Viral infections of the CNS - Aucoin Flashcards

1
Q

List some viral infections of the CNS.

A
  1. aseptic meningitis
  2. viral encephalitis
  3. paralysis
  4. AIDS dementia
  5. rabies
  6. prion diseases
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2
Q

Most patients with CNS infection may present with the clinical features of?

A

Fever, headache, AMS, or focal neurologic deficits.

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3
Q

Focal neurological deficits affect what?

A

Speech, sight, movement of limbs and includes altered mental status.

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4
Q

A person possesses numerous barriers to prevent viral entry after what?

A

Colonization of selected mucosal surfaces in the body.

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5
Q

If there has been previous contact with a virus, the mucosa of the GI tract and the respiratory tract may be coated with what?

A

IgA antibodies. These neutralize the viruses and prevent attachment and cell penetration.

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6
Q

If a virus is able to escape initial host defenses then what can happen?

A

They may replicate and disseminate - with potential to invade the CNS.

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7
Q

What types of viruses are able to infect the GI tract?

A

Naked capsule viruses because they are more hardy.

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8
Q

What are the steps of infection of most neurotropic viruses?

A

Includes replication at non-neuronal sites.

  1. replication at portal of entry
  2. establishes viremia
  3. crosses BBB and invades CNS
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9
Q

Where do enteroviruses initially multiply?

A

The peritonsillar lymphatics, Peyer’s patches, lamina propria of the intestine and vascular and endothelial cells.

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10
Q

What type of cells can mediate viral penetration from the gut lumen to lymphoid cells?

A

M cells.

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11
Q

Where do viruses go after invading lymphoid cells in the gut?

A

They disseminate to the circulatory system - traveling to the liver, spleen and muscle, where further multiplication augments the viremia.

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12
Q

During viremia, which cells clear the virus?

A

Phagocytic cells.

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13
Q

Some viruses use phagocytic cells to grow and for transportation because they are effectively hidden front eh immune system. Which viruses do this?

A

Examples include measles, mumps and herpes viruses.

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14
Q

CNS invasion by viruses occurs by what mechanisms?

A
  1. Invasion directly across cerebral capillary endothelial cells, the major site of the BBB
  2. Infection of glia without evidence of endothelial cell infection.
  3. Transport via infected immune cells (monocytes) between cerebral capillary endothelial cells after
  4. Via olfactory or peripheral nerves
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15
Q

Which virus infect neurons?

A

Varicella zoster, rabies virus and HSV-1. This is one way they are able to invade the CNS.

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16
Q

Monocytes in the blood can do what?

A

They can pass through endothelial cells of brain capillaries to become perivascular macrophages. If they are carrying a virus then the virus gains access to the CNS.

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17
Q

Production of viral disease in the CNS requires what?

A
  1. viral attachment to and penetration of susceptible cells - gains access to the subarachnoid space and dispersion into CSF
  2. spread within the CNS - spreads from meningeal cells to glia and neurons
  3. induction of cellular changes - causes inflammatory cells to accumulate, triggers a immunologically specific response with virus sensitized lymphocytes
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18
Q

What is characteristic of viral inflammation of the CNS?

A
  1. Monocytes may respond to a virus-specific protein that diffuses or is transported to the luminal surface of the endothelium
  2. Passage through endothelial cells releases inflammatory cytokines (IFNγ and IL-6 common)
  3. After development of a CSF inflammatory response, alterations in the BBB permit the traversal into CSF of serum proteins, including immunoglobulins
  4. Intracerebral accumulation of Ig is reflected by an increase in the CSF-to-serum ratios of specific Ig that persist for several weeks after infection - diagnostic feature of viral infection
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19
Q

What is needed for viral clearance from the CNS?

A

An intact host immune response. Without this there may be chronic viral infections.

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20
Q

In viral clearance, are T cell responses more important than B cell?

A

Yes.

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21
Q

What is meningitis?

A

Inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. Acute meningitis - has an onset of hours to several days. Characterized by the sudden oner of fever, headache, and stiff neck. If suspected then samples of blood and CSF are tested.

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22
Q

The common etiologic agents of acute meningitis are what?

