| Abstract|| |
Mucormycoses are a group of invasive infections caused by filamentous fungi of the Mucoraceae family, with the rhinocerebral form of the disease being the most common in a large case series. Uncontrolled diabetes and increased level of serum iron are regarded as the two leading predisposing factors for the development of the disease. We present a case of a 43-year-old male patient recently diagnosed with diabetes presenting with features of orbital apex syndrome and short-term memory loss. He was found to have rhino-oculocerebral mucormycosis on histopathological and radiological evaluations.
Keywords: Diabetes, rhino-oculocerebral mucormycosis, short-term memory loss
|How to cite this article:|
Rath B, Samant M, Swain KP, Mallick AK. Rhino-oculocerebral Mucormycosis. Ann Trop Med Public Health 2015;8:214-6
| Introduction|| |
Mucormycosis is an invasive fulminant fungal infection first described by Paulltauf in 1885. The disease may present with various manifestations but there is a predilection for the paranasal sinuses.  Ring-opening cross-metathesis (ROCM) is typically seen in patients with poorly controlled diabetes mellitus.  Despite the advances in diagnosis and treatment, invasive rhino-orbitocerebral infection is still the most lethal clinical form of the disease. , The mortality rate is reported to be as high as 20% even if the diagnosis and aggressive treatment are not delayed.  The common presenting symptoms and signs of this disease are headache, fever, acute sinusitis, decreased vision, unilateral periorbital or facial swelling, facial pain, alterations in mental state, and necrotic ulcer in the nasal or oral mucosa. , Although rare, orbital apex syndrome that presents with ptosis, proptosis, sensorial deficit, and visual loss may be the initial manifestations of the disease.
| Case Report|| |
A 43-year-old male patient, recently diagnosed with diabetes, presented with a history of ocular pain for 1 month with sudden onset of complete ophthalmoplegia and loss of vision in his left eye. In the next day, he developed altered sensorium. Emergency computed tomography (CT) and magnetic resonance imaging (MRI) scan of the patient's brain showed a diffuse mass lesion involving the left nasal cavity with mucosal thickening, heterogeneous mass, along the medial aspect orbit of the left eye [Figure 1]. After the presumptive diagnosis of mucormycosis was done, the patient was started on intravenous (IV) administration of amphotericin and his condition improved. The central nervous system (CNS) examination showed left orbital apex syndrome and involvement of the V2 and V3 divisions. The patient was treated with insulin and IV administration of amphotericin. Histopathological analysis of tissue obtained from the nasal sinuses by endoscopic sinus surgery revealed mucormycosis. His ophthalmoplegia did not improve and he had impairment of short-term memory; his mini-mental state examination (MMSE) score was 23/30. On repeat MRI of the brain, T2WI MRI showed a hyperdense lesion (mycetoma) involving the medial aspect of the left orbit (both intra- and extraconal components) with relative sparing of the left optic nerve, extending through the optic canal backward to involve the ipsilateral cavernous sinus with mucosal thickening of the frontal, left ethmoidal, and sphenoidal sinuses, and cerebritis of the left medial temporal lobe [Figure 2] and [Figure 3]. He was referred to an ophthalmologist for enucleation.
|Figure 1: T2WI MRI Brain and orbit showing hyperintense lesion (mycetoma) in the left ethmoidal, maxillary, and frontal paranasal sinuses sparing the left orbit|
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|Figure 2: MRI Brain showing hyperintense lesion (mycetoma) involving the medial aspect of the left orbit (both intra- and extraconal components) with relative sparing of left optic nerve, extending through the optic canal backward to involve the ipsilateral cavernous sinus and enhancement of extraocular muscles. There is mucosal mucosal thickening of the frontal, left ethmoidal, and sphenoidal sinuses|
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|Figure 3: MRI Brain showing hyperintense lesion in the left temporal lobe suggesting cerebritis|
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| Discussion|| |
Mucormycoses are a group of invasive infections caused by filamentous fungi of the Mucoraceae family. The most frequently isolated species of this family are Rhizopus oryzae followed by Rhizopus microsporus and Absidia corymbifera.  Based on the clinical presentation and site of involvement of these species, the following six manifestations of the disease can be described: Rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and localized infections not otherwise belonging to the previous categories. 
