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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 7  |  Issue : 2  |  Page : 282-288

COVID-associated rhino-orbito-cerebral mucormycosis: A comparative study between computed tomography and magnetic resonance imaging for its early detection in suspected cases of rhino-orbito-cerebral mucormycosis


Department of Radiodiagnosis, Mahadevappa Rampure Medical College, Gulbarga, Karnataka, India

Date of Submission06-Apr-2022
Date of Decision11-Apr-2022
Date of Acceptance17-May-2022
Date of Web Publication09-Sep-2022

Correspondence Address:
Priyanka C Megharaj
No. 31, 2nd Cross Road, AECS Layout 2nd Stage, RMV 2nd Stage, Sanjaynagar, Bengaluru - 560 094, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjhs.bjhs_51_22

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  Abstract 


INTRODUCTION: Rhino-orbito-cerebral mucormycosis (ROCM), a life-threatening, acute fungal infection of the nasal cavities and paranasal sinuses, once considered a rare and lethal complication in immunocompromised patients, is now having a massive increase in ROCM incidence in India associated with COVID-19, i.e., COVID-associated mucormycosis with more than 15,000 cases as of May 2021. Early imaging by computed tomography (CT) and magnetic resonance imaging (MRI) is not only helpful in assessing the extent of involvement of this lethal disease but also helps in early diagnosis leading to prompt and aggressive treatment. The present study is aimed at determining and comparing the imaging findings on CT and MRI in ROCM patients, for early diagnosis in suspected cases of ROCM.
MATERIALS AND METHODS: The present study is a comparative study of CT and MRI done on 11 patients suspected of ROCM, for 2 months from May to June 2021.
RESULTS: Among 11 patients in the study group, ranging from 29 to 65 years of age, 45.4% belonged in 41–60 years of age group, with female predominance. 90.90% cases (10 patients) had maxillary sinus involvement among which 7 cases were diagnosed with ROCM, followed by 63.60% cases (7 patients) had ethmoidal sinus involvement among which 6 cases were diagnosed with ROCM. The involvement of retromaxillary space, pterygopalatine fossa space and masticator space, and cellulitis in premaxillary and preseptal spaces were findings seen only in diagnosed cases of ROCM. Erosions of bones were seen in ROCM cases, 27.20% cases (3 patients) had erosions of walls of maxillary sinus and lamina papyracea each. Orbital involvement in the form of intraconal space and extraocular muscles involvement was seen in 27.20% cases (3 patients) each. Optic nerve involvement was seen in 18.10% cases (2 patients) followed by extraconal space involvement in 9.01% cases (1 patient). Taking KOH staining and/or histopathology (HPR) as standard of reference, CT has a Sensitivity (Sn) of 71.40%, Specificity (Sp) of 100%, Positive predictive value (PPV) of 100%, Negative Predictive Value (NPV) of 66%, and Diagnostic accuracy (DA) of 81% as compared to MRI which has a Sn of 85.7%, Sp of 100%, PPV of 100%, NPV of 80%, and DA of 90.9%.
CONCLUSIOIN: CT and MRI play a complementary role in diagnosis of ROCM, as CT is better in detecting bone erosions, whereas MRI is better in detecting soft tissue, orbital and central nervous system involvement. In the acute state of emergency as in the current pandemic with rising cases of ROCM and acute shortage of amphotericin-B, MRI is the single best modality for accurate detection of ROC, helping clinicians in the judicious use of Amphotericin-B.

Keywords: Computed tomography, magnetic resonance imaging, rhino-orbito-cerebral mucormycosis


How to cite this article:
Megharaj PC, Patil VM, Reddy S. COVID-associated rhino-orbito-cerebral mucormycosis: A comparative study between computed tomography and magnetic resonance imaging for its early detection in suspected cases of rhino-orbito-cerebral mucormycosis. BLDE Univ J Health Sci 2022;7:282-8

How to cite this URL:
Megharaj PC, Patil VM, Reddy S. COVID-associated rhino-orbito-cerebral mucormycosis: A comparative study between computed tomography and magnetic resonance imaging for its early detection in suspected cases of rhino-orbito-cerebral mucormycosis. BLDE Univ J Health Sci [serial online] 2022 [cited 2023 Jan 28];7:282-8. Available from: https://www.bldeujournalhs.in/text.asp?2022/7/2/282/355856



