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{{Aseptic meningitis}}
{{Viral meningitis}}
{{CMG}}; {{AE}} {{CZ}}
{{CMG}}{{AE}}{{CZ}},{{AEL}}


==Pathophysiology==
==Overview==
===Pathogenesis===
[[Viral]] [[meningitis]] pathophysiology differs from [[virus]] to another and depends on many factors like age, [[immune]] status and [[gene expression]]. Invasion into the [[meninges]] by a [[pathogen]] can set up a local [[inflammatory]] response. The clinical signs are due to this [[meningeal irritation]] - for example, [[Kernig's sign]] is due to pain produced by stretching of the inflamed [[meninges]].
Invasion into or past the [[meninges]] by a pathogen can set up a [[local]] [[inflammatory]] response. The [[clinical]] signs are due to this meningeal [[irritation]] - for example, [[Kernig's sign]] is due to pain produced by stretching of the [[inflamed]] meninges.


====Viruses Associated with the Pathogenesis of Aseptic Meningitis====
==Pathogenesis==
Many different viruses can cause meningitis. About 90% of cases of viral meningitis are caused by members of a group of viruses known as [[enterovirus]]es, such as [[coxsackievirus]]es and [[echovirus]]es. These viruses are more common during summer and fall months. [[Herpesvirus]]es and the [[mumps]] virus can also cause viral meningitis.
*The causative viral agents can reach the [[nervous system]] via the [[blood]] or the [[nerves]] themselves. There is a difference in both pathways pathogenesis. Viral spreading through the blood ([[viremia]]) is more common in viral meningitis pathogenesis. The viruses enter to the [[pulmonary]] and [[intestinal]] [[mucosa]] at which they spread into the [[blood]] to reach the [[lymph nodes]] where [[viral]] [[replication]] takes place and this is called primary viremia. At this point, the host cells try to prevent further [[replication]] from happening and if they fail to stop the [[replication]], secondary [[viremia]] will take place and the [[viruses]] can spread to the [[nervous system]] causing many clinical manifestations.<ref name="pmid11051293">{{cite journal| author=Rotbart HA| title=Viral meningitis. | journal=Semin Neurol | year= 2000 | volume= 20 | issue= 3 | pages= 277-92 | pmid=11051293 | doi=10.1055/s-2000-9427 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11051293  }} </ref>


