Patient-1
A 40-year-old male with a past medical history of unexplained thrombocytopenia and smoking was admitted to outside hospital following a four-day history of cough, fever, and shortness of breath. In the initial evaluation, the real-time reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal and oropharyngeal for SARS-CoV-2 was positive, blood sugar level: 343 mg (normal: 74–99 mg), platelet count: 43*10 3/mm3, and he was treated with intravenous (IV) remdesivir (200 mg IV on day one and 100 mg daily for four days), dexamethasone (8mg IV daily for seven days) and IV insulin. Abdominal sonography was consistent with liver cirrhosis. On day fourth of admission, he developed headache, binocular diplopia, left eye ptosis, and decreased vision in the left eye. Computed tomography (CT) of the brain was normal, and the paranasal sinuses (PNS) CT indicated thickening of the mucosa in the left sphenoid and ethmoidal sinuses. Because of the clinical suspicion of mucormycosis rhinosinusitis, amphotericin B deoxycholate (1 mg/kg/day IV) has been added to the treatment regimen. The patient was transferred to our facility eight days after his admission.
At arrival to our center, the patient has normal vital signs but mild tachycardia and tachypnea. He had left eye ptosis, mild proptosis, and swelling, associated with a mild chemosis in the left eye and a mild conjunctival injection in the right eye. Complete ophthalmoplegia of the left eye (III, IV, and VI nerve palsy) and partial ophthalmoplegia of the right eye (III and IV nerve palsy) were present. Both pupils were dilated and fixed, and there was no light perception on both sides. He had hypoesthesia involving the first and second branches of the left trigeminal nerve (V1, V2). Tenderness was observed on the frontal sinus. No significant findings were found on the oral and nasal cavity assessment.
A chest high-resolution computed tomography (HRCT) revealed an opacity in the upper lobe of the left lung with a central ground-glass opacity, compatible with COVID-19 infection. The brain Magnetic resonance imaging (MRI) showed no abnormalities on the brain parenchyma but identified mucosal thickening of all paranasal sinuses, mild proptosis, periorbital edema, and extraconal fat stranding, which was more prominent on the left side. Additionally, the MR venogram showed thrombosis of the left cavernous sinus and prominence of the posterior aspect of the left superior ophthalmic vein. MR angiography (MRA) showed no ICA aneurysm.
The patient was diagnosed with invasive mucormycosis rhinosinusitis and cavernous sinus thrombosis and treated with Vancomycin, Meropenem, liposomal amphotericin B (5 mg/kg/day IV), and therapeutic heparin. Abdominal ultrasound and gastrointestinal endoscopy were performed later, which confirmed splenomegaly and esophageal varices. An additional diagnosis of liver cirrhosis was performed then. Therefore, albumin was added, and anticoagulation therapy was discontinued.
He underwent Functional Endoscopic Sinus Surgery (FESS) and debulking on the second day of admission with histological findings compatible with mucormycosis infection. On the sixth day of admission, the patient developed a sudden loss of consciousness. The urgent brain CT showed a disseminated subarachnoid hemorrhage (Fisher Grading Scale:4, Hunt and Hess scale:5).
Brain CT angiography (CTA) revealed a 10x7x11mm irregularly-shaped globoid aneurysm in the clinoid portion of the left ICA (Fig. 1A).
On the eighth day of admission, he developed hypotension, electrocardiographic abnormalities, and a rise of troponins, all consistent with myocardial infarction. Unfortunately, the patient passed away on day ten after admission.
Patient-2
A 47-year-old male with a 6-year history of diabetes mellitus (DM) on metformin and glibenclamide came to our hospital with right eye ptosis and right ocular pain. He complained of body pain and cough twenty-one days before admission. Four days later, he experienced a severe throbbing headache in the bilateral frontotemporal area associated with nausea and numbness on the right side of his face and palate for ten days. He was treated with dexamethasone 8 mg IV daily for two days in an outpatient clinic. Three days PTA, he developed right eye ptosis, proptosis, blurred vision, and periorbital pain irradiated to the right ear.
At his admission, his vital signs were normal. On physical examination, he had right eye ptosis associated with proptosis and severe chemosis (mild on the left eye), with mydriatic and non-reactive pupils. The cranial nerve examination showed a right frozen eye (III, IV, and VI cranial nerves palsy), right face hypoesthesia (V1 and V2 branches of trigeminal nerve).
