A 59-year-old man with a 1-month history of headache was examined in an otolaryngological clinic of a general hospital. The patient’s anterior nasal septum was swollen, and he was diagnosed with nasal septal abscess and admitted to the hospital the same day. Enhanced computed tomography (CT) revealed a swollen, ring-enhanced lesion in the anterior nasal septum (Fig. ). He was treated with incisional drainage of the abscess and antibiotic drip for 1 month (fosfomycin, ampicillin/sulbactam, ceftriaxone, and meropenem). In addition, insulin-based therapy was started because the patient had uncontrolled diabetes and hemoglobin A1c of 13.3%. His symptoms persisted despite 1 month of antibiotic drip. Pus from the nasal septum was cultured three times. Culture tests detected low concentrations of Capnocytophaga spp. and Serratia marcescens, which were sensitive to the antibiotic drip. No fungi were detected. The septal lesion was biopsied twice and showed granulation-like tissue with infiltrated inflammatory cells (nothing indicating malignancy or fungus). Despite the antibiotic drip for >1 month, diplopia developed due to bilateral abducens nerve palsy, with subsequent impairment of right eye movement and eventual visual loss. The patient was then referred to our department.\nThe patient’s initial visit revealed a saddle nose. Nasal fiberscope revealed bulging of the nasal septum and granulation-like tissue on the right side of the nasal septum. The patient’s left eye fixed at the central position and the supraduction and adduction of the right eye were limited. His visual acuities were light perception in the right eye and “count fingers” in the left eye. The functions of the 5th, 7th, and 8–12th cranial nerves were intact.\nThe patient’s hemoglobin A1c was 9.2%. Plain CT showed a poorly marginated lesion with soft tissue density at the superior nasal septum, which was invading the anterior cranial fossa. Another mass with soft tissue density appeared in the left maxillary sinus (Fig. ). A spinal tap and cerebrospinal fluid culture were immediately performed, and the results revealed elevated glucose levels (130 mg/dL) and cell counts (mononucleosis 19/m3, polynucleosis 1/m3). No pathogen was detected by microscopic examination or culture methods. Owing to the possibility of a fungal and/or bacterial infection, we prescribed an antibiotic (ampicillin/sulbactam) and antifungal (amphotericin B) drip. Subsequently, we performed diagnostic endoscopic sinus surgery under general anesthesia. Histopathological examination revealed that the ball-like lesion in the left maxillary sinus harbored fungi, with filaments slightly thinner than those of Aspergillus spp. (Fig. ). A commercially available fungal DNA detection kit (Robust HotStart ReadyMix PCR Kit; KAPA biosystems, Inc., U.S.A.) was used to detect pathogens in tissues from the nasal septal lesion and ball-like fungal lesion in the left maxillary sinus. A broad-range polymerase chain reaction (PCR) was performed targeting the highly conserved sequence of the ribosomal RNA genes in fungal DNA shared by most fungi. Internal transcribed spacer (ITS) regions in ribosomal DNA were then amplified by PCR using primers ITS1F (5′-TCCGTAGGTGAACCTGCGG-3′) and ITS4R (5′-TCCTCCGCTTATTGATATGC-3′). PCR products of 150–500 bp were obtained and sequenced to match a known DNA sequence from a reference database (BLAST: Basic Local Alignment Search Tool). The organism detected by PCR and tissue cultures was S. apiospermum. Subsequent enhanced magnetic resonance imaging (MRI) revealed strongly enhanced lesions of the nasal septum, ethmoid sinuses, bilateral orbital apexes, and cavernous sinus. The dura along the anterior and bilateral middle cranial fossa was thickened and well-enhanced. (Fig. ). The diagnosis was orbital apex syndrome and hypertrophic pachymeningitis secondary to fungal nasal septal abscess caused by S. apiospermum.\nDrug susceptibility testing (Table ) led us to change the antifungal drip to voriconazole (500 mg/day). Since voriconazole had no apparent effect on the patient’s symptoms after four days, we surgically resected the lesion under general anesthesia.\nUsing endoscopy-assisted open skull base surgery, we removed the fungal ball-like lesion and the mucosa of the left maxillary sinus. We then incised the anterior border of the nasal septum and removed the mucosa of the bilateral ethmoid and sphenoid sinuses. After anterior craniotomy, we resected the anterior skull base between both sides of the ethmoid tegmen, from the frontal table anteriorly to the optic chiasm posteriorly. We avoided the extirpation of the eye ball or removal of the orbital content, because the medial bony wall of the orbit was intact.\nThe resected nasal septum was thickened and necrotic, strongly suggesting infectious inflammation and necrosis of the tissue. Mild mucosal edema was observed in the bilateral ethmoid and sphenoid sinuses. No fungal invasion or pus was observed. The dura was thinned just above the affected part of the cranial fossa, suggesting that the infection and inflammation had spread to the dura; however, there was no apparent dural deficit, and the dura was preserved. Following resection, we reconstructed the affected anterior cranial fossa with pericranium.\nThe patient’s headache decreased and almost disappeared 3 weeks postoperatively. His preoperative mild fever and inflammation normalized, and he was discharged on postoperative day 29. The patient continued oral voriconazole (400 mg/day) until 12 months post-surgery, when bilateral ocular movements completely improved; however, loss of visual acuity persisted. At 22 months post-surgery, a follow-up MRI demonstrated that the enhanced lesion in the orbital apex diminished. Thirty months has passed without any evidence of recurrence until now. The timeline of the patient’s illness is illustrated in Fig. .
