500 Nadkarni et al. Ischaemic complications after surgical resection of intracranial aspergilloma T.D. Nadkarni1 MCH, K.I. Desai1 MCH, D. Muzumdar1 MCH, A. Goel1 MCH, A. Shenoy2 MD 1 Department of Neurosurgery, King Edward Memorial Hospital, Seth G. S. Medical College, Parel, Mumbai, India, 2Department of Neuropathology, King Edward Memorial Hospital, Seth G. S. Medical College, Parel, Mumbai, India Summary A 32-year-old male presented with a paranasal sinus Aspergillus fungal infection. The nasal infection was cleared by endoscopic sinus surgery and the patient was treated with antifungal agents. The patient was otherwise healthy with no evidence of immunosuppresion. Five months later, the patient had to undergo excision of the left frontal intracranial infection for symptoms of raised intracranial pressure and seizures. Within 48 hours of surgery, the patient developed basilar artery thrombosis with infarction of the cerebellum and midbrain. The patient succumbed to this vascular catastrophe, which developed at a site distal to that from surgery. The pathophysiology of ischaemic complications after surgical resection of intracranial aspergilloma is discussed. ª 2003 Elsevier Science Ltd. All rights reserved. Journal of Clinical Neuroscience (2003) 10(4), 500–502 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0967-5868(03)00097-3 Keywords: aspergilloma, fungal granuloma, arterial thrombosis Received 16 May 2002 Accepted 19 August 2002 Correspondence to: Dr Trimurti D. Nadkarni, MCh, Department of Neurosurgery, King Edward Memorial Hospital, Seth G. S. Medical College, Parel, Mumbai 400 012. India. Tel.: +91-22-4129884; Fax: +91-22-4143435; E-mail: tdnadkarni@hotmail.com INTRODUCTION Aspergillus infection of the human central nervous system (CNS) is rare and involves the species Aspergillus fumigatus.1;2 General awareness of intracranial fungal infections has increased, especially in immunocompromised individuals.3;4 The detection rate of fungal infection has improved because of better neuroradiology, and more sensitive microbiological isolation techniques. We describe a patient developing a distal vascular event, remote from the site of intracranial surgery. The possible pathogenesis of this rather unusual clinical event is discussed. CASE REPORT A 32-year-old male patient presented with occasional epistaxis. He was diagnosed as having a bilateral ethmoidal mass for which he underwent an endoscopic biopsy revealing an aspergillous granuloma. A bilateral functional endoscopic sinuscopic surgical clearance of the sinuses was done and the patient started on antifungal therapy. At surgery, the frontal bone was noted to be soft and osteomyelitic. The floor of the frontal sinus and medial orbital walls were also osteomyelitic. All caseous material and dehiscent bone was curetted. Five months later he returned complaining of headache and 2 episodes of generalised convulsions. On examination he had no neurological deficit. Examination of the fundi showed papilledema. Computed tomography (CT) scan of the brain showed a left frontal peripherally enhancing irregular shaped isodense mass (Fig. 1A). The mass abutted the falx and was in continuity with the anterior skull base. The lesion had severe perifocal oedema and the resultant mass effect effaced both the frontal horns. Routine haematological investigations and blood coagulation profile were normal. There was no evidence of immunosuppresion. There was residual fungal disease in the ethmoid sinuses (Fig. 1B). The patient underwent a left frontal craniotomy and excision of the left frontal mass. At surgery a firm, fleshy and moderately vascular lesion was excised. The lesion was in continuity with the left frontal air sinus and ethmoids. Four doses of dexamethasone (4 mg i.v. at 6 h intervals) were given during the operation and immediately after. Histology confirmed the lesion to be an aspergilloma. Haematoxylin and eosin staining showed a large number of lymphocytes, epitheloid cells, and areas of fibrosis with hyaline changes. Many refractile filamentous structures were seen, some with giant cells. Grocott–Gomori methenamine-silver (GMS) staining showed the irregular septate branching hyphae characteristic of Aspergillus (Fig. 2). He was well immediately after surgery. Twelve hours later he had a generalised convulsion. He progressively worsened becoming unconscious. Postoperative CT scan of the brain showed Fig. 1 Post-contrast axial CT iamge shows (A) the left frontal granuloma surrounded by severe cerebral oedema, (B) residual chronic inflammatory disease is noted in the right ethmoidal sinuses. Journal of Clinical Neuroscience (2003) 10(4) ª 2003 Elsevier Science Ltd. All rights reserved. Ischaemic complications of intracranial aspergilloma 501 