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Aspergillosis of the central nervous system
Journal of the Neurological Sciences, 1978, 38: 229-233 © Elsevier/North-HollandBiomedicalPress
229
ASPERGILLOSIS OF THE CENTRAL NERVOUS SYSTEM
S. MOHANDAS, G. K. AHUJA, V. P. SOOD and V. VIRMANI Department of Neurology and Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi-16 (India)
(Received 15 March, 1978) (Accepted 12 May, 1978)
SUMMARY Aspergillosis of the central nervous system is rare. The spread to the CNS is usually from the lungs and uncommonly from paranasal sinuses. Four cases of CNS aspergillosis with spread of infection from the paranasal sinuses are described. Two patients had meningitis, one intracranial granuloma and one presented with subarachnoid haemorrhage resulting from a fungal mycotic aneurysm. Difficulties in establishing the diagnosis are discussed.
INTRODUCTION Central nervous system (CNS) aspergillosis is of uncommon occurrence; only 65 cases were reported in the world literature till 1973 (Visudhiphan, Bunyaratavej and Khantanaphar 1973). About 30 more cases have been added since (Lisbona, Lacourici~re and Rosenthal11973; Dayal, Weindling and Price 1974; Goldhammer, Smith and Yates 1974; Correa, Brinckhaus, Kesler and Martinoz 1975; Palo, Haltia and Uutela 1975; Sood, Goyal and Abrol 1975; Deshpande, Desai and Dastur 1975; Hedge, Laisung and Leung 1976; Horten, Abbot and Porro 1976; Kaufman, Thai and Farmer 1976; Banerjee, Singh, Kak, Talwar and Rout 1977). A solitary case of cerebral aspergillosis was reported prior to 1973 from India (Chitnis and Deshpande 1967) and 17 have been added subsequently (Deshpande et al. 1975 and Banerjee et al. 1977). The reported increase in incidence of fungal infection of the central nervous system in recent years is not only attributable to the increasing awareness of the condition but is probably also due to the widespread use of steroids, cytotoxic drugs and antibiotics. Aspergillus genus with more than 350 known species, of which fortunately few have been found pathogenic, has particular affinity for the central nervous system. The CNS may be affected either by spread from paranasal sinuses, which is extremely rare (Zinneman 1972; Hedge et al. 1976; Milosev, Mahgoub, Aal and E1 Hassan 1969;
230 M a h g o u b 1977) or by h a e m a t o g e n o u s spread f r o m a systemic source, the c o m m o n e s t being p u l m o n a r y (Young, Bennet, Vogel a n d C a r b o n e 1970). The susceptibility to infection is facilitated by the h o s t ' s altered i m m u n i t y due to co-existent debilitating disease ( Y o u n g et al. 1970), or i m m u n o s u p p r e s s i v e t h e r a p y . In the 4 cases r e p o r t e d here, C N S affection was n o t p r e c i p i t a t e d by any o f the a b o v e m e n t i o n e d p r e d i s p o s i n g factors. The spread o f infection was from the p a r a n a s a l sinuses in all. MATERIAL AND METHODS F o u r cases o f a s p e r g i l l o s i s o f the central nervous system were seen at the n e u r o l o g ical services o f All I n d i a I n s t i t u t e o f M e d i c a l Sciences ( A I I M S ) H o s p i t a l , New Delhi, d u r i n g the p a s t 6 m o n t h s . Biopsy o f the mass f r o m the p a r a n a s a l sinuses established the diagnosis in 3; one p r e s e n t e d as s u b a r a c h n o i d h a e m o r r h a g e resulting from a m y c o t i c a n e u r y s m o f fungal origin p r o v e d at a u t o p s y . Case 1
A 38-year-old male was admitted to the Otorhinolaryngology Service of AI1MS Hospital with a progressive painful swelling over the left cheek of 3 months duration. Four years prior to admission he had had episodic nasal obstruction for which he underwent repeated antral punctures and septal surgery. On examination, the swelling was firm in consistency and tender. The infraorbital margin was irregular and thickened. The left eyeball was displaced upwards. Ptosis o f the right eyelid was the solitary neurological finding. Skiagrams of the paranasal sinuses revealed haziness of the left maxillary antrum. Excision of the mass from the antrum proved aspergillous granuloma histopathologically (Fig. 1). Intravenous amphotericin B was administered, but on the 6th post-operative day the patient became apathetic and gradually lapsed into coma, with signs of meningeal irritation and was transferred to the Neurology Service. CSF showed 100 lymphocytes/cm8, total protein 1I6 mg/t00 ml, and sugar 35 rag/100 ml. Indian ink preparation and culture of the CSF for fungus were negative. Intrathecal amphotericin B (1 mg in 1 ml of distilled water) was administered but the patient died the next day.
