CNS Infections- PML

Question 1

Progressive Multifocal Leukoencephalopathy (PML) is

Answer 1

an uncommon, subacute, progressive demyelinating disease of the CNS

Question 2

Etiologic agent is a _________

Answer 2

papovaviruses / belonging to the Papovaviridae (naked dsDNA viruses with icosahedral symmetry)

Question 3

Polyomaviruses (subclass of papovaviruses) contain 3 human agents:

Answer 3

1. JC virus
2. BK virus – Polyomavirus hominis type 1
3. SV40

Question 4

________ are also members of the papovavirus family.

Answer 4

Human papillomaviruses (HPV)

Question 5

In the immunocompetent, PML causes a common, asymptomatic infection, and 60-90% of the adult population are ___________

Answer 5

seropositive for BK virus

Question 6

Each virus persist lifelong in the _________

Answer 6

kidney (BK and JC) and B lymphocytes (JC)

Question 7

A fatal disease is most often associated with some underlying disorder of the immune system. JC and BK viruses are reactivated by ___________.

Answer 7

immunosuppression (any disease and/or treatment which causes profound T cell depression)

Question 8

BK Virus causes

Answer 8

1. a fatal opportunistic kidney (nephropathy) reactivation disease in some renal transplant patients with a loss of graft function occurring in 50% of cases.
2. a severe urinary tract disease in advanced HIV/AIDS patients

Question 9

JC Virus causes

Answer 9

rare opportunistic CNS reactivation disease in advanced HIV/AIDS patients older adults, & people on Natalizumab

Question 10

PML was first human demyelinating disease shown to be __________

Answer 10

caused by a virus

Question 11

Pathogenesis: JC virus invades ______ and infects oligodendrocytes. Virus replication in oligodendrocyte nuclei (intranuclear inclusion) causes __________. Virus shed from infected oligodendrocytes spreads to contiguous cells, thus extension of infection occurs along __________. Also infects and causes an abortive infection in ________, in which morphologic features resembling ________ are present.

Answer 11

brain

cell dysfunction and death (lytic infection)

myelin tracts

astrocytes

neoplasia (glioblastomas)

Question 12

JC viral genes are present in many (>70% of all) __________

Answer 12

pediatric brain tumors

Question 13

Subcortical white matter is most affected with multiple foci of myelin destruction and shows (4 features in subcortical white matter during PML infection)

Answer 13

1. absence of oligodendrocytes
2. abnormal (bizarre-shaped) astrocytes,
3. sparing of neurons and their axons,
4. enlarged oligodendrocytes with intranuclear inclusion are present at the periphery of demyelination

Question 14

During PML (JV virus) infection, inflammatory cells are _________.

Answer 14

sparse or absent

Question 15

PML evolves rapidly (3-6 month from onset to death), S/S are

Answer 15

Very diverse: muscle weakness, ataxia, cognitive and speech defects, visual loss and other sensory abnormalities

Question 16

Differential

Answer 16

1. HAD
2. Primary brain tumor: EBV- associated primary CNS lymphoma (PCNSL)
3. Toxoplasmosis encephalitis
4. PML
5. Cryptococcal meningoencephalitis

Question 17

Diagnosis: Neuroimaging - MRI detects _________

Answer 17

demyelinating lesions, esp. in the white matter

NOTE: can use clinical s/s, PCR of CSF and characteristic pathology on brain biopsy

Question 18

Treatment for PML

Answer 18

1. Cidofovir appears effective
2. HAART has had a (+) effect on incidence and severity of PML in AIDS pt

-If patient’s CD4 count is 100 cells/μL, prognosis is good if HAART is initiated

Question 19

Natalizumab is a monoclonal antibody was initially used for

Answer 19

highly active, relapsing–remitting multiple sclerosis; recalled because it was causing PML
-currently used for MS and Crohn’s pts who don’t respond to conventional therapy