Brain and Behavior Flashcards
Acute Viral Encephalitis Overview
- Approximately 20,000 cases of encephalitis occur in the US each year, almost all of which are caused by viruses - Hallmark of encephalitis is acute onset of febrile illness accompanied with headache and altered mental status - HSV is most frequent etiology of sporadic encephalitis in US - HSV-1 associated with severe focal encephalitis in adolescents and adults - Untreated, disease has 70% mortality rate and 97% of untreated survivors left with permanent neurologic deficits HSV-2 associated with newborns
HSV Encephalitis Diagnosis
- Diagnosis of herpes encephalitis is suspected if adult pts have fever and focal cerebral cortical lesions, particularly in the frontal and temporal lobes - Increased CSF protein occurs in 90% of cases but rarely exceeds 200mg/dL - CSF glucose almost always normal - EEGs provide clues as 90% of pts have focal or generalized slowing - Presence of periodic sharp wave complexes in the temporal leads superimposed on a slow amplitude background is highly suggestive of HSV encephalitis - MRI shows abnormal areas involving the temporal lobes and orbitofrontal cortex in more than 90% of cases - Biopsy has been replaced by detection of HSV DNA in the CSF by PCR (specificity is 100% and sensitivity is 95%)
HSV Encephalitis Treatment
- Early recognition of HSV encephalitis is essential because effective antiviral therapy (acyclovir) is available, and prompt treatment can significantly decrease the morbidity and mortality of the disease - Acyclovir acts by inhibiting the viral DNA poly, thus interfering with viral replication - Acyclovir reduces mortality from 70% -> 19% in adults - Neurological impairment can still occur in 40%-60% of pts (outcome is related to the severity of disease at the time antiviral therapy is begun, hence the urgency) - Intravenous therapy should be continued for 14 to 21 days
Neonatal Herpes Simplex Virus
Case Study: - Case of neonatal HSV contracted during birth - During a breech presentation, a fetal monitor was placed on buttocks of baby, and due to the greatly prolonged labor, the baby was delivered by cesarean section - On sixth day, vesicles with an erythematous base appeared at the site where the fetal monitor had been placed - HSV was grown from vesicle fluid, as well as from spinal fluid, cornea, saliva, and blood - Baby became moribund w/ frequent apneic episodes and seizures - IV treatment w/ adenosine arabinoside (ara-A; vidarabine) - Baby also developed bradychardia and occasional vomiting while vesicles spread to cover lower extremities, back, palm, nares, and right eyelid - Within 72 hrs of ara-A treatment, Baby’s condition began improving - Normal development was reported at 1 and 2 years of age - 6 wks after birth, herpes lesion was found on mother’s vulva - Virus (HSV-2) was probably acquired through an abrasion caused by the fetal monitor while neonate was in birth canal - Ara-A has since been replaced with all around better drugs (acyclovir, valacyclovir, and famciclovir)
HSV infection in the neonate
- Devastating and often fatal disease (most often caused by HSV-2) - May be acquired in utero but more commonly is contracted either during passage of infant through the vaginal canal because the mother is shedding herpesvirus at the time of delivery, or it acquired postnatally from family members or hospital personnel - Baby initially appears septic, and vesicular lesions may be present - Because cell-mediated immune response is not yet developed, HSV disseminates to liver, lung, and other organs, as well as to the CNS - Progression of the infection to the CNS results in death, mental retardation, or neurologic disability, even with treatment
Varicella-Zoster Virus
- VZV causes chickenpox (varicella) and upon recurrence causes herpes zoster, or shingles - VZV shares many characteristics with HSV (as both are alphaherpesviruses) 1) Ability to establish latent infection of neurons and recurrent disease 2) Importance of cell-mediated immunity in controlling and preventing serious disease 3) Characteristic blister-like lesions - VZV also encodes a thymidine kinase and is susceptible to antiviral drugs - VZV spreads predominantly by the respiratory route
Varicella-Zoster Virus Structure and Replication
- Smallest genome of the human herpesviruses - Slower and in fewer types of cells than HSV - Establishes a latent infection of neurons, but unlike HSV, several viral RNAs and specific viral proteins can be detected in the cells - Large, enveloped virus that contain double-stranded DNA that is surrounded by an icosadeltahedral capsid
Varicella-Zoster Virus Pathogenesis and Immunity
- VZV is generally acquired by inhalation, and primary infection begins in the tonsils and mucosa of the respiratory tract - Virus then progresses via bloodstream and lymphatic system to the cells of the reticuloenothelial system - Secondary viremia occurs 11 to 13 days and spreads the virus throughout the body and to the skin - The virus infects T cells and is transmitted on cell-cell interaction - Virus causes a dermal vesiculopustular rash that develops over time in successive crops. - Fever and systemic symptoms occur w/ rash - Virus becomes latent in dorsal root or cranial nerve ganglia after primary infection - On reactivation, virus overcomes interferon-alpha to spread the rash along the entire dermatome known as herpes zoster, or shingles - Antibody is IMPORTANT for limiting the viremic spread of VZV
