▷ Infections involving the petro-clival junction of the temporal bone are rare and primarily caused by Pseudomonas aeruginosa.

▷ This presentation can occur in the setting of progressive malignant otitis externa (skull base osteomyelitis) or sinus disease.

▷ Invasive aspergillosis (IA) is not often considered in the evaluation of these patients, leading to late diagnosis and devastating complications.

▷ Local invasion from the external auditory canal or sinus can result in inflammation and thrombosis of vessels, with a particular pre-disposition to involvement of the internal carotid artery due to its course through the skull base.

Background

▷ We conducted a retrospective study of patients with fungal skull base infections and carotiditis at our institution between 2003 and 2018.

▷ We collected data including demographics, presentation, imaging, diagnostics treatment, microbiology, and outcomes on patients diagnosed with IFPAC.

▷ We conducted a search of the PUBMED database. All cases in adults with imaging, pathology, or autopsy findings of skull base infection and carotid invasion caused by Aspergillus species were included. Patients with hematogenous dissemination were excluded. Key words included aspergillus, aspergillosis, stroke, carotid artery, aneurysm, sinus, sinusitis, orbital apex.

Methods

Cases

▶ IFPAC Syndrome is a rare manifestation of IFD and was due to invasive aspergillosis in this series.

▶ All patients in this series experienced carotid vascular events despite improvement on antifungal therapy, suggesting that aggressive surgical or endovascular interventions need to be considered in this syndrome.

▶ Further review of the literature reveals that IFPAC syndrome is often misdiagnosed, and commonly leads to complications such as mycotic aneurysm, subarachnoid hemorrhage, cerebral infarct, and death.

▷ We identified 4 cases of IFPAC at our institution from 2003 to 2018. Median age at presentation was 73 years (range, 66-79), 3 were male.

▷ IFD risk factors included diabetes (n=3), glucocorticoid use (n=3), and lymphoid malignancy (n=2). Two patients were on additional T-cell immunosuppressants.

▷ All cases were caused by Aspergillus spp. Two cases were otogenic, two were sinusal in origin. Two patients developed cranial nerve deficits (III, V, VI).

▷ Median time from symptom onset to diagnosis was 17 weeks (range, 6-36).▷ All patients were treated with anti-Aspergillus antifungals with initial improvement

in symptoms, imaging, or decrease in serum galactomannan levels. ▷ All patients subsequently presented with occlusion of the internal carotid artery

(ICA) and multiple cerebral infarcts. Two patients developed mycotic aneurysms.▷ Three patients died following these vascular events, while one patient underwent

left superficial temporal artery (STA) to middle cerebral artery (MCA) bypass with improvement in symptoms.

Figure 1a. Absence of flow (arrow) within the left ICA.

Figure 2a. Large subarachnoid hemorrhage (arrow).

Figure 1b. Inflammation (arrow) in the cavernous sinus.

Figure 2b. Aneurysm at the basilar summit (arrow).

▶ Figure 1. Patient 1

▶ Figure 2. Patient 2

Invasive Fungal Petrositis and Carotiditis (IFPAC) Syndrome in Immunocompromised Hosts: An Unrecognized, Often Catastrophic Invasive Fungal Disease (IFD)

ReferencesResults

Discussion

Conclusions

Patient 1 ⎼ 79M with Diabetes Mellitus and Chronic

Lymphocytic Leukemia treated in 2007 with Alemtuzumab and Rituximab, in remission.

⎼ In August 2012, patient developed diplopia, headache, and periorbital pain.

⎼ In September, presented with acute vision loss. Exam revealed absent light perception, proptosis and left cranial nerve III palsy.

⎼ CT scan showed left retro-orbital mass extending from the sphenoid sinus to the orbit.

⎼ Patient underwent orbitotomy with positive immunohistochemistry for Aspergillus and was started on Amphotericin.

⎼ The patient experienced significant improvement in pain with antifungal treatment and transitioned to Isavuconazole with ongoing improvement.

⎼ Readmitted in December 2012 with altered mental status and fever. MRI showed progression of disease with narrowing of the left ICA and embolic infarcts. Biopsy of the sphenoid sinus was positive for fungal forms.

⎼ Ten days later, the patient had sudden loss of consciousness. MRI/MRA showed new infarcts and complete occlusion of the left ICA. The patient subsequently died.

Patient 2⎼ 66M with Follicular Lymphoma treated with

Fludarabine in 2004, complicated by Paraneoplastic Pemphigus treated with Alemtuzumab and IVIG.

⎼ In May 2008, patient presented with headache and photophobia. He was diagnosed with acute sinusitis. Sinus culture was negative for fungus.

⎼ In July, presented with worsening headache and fever. Exam revealed right cranial nerve III and VI palsy and photophobia.

⎼ MRI/MRA showed right parietal stroke, sinus disease, and complete occlusion of the right ICA.

⎼ The patient underwent surgical debridement of the sinuses, with fungus ball noted. Cultures were positive for Aspergillus fumigatus.

⎼ He was initiated on antifungal therapy with Amphotericin and switched to Isavuconazole three days later due to renal injury.

⎼ The patient experienced significant improvement in headache with antifungal therapy. Transitioned to Voriconazole after finishing Isavuconazole trial

⎼ Readmitted in November with acute onset headache and syncope. CT scan revealed diffuse subarachnoid hemorrhage and large P1 segment mycotic aneurysm. The patient subsequently died.

