CNS Infections

Question 1

what are some general key differences in CSF between CNS bacterial and viral infections?

Answer 1

Glucose is low and neutrophils and protein are high in bacterial infections

lymphocytes and monocytes will be high in viral infections, protein in CSF is slightly elevated

Question 2

what are the most common enteroviruses that cause encephalitis?

Answer 2

Coxsackie A and B viruses

Echo virus

Question 3

describe the infectious course of enteroviruses - pathogenesis

Answer 3

Virus replication begins in the intestinal
mucosa and lymphoid tissue of the tonsils
and pharynx

spreads by viremia to
cells of the lymph nodes, spleen and liver -> replicates some more

cytolysis - burst out of cells they infect

immune response is IgA and IgG antibodies

Question 4

what are the syndromes associated with coxsackie viruses?

Answer 4

Hand, foot and mouth disease

herpangina

pleurodynia

myocardinal and pericardial infections

aseptic meningitis

Question 5

what are the ways the viruses get into the CNS?

Answer 5

Transported over in infected white blood cells - hematogenous dissemination?

invading peripheral nerves and traveling into the CNS - neuronal retrograde dissemination

infecting cells that form anatomical barriers

Question 6

what’s the most common cause of encephalitis?

Answer 6

encephalitis - infection of the brain parenchyma

viral is more common than bacterial and fungal

often accompanied by viral meningitis

Question 7

how does viral meningitis present?

Answer 7

inflammation of the subarachnoid membrane

fever, headache, nuchal rigidity and photophobia

CSF - lymphocytic pleocytosis

viral meningitis is typically a milder disease than bacterial or fungal meningitis

Question 8

what classes of viruses are the most common causes of non-sporadic aseptic meningitis?

Answer 8

enteroviruses

arboviruses - responsible for epidemics

Question 9

acid fast stain

Answer 9

TB

Question 10

India Ink stain

Answer 10

cryptococcus neoformans

Question 11

how is viral meningitis diagnosed?

Answer 11

evaluation of the CSF profile - lymphocytic pleocytosis, with normal protein, glucose

negative acid fast and india ink stains

negative cultures

Question 12

what’s the primary diagnostic test for viral CNS infections?

Answer 12

PCR of the CSF

this is how you can tell the exact virus that’s infecting

Question 13

describe the pathogenesis of enteroviruses

Answer 13

they spread by the oral-fecal route and divide in the GI tract.

They get out of the GI tract through peyer’s patches

viremia - virus travels in blood to lymph nodes. spleen and liver to replicate some more (symptoms)

viral replication damages the cell -> signs and symptoms of disease

IgA is the primary immune defense

Question 14

hand, foot, and mouth disease

Answer 14

coxsackievirus virus syndrome - serotype A16

painful red blisters in the mouth, palms of hands and soles of feet.

self limited infection

Question 15

herpangina

Answer 15

infection of the throat - rid ringed blisters and ulcers on tonsils and soft palate

fever, sore throat, pain on swallowing and vomiting

self-limited, coxsackie A

Question 16

pleurodynia

Answer 16

bornholm disease - coxsackie B virus

acute illness with painful spasms in the muscles of the chest and upper abdomen, fever and pain ^

Question 17

myocardinal and pericardinal infection

Answer 17

coxsackie B virus

sporadic occurance in all ages, life threatening in newborns

in newborns -> febrile illness and sudden heart failure

Question 18

aseptic meningitis - coxsackieviruses

Answer 18

rarely encephalitis also occurs

can occur with petechiae/rash, full recovery in absence of encephalitis

can also be caused by echoviruses

Question 19

arboviruses - how do they spread? In what ways can they present?

Answer 19

arthropod borne viral illness - spread by mosquitos and ticks, ofter get the infection themselves from a bird

often presents with few flu-like symptoms but can lead to dangerous encephalitis

can also present with hemorrhagic fevers which are life threatening

complications of encephalitis - coma, permanent brain damage and death

Question 20

compare and contrast eastern and western equine encephalitis?