Fig. l. Soft tissue from the maxillary antrum showing a fungal granuloma. A septate, branching fungal hypha of the aspergillus group is seen in the centre of the field. HE, x 315.
231 Case 2 A 34-year-old male was admitted with severe headache and nuchal pain of 7 days duration. He had a swelling over the right cheek, associated with multiple episodes of upper respiratory catarrh, for which he had undergone repeated antral punctures during the past 5 years. On one occasion "pus" was drained from the swelling at another hospital. On admission he had a swelling over the right cheek with proptosis of the right eye. Restriction of eye movements in all directions and neck rigidity were also noted. Biopsy of the swelling showed aspergillous granuloma. CSF was clear, showed 80 lymphocytes] cm 3, protein 106 mg/100 mi and sugar 80 mg/100 ml. Smear and culture of CSF for fungus were negative. He left against medical advice and was lost to follow up. Case 3 A 48-year-old female noticed a progressive painful swelling over the left cheek 2 years prior to admission. Exploration of the maxillary sinus done at another hopsital revealed numerous polyps, histopathologically proved to be aspergillous granulomata. She received irregular amphotericin B therapy but pain persisted. Subsequently she developed diminution of vision and complete ophthalmoplegia on the right for which she was admitted to the Neurology Service of the AIIMS Hospital. A right carotid angiogram revealed a large temporal mass. Exploratory craniotomy was advised but the patient refused. She was readmitted two months later with 4 days history of fever, deterioration in consciousness, left-sided focal fits and generalised convulsions. On examination she was unconscious, responding to painful stimuli. Ocular fundi showed optic atrophy on the right, the left disc being normal. Complete right ophthalmoplegia with left hemiparesis, and neck stiffness were noted. The CSF was aceUular and showed a mild rise in proteins. Intravenous amphotericin B was started along with anticonvulsants. Fits did not recur. She regained consciousness within a week. Amphotericin B could not be continued due to toxic effects. Flourocytosine was started. The patient has shown clinical improvement and is being followed. Case 4
An 18-year-old male was admitted with sudden onset ofgeneralised seizures and unconsciousness with signs of meningeal irritation. Lumbar tap revealed subarachnoid haemorrhage. At autopsy, an aneurysm was seen on the right posterior communicating artery. Aspergillous hyphae were seen in the aneurysmal wall. DISCUSSION A s p e r g i l l o m a o f the p a r a n a s a l sinuses is u n c o m m o n except in N o r t h e r n S u d a n f r o m where a b o u t 60 cases have been r e p o r t e d , A. flavus being i n c r i m i n a t e d in all o f t h e m ( M i l o s e v et al. 1969; H e d g e et al. 1976; M a h g o u b 1977). I n t r a c r a n i a l s p r e a d f r o m the p a r a n a s a l sinuses is rare, there being only 2 d o c u m e n t e d cases ( Z i n n e m a n 1972; H e d g e et al. 1976). A s p e r g i l l o u s meningitis is rarely e n c o u n t e r e d ; when seen, it is restricted to the base o f the b r a i n ( K a u f m a n et al. 1976). Large single or m u l t i p l e g r a n u l o m a t a or a b scesses, m a y be e n c o u n t e r e d in the b r a i n o r spinal c o r d w i t h o u t a n y clinical features suggestive o f infection a n d are c o m m o n e r t h a n m e n i n g i t i s ( M u k o y a m a , G i m p l e a n d P o s n e r 1969; Linares, M c G a r y a n d B a k e r 1971; M e y e r , Y o u n g , A r m s t r o n g a n d Y u 1973; K a u f m a n et al. 1976). T h e C S F in these cases m a y be n o r m a l o r show m o d e r a t e pleocytosis a n d / o r rise in p r o t e i n s ( Y o u n g et al. 1970; L i n a r e s et al. 1971 ; M e y e r et al. 1973). D i r e c t s m e a r e x a m i n a t i o n o f the C S F is m o r e r e w a r d i n g for d e m o n s t r a t i o n o f the fungus t h a n culture. Cultures f r o m the e x t r a - c e n t r a l nervous sysem tissues, in cases o f d i s s e m i n a t e d disease, however, yield positive results m o r e often ( Y o u n g et al. 1970; M e y e r et al. 1973; K a m e r et al. 1974). D i a g n o s i s can also be e s t a b l i s h e d by testing sera for p r e c i p i t a t i n g a n t i b o d i e s b y i m m u n o d i f f u s i o n in a g a r gel ( M a h g o u b 1971).
