Viral CNS infections

Question 1

Types of CNS disease: definitions

Answer 1

1. Meningitis (inflamm of lining of brain; aseptic meningitis is NOT caused by bacteria)
2. Encephalitis (inflamm of brain tissues)
3. Meningoencephalitis (widespread infection of the meninges and brain)

Question 2

Aseptic (sterile meningitis): causes, symptoms, diagnosis, treatment, prognosis, sign of meningitis:

Answer 2

1. Viruses, fungi, TB, infections near the CNS; 80% enteroviruses, 10% HSV-1 and 2, 10% arboviruses, s sign a symptom of meningitis; neck so stiff that KNEES FLEX when neck is flexed

Question 3

Encephalitis: brain inflamm

Answer 3

1. Incidence: rare (usually infants and elderly, <20000/yr)
2. Causes: exposure to many types of viruses; influx of immune cells in brain; CEREBRAL EDEMA destroys neurons; intracerebral hemorrhage: distinguishing features from meningitis
3. Symptoms: mental status is altered!! Distinguishing feature from meningitis; fever, headache, photophobia, stiff neck and back, confusion, sleepiness, irritability, stumbling
4. Urgent symptoms: unresponsiveness, coma; seizures, muscle weakness or paralysis; neuro signs: memory loss, flat affect, withdrawal, poor judgement
5. Diagnosis: spinal tap indicates inflamm in CSF, blood may be present and viruses could be detected (PCR is gold standard for definitive diagnosis); EEG is suggestive of seizures; brain MRI or CT scan may show foci of inflamm or hemorrhage
6. Treatment: supportive care and symptom relief; antivirals for herpes (acyclovir); antiseizure meds (phenytoin, Dilantin); anti-inflamm (dexamethasone) to reduce edema
7. Prognosis: some cases are benign with a full recovery; some cases are severe, MAY BE FATAL!!
8. Complications: permanent neurologic impairments to memory, speech, vision, hearing, muscle control, or sensation in severe cases

Question 4

Pathogenesis of viral CNS disease:

Answer 4

1. Death of neurons (cytolytic viruses can directly kill tissues)
2. Host factors (age: infants and elderly most susceptible; immune status: impaired immunity allows viruses to flourish in all tissues, including CNS; genetics: innate differences in resistance to infections; activity: exercise may increase dissemination of viruses to CNS)
3. Acute disseminated encephalomyelitis (ADEM): postinfectious encephalitis follows viral infection by 1-2 wks; associated with measles, mumps, VZV, influenza, parainfluenza viruses; autoimmune disorder

Question 5

Examples of CNS infections:

Answer 5

1. Neuronal spread: herpesviruses (alphaherpesviruses), rabies)
2. Fecal-oral spread: picornaviruses (enteroviruses)
3. Insect vectors (arboviruses): flaviviruses, togaviruses (alphaviruses)

Question 6

Alphaherpesviruses are

Answer 6

neurotropic: HSV-1, HSV-2, VZV

Question 7

Herpesviruses:

Answer 7

1. HSV-2&raquo_space; HSV-1 primary infections often cause meningitis
2. Recurrent HSV-1 infections can cause encephalitis
3. Other herpesviruses: VZV, CMV, EBV meningitis occur more often in immunocompromised patients
4. In weak host, these CNS infections often progress to severe encephalitis
5. Treat HSV and VZV aggressively with acyclovir

Question 8

HSV-1 encephalitis:

Answer 8

1. Most common cause of sporadic viral encephalitis
2. Routes of infection: primary HSV-1 in the oropharynx to trigem to CNS; recurrent HSV-1 to trigem nerve to CNS; reactivation in situ HSV-1 to CNS
3. Symptoms and signs: altered mental stats, focal cranial nerve deficits, hemiparesis, slurred speech, stumbling, seizures, fever
4. Diagnosis: gold standard: PCR of CSF for HSV and other viruses; brain imaging: MRI shows predominantly unilateral temporal lobe abnormalities

Question 9

Rabies virus is

Answer 9

neurovirulent;

1. transmitted by saliva through bite of rabid animal or by aerosols in caves populated by infected bats
2. replicates in muscle at bite site
3. Incubation period of weeks to months, depending on inoculum and distance of bite from CNS
4. Infects peripheral nerves and travels to brain
5. Replication in brain causes hydrophobia, seizures, hallucinations, paralysis, coma, and death
6. Spreads to salivary glands from where it is transmitted
7. Postexposure immunization can prevent disease due to long incubation period

Question 10

Picornaviruses:

Answer 10

1. Transmission: enteroviruses (fecal-oral)
2. At risk or risk factors (poliovirus: young children, with asymptomatic or mild disease; older children, adults with asymptomatic to paralytic disease); coxsackievirus and enterovirus (newborns and neonates at highest risk for serious disease)
3. Distribution of virus: ubiquitous; poliovirus nearly eradicated; enteroviruses: disease more common in summer
4. Vaccines or antiviral drugs: poliovirus: live oral or inactivated polio vaccines; no vaccines for other enteroviruses or rhinoviruses; no antiviral drugs

Question 11

WNV Meningoencephalitis:

Answer 11

1. Occurs in <1% of WNV infections
2. Symptoms: headache, high fever, stiff neck, disorientation, coma, tremors, seizures, paralysis
3. Higher risk populations: cancer, diabetes, hypertension, and kidney disease
4. Prognosis: recovery over weeks or months; some of the neuro effects may be permanent
5. Mortality: 10%

Question 12

How can a virus enter the CNS? What can you do to see what’s happening in brain and meninges?

Answer 12

Olfactory route is a way, with virus latching onto the olfactory rods and enter the neuron; sample CSF!!

Question 13

Tropisms for picornaviruses? Where do they start?

Answer 13

Think replication in GI tract (oropharynx and intestine);
then go to
1. skin for Hand-foot-mouth disease and get rash, herpangina
2. Echovirus, coxsackie A and B viruses to muscle to give myocarditis or pericarditis, and pleurodynia
3. Poliovirus, coxsackie A and B viruses to get paralytic disease and encephalitis
4. Echovirus, poliovirus, coxsackie A and B viruses to get meningitis