Fungal meningitis pathophysiology
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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 pathophysiology of fungal meningitis is not very well studied however, it is known to have a lot of similarities with bacterial meningitis. Fungal meningitis usually occurs in immunocompromised patients.
Pathophysiology
Pathogenesis
The Steps in Meningeal Fungal Infection
The steps involved in the pathogenesis of fungal meningitis is a complex process. Majority of cases result from an imbalance between the host immune response and virulence factors of pathogen causing infection. Outlined below are the steps explaining the underlying process in a comprehensive way.[1][2]
- The initial step in fungal meningitis is the pulmonary exposure to the fungi by the inhalation of airborne fungal spores.
- Inflammatory results leading to a primary pulmonary and lymph node focus limiting the inhaled organism from further spread.[1]
- The pulmonary infection is usually self limited and maybe asymptomatic.
- With an associated impaired immune response the fungus may disseminate for instance in cryptococcal infection, the fungus may remain dormant in the lungs until the immune system weakens and then can reactivate and disseminate to the CNS. Cryptococcus has predilection for CNS dessimination. Although this remains unclear, the presence of a receptor on glial cells for a ligand on the organism has been suggested to enhance its invasion.[3]
- Fungal infections are not contagious so they do not spread from one person to another.
- In most cases of fungal meningitis, the fungi undergo hematogenous spread.
- Patients with immunosuppression are the most vulnerable to fungal meningitis.
- Fungal meningitis may uncommonly occur In patients with no underlying immunesuppresion. This usually is as a result of predisposing factors or immune abnormalities that permit dissemination of low-virulent pathogens.
- Once the fungi cross the blood brain barrier they cause an inflammation of the meninges and arachnoid space:
- The inflammation promotes cytokine release mainly tumor necrosis factor (TNF), interleukin 1 and interleukin 6
- The cytokines cause the fever observed in meningitis
- The cytokines promotes an increase in the permeability of the blood brain barrier and subsequent cerebral edema and increase in the intracranial pressure
- Cerebral edema leads to decreased blood flow to the brain and hypoxia
- The glucose level in the cerebral spinal fluid (CSF) will decrease due to a decreased transport of glucose coupled to an increased use of glucose by the fungi
- The increase in the permeability of the blood brain barrier is the cause of the observed elevation of the proteins level in the cerebral spinal fluid.[4]
The Underlying Mechanisms of the Symptoms
- Stimulation of the nociceptive fibers by inflammatory processes:
- Cerebral edema and obstructive of the cerebral spinal fluid's pathway:
- Increased intracranial pressure:
- Headache, vomiting, gait disturbance
- Vascular damage:
- Cognitive and behavioral changes, seizures, stroke, myelopathy
- Seeding of inflammatory processes by the cerebral spinal fluid to the brainstem and cranial nerves (CN):
- Vision loss (CN II), facial weakness (CN VII), hearing loss (CNV III), diplopia (CN III, IV, V), other cranial nerves involvement
- Injury to spinal motor and sensory roots:
- Radiculopathy with associated radicular pain, sensory loss, motor weakness[5]
Genetics
Homozygous neutrophil dependent mutation of caspase recruitment domain 9 (CARD9) have been discovered to predispose to invasive chronic Candida infections, especially of the central nervous system.[6]
Gross pathology
Microscopic pathology
References
- ↑ 1.0 1.1 Baker RD (1976). "The primary pulmonary lymph node complex of crytptococcosis". Am J Clin Pathol. 65 (1): 83–92. PMID 1246992.
- ↑ Gottfredsson M, Perfect JR (2000). "Fungal meningitis". Semin Neurol. 20 (3): 307–22. doi:10.1055/s-2000-9394. PMID 11051295.
- ↑ Merkel GJ, Scofield BA (1993). "Conditions affecting the adherence of Cryptococcus neoformans to rat glial and lung cells in vitro". J Med Vet Mycol. 31 (1): 55–64. PMID 8483058.
- ↑ John Marx. Chapter 107. Central Nervous System Infections. Marx: Rosen's Emergency Medicine, 7th ed.. Mosby: Elsevier; 2009.
- ↑ 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.
- ↑ Herbst M, Gazendam R, Reimnitz D, Sawalle-Belohradsky J, Groll A, Schlegel PG; et al. (2015). "Chronic Candida albicans Meningitis in a 4-Year-Old Girl with a Homozygous Mutation in the CARD9 Gene (Q295X)". Pediatr Infect Dis J. 34 (9): 999–1002. doi:10.1097/INF.0000000000000736. PMID 25933095.