infectious disease of CNS Flashcards
infections in the NS
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
How does infection manifest in the brain
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
Neurotropism
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
Meningitis
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,
Probablitity of bacterial pathogens based on age
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
meningitis antimicrobial treatment
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
Pathology of meningitis
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
Complications of bacterial meningitis
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
Bacterial meningitis neuropathology
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
h flue type b
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
conjugate Hib vaccinde development
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
Neisseria meningitidis (Nm)
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
Neisseria meningitidis diagnosis, pathology and prevention
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
Conjugate vaccines against N meningitidis
1000 people get meningococcal disease each yr 10-15% die, common in infants
Streptococci and meningitis
Usually alpha
B- kids
Group B streptococcus /strep agalactiae
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
Strep pneumoniae
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
Encephalitis vs meningits
Encephalitis- inflammation of the brain parenchyma associated with neurologic dysfunction
Meningitis- inflammation of the protective membranes covering the brain and spinal cord - aka meninges
Encephalitis common causes
Enterovirus (coxsackie, echovirus, polio,), arbovirus
Influenza and
HSV 1 and 2
Sexual HIV, HSV 2 and syphilis
HSV and VSV encephalitis
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
aseptic meningitis
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
Viral encephalitis charachteristic microscopic pathology
Perivascular and parenchymal lymphocytic infiltrate
Microglial nodules
Neuronophagia (remanant of neuronal cell body), inflammatory cells
CMV
common opportunistic viral infection in AIDS pts
Herpes simplex encephalitis acute morphology changes
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
CMV encephalitis
Huge cell- with intracytoplasmic viral inclusion, intranuclear viral inclusion
Viral meningoencephalitis HIV infection in the CNS
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
HIV
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
VIRAL encephalitis- progressive multifocal leukoencephalopathy
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
bacterial emningoencephalities Tuberculosis in the CNS
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
TB osteomyelitis
spondylitis (potts disease)
Granulomatous process involves vertebral bodies and discs, causes epidural abcess, cord compression, vertebral collapse, epidural extension of the granulomatous inflammation
Syphilis
Treponema pallidum- General paresis (thick meningges)-meningo genral – tabes dorsalis
Lymphocytes in the
tabes dorsalis
chronic inflammation on dorsal roots and ganglia, lightning pains or parasthesias in affected roots, evenullay loss of pistion and vibration sense
cryptococcosi
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
Brain abcesses
usually from poor dentition
Necrosis and inflammation in center the early fibrous wall surrounded by astrocytosis
direct inoculation
Toxoplasmosis
reactivation of latent disease
with brain abcess
MRI with multiple lesions with perivascular surrounding
Brain biopsy, T gondii
Primary CNS Lymphoma- EBV reactivation
