20/24: Neurological Problems

atherosclerosis

→ process in which lining of arteries develop a layer of plaque (deposits of cholesterol, fats, calcium, and cellular waste products), which narrow vessels and increase the risk of stroke

• Precursor to myocardial infarctions (heart attacks) and strokes

• Atherosclerotic plaques often form in the internal carotid artery (leads to the brain)

Diagnostics:

• Visualized with an angiogram → produced by injecting a radiopaque dye into the blood and examining vessels with x-ray imagery

• Risk factors include vulnerable age groups, ↑ BP, smoking, diabetes, ↑ cholesterol levels, poor diet, lack of exercise, obesity, etc.

strokes

→ refer to the event where damage of impairment of blood vessels cause brain damage

• Ischemic-

• Hemorrhagic-

Treatment:

• Brain damage may be permanent, but physical-, occupational-, and/or speech- therapies over long periods can dramatically improve brain functionality

  • Constraint-induced movement therapy (sensory stimulation)

  • Pharmacological relief (drugs that reduce swelling and inflammation)

Morbidity:

• Severity depends on the size of affected vessels and corresponding brain damage (which can be negligible to massive)

• Runner-up most frequent cause of death in the world (2nd to ischemic heart disease, which they are associated with)

Prevalence:

• 1 in 4 adults experience at least 1 in their lifetime

• Likelihood ↑ w/ age

  • x2 each decade after age 45

  • ↑ up to 2% after age 75

ischemic stroke

→ blockage of a cerebral blood vessel, resulting in a stroke

• Classifies 87% of all strokes

Ischemic occlusions (blockages that cause strokes):

• Thrombus → blood clot that forms within a blood vessel, reducing flow to an affected area

  • Embolus → when a piece of tissue (blood clot/thrombus, fat, or bacterial debris) dislodges from its site of origin and occludes a nearby artery

Pharmacological remedies:

• Thrombolytics → “clot-busting” drugs that dissolve blood clots to re-establish circulation and hopefully minimize the amount of brain damage

  • A popular example would be tissue plasminogen activator (tPA), which should be administered within 3-4 hours of a stroke

Technological remedies:

• Endovascular embolization → coils, aspiration devices, and/or strents are thread through the vascular system to reinforce the vessels the site of an occlusion affected

  • May or may not remove occlusion

  • Access usually through femoral artery

hemorrhagic stroke

→ rupture of a cerebral blood vessel, resulting in a stroke

tumors

→ mass of cells whose growth is uncontrolled and serves no useful function

2 types:

• Benign (non-malignent) → not cancerous; has some distinct border and cannot metastasize

  • Mass of tumor cells are encapsulated and contained;

  • It can be surgically cut out and will not regrow

• Malignant → cancerous; has no finite border and can metastasize

  • Tumor cells are not bound and may infiltrate surrounding tissue

  • Surgical removal can be attempted but missed cells can produce new tumors

metastatis

→ process by which cells break off from a tumor, travel through the vascular system, and grow elsewhere in the body

• Feature of malignant tumors; malignancy

brain tumors

→ irregardless to whether it’s malignant or benign, it can produce neurological symptoms that threaten life

• Damages by compression or infiltration (occupying space in and pressing the brain);

• Brain tissue can be directly destroyed via physical pressure, or indirectly by a blocked flow of CSF causing hydrocephalus (“water brain”)

gliomas

→ type of malignant brain tumor made from poorly differentiated glial cells (tumor initiating cells originate from the neural stem cells that make giia)

• Rapidly proliferates

• ↑ Resistance to chemotherapy and radiation than other tumor cells

• ↑ Mortality rate

meningioma

→ type of benign brain tumor made from cells that constitute the meninges (dura mater, arachnoid membrane, pia mater)

• Often develops right between the two cerebral hemispheres

encephalitis

→ inflammation of the brain caused by infection (bacterial or viral), toxic chemical poisoning, or allergic reactions

• Initial symptoms: Headache, fever, nausea

meningitis

→ inflammation of the meninges caused by an infection (bacterial or viral)

• Initial symptoms: Headache, stiff neck

well-known brain viruses

Polio (acute anterior poliomyelitis) → viral disease that destroys motor neurons of the CNS (brain and spinal cord)

Rabies → viral disease that fatal brain damage

• Commonly transmitted from infected animal bites

Herpes (simplex) → viral disease that can cause encephalitis or brain damage in severe cases where it enters the brain

• Normally causes cold stored near the lips or genitals

traumatic brain injuries

TBIs

• Closed-head injury (concussion)

• Open-head injury

Surviving consequences:

• Scarring forms within the brain around sites of injury

• ↑ Risk for seizures

• mTBI (mild, undiagnosed cases) greatly ↑ likelihood of developing brain problems later on

  • ex. There’s an ↑ likelihood for Alzheimer’s disease in people who took blows to the head earlier in life

Morbidity (US):

• 1.4 mil people visit ER for TBIs, 270K hospitalized, 52k die

• 1/3 of deaths caused by injury involve a TBI

closed-head injury (concussion)

→ TBI caused by a blow to the head with a blunt object or surface

• Usally little to no blood spilled or open wounding

Whiplash process:

