CNS Infections - Cochran

Question 1

Describe the four routes of access that infectious agents may take to reach the brain.

Answer 1

Hematogenous - Either arterial or retrograde venous.

Local extension - eg Infected tooth

Neural route - eg Retrograde neuronal

Direct implantation - eg Surgical infection

Question 2

Many CNS infections are caused by pathogens that are specific to nervous tissue (“neurotropic”); describe some mechanisms by which this may occur.

Answer 2

Viral-specific receptors on nervous tissue

Capsular proteins (unclear how this facilitates neurotropism)

Viral spread along nerves (eg Herpes)

Question 3

What are the classic symptoms in meningitis?

Describe the most likely pathogens in meningites with a <24hr, 2-7day, or longer history.

Answer 3

Headache, nuchal rigidity, fever, photophobia, and clouded consciousness.

Hyperacute (<24hr) = Meningococcus

Acute (2-7days) = Other bacteria (Strep pneumo, HiB)

Subacute/chronic (>1 week) = Tuberculosis, syphilis

Question 4

Bacterial meningitis is highly dangerous and often fatal. Describe its gross and microscopic morphology.

What will a CSF yield?

Answer 4

Purulent exudate under the meninges, with vasculitis and congestion. Abundant neutrophils in subarachnoid space.

High neutrophils and low glucose. Bacteria should be present for gram staining, PCR or culturing.

Question 5

Brain abscesses can be seen in bacterial or viral CNS infections. Describe the abscess and the usual culprits.

Answer 5

Focus of infection circumscribed by fibroblasts/collagen and gliosis. (“Ring-enhanced”)

Strep and Staph species are most common. Weird bugs seen in the immunocompromised… (toxo, nocardia, listeria, fungi, TB)

Question 6

Infection of the brain parenchyma is known as _____. It may be caused by bacteria, viruses, or fungi. The three major bacterial causes are ___________.

Answer 6

Encephalitis; bacterial eg Tuberculosis, Syphilis, and Borrelia (lyme disease).

Question 7

Who is most often afflicted by TB encephalitis?

Describe its gross and histologic morphology.

Answer 7

The immunocompromised mostly, but ~15% of anyone with acute TB.

Mostly involves the brain base. Granulomas (“Tuberculomas”) feature classic pattern with epithelioid histiocytes and giant cells surrounding caseating core.

Question 8

What is tuberculosis of the spine known as?

What are its complications?

Answer 8

Pott’s disease (TB spondylitis)

Epidural abscesses in the spinal cord cause cord compression, vertebral collapse.

Question 9

Tertiary syphilis has three major forms.

Describe paretic neurosyphilis. Include gross and micro morphologies!

Answer 9

In paretic neurosyphilis, the meninges thickens causing brain atrophy and subsequent cognitive and motor impairment. CSF outflow is impaired.

Histology reveals lymphocytosis with plasma cells and microglia.

Question 10

Tertiary syphilis has three major forms.

Describe Meningovascular syphilis. Include gross and micro morphologies!

Answer 10

Heavy involvement at the base of the brain causes arteritis–collagenous thickening of wall & vascular compromise cause infarcts, hydrocephalus. Focal deficits seen.

Looks like a fibrinoid necrosis…

Question 11

Tertiary syphilis has three major forms.

Describe Tabes Dorsalis. Include morphology and presentation!

Answer 11

Involvement of the posterior cord (cuneate and gracile) cause loss of discriminative touch and proprioception (leads to broad shuffling gait). Lightning pains & paresthesias also experienced.

Myelin stains reveal demyelination in the posterior columns.

Question 12

Viral CNS infections are generally (more/less) severe than bacterial.

Describe the three characteristic microscopic findings of viral encephalitis.

Answer 12

Less severe! (Rule of thumb; always exceptions eg Rabies)

1. Perivascular lymphocytic infiltrate.
2. Microglial nodules (rod-shaped)
3. Neuronophagia (inflammatory cells surround neuronal remnant)

Question 13

HSV-1 is one of the most common viral encephalites.

It has a distinctive clinical presentation, describe it.

What will imaging reveal?

Answer 13

Affects mood, memory, and behavior. Makes you act “crazy”!

MRI will reveal foci of involvement mostly in the frontal or temporal lobes.

Question 14

What are the complications of herpes simplex encephalitis?

How can it be diagnosed?

Answer 14

Congestion, swelling, hemorrhagic necrosis.

PCR for viral DNA, or check histology for Cowdry Type A bodies.

Question 15

HSV-2 and VZV are less likely to cause encephalitis than HSV-1. Describe who generally would get encephalitis from them.

Answer 15

HSV-2: Neonates infected through birthing.

VZV: Older patients experiencing reactivation (scarring, painful; lymphocytes present in nerve ganglia)

Question 16

What is the most common *viral *encephalitis in AIDS patients?

Describe its morphology.

Answer 16

Cytomegalovirus.

Forms microglial nodules and giant cells containing either intranuclear or intracytoplasmic inclusions.

Subacute presentation!

Question 17

When are arboviral meningoencephalitides seen? Why?

Name a few types.

How can you tell them apart?

Answer 17

Warmer months; transmitted by arthropods such as mosquitoes.

West nile, eastern, venezualan, St. Louis, California

PCR is the only way.

Question 18

What CNS cell is targeted by HIV?

What is the classic histological sign?