A

Viruses.

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23
Q

What is a diagnostic criteria of meningitis?

A

Pleocytosis - for meningitis this is an abnormally increased amount of WBC’s in CSF.

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24
Q

Describe some characteristics of aseptic (viral) meningitis.

A
  1. Pyogenic bacteria are not the cause of aseptic meningitis
  2. The cause of the meningitis is not apparent after initial evaluation and routine stains and cultures of CSF
  3. Viral meningitis is generally less severe and resolves without specific treatment
  4. Most viral meningitis cases in the United States, especially during the summer months, are caused by enteroviruses
  5. A small percentage of people with enterovirus infections develop meningitis
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25
Q

What are the most common causes of aseptic or viral meningitis?

A
  1. nonpolio enteroviruses
  2. mumps virus
  3. herpesvirus
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26
Q

what are the less common causes of aseptic meningitis?

A
Arboviruses
Lymphocytic choriomeningitis virus (LCMV)
Human immunodeficiency virus
Adenovirus
Influenza virus
Measles virus
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27
Q

What are some characteristics of meningitis caused by enterovirus?

A
  1. Most viral meningitis cases summer; caused by enteroviruses
  2. Viral meningitis occurs mostly in children younger than age 5
  3. Changing a diaper or using the toilet and not properly washing hands afterwards is a route of transmission
  4. Enteroviruses, are the leading recognizable cause of aseptic meningitis syndrome, account for 85% to 95% of all cases in which a pathogen is identified
  5. Estimates from the CDC indicate that 10 to 15 million symptomatic enteroviral infections occur annually in the United States, which includes 30,000 to 75,000 cases of meningitis
  6. Periods of warm weather and wearing sparse clothing may facilitate the fecal-oral spread of these viruses
  7. Enteroviruses have been recovered from wastewater and sewage; and disease has been reported after swimming in sewage-contaminated seawater
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28
Q

What are some symptoms that often accompany fever, headache and stiff neck in meningitis?

A
  1. nausea
  2. vomiting
  3. photophobia
  4. altered mental status
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29
Q

The symptoms of viral meningitis usually last for how long?

A

7-10 days - those with intact immune systems usually recover completely.

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30
Q

Which enterovirus serotypes were the most commonly isolated in meningitis cases in the US?

A
In descending order:
echoviruses 30, 11, 9, 6, and 7;
coxsackieviruses B2 and A9; 
echoviruses 18 and 16;
coxsackieviruses B1 and B3; 
enterovirus 71; 
coxsackievirus B4; 
echovirus 25
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31
Q

What are some important properties of Coxsackie virus?

A
  1. Group A and B
  2. Usually causes symptoms in young (naïve immune system)
  3. Transmitted by fecal-oral and respiratory aerosols
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32
Q

Group A Coxsackie virus causes what?

A

Group A – herpangina (ulcers in oropharynx, fever, sore throat)
Also called “Hand-foot-and-mouth disease” due to ulcer formation

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33
Q

Group B coxsackie virus causes what?

A

Group B – pleurodynia (fever and severe pleuritic-type chest pain)
Myocarditis (fever, chest pain, and signs of congestive heart failure)

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34
Q

Both Groups A and B coxsackie virus can cause what?

A
  1. Both A & B can cause aseptic meningitis and mild paralysis
  2. Diagnosis by PCR of enteroviral RNA in spinal fluid; no treatment
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35
Q

What are some important properties of the enterovirus Echovirus?

A
  1. ECHO – enteric cytopathic human orphan
  2. Over 30 serotypes
  3. Transmitted by fecal-oral route
  4. May be transmitted in pool water
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36
Q

Describe some clinical characteristics of Echovirus.

A
  1. Along with Coxsackie viruses, echoviruses are a leading cause of aseptic (viral) meningitis
  2. Also may cause upper respiratory tract infection, febrile illness, infantile diarrhea, and hemorrhagic conjunctivitis
  3. Also causes hand foot and mouth disease
  4. Diagnosis by PCR; no antiviral therapy or vaccine available.
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37
Q

Describe some characteristics of mumps virus.