1. Coup → brain comes into violent contact with the inside of the skull

2. Contrecoup → brain then recoils in the opposite direction and (perhaps) smashes against the other side of the skull again

open-head injury

→ TBI caused by penetrating the brain

• Results in some significant open wound

• Damaged blood vessels exacerbate the severity of the injury

  • ↑ BP due to blood loss and inflammation also worsen the damage

seizures

→ epileptic episodes caused by irregular brain activation (abnormal electrical discharges)

• Class of disorders = epilepsy

Types:

• Generalized-

  • Tonic-clonic (grand mal)-

  • Atonic-

  • Absence (petit mal)-

• Partial (focal)-

  • Simple partial-

  • Complex partial-

Symptomology:

• Seizing doesn’t always involve convulsions → violent sequence of uncontrollable muscle movements (motor system neurons going haywire

• Spells of absence → brief epileptic episodes, not as severe as tonic-clonic (grand mal) symptoms

Treatment:

• Anticonvulsant drugs (benzodiazepines, which work by increasing the effectiveness of inhibitory synapses)

  • Most people respond well enough to pharmacological interventions and lead a normal life

• Surgery (usually lesioning seizure foci)

  • Fewer instances

*Etiology:

• Scarring, which often relates to a TBI, stroke, growing brain tumor, or a developmental brain abnormality

• High fevers in young children (who are the most susceptible)

• Withdrawal from GABA agonists (substances with sedative effects, like alcohol or barbituates)

• Contributing genetic mutations that cause instability in neural networks by tinkering with the…

  • Quantity and quality/function of ion channels

  • Reciprocal wiring of excitatory and inhibitory neurons

  • Rules that govern synaptic plasticity (training neural circuitry)

  *Note that many cases are idiopathic (unknown causes)

generalized seizures

→ seizing effect is non-localized, involves most of the brain

• Tonic-clonic (grand mal) seizures

  • Most adverse physical symptoms:

    1. Aura phase → sensation that precedes a seizure; nature depends on the focus/location of the seizure

    2. Tonic phase → characterized by all skeletal muscles contracting or stiffening

    3. Clonic phase → characterized by rhythmic jerking movements (where convulsions occur)

• Atonic seizures

  • Involve a sudden loss of muscle tone and/or temporary paralysis

  • May cause additional physical injuries from falling

• Absence (petit mal) seizures

  • Have symptoms of complex seizures (may induce a brief loss of consciousness or general lack of awareness) that tend to last around 15 seconds, involving a sudden cease of activity and repeated blinking

partial (focal) seizures

→ seizing effect begins at a focus and remains localized in the brain

• Simple partial- → causes no loss of consciousness

• Complex partial- → induces some loss of consciousness

developmental brain abnormalities

Etiology:

• Exposure to certain toxins, viruses, bacteria, and drugs (notably alcohol) during pregnancy can impair fetal brain development and eventually cause intellectual disability

  • ex. Toxins: Organophosphates (from insecticides), lead and/or mercury (heavy metals)

  • ex. Viruses: Rubella (German measles), Zika

fetal alcohol syndrome

→ serious condition associated with alcohol consumption during the 3rd/4th week of pregnancy causing certain facial anomalies and severe intellectual disabilities for the fetus

• Babies born to alcoholic mothers are typically smaller than average and fall behind in development

errors of metabolism

→ genetic abnormalities in which the instructions for a particular protein are in error

• Typically, an enzyme (something that ends in -ase) is not synthesized on account of mutations in both copies of the gene

• Common origin for many inherited metabolic diseases

phenylketonuria

PKU → hereditary metabolic disorder caused by the absence of the enzyme that converts the amino acid phenylalanine to tyrosine

• Accumulation of phenylalanine causes brain damage unless a special diet is implemented soon after birth

tay-sachs disease

→ hereditary metabolic disorder caused by a lack of an enzyme in lysosomes, causing an accumulation of waste products and swelling of cells in the brain

down syndrome

trisomy 21 → congenital condition characterized by moderate-to-severe intellectual and physical disabilities resulting from having an extra chromosome on the 21st

• Not necessarily a hereditary abnormality

• Past age 30, patients begin to degenerate in a similar manner to that of Alzheimer’s disease

multiple sclerosis

MS → autoimmune demyelinating disease; a person’s own immune system attacks myelin sheaths at scattered location within the CNS, leaving behind hard patches of debris called sclerotic plaques and inhibiting successful action potential propagations

• Damage occurs in the white matter (axon paths) through the brain and spinal cord, leading to a wide variety of neurological disorders

Symptoms/Prognoses:

• Remitting-relapsing- → cyclical flare-ups + remission for varying periods

• Progressive- → slow, continuous ↑

Treatment:

• Interferon beta → protein that modulates immune system/redirects its focus (NOT an immunosuppressant)

• Glatiramer acetate → decoy peptides that mimic myelin

• Antibody remediation → More recent research suggests that injecting antibodies into the blood to attack the culprit autoimmune cells is more effective; instead of remedying consequences, remedy the cause

Onset: Usually presents in people’s late 20s

Etiology: Sporadic disease → not obviously caused by an inherited gene mutation or an infectious agent

Risk factors:

• People who grow up far from the equator (ie. people in polar regions are likely to have ↓ sun exposure - vitamin D levels, which may be related to MS)

  • Pre-disposition is said to be set at age 15, even if you move afterwards

• Enduring childhood diseases that disrupt the immune system or cause some degrees of demyelination