Lecture 9: Neurological Infections Flashcards
What are neurological infectious agents?
bacterium (e.g. tuberculosis)
virus (e.g. HIV)
fungus (e.g. cryptococcus)
protozoa (e.g. malaria)
prion (e.g. BSE)
helminth (e.g. cysticerosis)
What are the unique aspects of CNS infections?
localization of the infection dictates the clinical presentation (CNS vs. PNS), it makes a big difference were infection occurs, makes it distinct from other infections
brain is an immune privileged organ, blood-brain barrier protection (not an absolute road block), innate (macrophages, neutrophils) vs. adaptive (CTL and Abs) immunity
What are some of the common neurological infections?
viruses: HSV, VZV, HIV, WNV, rabies
bacteria: N. meningitides, S. pneumoniae, M. tuberculosis, Borreliosis (Lyme disease)
fungal: Cryptococcus neoformans, Histoplasmosis, Coccidiomycosis
parasite: Malaria, Toxoplasma gondi, Cysticercosis
What are the determinants of emerging infections?
susceptible populations: poverty, war, famine, immunosuppression
altered human and animal contact
disrupted environments: climate change and economic development
medical practices
rapid and frequent global movement of animals and humans
What is meningitis?
H/A, fever, nuchal rigidity +/- cranial neuropathies
meninges, spinal cord
What is encephalitis?
H/A, fever, confusion/altered behavior –> coma, seizure, focal signs
involves brain tissue
What is myelitis?
limb weakness, back pain, B&B dysfunction, sensory loss
spinal cord
What is abscess?
focal signs, fever, seizure
What is radiculopathy/neuropathy?
localized radicular pain, fever, weakness
What are the signs of meningitis?
Kernig’s sign: bent knee when lifted
Brudzinski’s sign: when neck is lifted up, knees bend
What are neural cells in the CNS?
neurons (+ axons)
astrocytes
oligodendrocytes (+ myelin)
endothelial cells and microglia/macrophages (protected by the blood-brain barrier)
What are the neural cells in the PNS?
neurons (+ axons)
Schwann cells
macrophages (protected by the blood-nerve barrier)
What are astrocytes?
the most abundant cell in the brain
contribute to blood barrier support other cells susceptible to viruses
What are the functions of microglia?
the brain’s phagocytes
immune “sensors”
What are the functions of activated microglia?
phagocytosis
chemotaxis
antigen presentation
cytotoxicity
morphological changes
proliferation
respiratory burst
What are human endogenous retroviruses (HERVs)?
HERVs constitute ~8% of human genome
HERVs are integrated into the human genome but are NOT replication competent
HERVs are implicated in the pathogenesis of cancer and autoimmune diseases
What is Syncytin-1?
Syncytin-1 RNA and protein are increased in demyelinating lesions in multiple sclerosis and induce endoplasmic reticulum (ER) stress in glial cells
What other diseases associated with NeuroHIV?
opportunistic infections
ART-assoc’d disorders
primary HIV neurological syndromes
What are HIV-associated neurocognitive disorders (HAND)?
affects 25% of patients with HIV infection, usually after the development of AIDS and heralds a poorer survival prognosis
HAND is a spectrum disorder defined by Asymptomatic Neurocognitive Impairment, Minor Cognitive-Motor Disorder and HIV-associated Dementia
memory loss, neuropsychiatric dysfunction, immuno-deficiency, motor abnormalities
What are some risk factors for HIV-associated neurocognitive disorders (HAND)?
extremes of age, CCR5 32, APOE 4, polymorphisms in promotors of TNF-alpha and MCP-1
What is encephalitis in humans?
encephalitis is associated multiple infectious and non-infectious etiologies
the global prevalence of encephalitis outbreaks ranges between 3.5 and 7.5 per 100,000
flaviviruses (e.g. WNV, JEV, Dengue, ZIKV) are known to cause encephalitis in humans
~50% of encephalitis cases have an unidentified etiologies
What is Herpes Simplex virus encephalitis (HSE)?
2-5/million annual incidence
immunocompromised patients not at greater risk
associated retinal necrosis
PCR for HSV-1: 94% specificity; 98% sensitivity
EEG-useful for seizure activity only
often fatal unless treated
mortality reduced to 20% with acyclovir
GCs anecdotally beneficial (level 3 evidence)
likelihood of recurrence is low >3% in adults
What is Zika virus and Guillain-Barre Syndrome?
a peripheral nervous system disorder in adults
What are the para-infectious symptoms of the brain associated with COVID-19?
anosmia
encephalopathy
stroke
seizures
meningitis/encephalitis
myositis
peripheral neurpathy