Initial blood sugar was 398 mg (normal: 74–99 mg), and the chest HRCT was negative for SARS-CoV-2 infection. The brain MRI didn’t show any parenchymal abnormalities but confirmed right exophthalmos with extraconal fat stranding and indicated mucosal thickness in all sinuses. The brain MRA revealed no aneurysm. The chest HRCT was normal. The sinus biopsy confirmed mucormycosis (Fig. 2), and liposomal amphotericin B 300 mg daily was started, followed by FESS and debulking surgery.
On the 21st day of his admission, he experienced right peripheral facial palsy associated with mild left-sided weakness. The brain MRI revealed multiple foci of diffusion restrictions in the right side cortical-subcortical and deep white matter, suggesting anterior and posterior watershed ischemia. The brain MRA showed a fusiform aneurysm measuring approximately 15x10x9mm in the terminal portion of the right ICA (Fig. 1B). Caspofungin 50 mg IV was added to amphotericin B daily.
The day after, he developed a generalized tonic-clonic seizure. The urgent brain CT confirmed a subarachnoid hemorrhage in the right Sylvian fissure and inferior to the right frontal lobe. The patient underwent digital subtraction angiography three days later, showing a mild increase in size on the aneurysm.
He had a competent and complete circle of Willis; therefore, a parent artery occlusion was considered. A balloon occlusion test was conducted, occluding the cervical portion of the right ICA for 20 minutes using an 8 Fr Cello balloon catheter (EV3 Endovascular, Inc., Plymouth, USA), developing no neurological deficits during the procedure. As the patient had no change in these examinations, the aneurysm and parent artery coiling was done without complications. The patient was discharged home 45 days after. In the last follow-up, performed 4 months after onset, he has a normal neurological assessment (Modified Rankin Scale = 1), but the visual acuity (VA) was counting fingers at one meter in the right eye and 5 meters in the left eye.
Patient-3
A 54-year-old male with a medical history of a gastrointestinal stromal tumor (GIST) on imatinib and had high blood glucose readings (no treatment) was admitted to our facility with a painful oral cavity lesion, nasal hemorrhage, periorbital edema, and binuclear diplopia, as well as left facial paresthesia. He had respiratory symptoms fourteen days before, and a COVID-19 infection was confirmed by a PCR test, and his blood sugar was 398 mg (normal: 74–99 mg). Insulin, remdisivir, and corticosteroids (Dexamethasone 8mg three times a day for 2 days, followed by 250mg methylprednisolone pulse daily for 6 days) were administered in an outside hospital.
On arrival, he was tachypneic and his oxygen saturation level was 84% on room air. The physical assessment showed left periorbital edema, ptosis, proptosis, and chemosis of the left eye. There was a left sixth nerve palsy associated with left face hypoesthesia (V1 and V2 branches of trigeminal nerve). There was a painful white lesion in the oral cavity and necrotic tissue in the left nasal cavity. The chest HRCT demonstrated bilaterally diffuse ground-glass opacity, and the PNS CT was consistent with mucosal thickening of the left maxillary sinuses and ethmoidal air cells.
A biopsy sample of nasal turbinates confirmed mucormycosis, and the nasal cavity was debrided; consequently, the patient was treated with liposomal amphotericin B (5 mg/kg/day IV). On the seventh day of admission, the patient underwent FESS and debulking surgery.
On day nine from admission, he suffered a sudden onset of aphasia, right-sided weakness, and a frozen left eye. The brain MRI demonstrated several foci of left parietooccipital diffusion restriction suggestive of an acute ischemic infarct. Additionally, the frontal, ethmoid, and sphenoidal sinuses exhibited opacification and mucosal thickening. The brain MRA revealed a 15x8x9mm irregularly-shaped fusiform aneurysm in the cavernous portion of the left ICA with severe narrowing of supraclinoid portion just after aneurysm (Fig. 1C). Two days later, the patient underwent DSA, which showed complete occlusion of the left ICA. He developed a decreased level of consciousness and left-sided weakness on the thirteenth day of hospitalization. A second brain MRI indicated several high-intensity T2 FLAIR signals with diffusion restriction in the left temporoparietal lobe and basal ganglia, consistent with acute infarction. The patient's condition deteriorated, and he developed vasogenic edema secondary to the ischemic stroke associated with a 4 mm midline shift. He underwent a hemicraniotomy; unfortunately, he did not improve clinically and was deceased 55 days after the initial diagnosis.