infectious disease of CNS

Question 1

infections in the NS

Answer 1

Unique features of brain/spinal cord: BBB- protects from organisms, but also restricts immune system access, Rigid skull/vertebral canal- with inflammation–> swelling and neurologic damage

Types of infections:
Leptomeningeal inflammation: meningitis,
Parenchymal inflammation (Encephalitis/cerebritis/myelitis (spinal cord), when meninges and brain tissue are affected meningoencephalitis, Brain abcess

Subdural or epidural inflammation- subdural or epidural empyemas

Question 2

How does infection manifest in the brain

Answer 2

Routes of entrance-
Hematogenous spread- Arterial spread, retrograde venous spread - anastomotic connections between face veins and cerebral circulation, paravertebral venous plexus, batson

Local extension- air sinuses, infected tooth

Neural route- extension from PNS to CNS

Direct implantation- trauma, iatrogenic

Question 3

Neurotropism

Answer 3

A specific affinity for nervous tissue
Mechanisms-
viral specific receptors on brain cells-
poliovirus for motor neurons of anterior horns of spinal cord
Mumps virus for ependymal cells lining ventricles

Capsule proteins that adhere to meninges and possess antiphagocytic properties- Group B strep ad E coli

Viral spread along nerves- herpes simplex virus, rabies, varicella zoster virus

Question 4

Meningitis

Answer 4

Infection of the meninges and subarachnoid space
Typical clinical manifestations- fever, headache, nuchal rigidity, altered mental status

Bacterial vs viral (8-12 p, if bacterial it will have higher pressure)
Bacteria will have more neutrophils, viral will have more lymphocytes
PMNs will eat up glucose, and produce proteins,

Question 5

Probablitity of bacterial pathogens based on age

Answer 5

the number one cause is Strep pneumonia,
Neisseria is more common in younger pts
H flu more common in asdults
Group B strep is in neonates

Listeria is common in elderly

Question 6

meningitis antimicrobial treatment

Answer 6

Drug penetration into the CSF reamains critically important
entry of antimicrobial agents into CSF is also enhanced by drugs that have a low molecular weight, low degree of ionization at physiologic pH, high lipid solubitility and low degree of protein binding
Want a drug that is bactericidal
Consider adjuctive dexamethasone depending on the organism

Question 7

Pathology of meningitis

Answer 7

Hyperacute (<24 hrs)- Meningococcal meningitis, sparse inflammation, numerous organisms, congestion

Acute (1 week, tb, syphilis, often brain parenchyma also affected, lymphocytes, plasma cells, macrophages appear in exudate

Question 8

Complications of bacterial meningitis

Answer 8

Brain infarcts, secondary vasculitis (inflammation of the blood vessels in the meninges) , phlebitis (inflammation of a vein may occur and cause infarct of underlying brain tissue

Question 9

Bacterial meningitis neuropathology

Answer 9

Brain damage during meningitis is mostly attributalbe to the side effects of the host inflammatory response

Streptococcus pneumoniae, the major pathogen of meningitis, activates leukocyte that release proteolytic enzymes that can damage host tissue

Problem- early signs of meningitis can resemble the symptoms of a flu- rapid diagnosis is key

No group b strep conjugate vaccine

Question 10

h flue type b

Answer 10

number one cause of meningitis worldwide, but we have a vaccine

6 serovars of H flu (a-f) with respoect to the the capsular polysaccharide
A- Glucos
B- ribose and ribitol
C- galactose, ets

Virtually all invasive H flu infections are due to type B

antibodies to theis polyribosylribose phosphate capsular atigen play a role in protection from infection by HiB

Maternal anitbodies in the first 3 months are bactericidal, , upt to 3 yrs old

Question 11

conjugate Hib vaccinde development

Answer 11

1st gen Hib vaccine, purified capsular polysaccharide of Hib in 1985, 90% effecting in kids older than 2 yrs
Problem- polysaccharides are poor immunogens, stimulate T independent Ab, poor immunologic memory

