Abstract
We report a case of invasive sphenoid sinus aspergillosis with progressive internal carotid artery (ICA) stenosis and contralateral carotid occlusion that was successfully treated with percutaneous transluminal angioplasty and stenting (PTAS). A 70-year-old man presented with right-sided visual disturbance, ptosis, and left hemiparesis. Magnetic resonance imaging of the head revealed a space-occupying lesion within the sphenoid sinus with infiltration of the bilateral cavernous sinuses, right ICA occlusion, and multiple watershed cerebral infarcts involving the right cerebral hemisphere. The patient was diagnosed with invasive sinus aspergillosis based on transnasal biopsy findings. Despite intensive antifungal therapy using voriconazole, rapidly progressive aspergillosis led to a new stenotic lesion in the left ICA, which increased the risk of bilateral cerebral hypoperfusion. We performed successful PTAS to prevent critical ischemic events. Finally, aspergillosis was controlled with voriconazole treatment, and the patient was discharged. He showed a favorable outcome, with a patent left ICA observed at a 3-year follow-up. PTAS may be feasible in patients with ICA stenosis and invasive sinus aspergillosis.
Introduction
Invasive sinus aspergillosis refers to the destructive fungal infiltration of the surrounding tissues and can cause a variety of symptoms such as pituitary dysfunction, visual disturbance, ptosis, ophthalmoplegia, subarachnoid hemorrhage secondary to the rapid formation and rupture of internal carotid artery (ICA) aneurysms, or cerebral infarction following steno-occlusive disease of the ICA.1-3) We report a case of progressive carotid stenosis and contralateral carotid occlusion caused by invasive sphenoid sinus aspergillosis in a patient who underwent successful percutaneous transluminal angioplasty and stenting (PTAS) and showed long-term stent patency with favorable outcomes.
Case Report
A 70-year-old man with an unremarkable medical history visited a local physician for evaluation of right-sided ptosis and lower extremity weakness. Magnetic resonance imaging (MRI) of the head revealed a space-occupying lesion within the sphenoid sinus with infiltration of the bilateral cavernous sinuses, occlusion of the right ICA, and multiple cerebral infarcts involving the right cerebral hemisphere. The patient was diagnosed with fungal sinusitis and referred to our hospital for further management. Physical examination performed on admission showed a temperature of 36.6°C, visual impairment in his right eye, right oculomotor nerve palsy, right facial paresthesia, and left hemiparesis. Laboratory investigations showed a normal white blood cell count (5640/μL), slightly elevated serum C-reactive protein level (1.76 mg/dL), and significantly elevated serum β-D glucan levels (18.2 pg/mL). Blood and cerebrospinal fluid cultures and cytology showed negative results.
Head MRI revealed a mass in the sphenoid sinus with infiltration of the bilateral cavernous sinuses. This lesion appeared isointense on T1- and T2-weighted images and hyperintense on post-gadolinium T1-weighted images (Fig. 1A). Diffusion-weighted imaging showed scattered high signal intensities in the watershed area of the right cerebral hemisphere (Fig. 1B), and magnetic resonance angiography (MRA) revealed right ICA occlusion (Fig. 1C). N-isopropyl-p-123I-iodoamphetamine single-photon emission computed tomography (IMP-SPECT) performed at rest showed hypoperfusion of the right cerebral hemisphere (Fig. 1D). Thoracoabdominal computed tomography revealed no lesions or infective foci.
Cerebral angiography performed on the 14th day of admission revealed complete occlusion of the right ICA and mild stenosis of the ophthalmic segment of the left ICA (Fig. 2A). Left ICA angiography showed that the right cerebral hemisphere was mainly perfused via cross flow through the anterior communicating artery (Fig. 2B). No atherosclerotic changes were observed in the other vessels.
The patient was preoperatively diagnosed with invasive fungal sinusitis associated with right ICA occlusion and cerebral infarction. Treatment was initiated with empiric antibiotics, including voriconazole (VRCZ), ceftriaxone, metronidazole, vancomycin, and antiplatelet agents (aspirin and clopidogrel), to prevent recurrent stroke on admission. Additionally, a transnasal biopsy was performed to confirm the causative microorganism.
On the 17th day of admission, the patient underwent a transnasal biopsy and debridement. Histopathological evaluation and culture studies confirmed the diagnosis of granuloma secondary to Aspergillus spp. infection. Antibiotic sensitivity testing showed susceptibility to VRCZ.
Follow-up cerebral angiography performed on the 28th day of admission revealed progressive stenosis (Warfarin-Aspirin Symptomatic Intracranial Disease: 69%) in the ophthalmic segment of the left ICA without neurological deterioration (Fig. 2C). Poorly controlled sinusitis accompanied by a high serum β-D glucan level (63.3 pg/mL) necessitated surgical intervention because further stenosis of the left ICA was associated with a high risk of life-threatening bilateral cerebral infarction.