A
  1. In an unimmunized population, mumps is one of the most common causes of aseptic meningitis and encephalitis
  2. Meningitis is estimated to occur in 10% to 30% of mumps patients, although in a recent outbreak of 2597 cases of mumps in the US, only 11 cases of meningitis was reported
  3. CNS disease caused by mumps virus can occur in patients without evidence of parotitis
  4. Meningitis is the most common neurologic manifestation of infection with mumps virus and is usually a benign and self-limited process
  5. Males are affected two to five times more often than females, and the peak incidence is in children aged 5 to 9 years
38
Q

What are some important properties of the mumps virus?

A
  1. Mumps virus causes painful swelling of the parotid gland
  2. It occurs primarily in childhood, transmitted via respiratory droplets
  3. Only a single serotypeInfects the upper respiratory tract spreads via blood to parotid glands, testes, ovaries, pancreas, and, in some cases, meninges
  4. Diagnosis is made clinically, although testing is available
  5. Low incidence in US
    Prevention consists of immunization with the live, attenuated vaccine
39
Q

What are some important properties of Lymphocytic choriomeningitis?

A
  1. LCM transmitted by aerosol inhalation, ingestion of contaminated food
  2. House mouse or hamsters common reservoirs (secretions & excretions)
  3. Worldwide distribution with low case fatality rate (<1%)
  4. Most infection are asymptomatic
  5. Influenza like symptoms, fever headache, myalgia, and malaise
  6. Aseptic meningitis, fever, headache and stiff neck in minority of patients
  7. No treatment of vaccine
    Serological testing for IgM or IgG is routine
40
Q

What is Encephalitis?

A
  1. Encephalitis is defined as an inflammatory process of the brain parenchyma associated with clinical or laboratory evidence of neurologic dysfunction
  2. half of encephalitis cases remain of unknown etiology despite an extensive diagnostic workup. Cases with identified etiologies, viruses accounted for almost two thirds
41
Q

What is the defined criteria for encephalitis?

A
  1. Altered consciousness for 24 hours or more and at least one of the following characteristics:
  2. fever
  3. seizures
  4. focal neurologic findings
  5. cerebrospinal fluid (CSF) pleocytosis or
  6. electroencephalogram (EEG) or neuroimaging findings
42
Q

How many members of the herpesvirus family can cause well-described neurologic diseases?

A
Six members:
herpes simplex virus-1 (HSV-1)
herpes simplex virus-2 (HSV-2)
varicella-zoster (VZV)
Epstein-Barr (EBV)
cytomegalovirus (CMV)
human herpes virus-6 (HHV-6)
43
Q

When herpesvirus infects the CNS…..?

A

The clinical presentation is nonspecific and confounding.

44
Q

When herpesvirus infects the CNS it is a clinical urgency because?

A

Infection is often underscored by progressive neurologic deficits, seizures or death. The prompt diagnosis and treatment rely heavily on neuroimaging.

45
Q

Encephalitis caused by herpesvirus 1 is caused by what?

A
  1. The retrograde transmission of virus from a peripheral site on the face following HSV-1 reactivation, along a nerve axon, to the brain
  2. The virus lies dormant in the ganglion of the trigeminal cranial nerve, but the pathway to gain access to the brain, remains unclear
  3. The olfactory nerve may also be involved, which may explain temporal lobes involvement, as the olfactory nerve sends branches there
46
Q

Cell death and tissue injury in HSV encephalitis is likely the result of what?

A

Direct viral killing of neurons and immune-mediated mechanisms of cell death.

47
Q

Describe some clinically important characteristics of HSV encephalitis.

A
  1. HSV encephalitis in the US, annual incidence of 1/250,000 (1250 to 2000 encephalitis cases annually)
  2. HSV encephalitis is the most common identified cause of viral encephalitis, but still accounts for only approximately 10% of all cases
  3. In immunocompetent adults, HSV-1 accounts for more than 90% of all cases of HSV encephalitis with the remainder caused by HSV-2
48
Q

How do patient’s with HSV encephalitis present?

