Abstract

A 64 year old diabetic hypertensive milkman presented in September 2011 with 4 months progressive constant right frontotemporal retro–orbital pain. It was worse at night affecting sleep with slight right field blurring and later vomiting. Full examination including blood pressure was normal with acuities 6/9. Tension type headache was considered. Initial brain CT was reported as normal. With concern about giant cell arteritis steroids were trialled although ESR was 8 and CRP 25 with no other clinical features: pain reduction was short–lived and temporal artery biopsy negative. Symptoms worsened despite analgesics. Noting his sister's Wegener's and his weekly positive ANCA the differential began to expand.

Claustrophobia delayed MRI several months until admission became necessary for pain control when he had new right partial ptosis. Examination showed asymptomatic upgaze diplopia and MRI a right orbital apex soft tissue mass, likely present on the CT when reviewed, along with minor proptosis and distension of the optic nerve. Whilst additional diagnoses then included meningioma and lymphoma, regional MDT proposed metastatic carcinoma advising against biopsy due to lesion location. Hence investigation for malignancy but LDH, CT Chest/Abdomen/Pelvis and PET CT were normal/negative.

Two weeks into admission he developed complete right visual loss due to compressive neuropathy. Differentials of aspergillosis and mucormycosis were raised and biopsy and debridement proposed. Amphotericin was commenced after discussion with the infectious diseases service, but contrary to microbiological opinion, with later change to voriconazole due to raised ALP and despite negative aspergillosis serology (IgG antibody 35, 0–40). Within a month, complete right ophthalmoplegia and loss of right light reflexes developed. Diagnostic progress was delayed by diverticular perforation, pneumonia and critical illness neuropathy on ITU. Repeat imaging showed the mass had enlarged (24×15×11 mm) and was eventually felt amenable to biopsy after very prolonged MDT consideration. On 4th May 2012 functional endoscopic sinus biopsy was performed, confirming fungal hyphae (most likely aspergillosis). He underwent orbitozygomatic craniectomy and removal of infected bone and tissue but internal carotid artery encasement limited full resection. At second operation the right eye was enucleated. Operations were complicated by extensive cerebral hemisphere infarction and pneumocephaly and he unfortunately suffered profound cerebral damage leaving severe and complex neurodisability and tracheostomy dependence. Anti–fungal treatment will continue a full year.

Diagnosis of CNS aspergillosis requires a high degree of clinical suspicion as there is no typical presentation. Patients are usually severely immunosuppressed or have underlying granulomatous disease; it is rapidly progressive and often fatal. CT may show low–density poorly enhancing lesions with limited mass effect; on MRI lesions may be more numerous showing intermediate–signal intensity within high–signal areas on T2–weighted images. Unfortunately, tissue biopsy is often not feasible and medical treatment should be commenced prior to histopathological confirmation. Voriconazole is the drug of choice, with better tolerance and improved mortality compared with amphotericin. This case highlights the importance of considering the diagnosis of invasive aspergillosis in immunosuppressed individuals and persevering with multidisciplinary discussion to obtain tissue biopsy.