Fungal meningitis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby; Prince Tano Djan, BSc, MBChB [2]

Overview

The differential diagnosis of fungal meningitis includes a range of medical conditions that can be broadly classified into infectious and non infectious. The cerebrospinal fluid analysis and radiological findings help distinguishing fungal meningitis from other causes of meningitis example bacterial meningitis, protozoal meningeal infection, viral meningeal infection, and non-infectious causes.

Differential Diagnosis

Fungal meningitis must be differentiated from other causes of meningeal irritation as shown below:

Differentiating fungal meningitis from other diseases

Diseases Diagnostic tests Physical Examination Symptoms Past medical history Other Findings
Na+, K+, Ca2+ CT /MRI CSF Findings Gold standard test Neck stiffness Motor or Sensory deficit Papilledema Bulging fontanelle Cranial nerves Headache Fever Altered mental status
Brain tumour[2][3] + Cancer cells[4] MRI + + + + + + Cachexia, gradual progression of symptoms
Delirium tremens + Clinical diagnosis + + + + + + Alcohol intake, sudden witdrawl or reduction in consumption Tachycardia, diaphoresis, hypertension, tremors, mydriasis, positional nystagmus,
Subarachnoid hemorrhage[5] + Xanthochromia[6] CT scan without contrast[7][8] + + + + + + + + Trauma/fall Confusion, dizziness, nausea, vomiting
Stroke + Normal CT scan without contrast + + + + + TIAs, hypertension, diabetes mellitus Speech difficulty, gait abnormality
Neurosyphilis[9][10] + ↑ Leukocytes and protein CSF VDRL-specific

CSF FTA-AbS -sensitive[11]

+ + + + + + Unprotected sexual intercourse, STIs Blindness, confusion, depression,

Abnormal gait

Viral encephalitis + Increased RBCS or xanthochromia, mononuclear lymphocytosis, high protein content, normal glucose Clinical assesment + + + + + + + Tick bite/mosquito bite/ viral prodome for several days Extreme lethargy, rash hepatosplenomegaly, lymphadenopathy, behavioural changes
Herpes simplex encephalitis + Clinical assesment + + + + + History of hypertension Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy Normal + + + History of alcohol abuse Ophthalmoplegia, confusion
CNS abscess + ↑ leukocytes >100,000/ul, ↓ glucose and ↑ protein, ↑ red blood cells, lactic acid >500mg Contrast enhanced MRI is more sensitive and specific,

Histopathological examination of brain tissue

+ + + + + + + History of drug abuse, endocarditis, ↓ immune status High grade fever, fatigue,nausea, vomiting
Drug toxicity + + Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder Diagnosis of exclusion + + + + + Tremors, blindness, difficulty swallowing
Electrolyte disturbance ↓ or ↑ Depends on the cause + + Confusion, seizures
Febrile convulsion Not performed in first simple febrile seizures Clinical diagnosis and EEG + + + + Family history of febrile seizures, viral illness or gastroenteritis Age > 1 month,
Subdural empyema + Clinical assesment and MRI + + + + + + History of relapses and remissions Blurry vision, urinary incontinence, fatigue
Hypoglycemia ↓ or ↑ Serum blood glucose

HbA1c

+ + + History of diabetes Palpitations, sweating, dizziness, low serum glucose


Differentiating fungal meningitis from other causes of meningitis

Fungal meningitis may be differentiated from other causes of meningitis by cerebrospinal fluid examination as shown below:[12][13][14][15][16]

Cerebrospinal fluid level Normal level Bacterial meningitis[15] Viral meningitis[15] Fungal meningitis Tuberculous meningitis[17] Malignant meningitis[12]
Cells/ul < 5 >300 10-1000 10-500 50-500 >4
Cells Lymphocyte:Monocyte 7:3 Granulocyte > Lymphocyte Lymphocyte > Granulocyte Lympho.>Granulocyte Lymphocytes Lymphocytes
Total protein (mg/dl) 45-60 Typically 100-500 Normal or slightly high High Typically 100-200 >50
Glucose ratio (CSF/plasma)[13] > 0.5 < 0.3 > 0.6 <0.3 < 0.5 <0.5
Lactate (mmols/l)[14] < 2.1 > 2.1 < 2.1 >3.2 > 2.1 >2.1
Others ICP:6-12 (cm H2O) CSF gram stain, CSF culture, CSF bacterial antigen PCR of HSV-DNA, VZV CSF gram stain, CSF india ink PCR of TBC-DNA CSF tumor markers such as alpha fetoproteins, CEA

References

  1. ↑ Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
  2. ↑ Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
  3. ↑
  4. ↑ Weston CL, Glantz MJ, Connor JR (2011). "Detection of cancer cells in the cerebrospinal fluid: current methods and future directions". Fluids Barriers CNS. 8 (1): 14. doi:10.1186/2045-8118-8-14. PMC 3059292. PMID 21371327.
  5. ↑ Yeh ST, Lee WJ, Lin HJ, Chen CY, Te AL, Lin HJ (2003) Nonaneurysmal subarachnoid hemorrhage secondary to tuberculous meningitis: report of two cases. J Emerg Med 25 (3):265-70. PMID: 14585453
  6. ↑ Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
  7. ↑ Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  8. ↑ DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease". J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.
  9. ↑ Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients". J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.
  10. ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  11. ↑ Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. doi:10.1097/OLQ.0b013e31824ee574. PMC 3746559. PMID 22421697.
  12. ↑ 12.0 12.1 Le Rhun E, Taillibert S, Chamberlain MC (2013). "Carcinomatous meningitis: Leptomeningeal metastases in solid tumors". Surg Neurol Int. 4 (Suppl 4): S265–88. doi:10.4103/2152-7806.111304. PMC 3656567. PMID 23717798.
  13. ↑ 13.0 13.1 Chow E, Troy SB (2014). "The differential diagnosis of hypoglycorrhachia in adult patients". Am J Med Sci. 348 (3): 186–90. doi:10.1097/MAJ.0000000000000217. PMC 4065645. PMID 24326618.
  14. ↑ 14.0 14.1 Leen WG, Willemsen MA, Wevers RA, Verbeek MM (2012). "Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice". PLoS One. 7 (8): e42745. doi:10.1371/journal.pone.0042745. PMC 3412827. PMID 22880096.
  15. ↑ 15.0 15.1 15.2 Negrini B, Kelleher KJ, Wald ER (2000). "Cerebrospinal fluid findings in aseptic versus bacterial meningitis". Pediatrics. 105 (2): 316–9. PMID 10654948.
  16. ↑ Brouwer MC, Tunkel AR, van de Beek D (2010). "Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis". Clin Microbiol Rev. 23 (3): 467–92. doi:10.1128/CMR.00070-09. PMC 2901656. PMID 20610819.
  17. ↑ Caudie C, Tholance Y, Quadrio I, Peysson S (2010). "[Contribution of CSF analysis to diagnosis and follow-up of tuberculous meningitis]". Ann Biol Clin (Paris). 68 (1): 107–11. doi:10.1684/abc.2010.0407. PMID 20146981.

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