Fungi are basically simple plants, lacking on chlorophyll and thriving on other living or dead organisms.

CNS fungus infections have been recognized since the beginning of this century. Recently they seem to be more frequent as opportunistic infections in hosts, immunologically compromised. Immunosuppressive therapy, prolonged use of broad spectrum antibiotics, drug addictions, diabetes mellitus, renal failure, AIDS and longer survival of lymphoproliferative malignancies have contributed to the higher incidence of late. CNS mycoses may also affect the healthy.

Fungi affecting the CNS can be divided into (1) pathogenic or endemic in healthy host, (histoplasmosis, blastomycosis) endemic in various part, (2) Opportunistic - in immuno compromised.

Cryptococus is found in both.

Pathogenesis:

With exception of mucormycosis, primary site is usually in the lung and rarely in skin. Spread to CNS is by blood. Rarely there is direct spread from osteomyelitis skull or vertebrae. Some (aspergillosis) spread directly from nose and para nasal sinuses.

Pathology:

Manifestations may be due to

(a) Meningitis :

Fungus that primarily causes meningitis is coccidioides immitis, typically widespread, basal meninges being maximally involved. The basic lesion is a combination of suppurative and granulomatous inflammation. This chronic inflammatory response leads to thickening of meninges, hydrocephalus, arteritis, cranial nerve palsies and infarction. Other fungi (Blastomyces, histoplasma) may also cause meningitis.

(b) Meningo encephalitis :

Cryptococcus neoformans and the candida are prone to cause meningoencephalitis. In crypto coccosis, clusters of fungi are spread throughout the brain, with little or no surrounding inflammatory responses; predominantly involve basal ganglia and cortical grey matter. The cystic lesion contains gelatinous poly saccharide which may be detected in CSF and forms the basis for latex agglutination tests which is 90% sensitive and highly specific for cryptococcosis.

(c) Abscess/infarction/Hge:

Asperigillus, zygomycetes, blastomyces, candidiasis cause these lesions as also nocardia, actinomyces and coccidioidomycoses. Disseminated candidiasis produce microabcesses. Vasculitis predispose to infarction and hge.

Clinical features:

There are no pathognomonic signs and symptoms. In nonendemic areas, history of travel to an endemic region may give a clue. However specifically affected organs and some characteristic features help:

(a) Rhino cerebral syndrome presents with orbital pain, nasal discharge and facial edema. There may be proptosis and visual loss. Involvement of carotids may cause hemi paresis. Subsequently trigeminal nerve and adjacent brain may be involved. This is classically found in mucormycosis where blackish necrotic areas are seen in the palate and nasal turbinates.

(b) Aspergillosis or mucormycosis may produce sudden onset of deficit due to vasculitis. Rarely there is SAH due to mycotic aneurismal bleed. Unlike bacterial aneurysms, fungus affects the larger arteries.

Diagnosis:

Suspicion is the first step.

CSF:

CSF exaination reveals higher proteins, lower glucose and higher mononuclear leucocytosis. CSF may be positive for fungi and cultures may be positive, but take a long time. Candida takes few days, Cryptococci 7 days, while histoplasma and coccidiodes may take 6 weeks.

Immunological tests:

Latex tests are positive in 90% of crypotococcal meningitis. In coccidioidomycosis complement fixating antibody is found in 95%.

Imaging : CT & MRI scans show the basal involvement, associated abscess and areas of infarction and also the status of the ventricles.
Treatment:	Sphenoidal sinus asperigillosis	Intracranial Aspergillosis	Intracranial Cladosporiosis

(1) Nonspecific measures to lower ICT.

(2) Specific agents commonly used are Amphotericin B, flucytosine and azole derivatives. The duration is for 4-6 weeks till active systemic or CNS infection has disappeared. Rifampicin given with amphotericin B potentiates the activity.

(3) Surgical therapy for abscess, hydrocephalus, may be indicated. Spinal decompression may be required at times. Intraventricular chemotherapy thro ommaya reservoir may be tried.

Prognosis:

It depends on the duration and the patient's immunity status. Without treatment it is a fatal disease.