Answer 18

Microglia.

Microglial nodules with HIV-containing multinucleated giant cells.

Question 19

Contrast between the appearance of HIV meningitis and encephalitis.

Answer 19

Meningitis: Acute flu-like illness.

Encephalitis: Cognitive & behavioral deterioation, dementia, ataia, and tremor. Diffuse atrophy with lymphocytosis, patchy demyelination, and astrocytosis.

Question 20

Progressive multifocal encephalopathy is caused by ____, a type of ____virus, which infects ________ in immunocompromised hosts. It usually results from (primary/reactivating) infection.

Answer 20

Caused by JC virus, a polyoma virus, infecting oligodendrocytes (note oligodendrocyte inclusions). Reults from re-activation following immunosuppression.

Question 21

Fungal encephalitis tends to hit the immunocompromised. Try to name 6-7 pathogens that can cause it.

Which are especially prone to cause vascular involvement?

Answer 21

Histo/Blasto/Coccidioides, Candida, Aspergillus, Cryptococcus, and the Mucormycoses.

Aspergillus & Mucor, watch out for infarcts.

Question 22

Cryptococcus is known as an AIDS-defining illness. Describe how it infects patients as well as its morphology.

Answer 22

From soil or bird guano, hits the lungs and then spreads hematogenously. Causes meningeal thickening as well as cysts/abscesses (characteristic “soap bubble” appearance with clear perimeter on PAS)

Question 23

Name two pathogens that can present with a CSF that features lymphocytosis, high protein, and reduced glucose.

Answer 23

Cryptococcus

Tuberculosis

Question 24

There are a host of parasites that can cause encephalitis in even the immunocompetent. We discuss toxoplasma, but try to name 3-4 others.

Answer 24

Plasmodium

Trypanosoma (sleeping sickness)

Taenia solium (neurocysticercosis)

Amoebae (eg Naegleria Fowleri)

These are awesome, and also horrifying.

Question 25

Who is generally affected by toxoplasma gondii? What is the source?

Answer 25

The immunocompromised, very young, very old, and also pregnant women. Cats are the definitive host (fecal spread), but also may be found in meat of intermediate hosts (sheep, pig).

Question 26

Describe the gross and microscopic morphology of toxoplasmosis.

Answer 26

Gross: Multiple localized necrotic lesion, appreciable on MRI. Microscopic: Liquefactive necrosis with organisms moving freely (tachyzoites) and within pseudocysts (bradyzoites)

Question 27

What is an empyema? Where are they seen? What bugs are to blame? How do they arise?

Answer 27

An accumulation of pus in a preexisting cavity or potential space (unlike abscesses) In addition to in the pleura, in the epidural and subdural spaces. Bacteria (staph, strep) Local extension of infectious process (sinusitis, OM, trauma, osteomyelitis, surgery)

Question 28

Recall: What is the most common viral encephalitis seen in HIV? Fungal encephalitis? What is the most common mass-forming CNS lesion in HIV?

Answer 28

Cytomegalovirus. All of them, but classically Cryptococcus. Toxoplasmosis.

Question 29

Are prion diseases, inherited, idiopathic, or transmissible? Which form is most common?

Answer 29

All three. Idiopathic (sporadic) \>\> Inherited (15%; eg Gerstemann-Straussler-Scheinker disease or fatal familial insomnia) \>\> Acquired (iatrogenic, kuru, vCJD)

Question 30

Describe the pathophysiology of Creutzfeld-Jakob disease. What about variant Creutzfeld-Jakob disease?

Answer 30

A mutated PrP protein (PrPsc) forms beta-sheets and accumulates as amyloid. It induces normal PrP (PrPc, a membrane protein of unclear function) to also misfold. Variant CJD presumably works the same way, and it seemed to correlate with a spike of Bovine Spongiform Encephalopathy in cattle.

Question 31

Describe the presentation of CJD. How is its outlook?

Answer 31

Rapidly progressive dementia, ataxia, and myoclonus. EEG shows slow (1-2sec) triphasic waves, and MRI shows increased signal from the basal ganglia. CSF is often normal. Bad outlook, most die within 1 year. No treatment or conclusive diagnostic options (besides post-mortem biopsy)

Question 32

How does CJD appear on biopsy?

Answer 32

Neurons take up the misfolded PrP, forming inclusions that appear clear and vacuolated. This makes the tissue look spongy, "spongiform".

Question 33

This is a histologic finding that is characteristic of a particular viral infection. Name the infection, and name what's pictured. Hint: These are eosinophilic, not basophilic.

Answer 33

Cowdry Type A bodies - Herpes encephalitis (Thought of owl's-eye inclusions? Those are basophilic)

Question 34

A 40yo male patient presented with a CD4+ count of ~50. He developed convulsions, hallucinations, and finally died of a hemorrhagic infarct. Pictured is his brain post-mortem. What is the diagnosis?

Answer 34

Cryptococcus neoformans; the classic soap-bubble lesions are presented and the patient clearly has AIDS.

Question 35

A 30yo female patient presents with complaint of headache, fever, and drowsiness. You aren't eager to biopsy her brain yet, but if you did, you would find this. What is pictured, and what other findings would you also expect based on the differential?

Answer 35

This is neuronophagia, a histologic sign of viral encephalitis. The other two signs are lymphocytosis (perivascular and/or parenchymal), and microglial nodules.