Patient 4⎼ 77F with history of Type II Diabetes Mellitus and

End Stage Renal Disease on hemodialysis. ⎼ In April 2017, the patient presented with left facial

and ear pain, and purulent nasal discharge. She was treated for sinusitis with amoxicillin.

⎼ In June 2017, admitted with malignant otitis externa. Cultures were negative and she was treated with Cefepime for presumed Pseudomonas otitis externa

⎼ In September, presented with left ear pain, and headache. Exam with purulent discharge from left ear and pain with leftward gaze. CT scan showed inflammation of left mastoid, sphenoid sinus, and narrowing of the left ICA.

⎼ Patient underwent tympano-mastoidectomy. OR cultures grew Aspergillus flavus, and she was started on Isavuconazole with improvement

⎼ In October, the patient presented with single episode epistaxis and anemia. The following day, the patient had sudden onset hematemesis and epistaxis requiring emergent intubation. Angiogram revealed ruptured left ICA aneurysm. Underwent coil embolization of the left ICA with interventional radiology. Subsequent MRI showed multiple bilateral embolic infarcts. The patient never recovered full neurologic function and died.

Poster 408October 4, 2018

▷ Our case series includes four cases of local invasion of the skull base from sinusitis or otitis with eventual vascular complications. In a review of the literature this presentation was shown to be highly morbid and widely underdiagnosed.

▷ 50 cases identified from 1948-2016, age range was 15-83 years (median, 65). ▷ 41% of patients had no previous risk factors for fungal infection, 27% were

immunosuppressed, and 25% had Diabetes Mellitus. ▷ Of note, one third of patients were treated with empiric steroids following

presentation, and 39% were only diagnosed with aspergillosis at autopsy.▷ 51% of patients had ICA aneurysm or rupture, 47% had ICA occlusion and 2%

had ICA stenosis. 45% pf patients had subsequent infarcts, 41% had SAH.

Patient 3⎼ 66M with Type II Diabetes Mellitus and Renal

Transplant on Tacrolimus and Azathioprine.⎼ In January 2014, patient presented with headache,

ear pain, and vision changes.⎼ Nasal biopsy without fungal elements. Imaging

showed osteomyelitis of the skull base and narrowing of the left ICA. The patient was started on steroids for presumed inflammatory pseudotumor.

⎼ In September 2014, presented with headache, vision changes, and right-sided weakness. MRI revealed left ICA occlusion, infarcts, and enlargement of skull base mass. The patient underwent left STA to MCA bypass. Biopsy was negative for fungal hyphae, but given concern for IA, patient was started on Voriconazole.

⎼ The patient experienced significant improvement in symptoms and was not seen for one year.

⎼ In December 2015, patient developed right sided headaches. Given concern for recurrent IA, Galactomannan and Beta-D-glucan were checked and elevated to 0.87 and >500 respectively. The patient was re-started on Voriconazole with marked improvement in headaches.

⎼ MRI/MRA showed new narrowing of the right ICA, but patient remains alive without complications

▶ Figure 3. Patient 3

Figure 4a. Left ICA ruptured mycotic aneurysm (arrow).

Figure 4b. Left ICA without flow after coil/glue sacrifice.

▶ Figure 4. Patient 4

Figure 3a. Absence of flow (arrow) within the left ICA. Figure 3b. Left hemisphere subacute infarct (arrow).

▷ Watanabe T, Okada T, Okada C, et al. An aspergillotic aneurysm of the internal carotid artery following allogeneic bone marrow transplantation: successful management with catheter coil embolization and long-term antifungal agents. Transpl Infect Dis. 2009;11(1):49-53. doi:10.1111/j.1399-3062.2008.00336.x

▷ Hot A, Mazighi M, Lecuit M, et al. Fungal Internal Carotid Artery Aneurysms: Successful Embolization of an Aspergillus-Associated Case and Review. Clin Infect Dis. 2007;45(12):e156-e161. doi:10.1086/523005

▷ Reischies F, Hoenigl M. The role of surgical debridement in different clinical manifestations of invasive aspergillosis. Mycoses. 2014;57:1-14. doi:10.1111/myc.12224

▷ Hurst RW, Judkins A, Bolger W, Chu A, Loevner LA. Mycotic aneurysm and cerebral infarction resulting from fungal sinusitis: imaging and pathologic correlation. AJNR Am J Neuroradiol. 2001;22(5):858-863. http://www.ncbi.nlm.nih.gov/pubmed/11337328. Accessed September 3, 2018.

▷ Corvisier N, Gray F, Gherardi R, et al. Aspergillosis of ethmoid sinus and optic nerve, with arteritis and rupture of the internal carotid artery. Surg Neurol. 1987;28(4):311-315. http://www.ncbi.nlm.nih.gov/pubmed/3629461. Accessed September 3, 2018.

Jessica S. Little, MDDepartment of Medicine

Brigham and Women’s Hospital75 Francis Street

Boston, MA 20115jlittle4@partners.org

Jessica S. Little, MD,1 Matthew P. Cheng, MD,2 Liangge Hsu, MD,3C. Eduardo Corrales, MD,4 and Francisco M. Marty, MD2

1Department of Internal Medicine, 2Division of Infectious Diseases, 3Department of Radiology, and 4Division of Otolaryngology,Brigham and Women's Hospital, Boston, MA