232 In the first 3 cases reported here, the diagnosis of CNS aspergillosis was based on the sequence of events and histopathologically confirmed fungal granulomata in the antra. In the 4th case the diagnosis was not suspected, in spite of a history of recurrent episodes of sinusitis. All the cases in the present report had intracranial extension from the paranasal sinuses. Fungal vasculitis or aneurysms, though documented, are rare. Four cases of mycotic aneurysm of fungal aetiology have so far been described, all confirmed at autopsy, the diagnosis not being suspected during life (Morriss and Spock 1970; Davidson and Robertson 1971 ; Visudhiphan et al. 1973; Horten et al. 1976). There is only one report of thrombosis of the extracranial part of the internal carotid artery of fungal aetiology (Kaufman et al. 1976). Another notable feature of the present cases was the absence of predisposing factors such as co-existent debilitating disease or administration of immunosuppressive drugs in any of our patients. Intravenous amphotenicin B has not proved uniformly effective in CNS aspergillosis because of the blood-brain barrier (Young et al. 1970; Bennett 1974; Utz 1974). Intrathecal amphotericin B has been tried but is too toxic (Utz 1974). Flourocytosine achieves high levels in CSF but clinical improvement is only occasional (Kammer and Utz 1974; Bennett 1974; Utz 1974). As mentioned above, the diagnosis of fungal meningitis is based on indirect evidence of demonstration of antral or systemic infection and pleocytosis and raised proteins content in the CSF; demonstration of fungus in the CSF being difficult. The autopsy rate from different hospitals and different parts of the world being variable, the reported incidence of aspergillous or fungal meningitis may not reflect the true incidence. With the advent of effective antifungal agents there is a need for awareness of this entity and for an extensive search for the fungi in all cases of undiagnosed meningitis. In intractable cases of recurrent sinusitis it is important to consider the possibility of fungal infection and to investigate accordingly.
REFERENCES Banerjee, A. K., M. S. Singh, V. K. Kak, P. Talwar and D. Rout (1977) Cerebral aspergillosis -Report of 8 cases, Ind. J. Path. Microbiol., 20: 91-100. Bennett, J. E. (1974) Chemotherapy of systemic mycoses, New Engl. J. Med., 289: 30-32, 320-322. Chitnis, V. R. and C. K. Deshpande (l 967) Disseminated aspergillosis, J. postgrad. Med., 13 : 131-134. Correa, A. J. E., R. Brinckhaus, S. Kesler and E. Martinoz (1975) Aspergillosis of the fourth ventricle, J. Neurosurg., 43 : 236-238. Davidson, P. and D. Robertson (1971) A true mycotic aneurysm leading to fatal subarachnoid haemorrhage in a patient with hereditary haemorrhagic telangiectasis, J. Neurosurg., 35: 71-76. Dayal, Y., H. K. Weindling and D. L. Price (1974) Cerebral infarction due to fungal embolus - - A complication of aspergillus infection on an aortic valve prosthesis, Neurology (Minneap.), 24: 76-79. Deshpande, D. H., A. P. Desai and H: M. Dastur (1975) Aspergillosis of the central nervous system- A clinical and mycopathological study of 9 cases, Neurology (India), 23 : 167-175. Goldhammery, Y., J. L. Smith and B. M. Yates (1974) Mycotic intrasellar abscess, Trans. Amer. ophthaL Soc., 72: 65-78. Gonty, A. A. and L. R. Page (1977) Aspergitlosis of the maxillary sinus, Oral Surgery, 43: 350-356. Hedge, T. R., E. Laisung and M. D. Leung (1976) Parasellar and orbital apex syndrome, Neurology (Minneap.), 26: 117-120.
