6/24- Infections of Nervous System II Flashcards Preview

Term 5: Neuro > 6/24- Infections of Nervous System II > Flashcards

Flashcards in 6/24- Infections of Nervous System II Deck (50):
1

General Features of Viral Infections

- Portal of entry: enteric, hematogenous, traumatic

- Spread: via peripheral nerve or across BBB to CNS

CSF:

- Mononuclear cells

- Increased protein

- Normal glucose (what really differentiates from bacteria)

- No organisms ID'd on gram stain or standard culture

2

Histopathology of viral encephalitis?

- Lymphocyte perivascular cuffing

- Microglial nodules

- Gliosis

- Necrsosis

- Inclusions (intranuclear or cytoplasmic)

3

What is Cowdry A?

Larger nuclear inclusions that push chromatin to outside

4

What are some intranuclear inclusions?

- Cowdry A

- Cowdry B

- Ground glass

5

What are some cytoplasmic inclusions?

Negri bodies (rhabdo/rabies!)

6

What is this?

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Lymphocytic vascular cutting

7

What is this? 

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Microglial nodule

8

What is this? Indicates what diseases?

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Cowdry A intranuclear inclusions

- Chromatin pushed to rim of nucleus

Seen in:

- CMV

- Herpes

- Varicella zoster

- Measles (SSPE)

9

What is this?

Q image thumb

Negri body

- Intracytoplasmic inclusion

- Eosinophilic

10

What disease(s) are indicated by Cowdry B bodies?

Poliovirus (acute)

11

What disease(s) are indicated by Ground glass inclusions?

JC virus (PML)

12

Herpes Simplex Encephalitis results in what? Histology? Latency?

- Hemorrhagic necrosis of temporal lobes (rapidly progressing)

- Cowdry type A intranuclear viral inclusions in neurons and glia

- Demonstrable with immunoperoxidase stains, in situ hybridization, PCR, or culture

- EM morphology: targetoid spheres

- Virus latent in sensory ganglia 

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13

What is this?

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Herpes simplex encephalitis

14

Characteristics of rabies?

DNA material?

Transmission?

Replication?

Symptoms?

Histology?

- RNA virus

- Contracted from bite of infected animal (bats, skunks, rarely dogs in US)

- Has been transmitted by corneal, solid organ, and tendon transplants!

- Virus replicates locally in skeletal muscle and muscle spindles; ascends to CNS via peripheral nerves

- Symptom free interval weeks-months

- Most start straight into encephalitis, but may be preceded by Guillain-Barre-like paralysis in some

- Intracytoplasmic neuronal inclusions: Negri bodies 

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15

T/F; rabies is fatal

True-ish; once symptoms start, rabies is fatal

- After bite but when pre-symptomatic, can administer immunoglobulin and rabies vaccination

16

Inclusions seen with arboviral encephalitis?

The epidemic associated arboviral encephalitides (Eastern equine, Western equine, St. Louis) DO NOT produce viral inclusion bodies and show only the non-specific histologic features

17

What is the most common form of seasonal or epidemic viral encephalitis?

West Nile encephalitis

- Most people are asymptomatic, but may be dangerous to young/elderly/immunocompromised

18

What causes poliomyelitis?

Enterovirus

19

Symptoms seen in poliomyelitis?

- Following ingestion, replicates in lymphoid tissue of intestine -> viremia

- Spinal cord involvement: loss of anterior horn cells/motor neurons

- Brainstem involvement: bulbar polio

20

What is this? 

Q image thumb

Poliomyelitis with spinal grey matter hemorrhage and edema

21

Characteristics of arboviruses? Transmission? Features? Symptoms?

- Arthropod vectors

- Often spread from birds

Other:

- Western, Eastern, and St. Louis strains

- Seasonal epidemics

- Don't produce viral inclusions

- Fairly rapidly progressive (days)

- Headache, delirium .... coma

- Potentially lethal to young/old

22

Characteristics of HIV (Human Immunodeficiency Virus) as it pertains to CNS?

- HIV enters the CNS early in the infection

- CNS involvement is a significant cause of mortality and morbidity

- Up to 50% of AIDS pts will have a neurologic complication

- > 80% have neuropathologic findings at autopsy

23

What diseases/conditions are caused by HIV in relation to the CNS?

What diseases of the CNS are associated with HIV?

HIV encephalitis

- Multinucleated giant cells, perivascular

- Dementia Vacuolar myelopathy

- Vacuolar degeneration of posterior and lateral white matter columns (looks like B12 deficiency)

Focal CNS Lesions Associated with HIV:

- Primary CNS lymphoma (driven by EBV)

- Progressive Multifocal Leukoencephalopathy (PML)

- Toxoplasmosis

24

What is PML? Histologic? Involves what cells?

