Lecture 9: Neurological Infections

Question 1

What are neurological infectious agents?

Answer 1

bacterium (e.g. tuberculosis)
virus (e.g. HIV)
fungus (e.g. cryptococcus)
protozoa (e.g. malaria)
prion (e.g. BSE)
helminth (e.g. cysticerosis)

Question 2

What are the unique aspects of CNS infections?

Answer 2

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

Question 3

What are some of the common neurological infections?

Answer 3

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

Question 4

What are the determinants of emerging infections?

Answer 4

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

Question 5

What is meningitis?

Answer 5

H/A, fever, nuchal rigidity +/- cranial neuropathies

meninges, spinal cord

Question 6

What is encephalitis?

Answer 6

H/A, fever, confusion/altered behavior –> coma, seizure, focal signs

involves brain tissue

Question 7

What is myelitis?

Answer 7

limb weakness, back pain, B&B dysfunction, sensory loss

spinal cord

Question 8

What is abscess?

Answer 8

focal signs, fever, seizure

Question 9

What is radiculopathy/neuropathy?

Answer 9

localized radicular pain, fever, weakness

Question 10

What are the signs of meningitis?

Answer 10

Kernig’s sign: bent knee when lifted

Brudzinski’s sign: when neck is lifted up, knees bend

Question 11

What are neural cells in the CNS?

Answer 11

neurons (+ axons)

astrocytes

oligodendrocytes (+ myelin)

endothelial cells and microglia/macrophages (protected by the blood-brain barrier)

Question 12

What are the neural cells in the PNS?

Answer 12

neurons (+ axons)

Schwann cells

macrophages (protected by the blood-nerve barrier)

Question 13

What are astrocytes?

Answer 13

the most abundant cell in the brain

contribute to blood barrier support other cells susceptible to viruses

Question 14

What are the functions of microglia?

Answer 14

the brain’s phagocytes

immune “sensors”

Question 15

What are the functions of activated microglia?

Answer 15

phagocytosis
chemotaxis
antigen presentation
cytotoxicity
morphological changes
proliferation
respiratory burst

Question 16

What are human endogenous retroviruses (HERVs)?

Answer 16

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

Question 17

What is Syncytin-1?

Answer 17

Syncytin-1 RNA and protein are increased in demyelinating lesions in multiple sclerosis and induce endoplasmic reticulum (ER) stress in glial cells

Question 18

What other diseases associated with NeuroHIV?

Answer 18

opportunistic infections

ART-assoc’d disorders

primary HIV neurological syndromes

Question 19

What are HIV-associated neurocognitive disorders (HAND)?

Answer 19

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

Question 20

What are some risk factors for HIV-associated neurocognitive disorders (HAND)?

Answer 20

extremes of age, CCR5 32, APOE 4, polymorphisms in promotors of TNF-alpha and MCP-1

Question 21

What is encephalitis in humans?

Answer 21

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

Question 22

What is Herpes Simplex virus encephalitis (HSE)?

Answer 22

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

Question 23

What is Zika virus and Guillain-Barre Syndrome?

Answer 23

a peripheral nervous system disorder in adults

Question 24

What are the para-infectious symptoms of the brain associated with COVID-19?

Answer 24

anosmia
encephalopathy
stroke
seizures
meningitis/encephalitis
myositis
peripheral neurpathy

Question 25

What are the post-viral symptoms of the brain associated with COVID-19?

Answer 25

acute disseminated encephalomyelitis

acute necrotizing hemorrhagic encephalopathy

limbic encephalopathy

Question 26

What are the “long-Covid” of the brain associated with COVID-19?

Answer 26

the symptoms resemble Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Question 27

What are the mechanisms of neurological disorders in COVID-19?

Answer 27

viral neuro-invasion

CNS endothelial damage

systemic inflammation

neuroinflammation

autoimmunity