On the 31st day of admission, the patient underwent percutaneous transluminal angioplasty (PTA) for left ICA stenosis under general anesthesia using a Gateway 3.0 × 12 mm device (Stryker Neurovascular, Kalamazoo, Michigan, USA), followed by stent placement (Multilink 8: 3.0 × 12 mm [Abbott Laboratories, Chicago, Illinois, USA]) for recurrent stenosis secondary to elastic recoil after PTA (Fig. 2D-F). This procedure improved cerebral perfusion without any complications.
Follow-up angiographies performed on the 52nd and 66th days revealed new progressive stenosis in the clinoidal segment of the left ICA, immediately proximal to the site of the previous stent (Fig. 3A-C). On day 66, we successfully repeated the PTA procedure (Gateway: 3.0 × 15 mm) with concomitant stenting (Multilink 8: 3.5 × 15 mm) under general anesthesia (Fig. 3D-F).
Final follow-up cerebral angiography performed on the 80th day revealed no restenosis, and the patient's serum β-D glucan levels were normalized. Therefore, the patient was transferred to the rehabilitation hospital on the 88th day of admission and was instructed to continue VRCZ treatment (Fig. 4). He was released from the hospital on the 157th day of his stay.
Although he had no recurrent cerebral infarction at the outpatient follow-up visit for 3 years, he was readmitted with transient loss of consciousness after alcohol consumption 42 months after the last intervention. He underwent right superficial temporal artery-middle cerebral artery (MCA) bypass because oxygen-15 positron emission tomography showed misery perfusion in the right MCA territory, although cerebral angiography revealed no restenosis and good patency of the stents in the left ICA.
Discussion
We report the first case of progressive ICA stenosis secondary to invasive sinus aspergillosis in a patient who was successfully treated using PTAS and showed long-term stent patency and a favorable outcome.
Invasive fungal sinusitis is rare, which accounts for 3.6% of all fugal sinusitis.4) The middle turbinate is the commonly affected site, and the various presenting symptoms include fever, headache, rhinorrhea, facial pain, and diplopia.5) Invasive fungal sinusitis is associated with rapid infiltration and destruction of adjacent tissues, such as the facial bone, and is therefore occasionally misdiagnosed as a tumor.6,7) Definitive diagnosis of this disease requires biopsy-documented identification of fungal elements in diseased tissues.8)Aspergillus is one of the most common causative agents of fungal sinus infections.5) Invasive aspergillosis is usually associated with immunosuppression or immune compromise,9) and treatment includes surgical debridement and antifungal agent administration.10) Previously, the mortality rate associated with this condition was reported to be 50%-80%. However, VRCZ therapy has been shown to improve survival rates in patients with invasive aspergillosis.11,12) Recent studies have reported a mortality rate of 18%, but the management of the disease remains challenging.13)
Fungal invasion of the ICA wall is a serious complication of invasive fungal sinusitis, which can precipitate catastrophic hemorrhagic or ischemic stroke.14) Reportedly, extracranial-intracranial (EC-IC) bypass concomitant with ICA surgical trapping and endovascular parent artery occlusion is effective in patients with infectious ICA aneurysm rupture.15,16) EC-IC bypass surgery is shown to be effective for ICA obstruction secondary to invasive fungal sinusitis.17) In this patient with an initially poorly controlled infection and an unfavorable prognosis, we performed minimally invasive PTA with concomitant stenting for progressive ICA stenosis and contralateral ICA occlusion. Fortunately, subsequent medical control of infection led to improved long-term survival and good ICA patency. This is the first case report that describes the efficacy of PTA and concomitant stenting for progressive ICA stenosis caused by invasive sinus aspergillosis.
The role of artificial device implantation in the management of infectious lesions remains controversial. However, several reports in the literature have highlighted the usefulness of this therapeutic approach. Coil embolization and coronary stent-assisted-coil embolization have been used for the treatment of fungal aneurysms with effective infection control.18,19) In a recent study, Desai et al. reported successful mycotic aneurysm embolization using the Onyx (Neurovascular, Inc., Irvine, California, USA) device or N-butyl-2-cyanoacrylate.20) We performed PTA and concomitant stent implantation for the management of progressive ICA stenosis in our patient. Although no stent is approved for cerebral artery stenosis secondary to fungal infection, we used Multilink 8 (balloon expandable coronary stent) because of its easy delivery and positioning. Artificial devices were implanted, but infection was well controlled with sustained VRCZ treatment. We recommend this approach as a feasible therapeutic strategy for patients with the aforementioned clinical presentation.
Conclusion
We report the first case of progressive ICA stenosis secondary to invasive sinus aspergillosis in a patient who was successfully treated using PTA and concomitant stenting and showed long-term stent patency and a favorable outcome. PTAS may serve as a useful therapeutic option for progressive ICA stenosis caused by invasive fungal sinusitis.
Acknowledgments
This case report was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (grant numbers 22K09257 and 21K09125).
Informed Consent
The patient consented to the publication of his information in a journal.
Conflicts of Interest Disclosure
All authors declare that the article content was composed in the absence of any commercial, financial, or institutional relationships that could be construed as conflicts of interest. The authors, who are members of the Japan Neurosurgical Society (JNS), have registered the online Self-reported COI Disclosure Statement Forms through the website for JNS members.
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