Progressive Multifocal Leukoencephalopathy (PML)

- Papova virus (JC strain*) infection of oligodendrocytes and astrocytes

- "Ground galss" intranuclear inclusions in oligodendrocytes (myelin loss)

- Involvement of astrocytes as well- bizarre forms, pleomorphic enough to be mistaken for neoplastic

- Can cause gliomas in rodents, but not seen in humans

- Seen in AIDs/immunocompromised and MS pts treated with immunosuppressie drugs

*No connection between JC virus and CJD

25

What is this? 

Q image thumb

Myelin loss seen in PML (Progressive Multifocal Leukoencephalopathy)

(little areas in bottom right)

- Can be multifocal (like MS)

- Symptoms depend on neurons de-myelinated

26

What is this? 

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Intranuclear inclusions in oligo's in PML

27

What is this? 

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Pleomophic astrocyte in PML

28

What is this?

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Toxoplasmosis

- Shaggy, ring-enhancing lesion; looks kinda like a tumor

29

What is this? 

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Bradyzooite (cyst form of organism)

- Toxoplasmosis

30

Toxoplasmosis may indicate what?

AIDs (may be presenting system)

31

What are 2ndary HIV nervous system infections (Opportunistic infections)?

Don't try to memorize...

- Cytomegalovirus

- Varicella Zoster

- Herpes Simplex

- Progressive Multifocal Leukoencephalopathy

- Candidiasis

- Cryptococcosis

- Toxoplasmosis

- Amebiasis

- Mycobacterial infection

- Neurosyphilis

- Bacterial infection

32

What is this? 

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Taenia solium (ingested from undercooked pork or food contaminated with feces)

- Can see scolex

33

What is this?

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Worm surface on right; GI on left

34

Neurocystercercosis may cause what?

Seizures!!

35

What is this? 

Q image thumb

Neurocystercercosis

36

When does neurocystercercosis cause problems?

When the worm dies (no longer cloaked from immune system)

- Edema

- New onset focal neurological deficit

- Possibly seizures

37

T/F: Neurocystercercosis should always be treated

False; not all cases need treatment

38

What causes spongiform encephalopathies?

Prion- transmissible agent

- 27K-32K MW (pretty significant)

- Transformation of alpha helix rich protein to pathologic beta sheet form (PrPc -> PrPsc-- scrabie)

39

T/F: Prions are killed by traditional disinfectants

False; must denature protein (fairly robust)

40

Relative incubation period of prion diseases?

Extremely long (even years - decades)

41

T/F: Prion diseases have antigenic/inflammatory response due to the abnormally folded protein

False; prion diseases have no antigenic or inflammatory responses

42

What is this?

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Spongiform change in CJD

- Cortex, deep matter of diencephalon..

- May see some reactive gliosis, but NO lymphocytic/PMN reaction or conventional inflammation

43

What is this? 

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Extracellular collection of PrP protein- prion plaque

44

What is this? 

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Immunohistochemistry showing accumulation of polymerized prion protein in CJD

45

Characteristics of Creutzfeld-Jakob Disease (CJD)? Cause? Symptoms

May be either:

- Sporadic (85%)

- Inherited (15%)- inherited mutation of prion gene (PrNP) on chrom 20; AD

Clinical quartet:

- Dementia (but rapidly progressing! over months)

- Myoclonus (in part of dz, not throughout)

- Periodic EEG (corresponding to myoclonus; massive hypersynchronous firing with jerks)

- Rapid disease progression

WARNING: broader clinical spectrum and longer incubation increasingly being recognized

46

What is iatrogenic CJD?

Acquired from:

- Use of human growth hormone

- Placement of intracerebral electrodes

- Corneal grafts

- Dural grafts

Ex) brain biopsy for supposed vasculitis in CJD pt with instruments used on 6 other pts without prion decontamination

47

What is new variant CJD (vCJD)?

- Recognized by a surveillance committee set up to monitor the BSE "mad cow" epidemic

- Epidemiology, morphologic, and molecular data indicate that BSA is the source of

vCJD Differs from sporadic CJD:

- Younger pts (mean 26 yo vs. 65 yo)

- Longer duration of illness (12 mo vs. 4 mo)

- Initial Sx: psychiatric and/or sensory dysethesias in vCJD

- LACK periodic discharges on EEG (and no myoclonus)

48

What is this?

Q image thumb

- BSE as the source of vCJD

- VERY prominent plaques ("florid plques") because of such high prion load

49

Nuances of brain biopsy in CJD?

- No frozen section!

- Snap freeze 20 mg for Western blotting

- Formalin fixation x 24 hrs (preserves tissue but doesn't kill prion)

- Immerse in 100% formic acid x 1 hr (kills prion)

- Formalin fx x 24 hrs and process routinely

50

Dr. Goodman's Dietary Advice

When in Europe, Japan, and Middle East:

- Eat no products of hoofed things (except swine)

- Sausage, brains, and meat pies are out

- Fish and fowl are okay

When in the US

- So far, so good on beef

- Theoretic risks with deer and elk