Viruses and prions can wreak havoc on the nervous system. From meningitis to encephalitis, these pathogens cause inflammation and damage to vital brain and spinal cord tissues. The effects can be devastating, leading to symptoms like paralysis, seizures, and altered mental states.

Prion diseases are particularly insidious. These misfolded proteins corrupt normal proteins in the brain, causing spongiform changes and neurodegeneration. With long incubation periods and no cure, prions pose unique challenges in diagnosis and treatment of fatal conditions like Creutzfeldt-Jakob disease.

Viral Infections of the Nervous System

Types of nervous system viral infections

• Meningitis: inflammation of the protective membranes covering the brain and spinal cord (meninges) caused by viruses such as enteroviruses (coxsackievirus, echovirus), herpesviruses (HSV-2, VZV), and arboviruses (WNV) leading to symptoms of headache, fever, stiff neck, photophobia, and altered mental status
• Encephalitis: inflammation of the brain tissue (parenchyma) caused by viruses such as herpesviruses (HSV-1, VZV), arboviruses (WNV, JEV), and rabies virus resulting in fever, headache, altered mental status, seizures, and focal neurological deficits
  • Some viruses exhibit neurotropism, preferentially infecting nervous system tissues
• Myelitis: inflammation of the spinal cord caused by viruses such as enteroviruses (poliovirus), herpesviruses (VZV, CMV), and West Nile virus leading to weakness, sensory changes, and autonomic dysfunction
• Poliomyelitis: infection of the motor neurons (anterior horn cells) of the spinal cord caused by poliovirus (an enterovirus) characterized by fever, headache, stiff neck, and asymmetric flaccid paralysis

Comparison of arboviral encephalitis diseases

• West Nile virus (WNV)
  • Transmission occurs through mosquito bites (Culex species)
  • Symptoms include fever, headache, muscle pain (myalgia), and in severe cases, encephalitis or meningoencephalitis
  • Treatment involves supportive care, as there is no specific antiviral therapy
• St. Louis encephalitis virus (SLEV)
  • Transmission occurs through mosquito bites (Culex species)
  • Symptoms are similar to WNV, but SLEV is more likely to cause encephalitis in older adults
  • Treatment involves supportive care, as there is no specific antiviral therapy
• Japanese encephalitis virus (JEV)
  • Transmission occurs through mosquito bites (Culex species)
  • Symptoms include fever, headache, vomiting, and in severe cases, encephalitis with high mortality rate
  • Treatment involves supportive care, as there is no specific antiviral therapy; a vaccine is available for prevention
• Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV)
  • Transmission occurs through mosquito bites (Culiseta, Coquillettidia, and Culex species)
  • Symptoms include fever, headache, vomiting, and in severe cases, encephalitis with high mortality rate (especially for EEEV)
  • Treatment involves supportive care, as there is no specific antiviral therapy

Viral neuroinvasion and neuropathogenesis

• Viruses can enter the nervous system through various routes, including:
  • Hematogenous spread: viruses cross the blood-brain barrier
  • Retrograde axonal transport: viruses travel along peripheral nerves
  • Olfactory route: viruses enter through the nasal cavity
• Neuroinvasion can lead to direct cellular damage, inflammation, and disruption of normal neuronal function

Prion Diseases

Prions and spongiform encephalopathies

• Prions are misfolded proteins (PrPSc) that induce misfolding of normal prion proteins (PrPC) in the brain leading to accumulation and neuronal degeneration, causing spongiform changes in the brain tissue
• Prions are unique infectious agents because they lack nucleic acids (DNA or RNA), are resistant to heat, chemicals, and radiation, have long incubation periods (months to years), and can be transmitted within a species and, in some cases, between species
• Examples of prion diseases include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE or "mad cow disease") in cattle, chronic wasting disease (CWD) in deer and elk, and scrapie in sheep and goats
• Transmission of prion diseases can occur through consumption of contaminated meat (variant CJD), exposure to contaminated surgical instruments or tissue grafts (iatrogenic CJD), or inherited mutations in the prion protein gene (familial CJD)
• Symptoms of prion diseases include rapidly progressive dementia, muscle jerks (myoclonus), uncoordinated movements (ataxia), and behavioral changes
• Diagnosis is based on clinical presentation, MRI findings, and detection of PrPSc in brain tissue (postmortem)
• Treatment is supportive, as there is no effective cure for prion diseases
• Prion diseases are characterized by progressive neurodegeneration due to protein misfolding