2nd gen hib vaccine- Prp protein conjugate, with vaccine, Hib has limited clinical concern in the US

Conjugate vaccine stimulate a T cell dependent anitobody response and a memory response

Question 12

Neisseria meningitidis (Nm)

Answer 12

Nm is gram- negative diplococci and is human specific pathogen responsible for septicemia and meningitis

2 virulence factors-
Lipopolysaccharide- component of the outer membrane (endotoxin) which stimulated TLR system to produce fever, spetic shock, and hemorrhage (inflammation)

Polysaccharide capsule- prevents host phagocytosis, and allows evasion of host immune response

Question 13

Neisseria meningitidis diagnosis, pathology and prevention

Answer 13

Diagnosis- gold standard isolate Nm as gram negative diplococci from CSF, culture CSF on chocolate agar, pcr

Path- fatality risk approaches 15% within 12 hrs of infection, so initiate testing as quickly as possible DONT wait for results before initiating antibiotic therapy, persons with confirmed Nm infection should be hospitalized for treatment with antibiotics (IV)

Prevention- Nm can be transmitted - people around infected person should get antibiotics

Question 14

Conjugate vaccines against N meningitidis

Answer 14

1000 people get meningococcal disease each yr 10-15% die, common in infants

Question 15

Streptococci and meningitis

Answer 15

Usually alpha

B- kids

Question 16

Group B streptococcus /strep agalactiae

Answer 16

Gram positive, beta hemolytic, group B lancefield typing, common inhabitant of pharynx, vagina, neonatal infections, meningitis (mortality in full term 2-8 %, while in pre term infants may rise to 30%)

No licesed vaccine- screen for group B in pregos at 35-37 weeks, selective prophylaxis abs for group B during labor for women testing postive for group b strep

At risk- premies, early membrane rupture, previous infant with group B strep disease

Question 17

Strep pneumoniae

Answer 17

elongated gram positive cocci arranged in pairs (diplococci) and short chains

virulence factors- colonize (surface protein adhesions), invasive ( spreads into normally sterile tissue), inflammatory (stimulate TLR inflammatory response, teichoic acid), Host resistance- polysaccharide capsule

Disease pneumonia, sinusitis and otitis media, meningitis, and bacteremia

PCV 13 to youngsters, PCV13 conjugate- for adults

CEFTRIAXONE

Question 18

Encephalitis vs meningits

Answer 18

Encephalitis- inflammation of the brain parenchyma associated with neurologic dysfunction
Meningitis- inflammation of the protective membranes covering the brain and spinal cord - aka meninges

Question 19

Encephalitis common causes

Answer 19

Enterovirus (coxsackie, echovirus, polio,), arbovirus

Influenza and

HSV 1 and 2

Sexual HIV, HSV 2 and syphilis

Question 20

HSV and VSV encephalitis

Answer 20

Epidemiology- biphasic age distribution (peaks at 5-30 yrs and then greater than 50

Etiology-
HSV: majority of cases are caused by HSV1 in children and adults (in adults, reactivation of disease likely mechanism for disease or neuroinvasion from the olfactory bulb, primary infection)
VZV- reactiviation of disease although primary infection can occur

Presentation- fever, altered mental status, headache most common

Diagnosis- clinical suspicion CSF analysis (high protein, lymphocytes, RBCs- xanthochromia), CSF PCR (high sensitivity, and specificity though false negative can occur, for HSV or VZV, MRI (temporal lobe, or temporal and frontal can be negative), EEG- localized spike and slow wave pattern

Treatment - high dose Acyclovir

Question 21

aseptic meningitis

Answer 21

aseptic- much less fulminant/slower than bacterial meningitis and less severe symptoms, Summer and early fall, lymphocytic infiltrate in meninges

