CNS INFECTIONS---TUBERCULAR AND FUNGAL

PREAMBLE

• Infections of the nervous system• Clinical features of infection depend on• (a)—location of the infection• --------brain ,spine and or meninges• (b)the causative organism• ---bacteria ,virus,fungus or parasitic and• (c)—the chronicity of the infection• --------acute or chronic

Tuberculosis

• MENINGEAL disease is the most important form of nervous system infection

• Untreated and unrecognised,it israpidly fatal• Even with appropriate

treatment ,mortalityrates of 30%,have been reported,while survivors may be left with neurogical deficits

INCIDENCE

Common in underdeveloped countriesSeen more frequentlyin immunocompromised

individuals with AIDSIncidence less in developed countries

PATHOPHYSIOLOGY• Usually occurs after primary infection in childhood or• As part of Miliary TB• Usual local source—caseous focus in the brain

substance or meninges adjacent to the CSFpathway-(subependymal/subpial granuloma)—” Rich Focus”

• Meningeal involvement may be due to rupture of tuberculoma adjacent to subarachnoid vessel or to rupture –of miliary tubercles in the brain or

• rarely due to contiguous spread—from mastoiditis

Pathophysiology--contd

• Poor defence of CSF –due to a paucity of WBC in the CSF—leads to a rapid spread in the meninges via the basal cisterns

• Cell mediated immunity is responsible for the thick gelatinous exudate --greenish yellow in colour—covering the entire brain especially around the base and numerous scattered tubercles are found in the meninges.

CLINICAL FEATURES

• Onset much slower than in other types of infection—over 2 to 3 weeks

• Symptoms• Headache –Vomiting-Low grade fever,

lassitude,depression,confusion and behavioural changes(psychiatric manifestations)

• Signs• Meningism(may be absent) and photophobia• Oculomotor palsies• Papilloedema• Depression of conscious levels • Focal hemishpheric signs—focal ischemic

syndromes

Staging of Severity

• Stage 1(early)non specific symptoms and signs with NO ALTERATION OF CONSCIOUS NESS

• Stage 2(intermediate)---altered conscious level but no COMA or Delirium orminor FOCAL Neurological deficits

• Stage 3---(advanced)----stupor or coma with severe neurological deficits,seizres or abnormal movements

INVESTIGATIONS• LUMBAR PUNCTURE---remains the diagnostic gold standard• ----Appearance—clear but on standing forms a coagulum”spider

web”• Pressure—raised• Cell Count---INCREASED mostly LYMPHOCYTES BUT therecan be

some neutrophils• PROTEIN---Increased• Sugar –decreased• SMEAR—Centrifuged specimen may show AFB BUT A NEGATIVE

SMEAR DOES NOT NEGATE THE DIAGNOSIS• CSF CULTURE---CONFIRMS—but takes 6 to 8 weeks• BRAIN IMAGING—May reveal hydrocephalus or brisk meningeal

enhancing or TUBERCULOMA

MANAGEMENT

• CHEMOTHERAPY• 4 DRUGS TO BE USED• RIFAMPICIN-10 mg /kg /day• PYRAZINAMIDE—30mg/kg/day in divided

doses• Ethambutol—15 to 25 mg/kg/day in

divideddoses• INH—300 MG/day and pyridoxine 50 mg/day

• COURSE of Treatment---• Good response—discontinue PZI and ETM

after 8 weeks and continue the rest for 9 to 12 months

• ROLE of STEROIDS---controversial it improves mortality but doesnot improve neuoro deficits

• Adequate nutrition and supportive care• Surgery is indicated if here is hydrocephalus—

obstuction.

FUNGAL INFECTIONS—SUBACUTE MENINGITIS

• Causative organisms• M Tuberculosis• Crypto coccus Neoformans• H .Capsulatum• C.immitis

• Fungal infections are typically acquired by inhalation of airborneFungal spores

• The initial pulmonary infection may be asymptomatic or quiet.It is often self limiting.

• Sometimes a pulmonary infection which is dormant can suddenly ,,under conditionsof reduced immunity re invent itselfand disseminate to CSF.

• Most common is C neoformans which is found in soil and bird excreta

CLINICAL FEATURES

Unrelenting HeadacheStiff neckLow grade feverLethargy forseveral daysCranial nerve abnormalitiesNight sweats

CSF ABNORMALITIES• Mononuclear or lymphocyticpleocytosis• Increased csf pressure• Diminished glucose concentration• India ink prep to demonstrate organism---

largevolumes of csf required• Cryptococcal poly saccharide antigen –highly

sensitive and specific• Detection of Histoplasma antigen establishs a

diagnosis but is not specific—get false positives inC immitis.

MANAGEMENT• CRYPTOCOCCAL MENINGITIS • AMPHOTERICIN B—sheet anchor of treatment• Dose-0.7MG/KG/DAY IV or Ambisone5MG/KG/DAY• PLUS FLUCYTOSINE –100/KG/DAY IN 4 DIVIDED DOSES• DURATION –ABOUT TWO WEEKS OR TILL CSF is

sterile---followed by 8 week course of Flucanozole(400-800mg/day).Once CSF is sterile reduce flucanozoleto 200 mg/day for 6 months to 1yr..HIVpatients may need treatment for a lifetime

Treatment -contd

• H .CAPSULATUM• AMPHOTERICIN B—0.7-1mg/kg /day for 4-12

weeks-Total dose not to exceed 30mg/kg/day• Discontinue when fungal cultures are sterile• Maintainence therapy with Itraconazole 200

mg/kg /day for 6to 12 months

• C. IMMITIS• High dose flucanozole

(1000mg/day.Monotherapy• Or• i/v AMPHOTERICIN B(0.5 TO 0.7MG/KG/DAY)• INTRATHECAL AMPHO B may be requiredto

eradicate infection.Lifelong therapy recommended to prevent relapse

• Complications --hydrocephalus

• THANK YOU