CNS Viral Infections Overview

Central Nervous System Viral Infections

• Most CNS viral infections are uncommon complications of common systemic infections
• Viral infections are the most common cause of aseptic meningitis
• Enteroviruses are the most common cause of aseptic meningitis
• Typical CSF findings in various types of meningitis
• There are non-infectious causes of aseptic meningitis
• Clinical features of aseptic meningitis: fever, meningism, and vomiting
• Encephalitis is an infection or inflammation of the brain
• Myelitis is inflammation of the spinal cord
• Encephalomyelitis occurs when both the brain and spinal cord are involved
• Meningoencephalitis is encephalitis with meningitis
• Clinical features of encephalitis: headache, fever, confusion, drowsiness; more advanced disease includes convulsions, seizures, hallucinations, memory loss, and coma
• Viral encephalitis may be a direct effect of acute infection or a complication of latent disease
• Most diagnosed viral encephalitis are caused by: enterovirus, HSV, rabies virus, and arboviruses
• Most AFM cases are in: children over 90%
• The large number of AFM cases identified in 2014 coincided with: a national outbreak of severe respiratory illness caused by EV-D68

Poliomyelitis

• Polio is: an acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis
• Poliomyelitis is caused by: an infection of the anterior horn cells by wild or vaccine polio virus or other viruses
• There are 3 poliovirus serotypes: 1-3 each with slightly different capsid proteins
• Poliovirus is transmitted by: faecal-oral route, contaminated food or water
• Poliovirus multiplies: in the intestine and enters the circulatory system
• Paralytic disease occurs mostly in: adolescents
• Poliomyelitis can cause irreversible paralysis in: 1 in 200 infections
• 5-10% of paralyzed persons die when: breathing muscles become immobilized
• Poliovirus infects: mucosal cells in the oropharynx and the intestine
• Most polio infections are short-term with mild viraemia: non-specific symptoms including fever, headache, nausea, sore throat, and myalgia
• If viraemia persists, the virus spreads to: the spinal cord and brain
• Invasion of motor neurons causes: flaccid paralysis
• Decades later, post-polio syndrome (PPS) occurs in: 25-50% of patients infected with polioviruses in childhood

Arboviruses

• Arboviruses are: viruses transmitted by arthropods (mosquitoes, ticks, etc.)
• Arboviruses can cause: encephalitis, meningitis, and other neurological diseases
• Examples of arboviruses: Japanese encephalitis virus (JEV), West Nile virus (WNV), Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), La Crosse encephalitis virus (LACV)
• JEV is transmitted by: Culex mosquitoes, from aquatic birds to pigs and other domestic animals, then to humans
• JEV can cause: neurological disorders such as encephalitis, meningitis, and acute flaccid paralysis

Japanese Encephalitis

• JEV is: an important cause of viral encephalitis in Asia and the Pacific
• JEV is a flavivirus that is transmitted by: mosquitoes
• JEV is spread by: Culex mosquitoes, initially from aquatic birds to pigs and other domestic animals, then to humans
• The nervous system is the main target of JEV: the virus enters the CNS through the bloodstream and infects neurons
• JEV can cause: severe encephalitis, leading to coma and death
• About 1 in 25 - 1:1000 infected people develop: symptomatic disease
• Around 30% of hospitalized patients with JE die: about half of survivors have severe neurologic sequelae
• About half of those classed with “good recovery” have: subtle neurologic sequelae such as learning difficulties, behavioral problems, and subtle neurologic signs

Herpes Simplex Virus

• HSV is*: an enveloped dsDNA virus that belongs to the Herpesviridae family
• HSV can cause: a range of infections including gingivostomatitis, herpes labialis, herpetic whitlow, ocular herpes, genital herpes, neonatal herpes, meningitis, and encephalitis
• HSV encephalitis is responsible for: about 10% of all encephalitis cases
• About 30% of encephalitis cases result from: initial infection with HSV
• The majority of HSV encephalitis cases are caused by: reactivation of an earlier infection
• HSV encephalitis can present as: neonatal HSVE (mortality rate >25%), or as focal disease following HSV reactivation (mortality 70% in the absence of treatment)

Varicella Zoster Virus

• VZV is: an enveloped dsDNA genome virus that belongs to the Herpesviridae family
• VZV causes: varicella (chickenpox) following primary infection and herpes zoster (shingles) following reactivation of VZV in sensory nerve ganglia
• Varicella is a self-limiting disease of children: morbidity and mortality can occur in other age groups and those who are immunocompromised
• Herpes zoster is most common in: the elderly or immunocompromised
• VZV can cause encephalitis in: immunocompromised patients

Rabies

• Rabies is caused by: an enveloped (-) ssRNA, bullet-shaped virus that belongs to the Rhabdoviridae (Lyssavirus) family
• Rabies is spread by: the bite of an infected animal, salivary contamination of mucous membranes, or aerosols
• The virus replicates first in: muscle, then moves along peripheral nerves to the CNS via retrograde flow in axons (typically via sensory and motor nerves at the site of the initial infection)
• Once the virus enters the nerves it is not: accessible to the host immune defenses
• The infection cycle is completed when: the virus replicates in the salivary glands
• The incubation period can range from: several weeks to up to 2 years
• Clinical phases of rabies: prodromal, furious, dumb, and coma
• The prodromal phase includes symptoms: fever, nausea, vomiting, headache, fatigue and pain, burning, tingling sensations at the site of the wound
• The furious phase includes symptoms: agitation, disorientation, seizures, twitching, hydrophobia
• The dumb phase includes symptoms: paralysis, disorientation, and stupor
• Progression to the Coma phase results in: death in ~ 100% of patients
• Vaccines can be given post-exposure for protection, but must be given before symptoms arise

HIV and the Nervous System

• HIV enters the nervous system early: at the time of initial infection, and may immediately cause symptoms or may remain asymptomatic for a lifetime
• HIV easily crosses: the blood-brain barrier
• Primary HIV disease can lead to: AIDS Dementia Complex (brain), Vacuolar Myelopathy (spinal cord), Peripheral Neuropathy (nerves), Meningitis (acute or chronic)
• Sustained viral replication and high viral load are associated with: brain tissue inflammation, permanent cell death, and HIV-associated neurocognitive disorders (HAND)
• HIV variants in CSF are not found in blood: the CNS is a compartmentalized viral reservoir

HIV-associated Neurocognitive Disorders

• HIV-associated neurocognitive disorders (HAND) are: a spectrum of neurocognitive impairments that can occur in people living with HIV.
• HAND can range in severity from: mild cognitive impairment to HIV-associated dementia
• The pathogenesis of HAND is complex and includes: various mechanisms including direct viral infection of neurons, inflammation, and immune activation
• HIV-infected macrophages and microglial cells release neurotoxic viral proteins that: trigger astrocyte activation, which results in increased glutamate release and reduced glutamate uptake
• Elevated extracellular glutamate levels cause: neuronal bioenergetic disturbances that lead to aberrant synapto-dendritic pruning and neuronal injury
• Systemic inflammation and microbial translocation products lead to: microglial activation and increased production of chemokines and cytokines that contribute to neuronal injury.