233 Horten, B. E., G. F. Abbot and R. S. Porro (1976) Fungal aneurysm of intracranial vessels, Arch. Neurol. (Chic.), 33 : 577-579. Hulter, R., P. Liberman and H. Collins (1964) Aspergillosis in a Cancer Hospital, Cancer, 17: 747-756. Kammer, R. and I. P. Utz (1974) Aspergillus species endocarditis, Amer. J. Med., 56: 506-521. Kaufman, D. M., L. J. Thal and P. M. Farmer (1976) Central nervous system aspergillosis in two young adults, Neurology (Minneap.), 26: 484-488. Linares, G., P. McGary and R. Baker (1971) Solid solitary aspergillotic granuloma of the brain, Neurology (Minneap.), 21 : 177-184. Lisbona, R.,Y. Lacourici6re and L. Rosenthall (1973) Aspergillomatous abscesses of brain and thyroid, J. nucl. Med., 14: 722-723. Mahgoub, E. S. (1971) Mycological and serological studies on Aspergillusflavus isolated from paranasal aspergilloma in Sudan, Thorax, 74, 162-165. Mahgoub, E. S. (1977) Mycoses of the Sudan, Trans. roy. Soc. trop. Med. ttyg., 71 : 184-188. Meyer, R., L. Young, D. Armstrong and B. Yu (1973) Aspergillosis complicating neoplastic disease, Amer. J. Med., 54: 6-14. Milosev, B., E. S. Mahgoub, O. Aal and A. M. El Hassan (1969) Aspergilloma of paranasal sinuses - Review of 17 cases, Brit. J. Surg., 56: 132-137. Morriss, F. H. and A. Spock (1970) Intracranial aneurysm secondary to mycotic orbital and sinus infection, Amer. J. Dis. Child., 119: 357-362. Mukoyama, M., K. Gimple and C. Posner (1969) Aspergillosis of the central nervous system - - Report of a brain abscess due to A.fumugatus and review of literature, Neurology (Minneap.), 19: 967-974. Palo, J., M. Haltia and T. Uutela (1975) Cerebral aspergillosis with special reference to cerebrospinal fluid findings, Europ. Neurol., 13 : 224-231. Sakaki, H., H. Kikuchi and K. Kose (1975) Case of cerebral aneurysm due to aspergillus angitis, Jap. J. clin. Radiol., 20: 95-96. Sood, V. P., N. K. Goyal and B. M. Abrol (1975) Aspergillosis of sphenoid sinus, Eye, Ear, Nose Thr. Monthly, 54: 454-455. Utz, J. (1974) Current and future chemotherapy of the central nervous system - - Fungal infections. In • R. A. Thompson and J. R. Green (Eds.), Infectious Diseases of the Ventral Nervous System (Advances in Neurology, Vol. 6), Raven Press, New York, pp. 127-132. Visudhiphan, P., S. Bunyatratvej and S. Khantanaphar (1973) Cerebral aspergillosis, J. Neurosurg., 38 : 472-476. Warder, F. R., P. G. Chikes and W. R. Herdson (1975) Aspergillosis of the paranasal sinuses, Arch. Otolaryng., 101: 683-685. Young, R. C., J. B. Bennet, C. L. Vogel and P. P. Carbone (1970) Aspergillosis - - The spectrum of disease in 98 patients, Medicine (Baltimore), 49: 147-173. Zinneman, H. H. (1972) Sino orbital aspergillosis - - Report of a case and review of the literature, Minn. Med., 55 : 661-664.