Rhino-orbito-cerebral mucormycosis (ROCM), once considered a rare, lethal complication in immunocompromised patients, is now having a massive increase in ROCM incidence in India associated with COVID-19, i.e., COVID-associated mucormycosis (CAM) with more than 15,000 cases as of May 2021.[1] ROCM is life-threatening, acute fungal infection of the nasal cavities and paranasal sinuses, spreading into adjacent neck spaces, orbits, and intracranial structures due to its necrotizing and angioinvasive properties of the mucormycosis infection. It is caused by saprophytic fungi belonging to the genera Mucor, Rhizopus, and Absidia.[2],[3] The disease progresses rapidly within a few hours to days leading to ocular and cerebral involvement leading to increased morbidity and mortality.

Early imaging by computed tomography (CT) and magnetic resonance imaging (MRI) is not only helpful in assessing the extent of involvement of this lethal disease but also helps in early diagnosis leading to prompt and aggressive treatment. CT and MRI both play an essential role in the diagnosis of ROCM, CT is better for assessing bone erosion, whereas MRI is superior in evaluating soft tissue, intraorbital extension, and in assessing intracranial and vascular invasion.[4]

The present study is aimed at determining and comparing the imaging findings on CT and MRI in ROCM patients, for early diagnosis in suspected cases of ROCM.


  Materials and Methods Top


The study was conducted in the Department of Radiodiagnosis, Basaweshwara Teaching and General Hospital attached to Mahadevappa Rampure Medical College, Kalaburagi-585105. It is a comparative prospective study conducted for 2 months from May to June 2021.

All patients giving consent with a history of hospitalization for severe COVID, treated with corticosteroids, now presenting with complaints suspecting ROCM with the duration of <7 days (early presentation) were included in the study. Patients with claustrophobia, contraindications such as metallic implants and refusing to be a part of the study were excluded from the study.

After applying inclusion–exclusion criteria, consent was taken from selected patients, and information was collected in prepared pro forma from each patient. All suspected cases of ROCM underwent CT and MRI scan of brain.

A total of 11 patients underwent CT and MRI scan of brain. CT scan was done in Philips 16-slice CT machine. It consists of contiguous axial sections of thickness 5 mm of brain in craniocaudal direction from the level of vertex till mentum. Reconstruction done with a slice thickness of 1.25 mm. All images were viewed in a range of soft tissue and bone window settings. MRI scan was done in Philips Achieva 1.5-Tesla magnet MR system, using a head coil with the patient in a supine position with slice thickness of 4–5 mm; with an inter-slice gap of 0.5 mm. The following sequences were obtained:

  • Axial and sagittal T1-weighted sequence
  • Axial and coronal T2-weighted sequence
  • Axial fluid-attenuated inversion recovery sequence
  • Diffusion-weighted imaging
  • Susceptibility-weighted imaging/gradient recalled echo
  • Coronal T2-weighted SPIR sequence for peripheral nervous system (PNS) and orbits
  • Axial T2-weighted spectral attenuated inversion recovery sequence for PNS and orbits.


All patients were followed up, swab from nasal discharge and/or nasopharynx was sent for KOH stain and histopathology. Patients with positive KOH stain and/or histopathology were diagnosed with ROCM and patients with negative KOH stain and/or histopathology were diagnosed with Sinusitis. Radiological findings in both the patients of ROCM and sinusitis were compared on CT and MRI. Radiological characteristics of the lesions were analyzed and described.

The statistical data collected were spread on excel sheet, and analyzed using IBM SPSS (Statistical package for social science) Software version 20.0 (IBM corporation, Headquartered at Armonk, NY state, USA). Percentage and proportion were used for qualitative data, mean and standard deviation was used for quantitative data. Tests of diagnostic validity such as sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA) were calculated with 95% confidence interval. Graphs and tables were used for representing the data.


  Observations and Results Top


The comparative prospective study was done on 11 patients suspected of ROCM referred to Department of Radiodiagnosis, Basaweshwara Teaching and General Hospital attached to Mahadevappa Rampure Medical College, Kalaburagi, for 2 months from May to June 2021. The imaging features of all ROCM and sinusitis patients on CT and MRI were compared and analyzed.

Age and gender wise distribution

A total of 11 patients in the study group were from 29 to 65 years of age, with mean of 52.3 years and maximum patients belonging in 41–60 years of age group. There were 9 females and 2 males in the study group, with female predominance [Chart 1].