Answer 20

Both are spread by mosquito, with a bird intermediate, and infect horses as well as humans

eastern is rare and in the eastern US, 1/3 of people with clinical encephalitis die from this virus infection

western is in the west of the US and canada, patient presents with flu-like symptoms, anorexia, altered mental status and sign of meningeal irritation

Question 21

st. louis encephalitis

Answer 21

SLE - leading cause of epidemic flavivirus encephalitis - most common mosquito transmitted disease in continental US

illness severilty ranges from febrile headache to meningoencephalitis

case fatality ratio of 5-15%

Question 22

west nile virus

Answer 22

started in queens, 1999

infection can be asymptomatic or mild febrile disease but can also be severe and fatal

migratory birds play a role in disease spread

most common is desert-y areas of the US (SoCal., Az) and the midwest.

Question 23

La Crosse Encephalitis

Answer 23

most cases are reported in children, 75 cases/yr

life cycle includes bird and small mammals (chipmunks and squirrels) Lives over winter in mosquito eggs - vector borne

Question 24

Colorado tick fever

Answer 24

.

Question 25

Colorado tick fever

Answer 25

most common tick borne viral disease in the US animal reservoirs - small mammals symptoms - headache, retro-orbital pain and muscle/joint aches dog tick - prevalent in the Rocky Mountains

Question 26

Japanese encephalitis

Answer 26

widespread in Asia, most important cause of arbovirus encephalitis worldwide life cycle involves aquatic birds and mosquitos there is a formalin-inactivated vaccine available

Question 27

diagnosis of an arbovirus infection

Answer 27

using symptoms - headache, drowsiness and fever (less common are vomiting and stiff neck) CSF lymphocytic pleocytosis, normal Glucose, normal or mildly elevated protein definite diagnosis is based on IgM presence in CSF (this means the BBB has been broken) also, PCR testing.

Question 28

powassan encephalitis and deer tick virus

Answer 28

Ixodid ticks powassan is rare but mostly found in the north east. Deer tick virus is a relative of powassan - also rare cause of encephalitis but is becoming more common in Hudson Valley region of NY serum/CSF detection using virus-specific monoclonal antibodies

Question 29

HSV 1

Answer 29

Cowdry type A intranuclear inclusion bodies - from viral replication infects epithelial cells at site of entry - mouth is most common - cold sores visualized by Tzanck Smear using Giemsa stain lives in the trigeminal ganglion where it stays latent, gets reactivated and replicated and reinfects.

Question 30

HSV2

Answer 30

Cowdry type A intranuclear inclusion bodies - from viral replication genital herpes - latency in sacral ganglia also forms painful fluid filled cysts - result of viral replication identified with a Tzanck smear via the giemsa stain

Question 31

HSV Encephalitis

Answer 31

typically caused by HSV 1 upon reactivation the virus can spread to the lips (cold sores) but also to the brain or the meninges most common cause of sporadic viral encephalitis adults and pediatric

Question 32

diagnosis of HSV Encephalitis

Answer 32

postive Tzanch smear - reveals the syncytia forming cells wit the cowdry type A intranuclear inclusions CSF - lymphocytic pleocytosis, elevated protein but normal glucose, erythrocytes in CSF - disrupted/damaged brain tissue.

Question 33

Varicella-Zoster Virus

Answer 33

chicken pox in primary infection subsequent infections causes shingles/herpes zoster requires cell-mediated immunity for control of infection herpes zoster infects dermatomes - forms a painful rash (postherpatic neuralgia) more common in elderly, also causes viremia

Question 34

diagnosis of VZV infection

Answer 34

veiwing of syncytia and Cowdry type A intranuclear inclusions microscopically or Tzanck smear

Question 35

JC virus - infection in immunocompetent vs immunocompromised individuals? How is it diagnosed?

