Viral infections of the CNS - Aucoin Flashcards
List some viral infections of the CNS.
- aseptic meningitis
- viral encephalitis
- paralysis
- AIDS dementia
- rabies
- prion diseases
Most patients with CNS infection may present with the clinical features of?
Fever, headache, AMS, or focal neurologic deficits.
Focal neurological deficits affect what?
Speech, sight, movement of limbs and includes altered mental status.
A person possesses numerous barriers to prevent viral entry after what?
Colonization of selected mucosal surfaces in the body.
If there has been previous contact with a virus, the mucosa of the GI tract and the respiratory tract may be coated with what?
IgA antibodies. These neutralize the viruses and prevent attachment and cell penetration.
If a virus is able to escape initial host defenses then what can happen?
They may replicate and disseminate - with potential to invade the CNS.
What types of viruses are able to infect the GI tract?
Naked capsule viruses because they are more hardy.
What are the steps of infection of most neurotropic viruses?
Includes replication at non-neuronal sites.
- replication at portal of entry
- establishes viremia
- crosses BBB and invades CNS
Where do enteroviruses initially multiply?
The peritonsillar lymphatics, Peyer’s patches, lamina propria of the intestine and vascular and endothelial cells.
What type of cells can mediate viral penetration from the gut lumen to lymphoid cells?
M cells.
Where do viruses go after invading lymphoid cells in the gut?
They disseminate to the circulatory system - traveling to the liver, spleen and muscle, where further multiplication augments the viremia.
During viremia, which cells clear the virus?
Phagocytic cells.
Some viruses use phagocytic cells to grow and for transportation because they are effectively hidden front eh immune system. Which viruses do this?
Examples include measles, mumps and herpes viruses.
CNS invasion by viruses occurs by what mechanisms?
- Invasion directly across cerebral capillary endothelial cells, the major site of the BBB
- Infection of glia without evidence of endothelial cell infection.
- Transport via infected immune cells (monocytes) between cerebral capillary endothelial cells after
- Via olfactory or peripheral nerves
Which virus infect neurons?
Varicella zoster, rabies virus and HSV-1. This is one way they are able to invade the CNS.
Monocytes in the blood can do what?
They can pass through endothelial cells of brain capillaries to become perivascular macrophages. If they are carrying a virus then the virus gains access to the CNS.
Production of viral disease in the CNS requires what?
- viral attachment to and penetration of susceptible cells - gains access to the subarachnoid space and dispersion into CSF
- spread within the CNS - spreads from meningeal cells to glia and neurons
- induction of cellular changes - causes inflammatory cells to accumulate, triggers a immunologically specific response with virus sensitized lymphocytes
What is characteristic of viral inflammation of the CNS?
- Monocytes may respond to a virus-specific protein that diffuses or is transported to the luminal surface of the endothelium
- Passage through endothelial cells releases inflammatory cytokines (IFNγ and IL-6 common)
- After development of a CSF inflammatory response, alterations in the BBB permit the traversal into CSF of serum proteins, including immunoglobulins
- Intracerebral accumulation of Ig is reflected by an increase in the CSF-to-serum ratios of specific Ig that persist for several weeks after infection - diagnostic feature of viral infection
What is needed for viral clearance from the CNS?
An intact host immune response. Without this there may be chronic viral infections.
In viral clearance, are T cell responses more important than B cell?
Yes.
What is meningitis?
Inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. Acute meningitis - has an onset of hours to several days. Characterized by the sudden oner of fever, headache, and stiff neck. If suspected then samples of blood and CSF are tested.
The common etiologic agents of acute meningitis are what?
Viruses.
What is a diagnostic criteria of meningitis?
Pleocytosis - for meningitis this is an abnormally increased amount of WBC’s in CSF.
Describe some characteristics of aseptic (viral) meningitis.
- Pyogenic bacteria are not the cause of aseptic meningitis
- The cause of the meningitis is not apparent after initial evaluation and routine stains and cultures of CSF
- Viral meningitis is generally less severe and resolves without specific treatment
- Most viral meningitis cases in the United States, especially during the summer months, are caused by enteroviruses
- A small percentage of people with enterovirus infections develop meningitis
What are the most common causes of aseptic or viral meningitis?
- nonpolio enteroviruses
- mumps virus
- herpesvirus
what are the less common causes of aseptic meningitis?
Arboviruses Lymphocytic choriomeningitis virus (LCMV) Human immunodeficiency virus Adenovirus Influenza virus Measles virus
What are some characteristics of meningitis caused by enterovirus?
- Most viral meningitis cases summer; caused by enteroviruses
- Viral meningitis occurs mostly in children younger than age 5
- Changing a diaper or using the toilet and not properly washing hands afterwards is a route of transmission
- Enteroviruses, are the leading recognizable cause of aseptic meningitis syndrome, account for 85% to 95% of all cases in which a pathogen is identified
- Estimates from the CDC indicate that 10 to 15 million symptomatic enteroviral infections occur annually in the United States, which includes 30,000 to 75,000 cases of meningitis
- Periods of warm weather and wearing sparse clothing may facilitate the fecal-oral spread of these viruses
- Enteroviruses have been recovered from wastewater and sewage; and disease has been reported after swimming in sewage-contaminated seawater
What are some symptoms that often accompany fever, headache and stiff neck in meningitis?
- nausea
- vomiting
- photophobia
- altered mental status
The symptoms of viral meningitis usually last for how long?
7-10 days - those with intact immune systems usually recover completely.
Which enterovirus serotypes were the most commonly isolated in meningitis cases in the US?
In descending order: echoviruses 30, 11, 9, 6, and 7; coxsackieviruses B2 and A9; echoviruses 18 and 16; coxsackieviruses B1 and B3; enterovirus 71; coxsackievirus B4; echovirus 25
What are some important properties of Coxsackie virus?
- Group A and B
- Usually causes symptoms in young (naïve immune system)
- Transmitted by fecal-oral and respiratory aerosols
Group A Coxsackie virus causes what?
Group A – herpangina (ulcers in oropharynx, fever, sore throat)
Also called “Hand-foot-and-mouth disease” due to ulcer formation
Group B coxsackie virus causes what?
Group B – pleurodynia (fever and severe pleuritic-type chest pain)
Myocarditis (fever, chest pain, and signs of congestive heart failure)
Both Groups A and B coxsackie virus can cause what?
- Both A & B can cause aseptic meningitis and mild paralysis
- Diagnosis by PCR of enteroviral RNA in spinal fluid; no treatment
What are some important properties of the enterovirus Echovirus?
- ECHO – enteric cytopathic human orphan
- Over 30 serotypes
- Transmitted by fecal-oral route
- May be transmitted in pool water
Describe some clinical characteristics of Echovirus.
- Along with Coxsackie viruses, echoviruses are a leading cause of aseptic (viral) meningitis
- Also may cause upper respiratory tract infection, febrile illness, infantile diarrhea, and hemorrhagic conjunctivitis
- Also causes hand foot and mouth disease
- Diagnosis by PCR; no antiviral therapy or vaccine available.