A
  1. With fever, altered consciousness, and headache
  2. Other features: seizures, behavior or personality change, memory disturbance, motor deficit, and speech disturbances
  3. Most all patients have a CSF pleocytosis (>5 white bloodcells/mm3) with a lymphocytic predominance
  4. Protein in CSF is usually elevated (mean and median 80 to 85mg/dL), and the glucose is normal in most of cases
49
Q

How is HSV encephalitis diagnosed?

A

MRI and PCR of HSV DNA in the CSF is the procedure of choice for diagnosis of HSV encephalitis.

50
Q

What is the treatment for HSV encephalitis?

A

Acyclovir is the drug of choice for treatment of HSV encephalitis.

51
Q

What are some clinically important characteristics of varicella zoster virus?

A
  1. Primary VZV infection (chickenpox) occurs mainly in children 1 to 9 years old, and seroprevalence by adult life is greater than 95%
  2. After primary infection, the virus establishes latency in dorsal root ganglia, and reactivation results in herpes zoster (shingles)
  3. VZV CNS infection (encephalitis or vasculopathy) can occur during primary infection or after viral reactivation from latency (shingles)
  4. During primary infection with VZV, acute cerebellar ataxia develops in 1 in 400 children younger than 15 years old
52
Q

What can happen after primary infection with varicella zoster virus?

A

Acute disseminated encephalomyelitis or ADEM can occur in 1/2500 cases.

53
Q

What are some characteristics of ADEM?

A
  1. The basic CSF profile in ADEM is typical for infectious encephalitis, including a pleocytosis with a predominance of lymphocytes, a normal glucose, and a normal or elevated protein
  2. VZV encephalitis is caused by vasculopathy
  3. Diagnosis of VZV vasculopathy can be made by presence of VZV-specific antibody or PCR of VZV DNA in CSF
  4. Major symptoms include fever, headache, drowsiness, seizures and coma.
54
Q

Varicella virus zoster infection can also cause what?

A

Meningitis - in about 8% of cases.

55
Q

How is Varicella zoster virus infection treated?

A

Acyclovir.

56
Q

What other viral infections can induce ADEM?

A

Viral infections thought to induce ADEM include influenza virus, enterovirus, measles, mumps, rubella, varicella zoster, Epstein Barr virus, cytomegalovirus, herpes simplex virus, hepatitis A, and coxsackievirus; while the bacterial infections include Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, and beta-hemolytic Streptococci

57
Q

What are some characteristics of HCMV (human cytomegalovirus)?

A

HCMV is a ubiquitous human virus, with a 90% to 100% antibody seroprevalence in adults

Transmitted via body fluids saliva, genital secretions, blood transfusions, and organ transplants

HCMV causes acute infection and reactivation disease from latent virus

Primary infection with HCMV is often clinically silent, may produce a mononucleosis syndrome

Neurologic complications from HCMV infection in adults
include retinitis, encephalitis, and neuropathy, occurring
in immunocompromised hosts

HCMV is also an important cause of congenital infections

58
Q

Congenital complications of HCMV infection include what?

A

Low birth weight, microcephaly, seizures, petechial rash similar to the “blueberry muffin” rash of congenital rubella syndrome, and moderate hepatosplenomegaly (with jaundice). Though severe cases can be fatal, with supportive treatment most infants with CMV disease will survive. However, from 80% to 90% will have complications within the first few years of life that may include hearing loss, vision impairment, and varying degrees of mental retardation.

59
Q

HCMV infection looks like what on histology?

A

Infected neurons and glial cells enlarge and develop cytoplasmic and nuclear inclusions that look like Owl eyes.

60
Q

What is the relationship between HCMV and AIDS?

A
  1. CMV encephalitis occurs in immunocompromised patients due to AIDS or transplantation
  2. In AIDS, CMV encephalitis occurs when the CD4+ cell count is less than 50cells/mm3
  3. 4.The CSF in patients with CMV encephalitis is nonspecific with mild lymphocytic pleocytosis and mild elevation in CSF protein
  4. HIV-associated CMV ventriculoencephalitis has a median survival of 42 days
  5. Diagnosis is confirmed by amplification of CMV DNA from CSF by PCR
  6. Recommended initial treatment for CMV neuroinvasive disease includes the combination of gancyclovir and foscarnet
61
Q

What are important properties of Epstein Barr virus?