Answer 35

human polyoma virus viral replication in host nucleus virus enters vis the respiratory tract, spreads to kidneys, B cells and monocytes. Latent infection people with competent immune systems. reactivation in immunosuppresed - most commonly AIDS patients and organ transplantation causes PML - progressive multifocal leukoencephalopathy: subacute demyelinating disease diagnosed by symptoms, MRI/CT, PCR amplification of CSF

Question 36

Rabies virus

Answer 36

acute encephalitis in all warm-blooded hosts reservoirs historically were dogs but now seen in raccoons, bats and rats - transmitted by salvia (bite) or through mucous membranes - eyes, nose, mouth travels to CNS by way of sensory or motor neurons and forms cyoplasmic inclusion bodies known as Negri Bodies

Question 37

Lymphocytic choriomeningitis

Answer 37

arenavirus flu-like disorder followed by meningitis found in rodents: gray house mouse and hamster - they excrete the virus in urine, feces, semen and nasal secretions. Spread by contamination

Question 38

Prion Diseases -Transmissible Spongiform Encephalopathies

Answer 38

isoform of a normal protein that causes the protein to change shape and aggregate. the altered protein is insoluble - amyloid-like plaques neuronal degeneration Creutzfeldt-Jakob disease is most common rare are kuru, gerstmann-straussler syndrome and fatal familial insomnia CJD is diagnosed by immunoassay

Question 39

treatment of HSV

Answer 39

acyclovir, valacyclovir, | penciclovir and famciclovir

Question 40

pathogenesis of the primary infection of VZV?

Answer 40

primary infection starts in the mucosa of the respiratory tract, replication happens in the lungs, disseminates through the bloodstream and causes the fluid-filled chicken pox vesicles. Travels on sensory nerves of the skin to lye latent in the DRG.

Question 41

Zostavax

Answer 41

vaccine for shingles can only be given to those over 60 who had not had shingles before similar to chicken pox vaccine

Question 42

Variant CJD

Answer 42

Variant creutzfeild jakob disease is thought to be caused by consumption of BSE infected meat/ prion protein can be detected in lymphoid tissue occurs in young patients - psychiatric manifestations and ataxia CJD is diagnosed by immunoassay

Question 43

whats the most common cause of bacterial meningitis in newborns?

Answer 43

s. agalactiae l. monocytogenes e. coli

Question 44

whats the most common cause of bacterial meningitis in the elderly?

Answer 44

L. monocytogenes

Question 45

whats the most common cause of bacterial meningitis in infants and toddlers? (up to 60mo)

Answer 45

S. pneumoniae

Question 46

presentation of acute bacterial meningitis

Answer 46

isolated clinical event. fever, stiff neck, headache, global/focal CNS dysfunction, petechia on trunk and lower extremities. causes elevated intracranial pressure because of blocked CSF flow due to pus accumulation fatal without treatment - immediate Ab followed by CSF gram stain

Question 47

what antibiotics are good treatments for bacterial meningitis?

Answer 47

beta-lactams despite being polar cefotaxime/ceftriaxone dexamethasone - h. influenzae chemoprophlyaxis for immediate contact

Question 48

which antibiotics are NOT for treating bacterial meningitis? WHY?

Answer 48

erthromycin tetracycline cefoxitin 1st generation cephalosporins why? because these polar compounds cannot cross the BBB

Question 49

streptococcus pneumoniae - treatment, transmission and virulence factors

Answer 49

lives in throat and nasopharynx spread by aerosol droplets infection is purulent and associated with severe neurologic deficits and 21% mortality often resistant to beta-lactams - treat with vancomycin 2 vaccines are available, the 13 valent is typically given to children and the 23 valent to elderly. bacteria is encapsulated, contains IgA protease and pneumolysin