The rhinocerebral form of the disease has been the most common in large case series,  accounting for 30-50% of all cases of mucormycosis and it has been predominantly associated with poorly controlled diabetes mellitus and diabetic ketoacidosis.  Other risk factors include immunocompromised state due to organ transplantation, hematologic malignancies, chronic corticosteroid treatment, and hemochromatosis. Impaired neutrophil and phagocyte responses and increased level of available serum iron are the two underlying conditions in majority of mucormycosis patients.
The locoregional spread pathway of rhinocerebral mucormycosis has not been adequately described. Based on their observations in a series of 10 patients, Hosseini et al. regard the pterygopalatine fossa as a reservoir of the disease through which it can spread to the neighboring structures, including the retroglobal space of the orbit and infratemporal fossa.
Rhinocerebral mucormycosis most commonly presents in an acute setting, reminiscent of sinusitis or periorbital cellulitis.  Facial pain and unilateral facial swelling are also important parts of the clinical picture of the patient, with variable grade fever being present although not in all cases. The only disease-specific finding described in the relative literature is blackened necrotic eschars of the nasal mucosa or palate. However, in large case series, it has been noted in less than half of the patients. The clinical picture may further progress to include unilateral ophthalmoplegia representing involvement of the orbital contents either by infection or vascular compromise.  Contralateral ophthalmoplegia suggests cavernous sinus thrombosis, although bilateral rhinocerebral mucormycosis, albeit rare, should be considered. Progression of the infection to the CNS is heralded by the development of confusion and disorientation,  with bloody nasal discharge also reported as a potentially early sign of disease extension to the brain. CNS damage may also result from cavernous sinus thrombosis and internal carotid artery encasement, leading to cerebral infractions  and hematogenous dissemination of the disease to other organ sites.
Early diagnosis of rhinocerebral mucormycosis is considered a step of grave importance. Symptoms of mucormycosis in a predisposed patient call for a prompt initiation of treatment  while appropriate steps are taken toward confirmation of diagnosis. Histopathological examination of surgical specimens can confirm the clinical diagnosis with the appearance of right-branching aseptate hyphae, which are considered typical of mucor species, along with evidence of angioinvasion and tissue necrosis. Fungal cultures can provide further confirmation. Imaging methods are of little help during the early stages of rhinocerebral mucormycosis with thickening of the sinus mucosa or extraocular muscles.  CT scans can be used to evaluate the progression of the disease. MRI scans may be more accurate in evaluating the extent of the disease due to fungal invasion of the soft tissues. Both CT and MRI scans should be frequently obtained due to the rapidity of disease progression and for appropriate planning of surgical interventions. 
Reversal of underlying predisposing conditions is of paramount importance. Euglycemia should be restored rapidly and any immunosuppressive conditions should be reversed if possible. The surgical approach should be based on the clinical state of the patient with timely interventions for appropriate debridement of the infected areas.  Polyene-based (amphotericin B) therapy should be considered as the main course of action. Iron chelation therapy and posaconazole therapy should be considered in cases of refractory infection and polyene intolerance. Regarding the duration of treatment, Spellberg et al. specify the resolution of immunosuppression, radiographical signs, and clinical symptomatology as the objectives of treatment.
Cases of localized sinonasal rhinocerebral mucormycosis have been reported to have low mortality rate (10%).  Progression of the disease is associated with worse prognosis and involvement of the CNS is considered fatal. 
| Conclusion|| |
In conclusion, rhinocerebral mucormycosis still remains a poorly understood disease with high mortality rate.
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Conflict of interest
There are no conflicts of interest.
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Department of Neurology, Senior Resident (Academic), Sriram Chandra Bhanja Medical College, Cuttack-753007, Odisha
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]