II. Pathophysiology
- Caused by Cryptococcus neoformans (fungal infection)
III. Epidemiology
IV. Risk Factors
- Consider in all at risk and known HIV patients with Headache
- Advanced HIV (AIDS)
- CD4 < 50 to 100 cells per mm3 or
- AIDS-Defining Illness
V. Symptoms
- Insidious onset
- Typically starts as occult, asymptomatic infection in 50% of cases
- Typically develops over a 2 week period
- Symptoms are often nonspecific at onset
- Headache (91%)
- Weight Loss (90%)
- Fever (52%)
- Malaise
- Altered Level of Consciousness or confusion
VI. Signs
- Fever (91%)
- Muscle wasting (90%)
- Motor weakness (40%)
-
Cranial Nerve palsy (29%)
- Hearing Loss
- Vision Loss (Optic Neuritis related)
- May progress within 12 hours following onset of Optic Neuritis
- Organ Involvement
- Neurologic involvement (Meningitis) (85-90%)
- Lung or skin involvement (25%)
VII. Precautions
- Do not rely on lack of meningismus (meningeal signs) to exclude Cryptococcal Meningitis
- Meningeal signs are only present in one quarter of Cryptococcal Meninigitis
- Best outcomes are for early diagnosis and treatment (including lowering of Intracranial Pressure)
VIII. Evaluation
- See Headache in HIV
IX. Differential Diagnosis
- See Headache in HIV
- Bacterial Meningitis
-
Toxoplasmosis
- Results in focal encephailitis
X. Imaging
-
CT Head
- Typically performed prior to Lumbar Puncture to exclude Brain Mass
- Lumbar Puncture is considered safe when there is no brain shift or significant space occupying lesion
XI. Labs
- Blood Cultures positive (>75%)
- Serum cryptococcal Antigen
- Test Sensitivity: 98 to 99%
- Test Specificity: 94%
- High titer (>1024:1)
-
CSF Exam
-
General Findings
- Glucose usually normal
- Protein mildly elevated
- White Blood Cell Count usually less than 20
- Definitive Diagnosis
- India Ink stain usually shows organism (Test Sensitivity 60 to 80%)
- Indicated when CSF Cryptococcal Ag test is unavailable
- CSF Cryptococcal Ag test (>95% Test sensitive, specific)
- India Ink stain usually shows organism (Test Sensitivity 60 to 80%)
- Increased CSF Opening Pressure
- Typically CSF Opening Pressure >350 mm H2O in Crytococcal Meningitis
- Increased pressure results from high fungal burden in CNS interfering with CSF reabsorption
- Differential diagnosis (other causes of increased CSF Opening Pressure in HIV)
- Toxoplasma Encephalitis
- CNS Lymphoma
- Tuberculous Meningitis
- Risk of obstructrive Hydrocephalus presenting as cognitive deficit and ataxic gait
- High pressure responsible for adverse sequelae
- Therapeutic CSF removal is indicated when opening pressure >30 mm H2O
- Treat with serial LPs, lumbar drain or VP Shunt
- Goal CSF Pressure reduction by 50% or to <20 mm H2O (normal pressure)
- Typically CSF Opening Pressure >350 mm H2O in Crytococcal Meningitis
-
General Findings
XII. Management: Acute (CNS and extraneural involvement)
- Precautions
- Start empiric therapy while awaiting definitive diagnosis when Cryptococcal Meningitis is suspected
- Lower Intracranial Pressure as soon as possible (initially via Lumbar Puncture)
- Critical factor in best neurologic outcomes
- Goal CSF Pressure reduction by 50% or to <20 mm H2O (normal pressure)
- First-Line Combination Antibiotic Therapy
- Amphotericin B (High dose) 0.7 mg/kg/day AND
- Flucytosine (100 mg/kg/day)
- Continue to lower Intracranial Pressure as needed
- Serial Lumbar Puncture
- Lumbar drain
- VP Shunt
-
Fluconazole (200 to 400 mg/day) Indications
- Normal Mental Status at baseline
- Time to sterilization of CSF is slower
- Prefer amphotericin B (short course first)
- Avoid harmful measures
- Avoid Dexamethasone
- Associated with increased mortality
- Beardsley (2016) N Engl J Med 374(6): 542-4 +PMID: 26863355 [PubMed]
- Avoid Dexamethasone
XIII. Management: Prophylaxis
-
General
- Relapse occurs in >80% if no suppression given
- Fluconazole 200 mg/day
XIV. Prognosis
- Uniformly fatal if left untreated
- Overall Mortality: 12%
- One year mortality in U.S. approaches 20 to 30%
XV. References
- Parker and Bond (2023) Crit Dec Emerg Med 37(10): 4-9
- Perkins (2013) Crit Dec Emerg Med 27(3): 2-9
- Friedmann (1995) Arch Intern Med 155(20): 2231-7 [PubMed]
- Mwaba (2001) Postgrad Med J 77(814): 769-73 [PubMed]