With Amphotericin B, the mortality has decreased to less than 50 %

Specific Fungal Infections:

Diffuse:

1. Coccidiodomycosis:

Endemic in south west united states most cases are sub clinical. Most common in males and agricultural workers. It is primarily a disease of the healthy and disseminates from a primary pulmonary site with about 30 - 50% risk of CNS involvement. Focal symptoms are uncommon, chronic meningitis is common. Bone and joint involvement including vertebrae occur in about 20%. X-rays reveal radio lucent lesions with minimal or no new bone formations. Thoracic and lumbar spines are commonly involved. The disc is relative spared and contiguous ribs may be involved. Body collapse occur only in late cases, Para spinal masses and sinus are common.

Amphotericin B in the mainstay. Keto corazole may help. Overall mortality is about 40% 1 year. Worse in patients with high intracranial tension. .

2. Cryptococcosis :

It was the commonest CNS fungi, replaced by candidiasis of late, affects, healthy and immuno compromised. Primary site is chest. 30 - 50% of disseminated case have CNS involvement. Meningitis in often the initial presentation. 30% of them have cranial nerve deficits. Patients are typically afebrile. India Ink preparation are positive in 60% but the antigen is found in 90% A titre greater than 1:8 is diagnostic. Mortality is about 30%. Shunting may be indicated in hydrocephalus.

3. Candidiasis :

Candidiasis is rare in healthy. Pulmonary primary is not the rule. Gastro intestinal urinary or respiratory tract involvement with subsequent dissemination by blood stream is common. Many enter into the blood stream via indwelling catheter. Disctitis following bowel surgery has been reported. CNS involvement is 50% of disseminated cases and 80% in patients with endocarditis. Meningitis is common in children, whereas micro or macroabcess in adults. Serological tests are not reliable. Survival is rare in patients with abscess formation. Death is usually a result of multiorgan failure.

Focal:

1. Aspergillosis :

Less common and spinal involvement is almost unknown. CNS involvement is almost unknown. CNS involvement is about 50% of disseminated cases from primary pulmonary or paranasal sinuses. Clinical presentation is abscess or mass lesion, meningitis is almost unseen. Vasculitis leading on to thrombosis and mycotic aneurysms in common involving proximal larger arteries. CSF findings are nonspecific. Culture is almost impossible. Few survive with abscess.

2. Mucormycosis :

This fungus is an occasional member of normal nasopharyngeal flora. It remains nonpathogenic except in patients with diabetic ketoacidosis in whom rhinocerebral form may develop. Like aspergillosis there is a strong tendancy to involve blood vessels. Rhinocerebral mucormycosis begins in the paranasal sinuses, may extend locally into the orbit with eye pain, facial and periorbital swelling and ext opthalmoplegia and proptosis and loss of vision secondary to central artery occlusion. Vision is usually preserved in most bacterial forms of cavernous sinus thrombosis. CSF is frequently normal. Death occurs rapidly unlike other fungal infection.

3. Actinomycosis :

Actinomyces Israeli is responsible. It is a gram positive, anaerobic intermediate between classical bacteria and fungi, found in normal oral flora, may become pathogenic in states of moderate debilitation. The disease has 3 forms, cervicofacial, pulmonary and abdominal. Pulmonary forms are becoming more common. CNS involvement occurs in 30-50% as either solitary abscess or purulent meningitis. Spinal involvement is always secondary to an infection of contiguous tissue, rarely destroys the discs. Vertebral body destruction and new bone formation give honey comb appearance. Penicillin for 3 - 4 months is recommended. Prognosis is much better than the true fungi infection.

4. Nocardia

It is a fungus like (similar to actinomycosis). gram +ve aerobe. Like fungi, from a primary pulmonary site dissemination occurs with 50% involvement of CNS. Single or multiple abscesses which may rupture causing purulent meningitis. CSF finding are non specific and culture is difficult. It is penicillin resistant. Culture is difficult. Gulfomethorazole 4 - 8 m/day for 6 - 12 months is recommended. Mortality is about 80%. Spinal form is rare.