#11 Neurological Infections Flashcards
What are three major concerns regarding neurological infections?
- The development of drug resistant infectious agents
- The increasing number of immunocompromised human populations
- The rising number of diseases previously considered rare
What are 4 things that are essential to preventing and treating neurological infections?
Education, surveillance, development of new drugs, and development of new vaccines
What are the 6 neurological infectious agents? What are the “big 3” global neurological infections?
Bacteria, viruses, prion, fungus, protozoa, and helminth
Big three: HIV/AIDS, tuberculosis, malaria
What are two unique aspects of CNS infections?
- Localization of infection dictates the clinical presentation (CNS, brain, spinal cord, PNS)
- Brain is an immune privileged organ meaning that it was its own immune system, via the BBB and innate immunity (macrophages and neutrophils) and adaptive (CTL and Abs)
What are 5 determinants of emerging infections?
Susceptible populations, disrupted environments, altered human and animal contact, medical practices, and rapid/frequent movement of animals and humans
TRUE OR FALSE: Neurological infections are different from other infections because the location in the CNS/PNS effects presentation. NI syndromes are a continuum
TRUE
How do infections invade the CNS in meningitis?
Via the meninges, which include the dura matter, the arachnoid matter, and the pia matter. This invasion causes clinical symptoms of meningitis
What is the common algorithm for neurological infections?
Presentation
Infection risk
physical exam
localization?
Brain imaging and blood tests
Management
Prognosis
What are the cells within the CNS? What about the PNS?
CNS: neurons, axons, astrocytes, oligodendrocytes, endothelial cells, microglia/macrophages and is protected by the BBB
PNS: neurons, axons, Schwann cells, macrophages protected by the blood-nerve barrier
What is the most abundant cell in the brain?
Astrocytes: responsive, proliferative, talk to all cell types, in BBB, permissive and responsive to bacteria and viruses
INNATE immune response in brain
What are oligodendrocytes essential for?
CNS myelin formation, have a large nucleus, structural stability, susceptible to viruses
What are microglia responsible for in the CNS/brain?
They are the brains phagocytes, they are the most dynamic cell and the fight infections all over the CNS
INNATE
Activated microglia play a role in brain inflammation, normally they are immune suppressors, but when they are activated they show phagocytosis, chemotaxis, antigen presentation, cytotoxicity, morphological changes, proliferation and respiratory burst
What is the role of neurons in the CNS?
They transmit messages, they are stable and exhibit no turnover, they are permissive to infections, they are not dynamic like glial cells
What are neurotropic retroviruses?
Viruses that integrate into the host DNA, once you have it you can never get rid of it
HIV 1/2 and HTLV 1/2 are human retroviruses
SIV: green monkey retrovirus
What are human endogenous retroviruses?
HERVS constitute about 8% of the human genome, and they are integrated into the human genome but are NOT replication competent.
They are implicated in the pathogenesis of cancer and autoimmune diseases
Several HERV glycoproteins are important for placental placement
What is an example of a HERV-W envelope glycoprotein?
Syncytin-1 RNA and protein, they are increased in demyelinating lesions in MS and induce endoplasmic reticulum damage stress in glial cells
How did HIV 1 spread to humans?
Its method of transfer is non-human primate to human xenoinfection (infection of one species by an organism that usually infects another)
Spread by chimpanzees (Pan troglodytes)
What is the HIV 1 disease course?
Primary infection, asymptomatic at first as the immune system becomes exhauseted by fighting the infection, once exhausted enough it becomes AIDS, and once you start antiretroviral therapy the presence of viruses in the blood decreases drastically
What are three different neurological side effects of HIV?
Opportunistic infections: due to immunosuppressants, the immune system is susceptible to other infections
ART associated disorders: the medications given for HIV can be toxic and cause infections
Primary HIV Neurological symptoms: symptoms of the primary HIV infection
What was the effect of ART on viral HIV DNA, RNA, and integrated DNA?
No impact, it did not change the DNA despite lowering viral load, this suggests that the brain is a reservoir for infections.
What is HAND?
HIV associated neurocognitive disorders
Affects 20-30% of patients with an HIV infection, usually after the development of AIDS, and heralds a poorer prognosis
It is a spectrum disorder defined by Asymptomatic neurocognitive impairment, minor cognitive motor disorder, and HIV associated dementia
What are the four hallmarks of HAND?
Memory loss, motor abnormalities, neuropsychiatric dysfunction, immunodeficiency
You also get larger ventricles and white matter changes, this is semi-reversible but not totally, can use cognitive enhancing drugs
What is a hallmark of HIV disease progression and HAND?
Chronic immune activation
What is the etiology of encephalitis in humans?
Associated with multiple infectious and non-infectious etiologies, and some even have unidentified etiologies (50%)
There is an increasing indidence of viral encephalitis, however 45% of encephalitis cases remain without a definitive diagnosis
