Lecture 8 (2): Causes of brain dysfunction (Bacterial & viral & parasite infections, mercury, lead, MS)

Overview of bacterial infections

Bacteria abnormally enter the brain (usually BBB and meninges protects the brain from it) → Immune system tries to fight it off and create pus—formation of cerebral abscesses, and this can damage the brain (secondary effect of bacteria)

Can cause encephalitis—inflammation of the brain (primary effect)

Often attack the meninges and produce meningitis—an inflammation in the meninges

• 25% chance of fatality

• Key marker: Neck stiffness (can be tested by chin-to-chest)

• Other symptoms: Drowsy, irritable, sensitive to light

Bacteria can be treatable by antibiotics (including meningitis)

Encephalitis

Inflammation of the brain due to bacteria

Pus

Formation of cerebral abscesses (damage to the brain) due to the immune system trying to fight it off

Bacterial Meningitis

An inflammation in the meninges

These types don’t cross BBB

Relatively treatable (by antibiotics), but 25% chance of fatality

Neck stiffness, drowsiness, irritable

Most common type: Streptococcus (Strep throat)

Bacterial infections: Syphilis

A type of bacteria that can attack the nervous system specifically

STI (Sexually transmitted infection)

Long dormancy stage (no symptoms) for 15-20 yrs

Syphilis is now easily detectable and treatable

General paresis

The syndrome of psychosis/dementia that results 15-20 years after initial syphilis infection (hallucination, etc.)

Viruses

They are not cells, they’re not alive, can’t self-replicate

The only way that works is to live in hosts, use the host’s genetic cells to make copies of themselves

Antibiotics don’t help

2 types of viral infections

Those that have a particular affinity for neural tissue (e.g. rabies)

Those that attack all tissues indiscriminately, including nervous tissue (e.g. herpes simplex)

Viral infection: Rabies

The rabies virus has an affinity for the nervous system

Gets bitten → rabies enter the motor neurons, travels backward along the axon (rmb? normally motor neuron is efferent, travel out of brain) to the brain → guaranteed death (1 month after the infection)

Rabies requires entering motor neurons, if it does, you’re dying, if it doesn’t, you won’t get rabies

15% chance of getting rabies if you get bitten by an animal with rabies

Some cases, high level of aggression

Why were rabies called Hydrophobia before?

“Fear of water”

One of its most distinctive symptoms is extreme difficulty swallowing, often triggered by water or even the thought of drinking

See dysfunction in the NS, but COVID doesn’t even reach the NS! There are 2 possible evidence (We don’t know for sure)

1. Excessive immune system response → inflammation in NS (like MS)

2. (Best evidence) Noticeable effects on vascular system (blood flow) → affects cerebral vascular system (blood flow in brain) → brain has put into mildly hypoxic state (hypoxia–reduced amount of oxygen)

So basically COVID doesn’t affect the brain itself, but affect the blood flow to your brain

A study examine the brain before and after getting COVID (Which brain region gets affected?)

Effect size is small, but significant results

Overall, the decrease in brain size, decrease in grey matter (esp in a couple of regions like orbital frontal cortex and parahippocampal gyrus in temporal lobe)

Changes in the brain is correlated to cognitive decline

Larger effects for ppl > 70s

Parasite infection: Toxoplasma gondii

Eukaryotic parasite (multi-cellular! closer to plants or animals than closer to bacteria)

Require to be in multiple types of animal, particularly life cycles between being inside of a rat/mouse and Cats over and over again

Rats get it → Damage the heart and the specific part in the amygdala that makes it afraid of cats! → Rat is not afraid of cats anymore, instead they get attracted to cats (like smell, urine)!! → Cat kills and toy with the rat and get this parasite → Parasite gets out of cat through urine or feces → Rat gets in contact with urine or feces and get parasite again → the cycle continues!

Ppl tell pregnant women to stay away from cat’s litter boxes, but it in fact it doesn’t do any harm to them.

