Neuro OI Flashcards
Differentials for SOL on imaging
Toxoplasmosis, primary CNS lymphoma, TB, cryptococcus, non-Hodgkin lymphoma, syphillitis gummae
Possible causes of encephalitis
HIV, VZV, HSV, syphilis
Causes of meningitis
HIV seroconversion, cryptococcus, TB, syphilis, bacterial (eg strep pneumoniae)
Different causes of spastic paraparesis
HIV-vacuolar myelopathy, transverse myelitis from VZV, HSV, HTLV-1, toxoplasmosis, syphilis
Causes of polyradiculitis
CMV, NHL
What organism is most commonly associated with HIV related cryptococcal disease in the UK?
Cryptococcus neoformans var grubii (serotype A)
2nd most is cryptococcus neoformans bar neoformans (serotype D)
Where is c. neoformans var neoformans found?
Bird (primarily pigeon) droppings
(Non avian sources are also found)
Where is c. Neoformans var gatii found?
Eucalyptus trees
Therefore infections mainly in tropical and subtropical regions
What does cryptococcal skin disease look like?
Molluscum
Pathway of cryptococcus through the body
Inhaled into lungs.
May then cause localised disease.
Spreads to blood and diseminates.
Prostate can be a sanctuary site.
Symptoms of cryptococcal meningitis
Headache, fever
Meningism variable
Raised ICP may cause nausea, vomitting, confusion, coma
What might you see on CXR in pulmonary cryptococcal disease
Variable but include -
Widespread infiltration, nodular disease, isolated abscess formation, pleural effision
Rarer presentations of cryptococcal disease
Ocular palsy, papilloedema, chorioretinitis, osteolytic bone lesions
How to diagnose cryptococcal disease
Serum CrAg - generally if negative this excludes disseminated disease
If CrAg positive needs LP with manometry (after CT/MRI)
Fungal culture
Possible causes of false positive serum CrAg
Rheumatoid factor, heterophile antibodies
What should CSF be sent for if suspecting cryptococcal disease?
CrAg
Microscopy - India ink stain
Culture
What would you expect to see on India ink stain?
Clear around the wall of the yeast as the carbon grains cannot penetrate the capsule
(Cryptococcus)
What role do fungal sensitivities play in tx of cryptococcal disease?
ONLY if not responding to treatment can be used to guide a switch
Factors indicating poor prognosis in cryptococcal disease
Blood culture positive
Low white cells in CSF
High CSF CrAg
Confusion
Raised ICP
What is the induction treatment for neuro cryptococcal disease?
Liposomal Amphotericin B (ambisome) 4mg/kg/day IV (preferred)
Plus flucytosine 100mg/kg/day
Historically amphotericin B deoxycholate 0.7-1mg/kg/day used
Role of flucytosine in cryptococcal meningitis treatment
Speeds rate of sterilisation of CSF
Reduces incidence of relapse in patients not on HAART
Associated with enhanced toxicity in some studies, no impact on mortality
Why do we use ambisome rather than standard amphotericin B?
At least equivalent efficacy
Less nephrotoxicity
What would be an alternative therapy for cryptococcal meningitis if ambisome not tolerated?
Fluconazole 400mg/day +/- flucytosine
May be used as first line if good prognostic factors as easier to administer
Treatment of refractory cryptococcal meningitis
If all normal meds not tolerated can try newer Azoles voriconazole and posaconazole - expensive.
Management of raised ICP in cryptococcal meningitis
If opening pressure >25 reduce to below 20 or to 50% initial pressure
Repeat daily until stable
If resistant may require shunt
What is the maintenance therapy for cryptococcal meningitis?
Oral fluconazole 400mg OD 10/52 started after 2 weeks if patient is well
After 10 weeks drop to 200mg OD
Alternative weekly ambisome (fluconazole superior and less toxicity)
When would you not want to switch to maintenance therapy for cryptococcal meningitis at 2 weeks?
If poor prognostic factors and poor response to treatment repeat LP and consider prolonging induction therapy
How does LP impact options of tx for cryptococcal meningitis??
Historically would wait until CSF sterile to move to maintenance therapy
Not all doctors do this - if HAART is going to be started after 2 weeks risk of relapse and mortality likely to be less than seen in older studies
Treatment for isolated pulmonary cryptococcal disease
LP TO CHECK FOR OCCULT CNS DISEASE
If this is negative - treat pulmonary disease with fluconazole if moderate symptoms
If severe treat with ambisome until symptoms are controlled
Follow with prophylaxis
Do we give primary prophylaxis for cryptococcal disease?
No.
No effect on survival, risk of resistance, high cost
When to start ARVs in cryptococcal meningitis?
After 2 weeks