#11 Neurological Infections

Question 1

What are three major concerns regarding neurological infections?

Answer 1

1. The development of drug resistant infectious agents
2. The increasing number of immunocompromised human populations
3. The rising number of diseases previously considered rare

Question 2

What are 4 things that are essential to preventing and treating neurological infections?

Answer 2

Education, surveillance, development of new drugs, and development of new vaccines

Question 3

What are the 6 neurological infectious agents? What are the “big 3” global neurological infections?

Answer 3

Bacteria, viruses, prion, fungus, protozoa, and helminth
Big three: HIV/AIDS, tuberculosis, malaria

Question 4

What are two unique aspects of CNS infections?

Answer 4

1. Localization of infection dictates the clinical presentation (CNS, brain, spinal cord, PNS)
2. 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)

Question 5

What are 5 determinants of emerging infections?

Answer 5

Susceptible populations, disrupted environments, altered human and animal contact, medical practices, and rapid/frequent movement of animals and humans

Question 6

TRUE OR FALSE: Neurological infections are different from other infections because the location in the CNS/PNS effects presentation. NI syndromes are a continuum

Answer 6

TRUE

Question 7

How do infections invade the CNS in meningitis?

Answer 7

Via the meninges, which include the dura matter, the arachnoid matter, and the pia matter. This invasion causes clinical symptoms of meningitis

Question 8

What is the common algorithm for neurological infections?

Answer 8

Presentation
Infection risk
physical exam
localization?
Brain imaging and blood tests
Management
Prognosis

Question 9

What are the cells within the CNS? What about the PNS?

Answer 9

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

Question 10

What is the most abundant cell in the brain?

Answer 10

Astrocytes: responsive, proliferative, talk to all cell types, in BBB, permissive and responsive to bacteria and viruses
INNATE immune response in brain

Question 11

What are oligodendrocytes essential for?

Answer 11

CNS myelin formation, have a large nucleus, structural stability, susceptible to viruses

Question 12

What are microglia responsible for in the CNS/brain?

Answer 12

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

Question 13

What is the role of neurons in the CNS?

Answer 13

They transmit messages, they are stable and exhibit no turnover, they are permissive to infections, they are not dynamic like glial cells

Question 14

What are neurotropic retroviruses?

Answer 14

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

Question 15

What are human endogenous retroviruses?

Answer 15

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

Question 16

What is an example of a HERV-W envelope glycoprotein?

Answer 16

Syncytin-1 RNA and protein, they are increased in demyelinating lesions in MS and induce endoplasmic reticulum damage stress in glial cells

Question 17

How did HIV 1 spread to humans?

Answer 17

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)

Question 18

What is the HIV 1 disease course?

Answer 18

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

Question 19

What are three different neurological side effects of HIV?

Answer 19

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

Question 20

What was the effect of ART on viral HIV DNA, RNA, and integrated DNA?

Answer 20

No impact, it did not change the DNA despite lowering viral load, this suggests that the brain is a reservoir for infections.

Question 21

What is HAND?

Answer 21

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

Question 22

What are the four hallmarks of HAND?

Answer 22

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

Question 23

What is a hallmark of HIV disease progression and HAND?

Answer 23

Chronic immune activation

Question 24

What is the etiology of encephalitis in humans?

Answer 24

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

Question 25

What are some details about herpes simplex virus encephalitis (HSE)?

Answer 25

2-5/million annual incidence, immunocompromised patients are not at greater risk, associated with retinal necrosis
Has good specificity (94%) and EEG is useful for seizure activity only, often fatal if left untreated but greatly reduced with acyclovir
Look at temporal lobes on the CT

Question 26

What is a PNS disorders in adults? What is some details about it?

Answer 26

Zika virus associated Guillain-Barre syndrome: affects nerves in brain and spinal cord via damaged myelin and exposed nerve fiber, lethal and no known cause

Question 27

Do human coronaviruses infect the brain?

Answer 27

YES, most do and are associated with neurological disease
For COVID specifically, there are parainfectious disorders and post-viral syndromes that have neurological symptoms

Question 28

What is an aspect of COVID 19 that has a neurological basis?

Answer 28

Long-covid, has many neurological symptoms such as brain fog