Varicella-Zoster Virus Epidemiology
- VZV is extremely communicable, with rates of infection exceeding 90% among susceptible household contacts - Disease spread principally by respiratory route but may also be spread via contact with skin vesicles - More than 90% of adults in developed countries have the VZV antibody - Herpes zoster results from reactivation of patient’s latent virus - The disease (zoster) develops in approx. 10%-20% of the population infected with VZV, and incidence rises with age
Varicella-Zoster Clinical Syndromes
- Varicella (chickenpox) is one of the 5 classic childhood exanthems - Maculopapular rash appears after 14 days and each lesion forms a thin-walled vesicle on an erythematous base (“dewdrop on a rose petal”) - Herpes zoster (zoster means “belt”) is a recurrence of a latent varicella infection acquired earlier in pt’s life - Severe pain in the area innervated by the nerver usually precedes the appearance of the chickenpox-like lesions - Rash is typically limited to a dermatome and resembles varicella - Cowdry type A intranuclear inclusions seen in infected cells as well as syncytia (use Tzanck smear) - Antigen detection and PCR are sensitive means of diagnosing VZV infection
What is Postherpetic Neuralgia?
- Chronic pain syndrome called postherpetic neuralgia, which can persist for months to years, occurs in as many as 30% of pts older than 65 years in whom herpes zoster develops - No good treatment, however analgesics and other painkillers, topical anesthetics, or capsaicin cream may provide some relief from the post-herpatic neuralgia that follows zoster
Varicella-Zoster Treatment, Prevention, Control
- Treatment is appropriate for adults and immunocompromised pts, but is typically unnecessary for children - Acyclovir, famcyclovir, and valacyclovir are drugs of choice (latter two have improved pharmacodynamics) - Because VZV infection in children is generally mild and provides “lifelong” immunity, their exposure is typically encouraged - Immunocompromised pts may be protected from serious disease via varicella-zoster immunoglobin (VZIG) - Live-attenuated vaccines are available to induce production of protective antibody and cell-mediated immunity in immune-deficient children and others - A stronger version of said vaccine is available for older adults to prevent the onset of zoster
Picornaviruses (Enteroviruses)
- Plus-strand RNA surrounded by a naked icosahedral capsid resembles messenger RNA - Enteroviruses do not usually cause enteric disease, but they do replicate within and are transmitted by the fecal-oral route - Upper respiratory tract, oropharynx, and the intestinal tract are the portals of entry for enteroviruses - Virions are impervious to stomach acid, proteases, and bile - Viral replication is initiated in the mucosa and lymphoid tissue of the tonsils and pharynx, and the virus later infects lymphoid cells of Peyer patches underlying the intestinal mucosa - Most enteroviruses are cytolytic, replicating rapidly and causing direct damage to the target cell - Enteroviruses are exclusively human pathogens - Poliovirus is a type of Enterovirus
Poliovirus Overview
- Poliovirus gains access to the brain by infecting skeletal muscle and traveling up the innervating nerves to the brain, like the rabies virus - Poliovirus is cytolytic for the motor neurons of the anterior horn and brain stem - The location and number of nerve cells destroyed by the virus govern the extent of paralysis and whether and when other neurons can re-innervate the muscle and restore activity - The combined loss of neurons to polio and to old age may result in paralysis later in life, termed postpolio syndrome - Antibody is the major protective immune response to the enteroviruses - Asymptomatic shedding can occur for up to a month, putting virus into the environment (summer is major season for enterovirus disease) - Wild-type poliovirus has been eliminated from Western Hemisphere and most of world via vaccine
Poliovirus can cause 4 outcomes in unvaccinated people:
1) Asymptomatic illness: Results if viral infection is limited to the oropharynx and the gut. At least 90% of poliovirus infections are asymptomatic 2) Abortive poliomyelitis: the minor illness, is a nonspecific febrile illness occurring in approx. 5% of infected people (fever, headache, sore throat, vomiting, etc.) 3) Nonparalytic poliomyelitis (aseptic meningitis): Occurs in 1% - 2% of pts with poliovirus infections. In this disease, the virus progresses into the CNS and the meninges, causing back pain and muscle spasms along with the minor illness 4) Paralytic polio: the major illness, occurs in 0.1% - 2.0% of persons. Most severe outcome. Biphasic illness that comes 3-4 days after minor illness subsides. Virus spreads from blood to anterior horn cells of the spinal cord and to the motor cortex of brain.
