gms | German Medical Science

ESBS 2005: Skull Base Surgery: An Interdisciplinary Challenge
7th Congress of the European Skull Base Society held in association with
the 13th Congress of the German Society of Skull Base Surgery

18. - 21.05.2005, Fulda, Germany

Invasive aspergillosis of the skull base – 4 case reports

Meeting Contribution

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  • S. Knipping - Department of Otorhinolaryngology Head and Neck Surgery, Martin-Luther-University Halle-Wittenberg, Germany
  • A. Sandner - Department of Otorhinolaryngology Head and Neck Surgery, Martin-Luther-University Halle-Wittenberg, Germany
  • M. Bloching - Department of Otorhinolaryngology, Helios Hospital Berlin-Buch, Berlin, Germany

ESBS 2005: Skull Base Surgery: An Interdisciplinary Challenge. 7th Congress of the European Skull Base Society held in association with the 13th Congress of the German Society of Skull Base Surgery. Fulda, 18.-21.05.2005. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc05esbs63

doi: 10.3205/05esbs63, urn:nbn:de:0183-05esbs633

Published: January 27, 2009

© 2009 Knipping et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.




The invasive aspergillosis of the skull base is a rare fungal disease caused by Aspergillus fumigatus, A. terreus, A. flavus or A. niger. In most cases it originates from the paranasal sinuses and involves the surrounding tissue such as the orbital cavity [1]. Fungal invasion, originating from the paranasal sinuses, causes intracranial growth mainly along the base of the skull and larger vessels. Usually it occurs in patients with immunodeficiency, mainly caused by malignant diseases, transplantations, diabetes mellitus or advanced AIDS. But diseases in immunocompetent patients after surgery are described in literature in particular for aspergillosis of the paranasal sinuses [2].

The therapy of the sinus aspergillosis first and foremost consists of a surgical debridement and an additive local antimycotic therapy combined with a systemic antimycotic agent, for example with Amphotericin B. Despite of radical surgical intervention and exhausting all conservative drug treatments there are high numbers of therapy failures and a high mortality, also in immunocompetent patients.


Case 1

A 60 year old male immunocompetent patient refered to our hospital because of otalgia and cephalgia right sided, and progressive hypaesthesia of the trigeminal nerve. Additionally, the patient described a loss of weight. The MRI and CT showed an extensive infiltrating process of the right skull base and of the petroclival region with bony destructions originating from sphenoid bone (Figure 1A [Fig. 1]). The histological investigation proved an invasive aspergillosis.

After surgical treatment of the mycosis via an endonasal approach according to Sturmann-Canfield and a postoperative systemic antimycotic therapy with liposomal Amphotericin B and Itraconazol as well as an intensive local treatment with Amphotericin B-irrigation there occurred an clinical improvement. After three months of maintenance therapy however, we observed a clear progredience of the process showing a severely reduced general condition of the patient and an infiltration of the right temporal lobe in MRI. As we had no further surgical opportunities left we increased Itraconazol above the maximum recommended dose of 600 mg/d. In addition we performed a hyperbaric oxygenation (40 treatment units). After this maximum of conservative therapy regredience could be observed, both clinically as well as during MRI.

Case 2

This is the report of the clinical course of an immunosuppressed 64 years old male with an invasive aspergillosis of the orbit with intracranial extension into the cavernous sinus (Figure 1B [Fig. 1]). The patient was refered to our hospital with amaurosis, ptosis and ophthalmoplegia since 3 months. Additional the patient suffered from kidney failure after kidney transplantation and diabetes mellitus II. The patient was undertaken an endonasal sinus debridement with decompression of the orbit after CT and MRI scan. Additionally, a systemical antibiotic therapy and a systemical and local antimycotic therapy was performed. Furthermore, hyperbaric oxygenation was performed (5 units). The patient died within 3 weeks of this intensive treatment due to intracerebral hemorrhage caused by a carotid artery dissection due to aspergillus invasion.