229
ASPERGILLOSIS OF THE CENTRAL NERVOUS SYSTEM
S. MOHANDAS, G. K. AHUJA, V. P. SOOD and V. VIRMANI Department of Neurology and Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi-16 (India)
(Received 15 March, 1978) (Accepted 12 May, 1978)
SUMMARY Aspergillosis of the central nervous system is rare. The spread to the CNS is usually from the lungs and uncommonly from paranasal sinuses. Four cases of CNS aspergillosis with spread of infection from the paranasal sinuses are described. Two patients had meningitis, one intracranial granuloma and one presented with subarachnoid haemorrhage resulting from a fungal mycotic aneurysm. Difficulties in establishing the diagnosis are discussed.
INTRODUCTION Central nervous system (CNS) aspergillosis is of uncommon occurrence; only 65 cases were reported in the world literature till 1973 (Visudhiphan, Bunyaratavej and Khantanaphar 1973). About 30 more cases have been added since (Lisbona, Lacourici~re and Rosenthal11973; Dayal, Weindling and Price 1974; Goldhammer, Smith and Yates 1974; Correa, Brinckhaus, Kesler and Martinoz 1975; Palo, Haltia and Uutela 1975; Sood, Goyal and Abrol 1975; Deshpande, Desai and Dastur 1975; Hedge, Laisung and Leung 1976; Horten, Abbot and Porro 1976; Kaufman, Thai and Farmer 1976; Banerjee, Singh, Kak, Talwar and Rout 1977). A solitary case of cerebral aspergillosis was reported prior to 1973 from India (Chitnis and Deshpande 1967) and 17 have been added subsequently (Deshpande et al. 1975 and Banerjee et al. 1977). The reported increase in incidence of fungal infection of the central nervous system in recent years is not only attributable to the increasing awareness of the condition but is probably also due to the widespread use of steroids, cytotoxic drugs and antibiotics. Aspergillus genus with more than 350 known species, of which fortunately few have been found pathogenic, has particular affinity for the central nervous system. The CNS may be affected either by spread from paranasal sinuses, which is extremely rare (Zinneman 1972; Hedge et al. 1976; Milosev, Mahgoub, Aal and E1 Hassan 1969;
230 M a h g o u b 1977) or by h a e m a t o g e n o u s spread f r o m a systemic source, the c o m m o n e s t being p u l m o n a r y (Young, Bennet, Vogel a n d C a r b o n e 1970). The susceptibility to infection is facilitated by the h o s t ' s altered i m m u n i t y due to co-existent debilitating disease ( Y o u n g et al. 1970), or i m m u n o s u p p r e s s i v e t h e r a p y . In the 4 cases r e p o r t e d here, C N S affection was n o t p r e c i p i t a t e d by any o f the a b o v e m e n t i o n e d p r e d i s p o s i n g factors. The spread o f infection was from the p a r a n a s a l sinuses in all. MATERIAL AND METHODS F o u r cases o f a s p e r g i l l o s i s o f the central nervous system were seen at the n e u r o l o g ical services o f All I n d i a I n s t i t u t e o f M e d i c a l Sciences ( A I I M S ) H o s p i t a l , New Delhi, d u r i n g the p a s t 6 m o n t h s . Biopsy o f the mass f r o m the p a r a n a s a l sinuses established the diagnosis in 3; one p r e s e n t e d as s u b a r a c h n o i d h a e m o r r h a g e resulting from a m y c o t i c a n e u r y s m o f fungal origin p r o v e d at a u t o p s y . Case 1
A 38-year-old male was admitted to the Otorhinolaryngology Service of AI1MS Hospital with a progressive painful swelling over the left cheek of 3 months duration. Four years prior to admission he had had episodic nasal obstruction for which he underwent repeated antral punctures and septal surgery. On examination, the swelling was firm in consistency and tender. The infraorbital margin was irregular and thickened. The left eyeball was displaced upwards. Ptosis o f the right eyelid was the solitary neurological finding. Skiagrams of the paranasal sinuses revealed haziness of the left maxillary antrum. Excision of the mass from the antrum proved aspergillous granuloma histopathologically (Fig. 1). Intravenous amphotericin B was administered, but on the 6th post-operative day the patient became apathetic and gradually lapsed into coma, with signs of meningeal irritation and was transferred to the Neurology Service. CSF showed 100 lymphocytes/cm8, total protein 1I6 mg/t00 ml, and sugar 35 rag/100 ml. Indian ink preparation and culture of the CSF for fungus were negative. Intrathecal amphotericin B (1 mg in 1 ml of distilled water) was administered but the patient died the next day.