There’s a small chance to get this type of parasite, and the damage they do to us is too small damage that we wouldn’t even wanna talk abt it

Parasite infection: Neurocysticercosis

Tape worm in the brain. It looks like a brain tumor

Mercury

It can accumulate in the brain and permanently damage it when it’s evaporated (turn into Methylmercury, which is toxic), and we breathe this stuff in

Evaporated mercury was once used to make a hat (like in Alice in wonderland) → hat makers get poisoned → toxic psychosis

Not very dangerous to human

Toxic psychosis

Delusion, hallucinations, and disorganized thinking caused by exposure to toxic substances, drugs, or metabolic imbalances

Methylmercury

A highly toxic organic form of mercury that accumulates in living organisms, particularly in aquatic food chains. It is bioaccumulative, meaning it builds up in fish, animals, and humans over time.

The poisoning is thankfully rare in North America NOW, but still sometimes occurs (News about a woman suffered from this from Pond’s lightening cream, from years of accumulation)

A bit of this in vaccines, BUT no evidence of harm

Whatsoever to suggest harmful neurological effects.

No Relationship between vaccines and autism

Causes of methylmercury poisoning

Consumption of Contaminated Fish and Seafood (esp. predatory large fish)

Contaminated water

Industrial pollution

Minamata disease

(Japan, 1950s-1960s)

Caused by severe methylmercury poisoning; ataxia, numbness, muscle weakness, damage to vision/hearing/speech, paralysis, coma, death; congenital effects

Ethylmercury poisoning

Ethylmercury is an organic mercury compound primarily found in certain medical and industrial products.

Unlike methylmercury, which accumulates in the body and is highly toxic, ethylmercury is processed and excreted more quickly, reducing its long-term toxicity.

After years of years of studying, there’s no relationship between vaccines. This one author studied selected 12 Autistic children that had MMRs vaccine with no control group…

Lead

Can also lead to toxic psychosis

There’s no safe level for leads.

Lead is toxic at much lower levels as well

Lead poisoning is especially dangerous to children, where it impairs physical and mental development. It can also cause a variety of neurological problems in adults

You don’t really run into lead, unless…

• “Crack pot,” we used to put lead in our dishware! So ceramic chips and crack, you drink it thru tea→ toxic psychosis

• Tap water, pipes were lead before (like our grandparents). The Vancouver city pipe is clean now, but if you live in an old building, it’s totally up to the owner of the building!

Multiple sclerosis (MS)

The immune system often appears to attack the CNS myelin as if it were a foreign substance. Myelin gets damaged → loss of action potential on the way cuz it decays along the axon (myelins are there to speed up the process rmb? cuz there’s less Voltage-gated channels)

It doesn’t just affect myelin (oligodendrocytes), but also attack neurons → glio-scarring in the brain called “bright spots” that can be detected on a structural MRI

Damage in Afferent (Sensory): Visual disturbances, numbness, tremor

Damage in Efferent (Motor): Loss of motor Coordination, Muscle spasm (contraction, chronic pain)

Form of MS: Relapsing-remitting MS (RRMS)

Most common form, it’s the cycle of relapse–new/worsening symptoms, remitting–symptoms improve/disappear

You can’t be diagnosed as MS in this stage

Symptoms in 20s: The cycle period is long, months of on, months of off

As you get older, in 30s, 40s, the cycle will be faster

In their 40s or 50s, it will progress into Secondary progressive MS (SPMS) have symptoms ALL THE TIME

Form of MS: Secondary progressive MS (SPMS)

Have MS symptoms all the time

If you previously have RRMS early in life (20s), it will one day turn into SPMS

Form of MS: Primary progressive (PPMS)

Some ppl that start to have MS in their 40s, they don’t experience RRMS first, but instead they just wake up one day and start having symptoms, and it gets worse as they grow older

Theories of pathogenesis (cuz we’re not sure how MS rises)

1. Outside-in theory: Primarily an autoimmune disease (Glia or outside thing damage from outside to inside the myelin)

2. Inside-out theory: Primarily a neurodegenerative disease, with inflammation in SOME patients (Immune system (inside) response damage the myelin)

*If it’s because of an autoimmune disease, myelin should be damaged from the outer layer first. BUT MS gets damaged in the inner most layer first.

