W images was seen in rest of the 16 (17.20%) cases. Conclusion: In clinically suspected post COVID-19 ROCM cases with typical imaging features (like mucosal thickening with hypointense components on T2W images, demonstration of spread beyond the sinus walls and presence of angioinvasion), even before microbiology or histopathology establish the diagnosis, empirical antifungal medication might be initiated. MRI plays important role in the evaluation of extent of the disease and planning treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Keywords : Brain infarction, Cavernous sinus thrombosis, Coronavirus disease-2019, Hypointense areas, Internal carotid artery occlusion, Magnetic resonance imaging, Sinusitis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DOI and Others :
DOI: 10.7860/IJARS/2022/52041.2800
Date of Submission: Aug 27, 2021 Date of Peer Review: Oct 07, 2021 Date of Acceptance: Feb 17, 2022 Date of Publishing: Jul 01, 2022 AUTHOR DECLARATION: • Financial or Other Competing Interests: None • Was Ethics Committee Approval Obtained for this study? Yes • Was informed consent obtained from the subjects involved in the study? Yes • For any images presented appropriate consent has been obtained from the subjects. Yes PLAGIARISM CHECKING MET |
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| INTRODUCTION |
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The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes COVID-19, with symptoms ranging from moderate to severe pneumonia (1),(2). The rhino-orbital mucormycosis co-infections in COVID-19 patients have increased in the second wave of the COVID-19 pandemic in India (3). Mucormycosis is a fungal infection, caused by the pathogenic genera Absidia, Mucor, Rhizomucor, and Rhizopus of the family Mucoraceae (4),(5). It was initially debatable whether someone taking immunosuppressive drugs was more likely to contract COVID-19 or whether the immunosuppressive state caused more severe COVID-19 infection (6). Severe COVID-19 disease is associated with an increase in pro-inflammatory markers, such as Interleukin (IL)-1, IL-6, and tumour necrosis alpha, decreased interferon gamma expression, cluster of differentiation (CD) 4 and CD8 cells; resulting in, increase in susceptibility to secondary bacterial and fungal infections (7). Mucormycosis is an uncommon fungal infection that is often fatal. It is characterised by vascular invasion by fungal hyphae, resulting in thrombosis and necrosis (8),(9). The fungi infect the host by causing necrotising vasculitis of the nose and sinuses, and quickly spread into the orbits, deep face, meninges, and cranial cavity after being inhaled into the nasal cavity and PNS (9). Early detection is critical for determining the amount of infection dissemination, as medical and surgical intervention can reduce death and morbidity (10). Studies reported MRI is a better choice than Computed Tomography (CT) because of the coincident therapy with nephrotoxic drugs and possible compromised renal function may be made worse by potential nephrotoxicity of iodinated contrast use in CT (4),(11),(12),(13),(14). MRI also provides better evaluation of intracranial and soft tissue involvement, skull base invasion, perineural spread, and vascular obstruction (15). Further, it is important for all radiologist to be familiar with the imaging features of rhino-orbital mucormycosis. Hence, the present study aimed to describe the imaging findings in the post COVID-19 patients who were diagnosed with ROCM. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Material and Methods |
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The present retrospective cross-sectional analysis was conducted at Belagavi Institute of Medical Sciences (BIMS), Belagavi, Karnataka, India, a tertiary care referral centre during the period of 1st June 2021 to 31st July 2021. Medical records of all 93 patients referred within the specified period with documented history of COVID-19 infection with clinically suspected and histopathologically confirmed ROCM were retrieved. The bioethical approval was obtained from BIMS Belagavi for this study (BIMS-IEC/147/2020-21). Inclusion criteria: Records of histopathologically confirmed mucormycosis cases irrespective of any age and sex who had undergone MRI examination were included. Exclusion criteria: Patients with known head and neck malignancy, postchemoradiation, on chronic steroid or immunosuppressive drug therapy (pre COVID-19 infection) were excluded. MRI images of ROCM cases were retrieved from the Picture Archiving and Communication System (PACS). Procedure All patients had MR imaging with a 1.5-T system. Both T1, T2-weighted images, diffusion-Weighted Imaging (DWI), Apparent Diffusion Coefficient (ADC) mapping were obtained as well as T1-weighted images after intravenous injection of gadopentetate dimeglumine (0.1 mmol/kg) were done in the patients. From the MRI images, detailed analysis was made on the signal character, anatomical site, extension, and complications of mucormycosis. Outcomes: Demographic data, common areas involved, type of involvement were noted. Radiological findings such as involvement of PNS, intracranial extension, extrasinus extension, orbit, brain parenchyma, perineural extension in ROCM were recorded. STATISTICAL ANALYSIS All numerical variables were counted and percentages were calculated in Microsoft excel version 2013. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Results |