Case 3

A 74 years old female with an invasive aspergillosis of the skull base was immunosuppressed due to diabetes mellitus II (Figure 1C [Fig. 1]). She reported about intensive headache, facial pain, and paresthesia of the left hemiface. At the physical examination a complete ophthalmoplegia on the left side was conspicuous. After transshpenoidal biopsy at the department of neurosurgery the histological diagnosis of invasive aspergillosis was ascertained. Endonasal sinus surgery and debridement was carried out. Postoperatively the patient was treated with systemic antimycotic therapy with liposomal Amphotericin B and Itraconazol as well as an intensive local treatment with Amphotericin B-irrigation. Additionally, hyperbaric oxygenation was performed (49 applications). After this intensive treatment the patient was released in the outpatient care. Up to now the patient is free of serious symtoms

Case 4

A 62 year old female patient demonstrated impairments of motility of bulbus oculi with double visions. Additionally, an epileptic seizure occurred. The patient suffered from paraaortal metastases of an endometrial carcinoma. Computed tomography exhibited sino-orbital and skull base lesions with bony erosions and involvement of sphenoid bone as well as the cavernous sinus (Figure 1D [Fig. 1]).

An endoscopic sinus drainage, debridement and histological examination shows an invasive aspergillosis of the lateral wall of sphenoid sinus with affection of the orbital apex. Postoperatively antimycotic treatment with liposomal Amphotericin B and Itraconazol as well as an intensive local treatment with Amphotericin B-irrigation was carried out. After the radiation therapy concering the systemic metastasis formations the patient died.


Aspergillus fumigatus is the most frequent germ causing invasive aspergillosis showing a frequency of 90 %. The infection with this ubiquitous occurring hyphal fungi in most cases happens exogenous via respiratory air. Due to its usually low virulence often only immunodeficient patients fall ill. Fundamental risk factors are quantitative or functional defects of the circulating neutrophilic granulocytes, for example after transplantations, or with patients having neutrophilic or macrophagic dysfunctions. The infection of the paranasal sinuses is a frequent form of extrapulmonary manifestation [3].

Invasive aspergillosis of the paranasal sinuses can be divided into three forms according to deShazo [4]: granulomatous form, acute-fulminating form, and chronic-invasive form.

The chronic-invasive aspergillosis shows neuropathies of the cerebral nerves and severe frontal cephalgias due to infiltration. Further neurologic symptoms, e.g. sinus cavernosus-syndrome or pseudo-tumor orbitae, may additionally occur in the course of the disease. This form is characterized by a protracted process, and it often shows a letal ending.

In terms of diagnostics an invasive aspergillosis can only be considered to be certain once there exists a positive histologic finding (characteristic fungal formations in the tissue). Laboratory parameters like CRP-increase or liquor-cerebrospinalis investigations as well as serologic investigations (e.g. concerning antibodies, galactomannan, evidence of aspergillus-DNA via PCR) show varying results, and they can only support a diagnosis.

In cases of assumed invasive aspergillosis a surgical confirmation of the diagnosis is necessary. Furthermore, CT and MRI scans can reveal invasive processes of the skull base.

The first and foremost therapy of invasive aspergillosis of the skull base is the radical surgical debridement supported by an intensified antimycotic drug therapy [5]. Despite this treatment the mortality of this disease extraordinarily high. According to references in literature cerebral aspergillosis shows a mortality up to 95 %.

In order to use a further therapy approach for our patients we carried out an additional hyperbaric oxygenation. According to the recommendations of the „Undersea and Hyperbaric Medicine Society“ the cerebral abscess gives a certain indication for hyperbaric oxygenation [6].

According to our limited experience hyperbaric oxygenation seems to be a useful tool in the therapeutic management of invasive aspergillosis.

Under this extensive treatment protocol a clinical recovery in 2 patients occurred. One patient died due to intracerebral hemorrhage caused by a carotid artery dissection, the other patient died because of accompanied complications.

In spite of the high mortality rate up to 95% invasive Aspergillosis can be treated effectively by early and rigorous therapy.


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