Imaging features of perineural and perivascular spread in rapidly progressive rhino-orbital-cerebral mucormycosis: A case report and brief review of the literature

INTRODUCTION

The term “Zygomycosis” describes a wide spectrum of rare infections caused by a group of molds belonging to the class of Zygomycetes, including Entomophthorales and Mucorales,[25] responsible for Entomophthoromycosis and Mucormycosis (MM), respectively.

The former is a rare mucocutaneous infection restricted to rhinosinusal district often occurring in immunocompetent hosts from developing countries.[4] The latter represents a group of life-threatening angioinvasive infections, more commonly affecting immunocompromised patients with diabetes mellitus (DM) being the main risk factor.[20]

MM typically affects the sinuses or the lungs by inhaling fungal spores from the air, and the skin after the fungus enters through a cutaneous break such as cut or scrape.[7]

Therefore, clinical spectrum of MM is wide including in decreasing order the following:[3,18]

1. Rhino-orbito-cerebral syndrome

2. Pulmonary MM

3. Cutaneous MM

4. Disseminated forms (≥2 noncontiguous sites)

5. Gastrointestinal presentation.

Some authors reported other forms of disease, including isolated cases of tracheal,[24] renal,[15] and temporal bone involvement.[8,16]

Here, we report the case of a 59-year old patient with an untreated diabetes who developed a rhinocerebral mucormycosis (ROCM) with rapidly progressive neurological symptoms.

CASE REPORT

A 59-year-old man presented with a recent onset of sinus pain, nasal congestion, bilateral periorbital edema, facial swelling, and headache. He was conscious and afebrile.

The patient underwent computed tomography (CT) scan examination showing a widespread sphenoid sinuses effusion with less evident involvement of maxillary and ethmoid sinuses [Figure 1].

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Figure 1:: Sinus computed tomography (CT) scan at the clinical onset. Axial (a) and sagittal (b) CT scan examination with soft-tissue algorithm showing right maxillary invasive sinusitis. Note focal sinus medial wall discontinuities (red arrows in a) and partial obliteration of normal fat planes in the pterygomaxillary fissure (arrowheads in a and b).

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Laboratory evaluations revealed decompensated Type 2 DM. Insulin therapy and a broad-spectrum of antibiotic treatment were promptly started. A paranasal sinus magnetic resonance imaging (MRI), performed 3 days after starting antibiotic treatment, showed a low T2W signal effusion in the left maxillary sinus, at the level of ethmoidal air cells and sphenoid sinus, predominantly on the right. It also showed a high T2W signal effusion in the right maxillary sinus, bilateral periorbital soft-tissue swelling, and minimal posterior subluxation of the left crystalline lens and right temporalis muscle swelling. No acute cerebral involvement was observed [Figure 2].

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Figure 2:: Sinus magnetic resonance imaging. Axial (a and b) and coronal (c and d) fast spin echo T2-weighted images show low signal effusion in the left maxillary sinus, at the level of ethmoidal air cells and sphenoid sinus, predominantly on the right (arrows).

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Due to the rapid and marked increase of facial swelling and masticatory dysfunction, 4 days following the initial TC scan, the patient underwent functional endoscopic sinus surgery.

Briefly, following mucosa decongestion by adrenaline instilling, the meatus medium was entered. Uncibullectomy with a large bilateral medium meatotomy was performed, allowing the drainage of the maxillary sinus. Further, bilateral anterior and posterior ethmoidectomy and release of the frontal recess were achieved. Intranasal sphenoidectomy, following the amputation of the tails of sphenoidal conchae and drainage of the sinuses’ secretion, was performed. Moreover, the sphenoidectomy was conducted in a transethmoidal fashion until the identification of Onodi’s cell was reached. Multiple tissue samples were collected for histological and microbiological analysis. Irrigation with antibiotic solution was performed leaving a drainage for 5 days.

Two days later, Rhizopus oryzae was isolated, then MM was diagnosed, and a systemic therapy by intensive intravenous amphotericin B (5 mg/Kg) was started.