A
  1. Primary EBV infection can be asymptomatic, or can result in a mononucleosis syndrome characterized by cervical lymphadenopathy, exudative pharyngitis, and splenomegaly
  2. CNS disease occurs in ~1% of EBV infectious mononucleosis cases and can cause, meningitis, encephalitis, transverse myelitis, and Guillain-Barré syndrome
  3. The frequency of EBV as a cause of encephalitis is unknown, although it has been reported to account for approximately 10% of childhood encephalitis cases
  4. Patients with EBV encephalitis present fever, headache, altered consciousness, seizures, and focal neurologic deficits
62
Q

What are some characteristics of HHV-6 virus?

A
  1. HHV-6 is a ubiquitous viral infection of T lymphocytes that causes a spectrum of disease on primary infection
  2. Causes exanthem subitum (roseola) in infants, febrile seizures, and lymphadenopathy syndromes
  3. Virus then becomes latent and can periodically reactivate to cause disease
  4. HHV-6 is recognized as a cause of encephalitis in immunocompromised adults, particularly patients with allogeneic bone marrow transplants (hematopoietic stem cell transplants)
  5. Patients typically have CSF lymphocytic pleocytosis, elevated protein, and normal glucose.
63
Q

Describe the diagnosis and treatment of HHV-6 encephalitis.

A

Diagnosis is typically made by CSF PCR or serum serology

Treatment of HHV-6 encephalitis is similar to that of CMV CNS infections.

Generally, HHV-6 is resistant to acyclovir therapy, but is responsive to ganciclovir and foscarnet

64
Q

List some vector borne causes of encephalitis.

A
The Arboviruses:
California encephalitis virus (La Crosse virus)
West Nile virus
St. Louis encephalitis
Eastern equine encephalitis
Western equine encephalitis
Venezuelan equine encephalitis
65
Q

What are some important properties of California encephalitis virus?

A
  1. CE is an arbovirus (arthropod-borne virus) mosquito
  2. CE subtype that causes encephalitis most often is La Crosse virus LACV
  3. ~70 cases/year; most cases in summer in children < 16 years old
  4. Occurs mainly on the East coast - especially the Northeast
66
Q

What are some characteristics of infection by California encephalitis virus?

A
  1. Severe headache, fever, stiff neck, vomiting and convulsions
  2. Half the patients develop seizures
  3. Mortality rate is 1% (aseptic meningitis) most recover completely
  4. Diagnosis is usually made serologically for IgM or IgG
  5. Seropositive individuals protected from re-infection
  6. No vaccine or effective drugs
67
Q

What are some important properties of West Nile virus?

A
  1. Arbovirus transmitted by bite of mosquitoes, birds (crows) susceptible
  2. Children and elderly at higher risk
  3. Virus inoculated into blood, spreads via monocytes/macrophages, brain is the target organ
68
Q

What are some characteristics of infection by West Nile virus?

A
  1. Less than 1% are symptomatic with serious neurological illness
  2. Symptoms range from flu-like to encephalitis
  3. Headache, nausea, high fever, malaise, myalgia, backache, neck stiffness
  4. No vaccine or specific treatment for WNV infection
  5. Diagnosed by the detection of virus-specific IgM in the serum or CSF
69
Q

What are some important properties of St. Louis encephalitis?

A

1.2.Arbovirus transmitted by mosquitoes that bite infected birds (no symptoms)
Outbreaks occur throughout US in late summer and early fall
3.Mainly affects US

70
Q

What are some characteristics of infection by St. Louis encephalitis?

A
  1. SLE symptoms range from flu-like febrile illness to encephalitis
  2. More serious neuroinvasive infections headache, nausea, high fever, malaise, myalgia, backache, neck stiffness
  3. Mortality rate from 3 – 30% with elderly at risk
  4. SLE serodiagnosis of IgM in serum or CSF
71
Q

What are some important properties of Eastern equine encephalitis virus?

A
  1. EEE is an arbovirus
  2. Mosquitoes transfer virus from wild birds (reservoir) to humans
  3. 33% mortality rate, 0 – 4 cases per year, outbreaks can occur
  4. Epizootics in horses have occur regularly in the United States
72
Q

What are some characteristics of infection by Eastern equine encephalitis virus?