Usually viral- Arboviruses, Enterovirus (most common)echovirus coxsackie

Question 22

Viral encephalitis charachteristic microscopic pathology

Answer 22

Perivascular and parenchymal lymphocytic infiltrate

Microglial nodules

Neuronophagia (remanant of neuronal cell body), inflammatory cells

Question 23

CMV

Answer 23

common opportunistic viral infection in AIDS pts

Question 24

Herpes simplex encephalitis acute morphology changes

Answer 24

Congestion, swelling, hemorrhagic necrosis of temporal lobes, insula, cingulate gyri, orbital cortex

Necrotizing hemorrhagic inflammation
Intranuclear inclusions- Cowdry type A (chromatin pushed out to the periphery

Question 25

CMV encephalitis

Answer 25

Huge cell- with intracytoplasmic viral inclusion, intranuclear viral inclusion

Question 26

Viral meningoencephalitis HIV infection in the CNS

Answer 26

HIV meningitis- Presents during acute flu like illness at time of seroconversion

HIV encephalitis/ leukoencephalopathy- present in 75% of autopsied HIV patients
Clinicall- AIDS dementia complex, complex cognitive and behavioral deterioration, eventually dementia ataxia and tremor
Slight Diffuse atrophy
Classic lesion- microglial nodule containing multinucleated microglial cells (contain HIV virus), also perivascular lymphocytes patchy demyelination and astrocytosis

Question 27

HIV

Answer 27

RNA retrovirus, microglia are most common cell infected in CNS by HIV, CNS is a major target of HIV infection, types of involvement (HIV meningitis, HIV encephalitis/leukocephalopathy, vacuolar myelopathy)

Multinucleated giant cell with beads of nuclei on the periphery

Question 28

VIRAL encephalitis- progressive multifocal leukoencephalopathy

Answer 28

Occurs in immunosuppressed hosts (often AIDs pt), caused by JC virus, polyomavirus, infects oligodendroctes multifocal ring enhacing lesions evident in white matter on imaging and at autopsy

Most have serologic evidence of prior JC virus infection by adolescence JC virus is reactivated with immunosuppression
Rapidly progressive usually fatal

Oligodencrocyte inclusion

Question 29

bacterial emningoencephalities Tuberculosis in the CNS

Answer 29

Mycobacterium TB- CNS involvement in 10-15% HIV infection is risk factor

Meningoencephalitis- most common form of TB in CNS, CSF- elevated pressure and protein , decreased glucose, lymphocytic pleocytosis (cultures for afb are positive in 50%), PCR for TB now always performed

SS- headach, lethargy, confusion, vomiting
Meninges contain lymphocytes, macrophages, granulomas with extension into underlying brain

Question 30

TB osteomyelitis

Answer 30

spondylitis (potts disease)
Granulomatous process involves vertebral bodies and discs, causes epidural abcess, cord compression, vertebral collapse, epidural extension of the granulomatous inflammation

Question 31

Syphilis

Answer 31

Treponema pallidum- General paresis (thick meningges)-meningo genral – tabes dorsalis

Lymphocytes in the

Question 32

tabes dorsalis

Answer 32

chronic inflammation on dorsal roots and ganglia, lightning pains or parasthesias in affected roots, evenullay loss of pistion and vibration sense

Question 33

cryptococcosi

Answer 33

Neoformans in the soil and bird dropings affects immnocompd,

Meningitis with or without brain parenchymal cysts, abcesses, lymphocytes and high protien norm or reduced glucose
India ink
assay for presence of crytococcal antigen is more sensitive

Meningitis- thickened meninges particularly over the sulci, multiple intra cysts, also called soap bubbles (secondary to gelatinous capsular material capsular material)

Periodic acid schiff, with clear

Question 34

Brain abcesses

Answer 34

usually from poor dentition
Necrosis and inflammation in center the early fibrous wall surrounded by astrocytosis

direct inoculation

Question 35

Toxoplasmosis

Answer 35

reactivation of latent disease

with brain abcess

MRI with multiple lesions with perivascular surrounding

Brain biopsy, T gondii

Primary CNS Lymphoma- EBV reactivation