The study of AM is complicated in that there can be a yearly variation in the viruses that are prevalent, as well as differences in geography, diagnostic techniques and the definition of AM.
*[[Enteroviruses]]:  
* One study (from 1960, in the U.S, Europe and the Far East) reported that out of 430 cases of AM, a specific cause was found in 71%.
**They include [[coxsackievirus]] A&B, [[echovirus]], [[hepatitis A]], and [[poliovirus]].
*:* 42% had [[enterovirus]], 22% [[mumps]], 12% [[poliovirus]], 12% [[lymphocytic choriomeningitis virus]], 5% [[leptospirosis]], 2% [[herpes simplex]], 1% [[arbovirus]]es and <1% had [[Tuberculosis]] (TB).
**[[Infection]] can be started in the [[nasal mucosa]] and after that it can be ingested in the [[stomach]]. It attaches to the [[enterocytes]] then the [[viruses]] reach the [[peyer's patches]] of the [[lamina propria]] where the [[replication]] takes place.
*:* If a study like this were to be repeated today, there would obviously be an increase in [[HIV]] and [[Lyme disease]] (as well as other previously unrecognized causes of AM such as epidural steroid injection and drugs) and a fall in polio and mumps.
**The replication which occurs at this site causes [[viremia]] to further [[organs]] like the [[lung]], [[brain]] and [[liver]] at which another replication takes place at these organs causing more viremia. [[Infection]] of the [[nervous system]] can occur via this viremia which is responsible for the clinical manifestaions of the disease.
* [[Enterovirus]]es currently are thought to account for > 80% of identifiable cases of AM.
*:* This group (members of the [[picornavirus]] family) includes [[coxsackievirus]] A&B, [[echovirus]], [[enterovirus]], [[hepatitis A]] and [[poliovirus]].
*:* Transmission is fecal – oral, and the viruses have a worldwide distribution.
*:* Although disease can occur year-round, it peaks in the summer and early fall.
*:* Children tend to be affected more commonly than adults, though community and hospital outbreaks can also occur.
*:* In addition to the typical presentation of [[meningitis]], patients also tend to have viral exanthems, and may get myopericarditis, [[conjunctivitis]] and other typical enteroviral syndromes (i.e. hand-foot and mouth disease).
*:* The CSF is typically not helpful and diagnosis typically depends upon identification of the viral antigen by ELISA (enzyme-linked immunosorbent assay).
*:* Rx is supportive and the majority of patients do well.
*:* In countries that don’t have the polio vaccine, 90% of cases are clinically insignificant, 4-8% will get AM (non-paralytic polio) and < 1% will develop paralytic [[poliomyelitis]].
* [[Mumps]]: a [[paramyxovirus]] that is spread via respiratory droplets, direct contact and by fomites.
*:* Although the incidence in the U.S. had dropped by 95% since the development of the vaccine, it continues to be a major problem worldwide with ~ 1 – 10% of infected patients developing AM.
*:* Again, although it can be seen year round, it most commonly occurs in the late winter and spring.
*:* [[Mumps]] should be specifically suspected when AM follows [[parotitis]], [[orchitis]], [[oophoritis]] and [[pancreatitis]].
*:* Diagnosis is by culture and the prognosis tends to be excellent.
* Lymphocytic choriomeningitis virus (LCM) is an arenavirus that is spread to humans via contact with rodents or their excrement.
*:* LCM AM peaks in the late-fall and early winter, and diagnosis is made via chest x-ray or by seeing a fourfold rise in antibody titer between acute and convalescent sera.
* [[Herpes simplex virus]] (HSV) is the most common cause fatal [[encephalitis]] in the U.S. and it is crucial to differentiate meningitis from [[encephalitis]].
*:* As opposed to [[encephalitis]], which is usually due to HSV-1, meningitis is more frequently caused by HSV-2.
*:* The diagnosis is usually clinical (occasionally seen in patients with genital lesions) but the virus can be Cx from the CSF or buffy coat.
*:* The prognosis is generally quite good, and it is not clear whether prescription alters the course for mild cases.
* Human immunodeficiency virus (HIV) is an increasingly recognized cause of AM.
*:* AM can occur during initial infection as well as during seroconversion.
*:* Additionally, HIV can cause recurrent and chronic meningitis, occasionally with cranial nerve abnormalities (esp. V, VII, and VIII).
*:* Diagnosis can be made via CSF Cx and polymerase chain reaction (PCR) for viral DNA, though availability is limited.
* [[Arbovirus]]es typically cause [[encephalitis]], but in their milder forms can cause AM.
*:* The most likely of these to present as AM is [[St. Louis encephalitis]], and all typically occur during the warmer months.
*:* Diagnosis is made serologically, and is mainly important as a public health measure.
*:* Prescription is supportive.
* Other, non-viral infectious causes include:
*:* TB: had CN abnormalities in 20 – 30% and is often accompanied by SIADH (inappropriate secretion of antidiuretic hormone), altered MS ([[multiple sclerosis]]) and a reduced CSF glucose.
*:* [[Mycoplasma pneumoniae]].
*:* [[Listeria monocytogenes]]: often thought to be aseptic due to a negative gram stain and a slightly higher frequency of a CSF lymphocytosis.
*:* [[Brucellosis]]: causes neuro disease in < 5% of cases but AM is the most common
*:* [[Leptospirosis]], Borrelia, and fungal meningitis (especially crypto, but also cocci and histo) can also be seen.
* The list of non-infectious causes of AM is huge:
*:* The most common drugs to cause AM are [[TMP]], [[TMP-SMX]], [[ibuprofen]] and other [[NSAID]]s (nonsteroidal anti-inflammatory drugs).
*:*:* Medication induced AM usually has a poly predominant CSF.
*:*:* The mechanism is thought to be an acute hypersensitivity reaction limited to the meninges.
* [[Sarcoidosis]], [[SLE]] ([[systemic lupus erythematosus]]) and [[Behçet's disease]] are the most common systemic illnesses to be associated with AM.


===Transmission===
*[[Arboviruses]]:
[[Enteroviruses]], the most common cause of viral meningitis, are most often spread from person to person through [[fecal]] contamination (which can occur when changing a diaper or using the toilet and not properly washing hands afterwards). Enteroviruses can also be spread through respiratory secretions ([[saliva]], [[sputum]], or nasal mucus) of an infected person. Other viruses, such as [[mumps]] and [[varicella-zoster virus]], may also be spread through direct or indirect contact with saliva, sputum, or mucus of an infected person. Contact with an infected person may increase your chance of becoming infected with the virus that made them sick; however you will have a small chance of developing meningitis as a complication of the illness.
**Common arvboviruses in the United States<ref name="pmid8118792">{{cite journal| author=Calisher CH| title=Medically important arboviruses of the United States and Canada. | journal=Clin Microbiol Rev | year= 1994 | volume= 7 | issue= 1 | pages= 89-116 | pmid=8118792 | doi= | pmc=358307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8118792  }} </ref>:
***St. louis encephalitis virus ([[Flavivirus]])
***[[Western equine encephalitis]] virus ([[Alphavirus]])  
***[[Colorado tick fever]] virus ([[Coltivirus]])
**They commonly cause [[encephalitis]]. However, they are responsible for causing [[viral]] [[meningitis]].
**Pathogenesis is similar to the [[enteroviruses]] pathogenesis. The difference between them is in the start process of the infection. The [[infection]] starts by the [[arthropod]] bite to the skin then virus replication takes place in the [[lymph nodes]] then [[viremia]] occurs in the distant [[organs]] and finally the virus reaches the [[brain]].