Why is MS NOT simply just an autoimmune disease? (3 evidence)

1. If the immune system attacks the myelin, then those autoimmune suppressants should stop it. However, the drugs DO suppress the symptoms, but they DON’T stop the progression!

2. There are a lot of ppl who have MS, who don’t have much immune system response!

3. If it’s because of an autoimmune disease, myelin should be damaged from the outer layer first. BUT MS gets damaged in the inner most layer first. (Strongest evidence)

Progression relapsing-remitting form (RRMS → SPMS) (Read the graph)

The diagonal line: Shows the build up of the degeneration across the yr

The dotted line: Clinical threshold: Above this line → doctor can diagnose that you have MS

These orange bars represent the immune system's response. Just the degenerative process happening is not enough to manifest symptoms (reaching the clinical threshold) and be diagnosed as MS

CIS presents symptoms like MS, but u can’t be sure it’s MS. It could be interpreted as bacterial infection or smth

When the diagonal line meets the clinical line, you have secondary progressive MS

Clinically Isolated Syndrome (CIS)

When you’re presenting smth like MS, but we can’t be sure if it’s MS or viral infections (this is when under the clinical threshold, or before RRMS), not until it reaches clinical threshold (doctor can diagnose as MS now)

Progression of primary progressive MS (PPMS)

Very low immune activity (orange bars)

When the diagonal line meets the clinical threshold (horizontal line), you will be diagnosed as PPMS

What can we assume for the chance of getting a MS after looking at the map?

The further North away from the equator, the more chance of getting MS.

More UV radiation or vitamin D from the sunlight for the first 15 yrs of your life, the less risk of MS

Genetic side of MS

Genetically closer, more risk of MS

What’s causing MS?

Strong correlation to Epstein-Barr virus (EBV, Herpes virus 4. Same virus that causes “mono”)

EBV is also a major causal factor of thousands of types of cancer!

The study w military:

• All have blood sampled (HIV screening)

• They selected EBV-negative participants and followed them

• Can see screenings over time, plus onset of MS years later (i.e. longitudinal design)

Found: Epstein-Barr Virus increases risk of MS by 32x! and almost all of them were exposed to EBV FIRST

Complication: Most of us have EBV

Implication for MS prevention: To develop the vaccine for the Epstein-Barr virus

Treatment/prevention of MS: Vitamin D supplements

Better than lack of it - Not sure, the study gives mixed results

Treatment/prevention of MS: Corticosteroid and immune system modulators (common treatment for many autoimmune diseases)

Suppress symptoms but don’t stop the progression.

Also not recommended cuz it could affect bone density, and other skin issues if you’re living regularly on it (not ideal).

Treatment/prevention of MS: Cannabis (Sativax)

This is the First reason how clinical cannabis became a thing!

Reduce pain from muscle spasm (like in the nasal spray form. 50/50 of THC and CBD)

Treatment/prevention of MS: Physical therapy and muscle relaxants

Physical therapy: Could help slow down the progress a bit

Muscle relaxants: Could help w muscle pain a bit

Treatment/prevention of MS: Liberation treatment

Drain blood from veins in the brain. High side effects, and it has absolute 0 benefits

Treatment/prevention of MS: High dose biotin

The benefits are modest. Not gonna cure MS tho

Treatment/prevention of MS: Hematopoietic stem cell transplantation

New, severe chemotherapy that will DESTROY your immune system, and REBUILD your immune system using stem cells.

Rough procedure, cuz there’s a period of time when you live w rlly low, brittling immune system.

The majority of the patients don’t see progression across one year! It didn’t go away, it just rlly slowed down the progression.