A
  1. Severe headaches, nausea, vomiting, fever; changes in mental status, seizures an coma occurs
  2. Survivors left with brain damage
  3. Diagnosis by isolating virus or detecting rise in antibody titer
  4. No antiviral or vaccine available (one available for horses)
73
Q

What are some important properties of Western equine encephalitis virus?

A
  1. WEE is an arbovirus, primarily seen west of Mississippi and South America
  2. Mosquitoes transfer virus from wild birds (reservoir) to humans
  3. 2% mortality rate, 5 - 20 cases per year
74
Q

What are some characteristics of infection with Western equine encephalitis?

A
  1. Illness similar to EEE but less severe
  2. Diagnosis by isolating virus or detecting rise in antibody titer
  3. No antivirus or vaccine available (available for horses)
75
Q

What are some important properties of Venezuelan equine encephalitis virus?

A
  1. VEE is an arbovirus
  2. Mosquitoes transfer virus from equines (reservoir) to humans
  3. Although predominantly a disease found in South and Central America, VEE has spread to the United States
76
Q

What are some characteristics of infection with Venezuelan equine encephalitis virus?

A
  1. Healthy adults develop flu-like symptoms, high fever, headache
  2. Those with weakened immune systems can die
  3. There is currently a vaccine available for both humans and horses
  4. In the U.S., only at risk military and laboratory personnel are vaccinated
77
Q

Poliovirus infection can include CNS involvement. What are some characteristics of this?

A
  1. The most common clinical form is abortive poliomyelitis, which is a mild, febrile illness characterized by headache, sore throat, nausea, and vomiting
  2. Nonparalytic poliomyelitis manifests as aseptic meningitis with fever, headache, stiff neck
  3. In paralytic poliomyelitis, flaccid paralysis is the predominant finding, but brainstem involvement can lead to life-threatening respiratory paralysis
  4. Painful muscle spasms also occur, motor nerve damage is permanent
  5. In paralytic polio, the meninges and brain parenchyma (meningoencephalitis) are involved
  6. If the spinal cord is also involved, the term meningomyeloencephalitis is often used
78
Q

What are some important properties of Poliovirus?

A
  1. Transmitted by fecal-oral route
  2. Paralytic polio remains high in developing countries
  3. Only 1% of infections are clinically apparent
79
Q

Describe some characteristics of Poliovirus infection.

A
  1. Initial replication: oropharynx and small intestine (nausea & vomiting)
  2. Disease ranges from asymptomatic to abortive, nonparalytic, and paralytic poliomyelitis
  3. Poliomyelitis (polio) is an acute viral infection of the meninges and the motor neurons of the spinal cord and the brainstem.
  4. Eradicated from Western hemisphere (Salk and Sabin vaccines)
  5. Still endemic to Nigeria, Pakistan and Afghanistan
  6. Diagnosis: Paralytic poliomyelitis may be suspected in individuals with acute onset of flaccid paralysis; recovery of poliovirus from a stool sample or a swab of the pharynx
80
Q

What is AIDS dementia?

A

AIDS-related dementia may result from HIV infection of the macrophages and microglial cells of the brain

Patients with this condition may undergo a slow deterioration of their intellectual abilities and exhibit other signs of a neurologic disorder

These symptoms are similar to the signs of the early stages of Alzheimer disease

Neurologic deterioration could also result from infection with one of the many opportunistic infections

81
Q

What are some characteristics of AIDS dementia?

A

In late stages of HIV infection, the most common neurologic complication is a subacute or chronic HIV encephalitis presenting as a form of dementia

Formerly called AIDS encephalopathy or encephalitis, but it is now generally referred to as the AIDS dementia complex

Estimated that only 3 percent of AIDS cases present in this manner

Frequency is far higher, close to two-thirds, after the constitutional symptoms and opportunistic infections of AIDS have become established

In children with AIDS, dementia is more common than all opportunistic infections, more than 60 percent of children eventually being affected

82
Q

Describe how AIDS dementia progresses and what lab findings may be associated.

