Neurological infections lecture

  1. Major concerns
    • development of drug resistant organisms
    • increasing number of immunicompromised populations
    • rising number of diseases previously considered rare.

    education, surveillance, development of new drugs and vaccines are essential to prevent and treat resurging and emerging neurological infectious diseases.
  2. Unique aspects of CNS infections
    localization of the infection dictates the clinical presentation e.g. whether it is in the CNS or PNS

    • The brain is an immune privileged organ
    • - blood brain barrier
    • - no lymphoid cells--only resident immune cells are innate, during infection, get more (adaptive)
  3. Emerging neurological infections
    • 1. Variant CJD--vairant of mad cow, dementing disease of old people, started showing up more in younger
    • 2. Nipah virus encephalitis-- from bats to pics to the food supply to humans
    • 3. West Nile virus encephalitis-- RNA virus
    • 4. Enterovirus 71 encephalitis--in kids in Taiwian

    are usually xenotropic (can grow in a foreign host) and RNA viruses (mutate more readily)
  4. zooinosis
    infections coming from other species
  5. Determinants of emerging infections
    • Providing a pool of susceptible populations--increasing gloab populations and contact between humans
    • Altering forms of human or animal contact--e.g. eating animals
    • Societal mores--increased sexual contact, day car, agricultural clearing, irrigation (possible mvmt of virus)
    • Global movement of animals and animal products
    • Medicinal practises--blood transfusions, transplants, drug resistant microbes
  6. Evolution of west nile
    • -isolated in blood of febrile Uganda women
    • -endemic in kids in Egypt and Sudan, epidemic in Isreal, S.Africa, India
    • -cancer patients experimentally infected in NY
    • -some in Franch
    • -Algerian epidemic
    • -Southeast Romania, 10% fatality
    • -Epidemic in Russia, NYC outbreak--spreads to NA
  7. Clinical principles of neurological infections
    • - few infectious pathogens cause neurological disease, but there are the big three: HIV, TB and malaria
    • - fever with acute (sudden onset) neurological signs are indicators of neurological infections
    • - intra and extra neurological parameters looked at by a team
    • - treatment with specific and supportive interventions,
    • - prognosis on basis of severity of actue neurological impairment and defined by protracted morbidity (how long till estimated death)
  8. Principles of infection
    neuroinvasion, neurotropism, neurvirulence, neurosusceptibility
    neuroinvasion --pathogent specific but does not necessarily lead to disease virulence-- capable of entering the CNS

    neurotropism--pathogen specific to anatomical site and cell type (capable of infecting NS, preferential)

    neurovirulence--neurological disease related with or without pathogen benefits (capable of causing disease in the NS)

    neurosusceptibility--age, immunocompetence, genetically dependent (refers to the host's vulnerability to virus-induced neurological disease and is dictated by host age, species, immune status, and genetic background)
  9. Common neurological infections (first world)
    • viruses--HSV (herpes) VZV (chicken pox), HIV, rabies
    • bacteria--N meningiditis, Borreliosis (limes disease)
    • fungal--crypto, neoformans,
    • parasite--malaria
  10. Neural cells
    CNS--neurons, astrocytes (most abundant, divide all throughout life, limited to NS), oligodendrocytes (make myelin, can regenerate a bit) , endothelial cells (line blood vessels) and microglia(first to respond)/ macrophages (respond to damage, from bone marrow, constantly replenished through circulation)-- BBB

    PNS--neurons, Schwann cells, macrophages--BBB

    neurons are the targets of disease, the brain is not completely isolated, lymphocytes check NS, macrophages in come from blood
  11. Human endogenous retroviruses (HERVs)
    • --have been entering human genome for millions of years and accumulating, 8% of genome
    • --implicated in autoimmune disease like MS
    • --can be turned on but can't be submitted.
  12. Sources of HIV 1 and 2
    • Cameroon, Congo, Central African Repulic
    • first jump from monkeys to humans about 100 years ago

    • jumped by killing and eating non human primates (chimps)
    • when virus changes host, behaviour of virus changes
  13. Course of HIV
    Primary infection (4-8 weeks), seroconversion, asymptomatic period (10 years), AIDS (immunosuppression) (1-4 years), treatment phase (>10 years)

    lymphocytes decrease during asymptomatic and are very low during AIDS period but increase with treatment
  14. HIV associated dementia
    • Affects 10-20% of HIV patents , usually after development of AIDS and leads to poorer survival rates
    • Usually preceeded by minor cognitive motor disorder (MCMD)
    • risk factors--extremes of age, mutations in CCR5 and APOE genes , polymorphisms in promoters of TNF and MCP1 genes

    AKA AIDS dementia complex, HIV dementia, AIDS encephalopathy
  15. HIV associated dementia early symptoms/progression
    behaviour--apathy, depression, agitation

    cognition--memory loss, concentration, mental slowing

    motor functioning-- unsteady gait, leg weakness, poor coordination, tremor

    some advance quickly, quality of life decreases
  16. HAD--neuroimaging
    • large ventricles, atrophy, white matter chagnes , highly active antiviral retroactive therapy (HAART)
    • perivascular cuffing, multinucleated giant cells,
    • density of virus highest in subcortical features, huntingtons/parkinsons--subcortical dementias
  17. Treatment for HIV related neurocognitive disorders
    • HAART- dependent on dementia severity
    • neuroprotective drugs, NMDA receptor antagonists , growth hormomes, SSRIs etc
  18. HIV
  19. sensory
  20. HIV
  21. HIV sensory neuropathies
    • systematic bilateral burning neuropathic pain, feet>>hands
    • bowel/bladder and gait effects
    • axonal loss, degeneration
    • inflammation within the nerve or dorsal root ganglion
  22. Herpes Simplex encephalitis (HSE)
    • 1-2 infections per 1 million people
    • immunocompromised patients not at greater risk
    • retinal necrosis
    • EEG useful for seizure activity only
    • often fatal unless treated
    • motrality reduced to 20% with acyclovir
    • doesn't tend to reoccur

    • lives in trigeminal neuronal cell bodies
    • can affect temporal lobe and cause temporal seizure

    causes swelling, lymphocytes surround blood vessles, disrupt BBB, let serum in, cause swelling
Card Set
Neurological infections lecture
dr power, march 9th