Question 50

neisseria meningitidis - treatment, transmission and virulence factors

Answer 50

colonizes healthy people, spread by aerosol droplets grows on blood agar encapsulated, IgA protease, B-lactamase host immunity complement systems is very important treatment with 3rd generation cephalosporins vaccines available for A, C, Y and W135 serotypes but none for B

Question 51

listeria monocytogenes - treatment, transmission and virulence factors

Answer 51

most prevalent in immunocompromised patients with high mortality in elderly and neonates. can be transmitted maternally through the placenta treatment with ampicillin salt and nitrite tolerant, can grow at low temperatures (4C) vireulence factor - listerolysin O and actin polymerization

Question 52

streptococcus agalactiase - group B

Answer 52

group B strept colonizes URT and GU tract acquired by neonates during pregnancy or birth no vaccine, treat with penicillin G Gram stain of CSF and PCR for organism identification increases risk for premature rupture of membranes. prolonged labor, preterm birth, disseminated maternal group B streptococcal disease and decreases maternal complement.

Question 53

chronic meningitis - bacterial causes

Answer 53

caused by latent TB activation bacilli gets into CSF, settles in subarachnoid space where it causes an intense type 4 hypersensitivity reaction causing inflammation around CN's leading to coma. Acid fast stain for identification - only positive a small percentage of the time --> PCR treated with several Abs

Question 54

Bacteria - brain abscess - what is it?

Answer 54

infection of the brain parenchyma can comes directly from paranasal sinuses, middle ear or mastoids. can happen from dental surgery, trauma (penetration/surgery) or spread from blood during acute bacterial endocarditis

Question 55

Bacteria - brain abscess - what causes it?

Answer 55

staph aureus anerobic and arobic microflora group A or B strept chronic - mycobacteria - TB

Question 56

bacteria - brain abscess - diagnosis and treatment

Answer 56

diagnosed by CT, MRI, aspiration of abscess treated with antibiotics - Methicillin/vancomycin, ceftriaxone/cefotaxime & metronidazole not always effective, still 10-20% mortality with treatment, fatal without.

Question 57

chronic meningitis - clinical presentation

Answer 57

meningeal infection with pleocytosis lasting more than 4 weeks Initial symptoms are headaches and fever. Progression - seizures, change in mental status, confusion, hallucinations, development of focal neurologic deficits, hydrocephalus and increased ICP Nuchal rigidity is either subtle or absent

Question 58

What type of microbial agents cause chronic meningitis?

Answer 58

fungal and parasitic microbes infection and progression into meningitis in opportunistic - immunodeficit or suppressed peoples

Question 59

cryptococcus neoformans

Answer 59

fungi - india ink stain (only fungus with capsule) presents as subacute meningoencephalitis with progression to fever and hydrocephalus Lab tech - Cryptococcal antigen latex agglutination

Question 60

What is the treatment for crypococcus neoformans caused chronic meningitis?

Answer 60

amphotericin B flucytosine - nucleoside analogue that inhibits replication by inserting itself into the growing strand.

Question 61

histoplasma capsulatum

Answer 61

rare - endemic in Ohio River Valley chronic meningitis presents with fever, oral lesions, hepatosplenomegaly and hydrocephalus lab diagnosis - seeing yeast cells inside macrophages, sometimes cultures, histoplasma polysaccharide antigen in urine/CSF/Blood

Question 62

Treatment of histoplasma capsulatem - chronic meningitis

Answer 62

amphotericin B

Question 63

Pseudallescheria - p. boydii

Answer 63

most common fungal agent of mycetoma in immunocompromised - meningitis, meningoencephalitis and brain abscesses organism acquired from polluted water, sewage and swamps near drowning victim resistant to amphotericin B

Question 64

taenia solium

Answer 64

parasitic pork tapeworm - neurocysticercosis chronic meningitis presents with seizures, obstructive cysts, and space-occupying lesions endemic in Mexico. South America and Asia Lab Diag - CT and lymphocytic pleocytosis with eiosinophils (CNS?)