DISCUSSION Fig. 2 Photomicrograph of the left frontal granuloma shows filaments of Aspergillus lying amidst necrotic tissue (GMS x 250). total excision of the left frontal mass (Fig. 3A) with severe left frontal lobe oedema. Both the frontal horns were well seen. In addition, there were bilateral cerebellar non-haemorrhagic infarcts, the left larger than the right (Fig. 3B). The patient succumbed on the second postoperative day. Examination of the brain at post-mortem showed a swollen brain. The meninges were hazy. The basilar artery was embedded in thick basal exudates. There was evidence of bilateral cerebellar and midbrain infarction (Figs. 4A and B). The site of surgery showed the postoperative defect and softening. Histopathological examination of the basilar artery showed the vessel to be surrounded by Aspergillus filaments and inflammatory exudate on GMS stain (Fig. 5). Aspergillus fungal spores are commensals in the respiratory tract and external auditory canal. The most common sites of primary Aspergillus infection are maxillary sinusitis of dental origin or the lungs.5;6 Intracranial infection occurs through haematogenous and less frequently through direct or contiguous spread.7;8 Direct infiltration into the skull base leads to the more commonly encountered basal osteomyelitis.9 The infection may affect the parenchyma or the meninges. According to the site and nature of infection, the patient may present with features of meningitis, focal neurological signs or symptoms of raised intracranial pressure.5;10–12 The intracranial vasculature can be involved by mycotic aneurysms or intra-arterial thrombosis.2;13 Subarachnoid haemorrhage due to a fungal mycotic aneurysm is rare.1 The Aspergillus invasion of blood vessels is frequent and this may cause haemorrhagic infarction. Aspergillus hyphae invade directly into the vessel wall, which becomes weakened due to necrosis and polymorphonuclear infiltration.2;10 Intraluminal extension of hyphae can initiate thrombus formation. Rarely, major arterial stenosis may occur following leptomeningeal infection.10 Steroids can inhibit the macrophage response to intracellular fungus and may permit enhanced germination.14;15 CNS aspergillosis occurs in 2 different groups of patients.16 In first group the patients are immunocompromised. They may be suffering from leukemia, lymphoma, aplastic anemia, or underwent renal transplantation. These patients have received cytotoxic drugs, often have granulocytopenia, less commonly have focal neurological deficits, and seldom have seizures. The second group is not granulocytopenic, have received no cytotoxic agents, have undergone non-transplant surgery, and more frequently have focal neurological deficits. Fig. 3 Postoperative post-contrast axial CT shows (A) the granuloma to have been completely excised through a left frontal craniotomy, (B) multiple infarcts are noted in the posterior fossa. The largest is noted in the left cerebellar hemisphere. Fig. 4 Post-mortem examination of the brain shows (A) the extensive left cerebellar infarct, (B) right midbrain infarct (arrow). ª 2003 Elsevier Science Ltd. All rights reserved. Journal of Clinical Neuroscience (2003) 10(4) 502 Upjohn et al. Fig. 5 Photomicrograph of the basilar artery examined after post-mortem brain examination shows an artery lying in an exudate containing many fungal filaments of Aspergillus (GMS x 250). Aspergillosis is generally treated with surgical debridement and antifungal agents. Amphotericin B, rifampicin, 5-fluoro-cytosine, miconazole, fluconazole, and itraconazole are agents of varying efficacy and systemic toxicity. Liposomal amphotericin B and interferon-c are undergoing trials. Surgical debridement enhances abscess penetration by removal of necrotic debris.17 The prognosis of CNS aspergillosis is poor, with most reported cases being fatal. The authors have earlier presented 2 aspergillomas of the paracavernous region whose postoperative recovery was marred by vascular events of vessels distal from the site of surgery.18 The clinical course of events were similar to the present case. Both patients were young as the present patient, aged 30 and 40 years, otherwise in good health with no immunocompromise or detectable primary source of fungal infection. One lesion was located exclusively in the dural cover of Meckel’s cave while the other was densely adherent to the lateral wall of the cavernous sinus. Both these lesions resembled benign tumours on preoperative imaging and on intraoperative consistency and vascularity. These lesions were successfully and completely excised. Case 1 suffered an arterial infarct in the basilar territory 1 month after surgery while on antifungal therapy. Case 2 died on the tenth postoperative day of complications due