CNS Infections- HSV 1 & 2

Question 1

Most common cause of all non-epidemic/sporadic, FOCAL encephalitis with peak incidence in:

(versus arbovirus epidemic diffuse encephalitis)

Answer 1

1. Neonates - infection occurs during natural child birth with an infected mother
2. Young adults and the elderly via a reactivation of latent infection

Question 2

Transmission

Answer 2

1. is via direct contact with secretions containing virus (saliva, vaginal secretions, semen)
2. in utero infection rarely occurs
3. More commonly, intrapartum contact of fetus with infected maternal genital secretions.

There is much greater risk of neonatal infection if the pregnant mother has a primary HSV infection versus a recrudescent/recurrent infection

Question 3

Spreads to CNS via

Answer 3

1. hematogenous route (blood)

2. neural routes along the PNS via retrograde axoplasmic flow as per polio and rabies viruses

Question 4

Herpes is a _____ virus

Answer 4

lytic

Question 5

In the neonate, the primary infection may progress to disease. In adult, CNS disease is due to __________.

Answer 5

reactivation of latent infection, recrudescence!

Question 6

In the adult, herpes infection (usually HSV-1) in the brain is usually a _________ with distinctive clinical features due to its remarkable localization. Usually one lobe, primarily the _________ with characteristic localization of lesions (inflammation, focal hemorrhage, necrosis) in inferior-orbito-frontal and medial temporal regions of brain.

Answer 6

focal encephalopathy

cerebral cortex

Question 7

With temporal lobe involvement (areas of brain affected/infected) clinical manifestations are _________

Answer 7

memory defects, psychosis, slurred speech, personality changes

Question 8

Fatality and relapse rate are ______

Answer 8

HIGH

• Many (>90% of) survivors show considerable disability
• Relapse is common due to HSV reactivation

Question 9

In the adult, primary genital herpes infections can result in a benign, aseptic meningitis during which _________ may also occur.

Answer 9

ascending myelitis or transverse myelitis

transverse myelitis results in urinary retention, paresthesias, weakness of the lower extremities.

Question 10

In the neonate, there are 3 possible presentations of HSV 1 & 2

Answer 10

1. Localized herpes infection - SEM classic triad:
   Skin (vesicular rash), Eye (keratitis), Mouth (papular→vesicular→ pustular → crusted rash).
2. Disseminated disease: Systemic infection of many organs (liver, lungs, skin, eye, CNS); fatality rate is high (70%)
3. CNS disease: diffuse or focal encephalitis + systemic infection involving many organs. Refer to enterovirus encephalitis for manifestations.
   - Fatality rate is high; most survivors have significant neurological sequelae

Question 11

Aseptic (Mollaret’s) meningitis description

Answer 11

• most often caused by HSV-2
• in young adults and elderly via a reactivation of latent infection
• a recurrent/recurring meningitis

Question 12

Acute peripheral facial palsy (APFP) and idiopathic peripheral facial palsy (Bell’s palsy) description

Answer 12

-major etiologic agents are HSV or varicella-zoster virus (VZV)

Question 13

HSV encephalitis is _________ other causes focal encephalitis are NOT.

Answer 13

treatable with antiviral agents

Question 14

Complete differential

Answer 14

1. Other viral agents of focal encephalitis include any viral agent of diffuse encephalitis:
   rabies, arboviruses, enteroviruses.
2. Some bacterial agents of CNS abscess or encephalitis can also cause a focal encephalitis
3. Tumor
4. Intracerebral hemorrhage
5. Temporal lobe epilepsy

Question 15

CSF will show

Answer 15

1. Protein and glucose levels as per viral infection and mononuclear pleocytosis.
2. large numbers of RBCs are present – HSV causes a vasculitis → RBC in CSF!

PCR on CSF specimen (is done) because there is a successful treatment regimen

Question 16

CT scan or MRI will show lesions localized to _________

Answer 16

inferior-orbito-frontal and medial temporal regions of brain

Question 17

The gold standard is the

Answer 17

viral culture, but is not usually done

Question 18

Treatment

Answer 18

• Antiviral agents(s), nucleoside analogs, not a cure!
• Inhibits HSV DNA Polymerase and acts as a chain terminator.

Acyclovir has selective toxicity because it is activated by HSV’s thymidine kinase, so only HSV infected cells will be killed

Question 19

CNS or disseminated disease in neonates is treated with

Answer 19

high-dose Acyclovir (60mg/kg/d; IV in 3 divided doses)

Question 20

Must initiate treatment immediately after obtaining sample, if test results are negative, __________

Answer 20

stop treatment. Only treatment can decrease both fatality rate and neurological sequelae

Question 21

Pregnant women will shed virus in vaginal tract if lesions are ___________

Answer 21

present but MAY also if the lesions are absent (women is asymptomatic)

Question 22

Most common way child is infected from mother is

Answer 22

intrapartum (during birth)

Question 23

To diagnose pregnant mother, must do

Answer 23

1. Clinical exam PLUS
2. Swab specimen tested by PCR or viral culture
   - -OR–
3. Serology for type-specific antibody tests, not full antigen assays

Question 24

Cesarean section is recommended if

Answer 24

there are lesions present at the onset of labor, or if primary infection was acquired during the last trimester

Treat with suppressive therapy only during the last 4 weeks of pregnancy

Question 25

Herpes is most likely _______ and Arbovirus is most likely __________.

Answer 25

herpes usually focal

arbovirus usually diffuse