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In the present study, there were 65 males and 28 females of varying age groups (Table/Fig 1). Patient’s age ranged from 20-80 years with predominant age group was 41-50 years (Table/Fig 1). Most common sinus involved was ethmoid sinus (98.92%) followed by maxillary (96.77%), sphenoid (81.72%), and frontal sinus (65.59%) (Table/Fig 1). Involvement of infratemporal and pterygopalatine fossa (n=73, 78.49%), orbit (n=58, 62.36%), cavernous sinus (n=22, 23.65%), ICA (n=12, 12.90%), cranial nerves (CN) (n=6, 6.45%), brain parenchyma (n=22, 23.65%) and skull base (n=1, 1.07%) was seen. In brain parenchyma, infarction (n=11, 11.83%), cerebritis (n=3, 3.22%), cerebellitis (n=2, 2.15%), brain abscess (n=6, 6.45%) were noted. Further details of sinus and extra sinus extension including the type of involvement are given in (Table/Fig 2), (Table/Fig 3). Paranasal Sinuses (PNS): PNS in cases of the present study were most common site of infection and showed mucosal thickening to compete opacification. The mucosa was hypointense on T1W images in all cases (100%). Hypo to isointense components in thickened hyperintense mucosa on T2W images was seen in 77 cases (82.79%) (Table/Fig 2). Thickened hyperintense mucosa on T2W images was seen in rest of the 16 (17.20%) cases. These hypointense areas represent fungal ball and are hypointense due to its high iron and manganese content. On the postcontrast, mucosa showed heterogeneous enhancement with fungal balls appeared as non enhancing areas in 77 cases (82.79%). Mild homogenous enhancement noted in the rest of 16 cases (17.20%) (Table/Fig 2). Mixed leptomeningeal, pachy meningeal enhancement with ring enhancing lesions were present in 22 patients (23.65%). Extrasinus extension: Initially periantral fat was involved latter fungal infection was seen extending to premaxillary soft tissues in 70 cases (75.27%). The infection was seen extending to deeper planes involving infratemporal fossa and pterygopalatine fossa in 73 cases (78%). These areas were appeared as T2/FLAIR hyper intensities representing inflammation (Table/Fig 3), (Table/Fig 4). Orbit: Infection was seen extending to the orbits in 58 cases (62.36%) through medial wall of ethmoid sinus. Thickening and lateral displacement of medial rectus was observed in cases of the present study. Intra and extraconal spaces were showed T2/STIR (Short Tau Inversion Recovery) hyper intensities with postcontrast enhancement representing cellulitis. Involved optic nerve was thickened with prominent perioptic space (Table/Fig 1), (Table/Fig 5). Intracranial extension: From the PNS, mucor fungi often invade the orbit and progress posteriorly into the cavernous sinus. In 22 patients (23.65%), the cavernous sinus was distended and showed no elevation on postcontrast, indicating thrombosis. ICA narrowing was found in 7 (7.53%) of the individuals in the present study. Due to the sporadic blood supply in watershed territory, there were tiny infarcts in the watershed distribution with high parietal convexity. Absence of ICA flow voids was noted in the 5 (5.38%) cases indicating arterial occlusion secondary to invasion by fungus (Table/Fig 3), (Table/Fig 6), (Table/Fig 7). Brain parenchyma: Spread to the brain may occur via the orbital apex, perineural and the cribriform. In the present study, direct extension to frontal lobe via cribriform was seen. We observed perineural extension from the cavernous sinus to the pons along the right trigeminal nerve. In this study, 3 (3.22%) cases of cerebritis and 2 (2.15%) cases of cerebellitis were noted. In 6 cases (6.45%), the authors noticed well-formed peripherally enhancing brain abscess (Table/Fig 3). Intracranial extension may be in the form of distal mycotic emboli were noted in cases of this study, without direct continuity of infection (Table/Fig 8). Perineural extension (Cranial Nerves): In total of 6 (6.45%) patients, there was thickened and enhancing maxillary division of the trigeminal nerve, thickened, and enhancing cavernous and cisternal portions of the trigeminal nerve (Table/Fig 3). In few patients, the authors observed thickened, enhancing mandibular nerve and with widened foramen spinosum (Table/Fig 9). Skull base involvement: The present study showed skull base involvement in 1 patient (1.07%). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Discussion |
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Accurate and rapid diagnosis of fungal aetiology is the keystone of effective treatment (16),(17). Imaging aids in determining the extent of disease and detecting complications such as thrombosis, which are important for surgical planning (16),(17). The presence of angioinvasion and evidence of spread outside the sinus walls are the two most critical imaging characteristics that indicate a likely fungal aetiology. On contrast-enhanced MRI, the presence of necrosis in the affected structures can be clearly seen. It helps to see periantral and infratemporal fossa extension, orbital soft tissue involvement, and skull base invasion more clearly. Cavernous sinus involvement, vascular invasion, perineural dissemination, optic nerve infarction, and distinction of cerebral parenchymal invasion from infarction can all be detected using the extensive range of contrast mechanisms available on MRI (16),(17). In the present investigation, MRI of ROCM in post COVID-19 patients helped to visualise the disease’s extent. In the present study, from the PNS fungal infection was seen extending to involve infratemporal and pterygopalatine fossa, orbit, cavernous sinus, ICA, cranial nerves, and brain parenchyma. Yousem DM et al., and McDevitt GR et al., concluded in their studies that MRI was highly useful in detection of complications like orbital cellulitis, cavernous sinus thrombosis and ICA thrombosis (11),(18). Most common sinus involved in the present study was ethmoid sinus followed