==References==
*[[Mumps]]:
**[[Infection]] occurs through [[respiratory]] [[droplet]] that infects first the [[parotid gland]] causing [[parotitis]].
**After the infection, [[viremia]] takes place and the [[virus]] reaches the [[brain]] causing [[meningitis]].
 
*[[Human herpes virus 5|Human herpes viruses]]:<ref name="pmid28076019">{{cite journal| author=Koeller KK, Shih RY| title=Viral and Prion Infections of the Central Nervous System: Radiologic-Pathologic Correlation: From the Radiologic Pathology Archives. | journal=Radiographics | year= 2017 | volume= 37 | issue= 1 | pages= 199-233 | pmid=28076019 | doi=10.1148/rg.2017160149 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28076019  }} </ref>
**They include: [[Herpes simplex virus]] 1, [[Herpes simplex virus 2]], human herpes virus 1, [[Cytomegalovirus]], [[Epstein barr virus mononucleosis|epstein barr virus]] and [[HHV-8|human herpes virus 8.]]
**Primary [[infection]] by the herpes viruses is like the other [[viral infections]] by invasion through the [[respiratory]] and [[gastric]] [[mucosa]] and the [[replication]] followed by the [[viremia]] till reaching the brain causing [[meningitis]].
**Latent [[infection]] may occur when the virus is stimulated again by [[tissue]] damage or exposure to [[ultraviolet light]].
 
==Transmission==
Infectious transmission is different among the [[viruses]] causing viral meningitis:
*[[Enteroviruses]]: Feco-oral transmission and may be transmitted by the respiratory droplet
*[[Herpes simplex virus]]: Inter-human transmission
*[[Arboviruses]], such as [[West nile virus]] : Transmitted through mosquitoes bite
*[[Mumps]]: Transmitted via the blood
*[[Influenza]]: Postinfections - airborne transmission
*[[Lymphocytic choriomeningitis virus]]: Transmitted from the rodents
 
==Genetics==
There is no genetic inheritance correlated with the viral meningitis.
 
==Microscopic pathology==
Microscopic pathological findings in viral meningitis may include the following:
*[[Pleocytosis]] (10-1000 cells/µl)
*Polymorphous population of [[lymphocytes]]
*Activated lymphocytes
*[[Plasma cells]] may be binuclear or multinuclear
*Activated [[monocytes]]
 
==References==  
{{Reflist|2}}
{{Reflist|2}}
{{clr}}
{{Medicine}}


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[[Category:Emergency mdicine]]
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Latest revision as of 00:41, 30 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2],Ahmed Elsaiey, MBBCH [3]

Overview

Viral meningitis pathophysiology differs from virus to another and depends on many factors like age, immune status and gene expression. Invasion into the meninges by a pathogen can set up a local inflammatory response. The clinical signs are due to this meningeal irritation - for example, Kernig's sign is due to pain produced by stretching of the inflamed meninges.

Pathogenesis

Transmission

Infectious transmission is different among the viruses causing viral meningitis:

Genetics

There is no genetic inheritance correlated with the viral meningitis.

Microscopic pathology

Microscopic pathological findings in viral meningitis may include the following:

References

  1. ↑ Rotbart HA (2000). "Viral meningitis". Semin Neurol. 20 (3): 277–92. doi:10.1055/s-2000-9427. PMID 11051293.
  2. ↑ Calisher CH (1994). "Medically important arboviruses of the United States and Canada". Clin Microbiol Rev. 7 (1): 89–116. PMC 358307. PMID 8118792.
  3. ↑ Koeller KK, Shih RY (2017). "Viral and Prion Infections of the Central Nervous System: Radiologic-Pathologic Correlation: From the Radiologic Pathology Archives". Radiographics. 37 (1): 199–233. doi:10.1148/rg.2017160149. PMID 28076019.
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