A few days after surgery, a sudden onset of bilateral ophthalmoplegia (III, IV, VI cranial nerves palsy) and sensory trigeminal loss (V1–V2 cranial nerves impairment) was observed. These clinical features, suggestive of bilateral cavernous sinus syndrome, were confirmed by an emergency brain MRI [Figure 3]. Main significant MRI findings were bilateral cavernous sinuses thrombosis, more evident on the left side, and slight swelling of the V2–V3 nerve roots on both sides without evidence of contrast enhancement. Bilateral trigeminal cisternal tract swelling was also demonstrated along with bilateral pontine foci, with evidence of increase in signal intensity on DWI and FLAIR sequences at the level of trigeminal “Root Entry Zone.”

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Figure 3:: Brain magnetic resonance imaging examination at neurological onset. Coronal contrast-enhanced fat saturation T1-weighted (a and b), coronal basal fat saturation T1-weighted (c), axial fluid-attenuated inversion recovery (d), axial diffusion-weighted (e) images. (a and b): Bilateral cavernous sinus thrombosis (arrows), bilateral V3 swelling without contrast enhancement (arrowheads); (c): bilateral V2 swelling (arrowheads); (d and e): high signal bilateral pontine foci, due to perineural diffusion. Note diffusion restriction at intracisternal tract of right trigeminal nerve (white arrow).

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The next day, together with a significant worsening of the neurological status, further MRI imaging showed multiple bilateral watershed ischemic lesions, more evident on the left, and occlusion of the left internal carotid artery. Last follow-up MRI examination performed a week later, before the exitus, also demonstrated left endophthalmitis with c rystalline lens dislocation and significant extension of parenchymal ischemic foci [Figure 4].

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Figure 4:: Follow-up brain magnetic resonance imaging examination Axial fluid-attenuated inversion recovery (a), axial diffusion-weighted (b), axial contrast-enhanced fat saturation T1-weighted (c and d) images. Volume rendering technique (VRT) time-of-flight magnetic resonance angiography. (a and b) Bilateral acute frontoparietal watershed infarction; (c): left internal carotid artery (ICA) wall enhancement, due to mucormycosis vasculitis (arrow); (d): left endophthalmitis with crystalline lens dislocation (arrowhead) VRT angiography well depicts left ICA thrombosis.

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DISCUSSION

ROCM defines an infection originating from the paranasal sinuses with possible extension to the brain.[27] In these cases, sporangiospores enter the nasal mucosa and paranasal sinuses. The main underlying conditions associated with ROCM are DM[22] and leukemia.[19]

Molds belonging to the order of “Mucorales” are saprophytic aerobic microorganisms that grow rapidly and are able to release a large number of airborne spores. They are ubiquitous in nature and widely found on organic substrates (e.g. bread, decaying fruits, vegetable matter, or soil).[21]

The genera most commonly responsible for human infections are Rhizopus, Mucor, and Absidia (now reclassified as Lichthemia)[29] while Rhizomucor, Cunninghamella, Saksenaea, Syncephalastrum, and Apophysomyces are less frequently implicated.[14] Overall, R. oryzae is the most common pathogen isolated from specimens in MM disease.[25]

It is well known that a regular phagocytic activity is able to kill fungal spores. In this regard, experimental studies have shown that a compromised phagocytic activity and/ or neutropenic situations are the two conditions that most favor opportunistic molds infections.[2] According to several studies, the main risk factors for MM[9,22] are the following:

• Poorly controlled DM, with or without ketoacidosis,

• Hematologic malignancies,

• Long-lasting corticosteroids therapies,

• Hematopoietic cell/solid organ transplantation,

• Treatment with deferoxamine and iron overload,

• Illicit intravenous drug use,

• Disruption of mucocutaneous barriers by catheters and other devices,

• Malnutrition.

A review of 929 cases of MM between 1940 and 2003, conducted by Roden et al.,[22] confirmed that DM was the most common risk factor (36%) followed by hematologic malignancies (17%) and solid organ or hematopoietic cell transplantation (12%).

In diabetic population, phagocytic function seems to be altered, especially in neutrophilic chemotaxis, diapedesis, and hydrogen peroxide production.[1,10] In vivo studies on diabetic mice with intrasinus inoculation R. oryzae confirmed the rapid progression to intracerebral MM and high rate mortality within 11 days.[28]

Our case suggests all the possible common complications of ROCM in both endocranial and orbital sites, by three main mechanisms of infection that is direct diffusion, perineural, and perivascular spreading.

CONCLUSION

MMs are life-threatening fungal infections in patients with DM, cancer, and organ transplantation.

Clear identification of the main risk factors, careful assessment of clinical features, and radiological findings may improve the chance for an early diagnosis and patient survival.