Symptom wise distribution

Patients suspected of having mucormycosis (ROCM) presented with various overlapping symptoms such as swelling and tenderness in premaxillary region, nasal discharge, periorbital swelling and tenderness, discharge from eye, ptosis, fever, and headache.

63.60% cases (9 patients) presented with swelling in premaxillary region with tenderness in 54.50% cases (6 patients), 45.40% cases (5 patients) presented with swelling and tenderness in periorbital region. Headache was seen in 54.50% cases (6 patients). Patients diagnosed with ROCM also presented with blurring of vision (27.20%), nasal discharge (27.20%), discharge from eye (18.10%), ptosis (18.10%), and fever (9.01%), which were not seen in patients diagnosed with only sinusitis [Chart 2].



Imaging features in patients suspected of rhino-orbito- mucormycosiscerebral

Sinus involvement

Bilateral or unilateral involvement of maxillary, ethmoidal, sphenoidal, and frontal sinus was noted [Figure 1]a and [Figure 1]b; [Figure 3]a.
Figure 1: Axial (a) and Coronal (b) CT sections of PNS shows bilateral maxillary, ethamoidal and frontal sinus involvement (Left > Right), with subtle fat stranding in premaxillary space (#) and retromaxillary space (*) on left side. Coronal section through orbit reveals bulky medial and inferior rectus with intraconal fat stranding (+). Axial STIR (c) and Coronal SPIR (d) sections shows hyperintensities in premaxillary space (#) and retromaxillary space (*) on left side with intraconal fat stranding (+) and bulky medial and inferior rectus. Suggesting Invasive fungal sinusitis with orbital involvement. CT: Computed tomography, PNS: Peripheral nervous system, STIR: Short tau inversion recovery

Click here to view
Figure 2: Axial CT (a) and Axial SPIR (b) sections reveals right sided maxillary sinusitis with hyperintensities involving premaxillary and retromaxillary (*) space on right side, compared to the normal retromaxillary space (#) on left side. Suggesting early features of invasive fungal sinusitis. CT: Computed tomography

Click here to view
Figure 3: Axial CT (a) reveals bilateral maxillary sinusitis with hyperdense sinus (*), Coronal CT (b) reveals bulky medial rectus with intraconal fat stranding (+). Axial STIR (c) and Coronal SPIR (d) sequences reveals hyperintensity involving left optic nerve along with hypeintensity involving medial intraconal space and bulky medial rectus on left side. Suggesting Invasive fungal sinusitis with orbital and optic nerve involvement. CT: Computed tomography, STIR: Short tau inversion recovery

Click here to view


90.90% cases (10 patients) had maxillary sinus involvement [Figure 4]a among which 7 cases were diagnosed with ROCM, followed by 63.60% cases (7 patients) ethmoidal sinus involvement among which 6 cases were diagnosed with ROCM. Sphenoid sinus [Figure 4]b and frontal sinus were involved in 54.50% (6 patients) and 45.40% (5 patients) cases, respectively, both seen in ROCM diagnosed cases [Chart 3].
Figure 4: Axial CT (a) and Sagittal CT section (b) in bone window reveals left-sided maxillary and sphenoidal sinusitis with bony erosions involving posterolateral wall of the left maxillary sinus (*) and floor of sphenoid sinus and part of clivus (#). DWI sequence (c) showing increased signal intensity on iso sequence with corresponding dark signal intensity on ADC image (not shown) suggestive of acute infarct involving genu of internal capsule on left side (Left ICA territory). On Axial STIR sequence shows sphenoid sinus involvement with loss of flow void in left ICA (arrow) suggesting thrombosis of left ICA. Overall features suggesting Invasive fungal sinusitis with bony erosions and ICA thrombosis causing acute infarct. DWI: Diffusion-weighted imaging, ADC: Apparent diffusion coefficient, ICA: Internal carotid artery, STIR: Short Tau Inversion Recovery, CT: Computed tomography

Click here to view



Cellulitis and spaces involved

Cellulitis was seen in premaxillary and preseptal spaces as soft tissue thickening on CT and short tau inversion recovery (STIR) hyperintensities on MRI [Figure 1]c. The involvement of retromaxillary space, pterygopalatine fossa space, and masticator space was seen as fat stranding on CT, and SPIR hyperintensities on MRI in involved spaces [Figure 1]c; [Figure 2]a and [Figure 2]b.