A 48-year-old man with diabetes mellitus who had failed to adhere to his treatment presented to the emergency department with complaints of a right-sided headache and toothache for two weeks, with nausea and vomiting for two days prior to presentation. The patient was managed for septic shock secondary to dental abscesses. Non-contrast brain computed tomography (CT) was performed. The CT scan showed no significant intracranial abnormality other than pansinusitis, without obvious retro-orbital fat streakiness (Figure ). Four days later, tooth number 17 and 18 in the left mandibular region, both of which had abscesses, were extracted. The patient noted progressive painless blurring of the vision in his right eye post-extraction of the abscessed teeth and was referred to the ophthalmology team two days later. At this time, the patient was receiving day five of treatment with intravenous (IV) amoxicillin-clavulanate, (1.2 g three times a day), with the addition of IV metronidazole (400 mg twice a day).\nThe visual acuity (VA) in his right eye was 4/60, with no improvement in the pinhole test. A relative afferent pupillary defect was present, with an associated decrease in the optic nerve function, in addition to ophthalmoplegia and restrictions in the superior and lateral gaze. No proptosis, ptosis or lid swelling was present, and all other anterior segment findings were normal. A fundus examination of the right eye showed only proliferative diabetic retinopathy. The VA in the patient’s left eye was 6/18 and 6/9 in the pinhole test. An examination of the anterior segment was unremarkable. Moderate non-proliferative diabetic retinopathy was detected in the posterior segment. Dental caries were present in the upper molars, with mucopurulent discharge from the right sphenoid sinus region. The clinical diagnosis was OAS, and emergency functional endoscopic sinus surgery and septoplasty were performed by the ear, nose and throat (ENT) team. Intra-operatively, pus (6cc) was drained from the right sphenoid sinus. The pus breached the anterior sphenoid wall, tracked down to the septum polypoidal mucosa over the right maxillary sinus and right anterior and posterior ethmoid sinuses.\nEmpirical treatment with IV ceftriaxone (1 g twice a day) and IV fluconazole (400 mg once a day) was started. Despite the commencement of IV antibiotic and antifungal treatment, the patient’s condition deteriorated, and the VA in this right eye was classified as no perception of light (NPL) and almost total ophthalmoplegia four days post-presentation (Figure ). Treatment with IV methylprednisolone was not started in view of the infective nature of the disease and the possibility of a fungal infection, which could worsen his condition.\nMethicillin-resistant Staphylococcus aureus was isolated from the pus and from a nasal swab. IV vancomycin (1 g twice a day) and IV metronidazole (400 mg twice a day) were added. An urgent non-contrast CT brain scan was repeated and revealed features suggestive of fungal pansinusitis, with the involvement of the right orbital apex and right orbital contents (Figure ). No suspicious intracranial lesion was seen. The patient underwent emergency nasal debridement for the second time and septotomy. A bony dehiscence was noted over the right posterior ethmoid supralaterally, exposing the orbital apex.\nOn day 13 after the first surgical drainage, tissue culture from the septal wall yielded S. apiospermum. IV amphotericin B (35 mg once a day) was commenced. However, the patient’s renal profile deteriorated following the amphotericin B treatment. Thus, the antifungal regime was changed to oral voriconazole (200 mg twice a day), but the patient failed to respond to the treatment. Forty days after the initial presentation, he developed invasive pansinusitis, with disease progression involving the base of the skull (both orbits) and intracranial extension.\nAt this stage, the VA in the patient’s right eye was classified as NPL in all four quadrants, with almost total ophthalmoplegia. The VA in his left eye was 6/12, with full extraocular movement. The neurosurgical team decided against any surgical intervention. Functional endoscopic sinus surgery was performed for the third time, with nasal toileting. Intra-operatively, minimal crusting was observed over the right nasal cavity. The right sphenoid, pterygoid, maxillary sinuses and the frontal sinuses were clear, with no pus. The mucosa was healthy, with minimal bleeding. The left maxillary sinus was also clear.\nIV amphotericin B was restarted, but the patient developed gastrointestinal intolerance. The antifungal treatment was again changed to oral voriconazole (200 mg twice a day). Fifty-seven days after the initial presentation, the VA in the patient’s left eye decreased suddenly to 6/30 (reduced Snellen chart), and his colour vision decreased. A plain and contrast-enhanced CT scan of the brain, orbit and the paranasal sinuses showed invasive pansinusitis, with bilateral orbital apex involvement (Figure ). It also showed an increasing intracranial extension involving the right cavernous sinus anteriorly, the roof of the sphenoid sinus, the floor of the anterior cranial fossa and right medial cranial fossa anteriorly, as well as osteomyelitis changes at the base of the skull. In view of the acute progression of the infection, surgical intervention was considered. However, the area of the lesion was too extensive and was beyond ophthalmology coverage. Following a reassessment by the neurosurgical team, a decision was made to continue medical treatment rather than perform a surgical intervention.\nSIxty-seven days after the initial presentation, the patient’s VA decreased to NPL in both eyes. Although his Glasgow coma scale was full, his general condition worsened, with lethargy, irritability and dizziness, accompanied by nausea and vomiting. The patient decided to discharge himself from the hospital (at own risk discharge) and subsequently failed to attend an appointment in the ophthalmology clinic.