A 54-year-old man presented with a three-month history of headache during the fourth wave of the Delta variant of COVID-19 in Iran. The headache was progressively worsening and intensified during exertion or walking but improved when lying down. Additionally, for the past week, he had been experiencing speech difficulties, hypernasality, swallowing difficulties due to loss of gag reflex, and purulent otorrhea on the right side.
During detailed history taking, the patient did not mention any accompanying diseases, current medication consumption, trauma, or recent COVID-19 infection, despite receiving the Sinopharm vaccine. However, he did have a history of previously treated Tuberculosis and Brucellosis several years ago. Three months ago, during initial evaluations at another medical center, sphenoid sinusitis was detected. Despite receiving maximum medical treatment with antibiotics, the patient did not respond, leading to the decision of performing endoscopic endonasal sinus surgery. However, there were no obvious mucosal changes except for discharge from the sphenoid sinus. Histopathologic examination results showed no specific findings other than inflammation.
During the physical examination, the patient appeared ill but was conscious and oriented. There was no evidence of orbital involvement, and cranial nerve 7 (facial nerve) was intact. The patient presented with trismus (difficulty in opening the mouth) and unilateral deviation of the uvula to the left, indicating involvement of cranial nerves 9 (glossopharyngeal), 10 (vagus), and 12 (hypoglossal). Due to the patient's general condition, it was not possible to examine cranial nerve 11 (accessory nerve). Additionally, there was loss of sensation in the region innervated by the V2 branch of the trigeminal nerve (maxillary nerve), but no mucosal changes were observed in the palate or nasal cavity.
A comprehensive work-up was conducted, taking into account the differential diagnosis. The initial laboratory data showed anemia and elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fasting blood sugar (FBS) at 229 (Table 1).
A brain CT scan was performed, which revealed a destructive lesion forming sequestration in the skull base. The lesion involved the clivus, occiput, greater wing, and pterygoid process of the left-sided sphenoid, indicating the presence of skull base osteomyelitis. Additionally, mucosal thickening was observed in the sphenoid sinus (Fig. 1).
To further evaluate the condition, a multiplanar contrast-enhanced brain MRI was conducted. The results showed abnormal bone marrow infiltration in the clival, skull base, and pterygoid plates, with the most prominent involvement on the left side. The post-contrast enhancement was heterogeneous, suggesting skull base osteomyelitis. However, the possibility of neoplastic infiltration could not be completely ruled out. Furthermore, the right cavernous sinus, Meckel's cave, and oval foramen showed involvement, and abnormal enhancement of leptomeninges and dura was observed (Fig. 2).
A cervical spine MRI study did not reveal any significant lesions. A neck MRV (Magnetic Resonance Venography) showed no evidence of thrombosis in the cervical venous system, and both jugular veins exhibited normal signal and diameter. A chest HRCT (High-Resolution Computed Tomography) scan did not show any remarkable findings.
Based on the imaging findings, osteomyelitis, tuberculosis (TB), and malignancy were considered more likely in the case of the patient, while fracture was ruled out. Mucormycosis was also considered as a possible differential diagnosis based on the patient's physical examination findings and the presence of the ongoing COVID-19 pandemic, along with the imaging data.
Due to the imaging findings and clinical presentation, the patient was admitted to the intensive care unit (ICU), where he gradually developed respiratory distress and required intubation. Neurosurgery and rhinology specialists consulted on the case and decided to perform skull base debridement and biopsy of the skull base lesion.
During endonasal endoscopy of the sinonasal cavity, the mucosa appeared normal without typical necrosis, except for the presence of purulent discharge from the sphenoid sinuses. Using the endoscopic endonasal trans-pterygoid approach, all the necrotic bone involved in the pterygoid palates, greater and lesser wings of the sphenoid, and clivus were resected extradurally. Macroscopically, the involved bone exhibited typical necrosis characteristic of an increasing number of mucormycosis cases. Additionally, through the endoscopic endonasal access to the craniovertebral junction, the remaining necrotic bone and sequestra, including the occipital condyles, were resected extradurally. The dura appeared thick and had adjacent granulation tissue near the involved bone. No cerebrospinal fluid (CSF) leak was observed, and considering the infectious nature of the disease, no reconstruction was performed.
Following the surgery, a tracheostomy was performed, and the patient's neck was stabilized using a collar. The day after the surgery, a percutaneous endoscopic gastrostomy (PEG) tube was inserted to provide nutritional support.
Surprisingly, both the KOH smear and culture of the surgical tissue sample revealed the presence of aseptate hyphae, consistent with Mucormycosis. The histopathologic examination confirmed the angioinvasion by fungal hyphae, further confirming the diagnosis (Fig. 3).
The patient received amphotericin B treatment for 38 days following the surgery. After spending 12 days in the ICU, the patient regained consciousness and achieved physical stability, leading to a transfer to the ward. However, he developed high blood sugar levels and was diagnosed with new-onset diabetes. Unfortunately, after 30 days, his general condition deteriorated due to uremia, due to acute renal injury (AKI), and he passed away 8 days later.