True-ish; once symptoms start, rabies is fatal - After bite but when pre-symptomatic, can administer immunoglobulin and rabies vaccination

6/24- Infections of Nervous System II Flashcards by Kathryn Kudlaty

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

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Histopathology of viral encephalitis?

Lymphocyte perivascular cuffing
Microglial nodules
Gliosis
Necrsosis
Inclusions (intranuclear or cytoplasmic)

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What is Cowdry A?

Larger nuclear inclusions that push chromatin to outside

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What are some intranuclear inclusions?

Cowdry A
Cowdry B
Ground glass

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What are some cytoplasmic inclusions?

Negri bodies (rhabdo/rabies!)

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What is this?

Lymphocytic vascular cutting

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What is this?

Microglial nodule

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What is this? Indicates what diseases?

Cowdry A intranuclear inclusions

Chromatin pushed to rim of nucleus

Seen in:

CMV
Herpes
Varicella zoster
Measles (SSPE)

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What is this?

Negri body

Intracytoplasmic inclusion
Eosinophilic

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

Poliovirus (acute)

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

JC virus (PML)

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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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What is this?

Herpes simplex encephalitis

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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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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

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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

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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

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What causes poliomyelitis?

Enterovirus

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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

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What is this?

Poliomyelitis with spinal grey matter hemorrhage and edema

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Characteristics of arboviruses? Transmission? Features? Symptoms?

Study These Flashcards

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

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

Study These Flashcards

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

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

What diseases of the CNS are associated with HIV?

Study These Flashcards

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

What is PML? Histologic? Involves what cells?

Study These Flashcards

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

What is this?

**Myelin loss seen in PML** (Progressive Multifocal Leukoencephalopathy) (little areas in bottom right) - Can be multifocal (like MS) - Symptoms depend on neurons de-myelinated

What is this?

**Intranuclear inclusion**s in oligo's in PML

What is this?

Pleomophic astrocyte in PML

What is this?

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

What is this?

**Bradyzooite** (cyst form of organism) - **Toxoplasmosis**

Toxoplasmosis may indicate what?

AIDs (may be presenting system)

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

What is this?

Taenia solium (ingested from undercooked pork or food contaminated with feces) - Can see scolex

What is this?

Worm surface on right; GI on left

Neurocystercercosis may cause what?

Seizures!!

What is this?

Neurocystercercosis

When does neurocystercercosis cause problems?

**When the worm dies** (no longer cloaked from immune system) - Edema - New onset focal neurological deficit - Possibly seizures

T/F: Neurocystercercosis should always be treated

**False**; not all cases need treatment

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)

T/F: Prions are killed by traditional disinfectants

**False**; must denature protein (fairly robust)

Relative incubation period of prion diseases?

Extremely long (even years - decades)

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

**False**; prion diseases have no antigenic or inflammatory responses

What is this?

**Spongiform change in CJD** - Cortex, deep matter of diencephalon.. - May see some reactive gliosis, but NO lymphocytic/PMN reaction or conventional inflammation

What is this?

Extracellular collection of PrP protein- prion plaque

What is this?

Immunohistochemistry showing **accumulation of polymerized prion protein in CJD**

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

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

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)

What is this?

- **BSE as the source of vCJD** - VERY **prominent plaques** ("florid plques") because of such high prion load

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

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

6/24- Infections of Nervous System II Flashcards

(50 cards)