by maxillary, sphenoid, and frontal sinus. Sharma RR et al., reported the involvement of the ethmoid sinus is the most commonly involved PNS (100%) among the included patients (4). Another meta-analysis study found that the most prevalent symptom is PNS involvement, with the ethmoid sinus being the most commonly implicated sinus, trailed by the maxillary sinus. The mucosa of PNS in all the cases was hypointense on T1W images. The mucosa was hypointense on T1W images in all cases and patchy hypointense areas in the hyperintense mucosa on the T2W images in most of cases. Rest of the cases mucosa was hyperintense on T2W images.T2W images showing the hypo to isointense components in thickened hyperintense mucosa in 77 cases (82.79%) represents the fungal infection. The variable signal intensity on the sinus contents was due to the iron and manganese contents in the fungal elements. In their investigation, Herrera DA et al., found that in T1-weighted imaging, the majority of the patients (80%) showed isointense lesions relative to the brain (12). In T2-weighted images, signal intensity was more varied, with only 1 (1.07%) patient showing hyperintensity. The rest of the lesions were either hypointense or isointense in long retention time images. Shrestha DB et al., also described that mucosal thickening with hypointense components on T2W images was suspicious for fungal aetiology (16). On the postcontrast mucosa showed heterogeneous enhancement and fungal balls were appeared as non enhancing areas in most of the cases. The observation was similar as in study by Taylor AM et al., and the enlarged mucosa and associated tissues are seen in Safder S et al., investigations describing postcontrast enhancement (19),(20). The “black turbinate sign” is defined as patches of non enhancing soft tissue within the afflicted turbinates and/or PNS (11),(21). Although, normal PNS are usually hypointense on all sequences, during the infection, mucor fungi often invade the orbit and progress posteriorly into the cavernous sinus from the PNS. Thrombosis of the cavernous sinus and cavernous carotid artery may then occur, and intracranial extension may be in the form of distal mycotic emboli or direct meningeal inflammation (13). Extension beyond the sinuses is one of the most important indicators suggesting fungal aetiology. Orbit was the most common site of extrasinus involvement followed by the face (22). Similarly, in this study, infection extended to the orbits in 62% cases through medial wall of ethmoid sinus. In a comparable study, Therakathu J et al., found that the orbit (76%) and face (57%) were the most prevalent sites of extrasinus involvement, followed by the orbital apex, masticator space, pterygopalatine fossa, bone, skull base, cavernous sinus, brain, and ICA (22). Press GA et al., described from the PNS, mucor fungi often invade the orbit and progress posteriorly into the cavernous sinus (13). Thrombosis of the cavernous sinus and cavernous carotid artery may then occur, and intracranial extension may be in the form of distal mycotic emboli or direct meningeal inflammation. According to Chan LL et al., in ROCM, thickening and lateral displacement of the medial rectus muscle are signs of orbital invasion from ethmoid sinus illness (14). It’s possible to notice a lack of elevation in the ICA, which is linked to vasculitis and thrombosis. Infarcts caused by arterial thrombosis, mycotic emboli, and frontal lobe abscesses are among the intracranial findings. Mc Lean FM et al., study showed that fungal hyphae tend to involve nerves and vessel wall leading to perineural spread and cavernous sinus invasion (23). In patients of the present study, involvement of trigeminal nerve and perineural spread to the pons along trigeminal nerve were observed. Skull base osteomyelitis and bony involvement is usually not present occurs last in the course of the disease (10),(11). This occurs due to the angioinvasiveness of the fungi and their susceptibility to extend into the soft tissues of the orbit and deep face and into the brain through vessels penetrating out of partitions in the skull base (14). In the present study, skull base was involved in only in one case indicating the severity or later stage of the disease. In another similar study, five patients with acute mucormycosis developed chronic infection with bone involvement following the initial treatment (22). Overall, the study states that MRI proved to be very useful in detection of extent of the disease and complications. However, the study has few potential limitations that need to be acknowledged. COVID-19 patients with high-risk features should be monitored carefully. Even with a slight suspicion of ROCM, clinicians should initiate early treatment with appropriate antifungal therapy need to be recommended. Diabetes and other any underlying risk factors should be treated at an earliest by clinicians to minimise patient’s morbidity and mortality. Authors also recommend multi-centre studies with larger sample size to evaluate diagnostic potential of MRI. Limitation(s) First, it was a retrospective study with a limited number of patients and lacking control group. second, as the present analysis was retrospective, there were some differences in the imaging methodology utilised to evaluate suspected mucormycosis cases. The presence of metallic dental work and the presence of air within the sinuses alter the magnetic field, contributing to the artefacts in these areas. Finally, we needed follow-up data to evaluate whether the MRI anomalies were transient or not and their effects on visual acuity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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