The involvement of retromaxillary space, pterygopalatine fossa space and masticator space, and cellulitis in premaxillary and preseptal spaces were findings seen only in diagnosed cases of ROCM. 45.40% cases (5 patients) had predominant retromaxillary, 36.30% cases (4 patients) had masticator space involvement, only 9.01% cases (1 patient) had pterygopalatine fossa involvement. 36.30% cases (4 patients) had premaxillary cellulitis and 18.10% cases (2 patients) had preseptal cellulitis [Chart 4] and [Chart 5].



Bones involved

Walls of four sinuses, superior, middle and inferior turbinates, lamina papyracea, and cribriform plate were among the commonly involved bones in ROCM, seen as erosions of bones on CT.

In the present study, erosions of bones were seen in ROCM cases, 27.20% cases (3 patients) had erosions of walls of maxillary sinus (posterolateral wall) and lamina papyracea each [Chart 6].



Orbital involvement

Extraconal and intraconal space involvement is seen as areas of fat stranding on CT, and STIR hyperintensities on MRI [Figure 1]d. Extraocular muscles (EOM) appear as bulky muscles on CT and MRI, showing STIR hyperintensities on MRI when involved [Figure 3]b,[Figure 3]c,[Figure 3]d.

Orbital involvement in the form of intraconal space and EOM involvement was seen in 27.20% cases (3 patients) each, optic nerve involvement was seen in 18.10% cases (2 patients) followed by extraconal space involvement in 9.01% cases (1 patient) [Chart 7].



Central nervous system involvement

Central nervous system (CNS) involvement is seen as areas of infarct, abscess, leptomeningeal, internal carotid artery (ICA), and cavernous sinus involvement. Only severe cases of ROCM had cerebral involvement [Figure 4]c.

One patient (9.01%) diagnosed with ROCM had CNS involvement in the form of ICA thrombosis [Figure 4]d causing a cerebral infarct [Chart 8].



Comparison between computed tomography and magnetic resonance imaging in rhino-orbito-cerebral mucormycosis patients

In the present study of 11 patients, 7 patients were diagnosed with mucormycosis on KOH staining and/or histopathology (HPR). Taking KOH staining and/or histopathology (HPR) as gold standard, CT, and MRI detection of ROCM was compared.

As per the analysis, considering KOH staining and/or histopathology (HPR) as standard of reference, CT has a Sn of 71.40%, Sp of 100%, PPV of 100%, NPV of 66% and DA of 81% as compared to MRI which has a Sn of 85.7%, Sp of 100%, PPV of 100%, NPV of 80% and DA of 90.9%.


  Discussion Top


COVID-19-associated ROCM (CAM) usually manifests as an acute fulminant invasive form during the active or convalescent phase of COVID-19 disease and has a high mortality of up to 49%.[5] Hence, high index of suspicion and early imaging is needed for timely diagnosis and treatment of ROCM. Therefore, the present study is aimed at determining and comparing the imaging findings on CT and MRI in ROCM patients, for early diagnosis in suspected cases of ROCM presenting early (<7 days of onset of symptoms).

In the present comparative prospective study of 11 suspected cases of ROCM, the mean age of the patients was 52.3 years with a female predominance. All patients with a history of hospitalization for severe COVID, treated with corticosteroids, now presenting early (<7 days of onset of symptoms) with complaints suspecting ROCM were analyzed and, among 7 patients who were diagnosed with ROCM on KOH and/or histopathology 5 patients had Diabetes Mellitus (DM) indicating the predominant risk factor of DM-associated with CAM. According to a study by Nithyanandam et al., uncontrolled diabetes was the most common underlying disease in ROCM.[6] Another study Yadav et al., also found DM as the most common associated comorbidity.[7]

Patients presented with overlapping symptoms with most of the patients presenting with Swelling and tenderness in premaxillary region and periorbital region. Patients of ROCM presented with blurring of vision, nasal and eye discharge, ptosis and fever, which were not seen in patients diagnosed with sinusitis.

90.90% cases (10 patients) showed maxillary sinus[8] involvement followed by ethmoidal and sphenoidal sinus, frontal sinus was involved in least number of cases (5 cases). CT and MRI both showed equal Sn in detecting the sinus involvement.