Fig. l. Soft tissue from the maxillary antrum showing a fungal granuloma. A septate, branching fungal hypha of the aspergillus group is seen in the centre of the field. HE, x 315.
231 Case 2 A 34-year-old male was admitted with severe headache and nuchal pain of 7 days duration. He had a swelling over the right cheek, associated with multiple episodes of upper respiratory catarrh, for which he had undergone repeated antral punctures during the past 5 years. On one occasion "pus" was drained from the swelling at another hospital. On admission he had a swelling over the right cheek with proptosis of the right eye. Restriction of eye movements in all directions and neck rigidity were also noted. Biopsy of the swelling showed aspergillous granuloma. CSF was clear, showed 80 lymphocytes] cm 3, protein 106 mg/100 mi and sugar 80 mg/100 ml. Smear and culture of CSF for fungus were negative. He left against medical advice and was lost to follow up. Case 3 A 48-year-old female noticed a progressive painful swelling over the left cheek 2 years prior to admission. Exploration of the maxillary sinus done at another hopsital revealed numerous polyps, histopathologically proved to be aspergillous granulomata. She received irregular amphotericin B therapy but pain persisted. Subsequently she developed diminution of vision and complete ophthalmoplegia on the right for which she was admitted to the Neurology Service of the AIIMS Hospital. A right carotid angiogram revealed a large temporal mass. Exploratory craniotomy was advised but the patient refused. She was readmitted two months later with 4 days history of fever, deterioration in consciousness, left-sided focal fits and generalised convulsions. On examination she was unconscious, responding to painful stimuli. Ocular fundi showed optic atrophy on the right, the left disc being normal. Complete right ophthalmoplegia with left hemiparesis, and neck stiffness were noted. The CSF was aceUular and showed a mild rise in proteins. Intravenous amphotericin B was started along with anticonvulsants. Fits did not recur. She regained consciousness within a week. Amphotericin B could not be continued due to toxic effects. Flourocytosine was started. The patient has shown clinical improvement and is being followed. Case 4
An 18-year-old male was admitted with sudden onset ofgeneralised seizures and unconsciousness with signs of meningeal irritation. Lumbar tap revealed subarachnoid haemorrhage. At autopsy, an aneurysm was seen on the right posterior communicating artery. Aspergillous hyphae were seen in the aneurysmal wall. DISCUSSION A s p e r g i l l o m a o f the p a r a n a s a l sinuses is u n c o m m o n except in N o r t h e r n S u d a n f r o m where a b o u t 60 cases have been r e p o r t e d , A. flavus being i n c r i m i n a t e d in all o f t h e m ( M i l o s e v et al. 1969; H e d g e et al. 1976; M a h g o u b 1977). I n t r a c r a n i a l s p r e a d f r o m the p a r a n a s a l sinuses is rare, there being only 2 d o c u m e n t e d cases ( Z i n n e m a n 1972; H e d g e et al. 1976). A s p e r g i l l o u s meningitis is rarely e n c o u n t e r e d ; when seen, it is restricted to the base o f the b r a i n ( K a u f m a n et al. 1976). Large single or m u l t i p l e g r a n u l o m a t a or a b scesses, m a y be e n c o u n t e r e d in the b r a i n o r spinal c o r d w i t h o u t a n y clinical features suggestive o f infection a n d are c o m m o n e r t h a n m e n i n g i t i s ( M u k o y a m a , G i m p l e a n d P o s n e r 1969; Linares, M c G a r y a n d B a k e r 1971; M e y e r , Y o u n g , A r m s t r o n g a n d Y u 1973; K a u f m a n et al. 1976). T h e C S F in these cases m a y be n o r m a l o r show m o d e r a t e pleocytosis a n d / o r rise in p r o t e i n s ( Y o u n g et al. 1970; L i n a r e s et al. 1971 ; M e y e r et al. 1973). D i r e c t s m e a r e x a m i n a t i o n o f the C S F is m o r e r e w a r d i n g for d e m o n s t r a t i o n o f the fungus t h a n culture. Cultures f r o m the e x t r a - c e n t r a l nervous sysem tissues, in cases o f d i s s e m i n a t e d disease, however, yield positive results m o r e often ( Y o u n g et al. 1970; M e y e r et al. 1973; K a m e r et al. 1974). D i a g n o s i s can also be e s t a b l i s h e d by testing sera for p r e c i p i t a t i n g a n t i b o d i e s b y i m m u n o d i f f u s i o n in a g a r gel ( M a h g o u b 1971).