Question 65

treatment of chronic meningitis causes by taenia solium

Answer 65

albendazole steroids analgesics anti-epileptic drugs surgical resection of lesions and placement of ventricular shunts

Question 66

angiostrongylus cantonensus

Answer 66

parasitic chronic meningitis rat lung worm - round worm endemic in Asia and Pacific Islands from ingestion of undercooked or raw shellfish or snails can incubate for up to a year presents with nausea, vomiting, neck stiffness and headaches that are global and severe. Rash with pruritus is also common (itchy) diag - history and CSF - peripheral eosinophilia no treatment

Question 67

Naegleria fowleri

Answer 67

Parasitic encephalitis Protozoan - thermophile Amebic meningoencephalitis - brain-eating disease fatal enters nose while swimming - freshwater in southern states, summer months, children and young adults are at highest risk altered level of consciousness and lost sense of smell lab diag - neutrophilic pleocytosis, motile trophozoites on wet mound of CSF, brain histopathology

Question 68

Balamuthia mandrillaris

Answer 68

parasitic encephalitis protozoan in soil of Central America entry - Cuts and wounds on skin or inhalation Granulomatous Amebic Encephalitis - often misdiagnosed as TB a) Subacute progressive disease with Space- occupying lesions b) Cranial nerve palsies c) Hydrocephalus lab DX - Serology and brain histopathology, Lymphocyte pleocytosis and depressed glucose, Real-time PCR of brain poor prognosis, high mortality and slow progression (2yrs)

Question 69

Baylisascaris procyonis

Answer 69

Raccoon roundworm (helminthes) caught by ingestion of eggs (contanmation) - eating dirt Lab Dx - eosinophillic pleocytosis, peripheral eosinophillia and deep matter abnormalities, serology on CSF/Serum mid-Atlantic, northeastern & Midwestern states & California

Question 70

Gnathostoma spp

Answer 70

round worm Eating undercooked or raw freshwater fish, eels, frogs, birds, & reptiles tropical and subtropical areas - Thailand and Japan Moves from skin to brain DX - microscopic ID or larvae in tissue and ELISA

Question 71

Entamoeba histolytica

Answer 71

Predominantly a GI disease Diagnosis: serology & PCR of brain abscess aspirate or CSF Treatment Metronidazole or tinidazole Followed by paromomycin or iodoquinol

Question 72

Schistosoma japonicum aka Bilharzia

Answer 72

blood fluke - not found in the US second highest impact worldwide after malaria - most devastating parasitic disease lives in fresh water snails Lab DX - Microscopic,, ELISA for anti-schistosomal Abs, granuloma formation in brain

Question 73

Paragonimus spp.

Answer 73

Lung fluke (flat worm) Ingestion of raw or undercooked crab or crayfish - rare in US but in Midwest (river raft in Missouri) P. kellicotti - Symptoms similar to TB Dx - microscopic examination of eggs and peipheral eosinophilia

Question 74

Parasites that can causes brain abscesses

Answer 74

Taenia solium Entamoeba histolytica Schistosoma japonicum Paragonimus spp

Question 75

fungi that can cause brain abscesses

Answer 75

aspergilliuss spp - bone marrow and transplants cryptococcus neoformans - T-cell immunity defects Neutropenia pts - Aspergillis, Mucor and Candida

Question 76

symptoms of brain abscesses

Answer 76

``` headache altered mental status focal neurologic findings fever nausea and vomiting seizure ```

Question 77

Labs of brain abscesses

Answer 77

``` peripheral leukocytosis Low serum Na+ platelet counts may be high or low elevated erythrocyto sedimentation rate elecated CRP ```

Question 78

Schistosoma japonicum - brain abscess treatment

Answer 78

praziquantel

Question 79

Paragonimus spp. - brain abscess -- Treatment

Answer 79

praziquantel