Imaging features in ROCM such as retromaxillary and masticator space involvement were seen in 45.40% and 36.30% cases, respectively. Premaxillary and preseptal cellulitis were seen in 36.30% and 18.10% cases, respectively. EOM and intraconal space involvement were seen in 27.20% cases each, optic nerve involvement in 18.10%, ICA involvement with cerebral infarct was seen in 9.01%. On comparing to a study done by Yadav et al., describing MRI features in CAM.[7] Their studies showed 74% periantral soft tissue cellulitis and EOM involvement in 76% cases, which is greater than those seen in our study as only early cases of suspicious ROCM were included in our study.

Rest of the findings showing involvement of spaces, cellulitis, orbital, and cerebral invasion were seen only in patients diagnosed with ROCM on follow-up. Taking KOH staining and/or histopathology (HPR) as standard of reference, CT has a Sn of 71.40%, Sp of 100%, PPV of 100%, NPV of 66%, and DA of 81% as compared to MRI which has a Sn of 85.7%, Sp of 100%, PPV of 100%, NPV of 80%, and DA of 90.9% for detecting ROCM. CT was better in detecting bone erosions,[9] compared to MRI, whereas MRI was better in detecting soft tissue, orbital, and CNS involvement.

In a retrospective case–control study by Eli R Groppo on CT and MRI imaging characteristics in acute invasive fungal sinusitis,[10] MRI was more sensitive than CT for diagnosis of acute invasive fungal sinusitis (Sn 85%). This was comparable to our study with a MRI Sn of 100%.

Our results are comparable to a study by Mazzai et al. who have concluded that CT is better for assessing bone erosion, whereas MRI is superior in evaluating soft tissue, intraorbital extension, and in assessing intracranial and vascular invasion.[4]


  Conclusion Top


COVID-associated ROCM is a lethal fungal infection predominantly of nasal cavity and paranasal sinuses extending into orbital and intracranial structures leading to increased mortality and morbidity. Hence, early imaging by CT and MRI helps in early diagnosis and assess the extent of involvement for prompt and aggressive treatment. CT and MRI play a complementary role in diagnosis of ROCM, as CT is better in detecting bone erosions, whereas MRI is better in detecting soft tissue, orbital and CNS involvement.

In the acute state of emergency as in the current pandemic with rising cases of ROCM and acute shortage of Amphotericin-B, MRI is the single best modality for accurate detection of ROC, helping clinicians in the judicious use of Amphotericin-B.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: Another challenge for India amidst the second wave? Lancet Respir Med 2021;9:e77.  Back to cited text no. 1
    
2.
Reddy SS, Rakesh N, Chauhan P, Sharma S. Rhinocerebral mucormycosis among diabetic patients: An emerging trend. Mycopathologia 2015;180:389-96.  Back to cited text no. 2
    
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Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54 Suppl 1:S23-34.  Back to cited text no. 3
    
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Mazzai L, Anglani M, Giraudo C, Martucci M, Cester G, Causin F. Imaging features of rhinocerebral mucormycosis: From onset to vascular complications. Acta Radiol 2022;63:232-44.  Back to cited text no. 4
    
5.
John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: The perfect storm for mucormycosis. J Fungi (Basel) 2021;7:298.  Back to cited text no. 5
    
6.
Nithyanandam S, Jacob MS, Battu RR, Thomas RK, Correa MA, D'Souza O. Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J Ophthalmol 2003;51:231-6.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Yadav T, Tiwari S, Gupta A, Garg PK, Khera PS, Rajagopal R, et al. Magnetic resonance imaging in coronavirus disease – 2019 associated rhino-orbital-cerebral mucormycosis (CA-ROCM) – Imaging analysis of 50 consecutive patients. Curr Probl Diagn Radiol 2022;51:112-20.  Back to cited text no. 7
    
8.
Groppo ER, El-Sayed IH, Aiken AH, Glastonbury CM. Computed tomography and magnetic resonance imaging characteristics of acute invasive fungal sinusitis. Arch Otolaryngol Head Neck Surg 2011;137:1005-10.  Back to cited text no. 8
    
9.
Jindal G, Sethi A, Bhargarva K, Sethi S, Mittal A, Singh U, et al. Imaging findings in invasive rhino-orbito-cerebral mucormycosis in post-COVID-19 patients. Proc (Bayl Univ Med Cent) 2022;35:32-4.  Back to cited text no. 9
    
10.
Patel DD, Adke S, Badhe PV, Lamture S, Marfatia H, Mhatre P. COVID-19 associated Rhino-Orbito-Cerebral Mucormycosis: Imaging spectrum and Clinico-radiological correlation- a single Centre experience. Clin Imaging 2022;82:172-8.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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