to intra-arterial thrombosis and fungal growth in the wall of the basilar artery. Cerebrospinal fluid examination was not carried out in these patients so dissemination of fungi in the cerebral spaces could not be ascertained. The stress of surgery and the use of steroids to control cerebral oedema in the immediate postoperative phase may have been contributory factors for the fungal growth. Our experience with these 3 patients suggests that the possibility of an ischaemic event should be considered in the postoperative phase. We are not sure if a high suspicion of fungal infection on the basis of radiology or operative findings, avoidance of steroids, and early treatment with antifungal agents may help to avoid such a vascular insult. The effect of surgery and antifungal agents on the ultimate clinical prognosis for such fungal lesions remains unclear. REFERENCES 1. Dyken ME, Biller J, Yuh WTC, Fincham R, Moore SA, Justin E. Carotidcavernous sinus thrombosis caused by Aspergillus fumigatus: magnetic resonance imaging with pathological correlation. A case report. Angiology 1990; 41: 652–656. 2. Nov AA, Cromwell LD. Computed tomography of neuraxis aspergillosis. J Comput Assist Tomogr 1984; 8: 413–415. Journal of Clinical Neuroscience (2003) 10(4) 3. Cravens G, Robertson H, Banta C, Garcia C, Neveille P. Spina cord compression due to intradural extramedullary aspergilloma and cyst: a case report. Surg Neurol 1989; 31: 315–318. 4. Walsh TJ, Hier DB, Caplan LR. Aspergillosis of the central nervous system: clinicopatholgical analysis of 17 patients. Ann Neurol 1985; 18: 574–582. 5. Fuchs HA, Evans RM, Gregg CR. Invasive aspergillosis of the sphenoid sinus manifested as a pituitary tumor. South Med J 1985; 78: 1365–1367. 6. Fujiwara S, Fujino H, Nogami K, Fukui M. Aspergillosis of the sphenoid sinus with cavernous sinus syndrome. Neuroradiology 1989; 31: 443. 7. Morioka T, Tashima T, Nagata S, Fukui M, Hasuo K. Cerebral aspergillosis after burr-hole surgery for chronic subdural hematoma: a case report. Neurosurgery 1990; 26: 332–335. 8. Salaki JS, Louria DB, Chmel H. Fungal and yeast infections of the central nervous system. Medicine (Baltimore) 1984; 63: 108–132. 9. Carr MM, Cusimano MD, Muller PJ, Bilbao J. Aspergillosis of the cranial base. Skull Base Surg 1994; 4: 159–163. 10. Aung UK, Lin UK, Nyunt US. Leptomeningeal aspergillosis causing internal carotid artery stenosis. Br J Radiol 1979; 52: 328–329. 11. Bickely LS, Betts RF, Parkins CW. Atypical invasive external otitis from Aspergillus. Arch Otolaryngol Head Neck Surg 1988; 114: 1024–1028. 12. Murai H, Kobayashi T, Gito I, Inoue H, Hasuo K. Hypertrophic cranial pachymeningitis due to Aspergillus flavus. Clin Neurol Neurosurg 1992; 94: 247–250. 13. Yanai Y, Wakao T, Fukamichi A, Kunimine H. Intracranial granuloma caused by Aspergillus fumigatus. Surg Neurol 1985; 23: 597–604. 14. Bodey GP, Glann AS. Central nervous system aspergillosis following steroidal therapy for allergic bronchopulmonary aspergillosis. Chest 1993; 103: 299–301. 15. Wagner DK, Varkey B, Sheth NK, DaMert GJ. Epidural abscess, vertebral destruction, and paraplegia caused by extending infection from an aspergilloma. Am J Med 1985; 78: 518–522. 16. Walsh TJ, Hier DB, Caplan LR. Aspergillosis of the central nervous system:clinicopathological analysis of 17 patients. Ann Neurol 1985; 18: 574–582. 17. Kitani S, Yumoto E, Okamura H, Yanagihara N. Sino-orbital aspergillosis associated with total opthalmoplegia. Laryngoscope 1985; 95: 190–192. 18. Goel A, Nadkarni T, Desai AP. Aspergilloma in the paracavernous region. Two case reports. Neurol Med Chir 1996; 36: 733–736. Spinal cord ischaemic stroke associated with vertebral body infarction Edward Upjohn MB BS, Bhadrakant Kavar MB CHB FCS FRACS, Peter J. Mitchell MBBS MMED FRANZCR, Michael Gonzales MBBS FRACPA The Royal Melbourne Hospital, Parkville, Victoria, Australia Summary Only eight cases of spinal cord ischaemic stroke causing paraplegia with associated vertebral body infarction have been previously described. We describe a ninth case with histopathology confirming the Magnetic Resonance Imaging (MRI) appearance of vertebral body infarction. We have reviewed the literature concerning this condition and discuss its diagnosis and aetiology. ª 2003 Elsevier Science Ltd. All rights reserved. Journal of Clinical Neuroscience (2003) 10(4), 502–506 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0967-5868(03)00095-X Keywords: vertebral body infarction, spinal cord stroke, paraplegia, magnetic resonance imaging Received 16 May 2002 Accepted 25 July 2002 Correspondence to: Dr. Edward Upjohn, MBBS, 402 Glenferrie Road, Kooyong 3144, Australia. Tel.: +61-3-9342-7000; Fax: +61-3-9347-7695. ª 2003 Elsevier Science Ltd. All rights reserved.