A

Slowly progressive dementia (loss of retentive memory, inattentiveness, language disorder, and apathy) abnormalities of motor function

The dementia evolves, over a period of months; survival after the onset of dementia is generally 3 to 6 months but may be longer if treated

The CSF of patients may be normal or show only a slight elevation of protein content

HIV can be isolated from the CSF

Evidence of CMV infection may occur but evidence indicates that the AIDS dementia complex is a result of direct infection with HIV

83
Q

What are some important properties of Rabies virus?

A
  1. Rabies virus the only medically important Rhabdovirus
  2. Broad host range, infects all mammals
  3. Transmitted by the bite of a rabid animal (bats, raccoons, skunks)
  4. <10 cases/year in US (dog vaccination); ~50,000 worldwide
84
Q

What are some characteristics of Rabies virus infection?

A
  1. Incubation phase: 2 weeks to year
  2. Prodrome phase: Fever, nausea, headache, spread to CNS from muscle
  3. Neurologic phase: Hydrophobia, anxiety, paralysis, coma, death
  4. Following bite of rabid animal administer vaccine and human rabies IgG
  5. Diagnosis: cytologic detection of inclusion bodies (Negri bodies) or immunochemical detection of viral antigen in brain tissue
85
Q

Rabies virus infection involves the CNS - how?

A

Rabies infection of an animal causes secretion of the virus in the animals saliva, and is spread though biting

Virus remains at the site of infection (muscle) for days to months before CNS involvement

The virus eventually infects nerve endings by binding to receptors on neurons (Rabies virus travels by retrograde axoplasmic transport to the dorsal root ganglia and the spinal cord.)

The virus disseminates from the CNS via afferent nerves to the salivary glands and other tissue

After the virus invades the brain and spinal cord encephalitis develops and neurons degenerate

86
Q

What is the progression of the CNS involvement of Rabies virus?

A

Following the incubation period (60-365 days!) symptoms include fever, malaise, headache, fatigue, and gastrointestinal symptoms.

Hydrophobia is common and results from the pain associated with swallowing water.

Seizures and hallucinations are common, paralysis may occur which may lead to respiratory failure.

Following the neurologic phase the patient becomes comatose then death occurs due to neurologic and pulmonary complications.

87
Q

In what phase of Rabies infection is the virus detectable in serum and the CNS?

A

The neurologic phase.

88
Q

Describe Creutzfeldt-Jakob disease (CJD).

A

Prions are infectious proteins that cause degeneration of the CNS

Prion diseases are disorders of protein conformation, in humans called Creutzfeldt-Jakob disease (CJD) (1 case/million people)

CJD typically presents with dementia, ataxia, myoclonus, is relentlessly progressive, and generally causes death within a year of onset

It usually affects people aged 45–75, most commonly appearing in people between the ages of 60–65, 5-20 year incubation period

Prions reproduce by binding the normal cellular isoform of the prion protein (PrPC), stimulating conversion of PrPC into disease-causing isoform (PrPSc)

Prions are devoid of nucleic acid; all infectious agents possess genomes that direct the synthesis of their progeny

89
Q

Describe the ways a person might contract CJD.

A

CJD is the most common of the human prion diseases

There are three types of CJD:

  1. sporadic, also called spontaneous, for which the cause is not known
  2. familial, also called genetic or inherited, which is due to a defect in the prion protein gene
  3. acquired, which is transmitted by infection due to exposure to the infectious prion from contaminated meat, or from transplant of contaminated tissues or use of contaminated instruments during surgical procedures
90
Q

Describe the neuropathology of CJD.

A

On light microscopy, the pathologic hallmarks of CJD are spongiform degeneration

Classic histologic appearance is spongiform change in the gray matter

The spongiform changes occur in the cerebral cortex and many regions of the brain

The presence of many round vacuoles from one to 50 μm

These deficits progress over months to a state of dementia characterized by memory loss, impaired judgment, and decline intellectual function

Abnormalities in cerebrospinal fluid are subtle and rarely helpful

91
Q

How would a histopathology slide of CJD brain tissue look?

A

It would show a spongy appearance.