232 In the first 3 cases reported here, the diagnosis of CNS aspergillosis was based on the sequence of events and histopathologically confirmed fungal granulomata in the antra. In the 4th case the diagnosis was not suspected, in spite of a history of recurrent episodes of sinusitis. All the cases in the present report had intracranial extension from the paranasal sinuses. Fungal vasculitis or aneurysms, though documented, are rare. Four cases of mycotic aneurysm of fungal aetiology have so far been described, all confirmed at autopsy, the diagnosis not being suspected during life (Morriss and Spock 1970; Davidson and Robertson 1971 ; Visudhiphan et al. 1973; Horten et al. 1976). There is only one report of thrombosis of the extracranial part of the internal carotid artery of fungal aetiology (Kaufman et al. 1976). Another notable feature of the present cases was the absence of predisposing factors such as co-existent debilitating disease or administration of immunosuppressive drugs in any of our patients. Intravenous amphotenicin B has not proved uniformly effective in CNS aspergillosis because of the blood-brain barrier (Young et al. 1970; Bennett 1974; Utz 1974). Intrathecal amphotericin B has been tried but is too toxic (Utz 1974). Flourocytosine achieves high levels in CSF but clinical improvement is only occasional (Kammer and Utz 1974; Bennett 1974; Utz 1974). As mentioned above, the diagnosis of fungal meningitis is based on indirect evidence of demonstration of antral or systemic infection and pleocytosis and raised proteins content in the CSF; demonstration of fungus in the CSF being difficult. The autopsy rate from different hospitals and different parts of the world being variable, the reported incidence of aspergillous or fungal meningitis may not reflect the true incidence. With the advent of effective antifungal agents there is a need for awareness of this entity and for an extensive search for the fungi in all cases of undiagnosed meningitis. In intractable cases of recurrent sinusitis it is important to consider the possibility of fungal infection and to investigate accordingly.
REFERENCES Banerjee, A. K., M. S. Singh, V. K. Kak, P. Talwar and D. Rout (1977) Cerebral aspergillosis -Report of 8 cases, Ind. J. Path. Microbiol., 20: 91-100. Bennett, J. E. (1974) Chemotherapy of systemic mycoses, New Engl. J. Med., 289: 30-32, 320-322. Chitnis, V. R. and C. K. Deshpande (l 967) Disseminated aspergillosis, J. postgrad. Med., 13 : 131-134. Correa, A. J. E., R. Brinckhaus, S. Kesler and E. Martinoz (1975) Aspergillosis of the fourth ventricle, J. Neurosurg., 43 : 236-238. Davidson, P. and D. Robertson (1971) A true mycotic aneurysm leading to fatal subarachnoid haemorrhage in a patient with hereditary haemorrhagic telangiectasis, J. Neurosurg., 35: 71-76. Dayal, Y., H. K. Weindling and D. L. Price (1974) Cerebral infarction due to fungal embolus - - A complication of aspergillus infection on an aortic valve prosthesis, Neurology (Minneap.), 24: 76-79. Deshpande, D. H., A. P. Desai and H: M. Dastur (1975) Aspergillosis of the central nervous system- A clinical and mycopathological study of 9 cases, Neurology (India), 23 : 167-175. Goldhammery, Y., J. L. Smith and B. M. Yates (1974) Mycotic intrasellar abscess, Trans. Amer. ophthaL Soc., 72: 65-78. Gonty, A. A. and L. R. Page (1977) Aspergitlosis of the maxillary sinus, Oral Surgery, 43: 350-356. Hedge, T. R., E. Laisung and M. D. Leung (1976) Parasellar and orbital apex syndrome, Neurology (Minneap.), 26: 117-120.
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