Pathophysiology of ABI

Statistics of Stroke

795,000 strokes/yr in the US, Leading cause of long-term disability, economic impact of stroke = 46 billion/yr, fifth leading cause of death (150,005 deaths in 2019), more common in younger females and older men, and higher rates of stroke and stroke-related deaths are in blacks, with an increase in stroke-related death rates in hispanics

Why are strokes more common in young women?

Birth control and hormonal supplements

Signs of Stroke

FAST

Face drooping

Arm weakness

Speech difficulty

Time to call 911

Face Drooping

Does one side of the face droop or is it numb?

Ask the person to smile, is the smile uneven or lopsided?

Arm Weakness

Is one arm weak or numb?

Ask the person to raise both arms, does one arm drift downward?

Speech

Is the speech slurred?

Is the person unable to speak or hard to understand? Ask the person to repeat a simple sentence

Speech problems during stroke can lead to...

Dysarthria or aphasia

Time (911)

If the person shows any of these symptoms even if the symptoms go away, call 911 and get them to a hospital immediately

Other signs and symptoms of stroke?

Numbness, confusion, trouble walking, trouble seeing and severe headache

Modifiable Risk Factors of ABI

High blood pressure (Hypertension)→ Major risk for hemorrhagic and ischemic strokes.

Atrial fibrillation→ Increases risk for embolic stroke → ischemic ABI.

Cigarette smoking→ Damages cerebral vasculature, increases stroke risk.

Drug and alcohol abuse→ Can cause hypoxia, liver damage (leading to hepatic encephalopathy), or traumatic brain injuries.

Hyperlipidemia→ Contributes to atherosclerosis, stroke.

Poor diet / Obesity / Insufficient physical activity→ Contribute to metabolic syndrome → increased cerebrovascular risk.

Diabetes mellitus→ Increases small vessel disease risk and ischemic stroke.

Genetic disorders (modifiable in expression)→ E.g., Sickle cell

Number 1 Risk Factor for Stroke?

High BP

Number 1 Risk Factor for Embolic Stroke?

A-Fib due to blood coagulation

Non-Modifiable Risk Factors

Age, Sex, Heredity, Race/Ethnicity, and TIA (Transient Ischemic Attack)

TIA is described as?

Mini-Stroke, big major stroke warning sign

Stroke is described as?

Abrupt neurological impairment caused by diminished blood flow to the brain

Ischemic Stroke

Occurs in 87% of stroke cases, occurs when a blockage of a blood vessel results in brain tissue ischemia

Ischemic Stroke Causes

Can be cardioembolic or thrombolytic

Cardioembolic vs Thrombolytic Origin

Embolic: Distant clot (often from heart, like in atrial fibrillation) travels to cerebral vessels.

Thrombotic: Local clot formation developed over time (often atherosclerotic plaque buildup).

Hemorrhagic Stroke

13% of stroke cases, occurs when there's a rupture of a blood vessel, blood accumulates in the brain resulting in ischemia and compression

Hemorrhagic stroke causes increases in?

ICP and compression

intracerebral hemorrhage

Often due to chronic hypertension, or anticoagulants.

Subarachnoid Hemorrhage

Due to aneurysm rupture, AV malformations, or trauma.

CSF fluid circulates here

In an older brain, are their vessels more susceptible to shear forces in SAH?

YES

TIA (transient ischemic attack)

"Mini Stroke", occurs as a "warning sign" before stroke in 12% of cases. Transient blockage of blood vessels, leading to ischemia but resolution of symptoms with perfusion

Ischemic Stroke Zones

Core, Penumbra, and Oligemia

Core Stroke Zone

Site of irreversible ischemic damage. Complete cell death occurs here within minutes with the neurons experiencing necrosis

Core Stroke Zone Blood Flow Limit

Blood flow is severely reduced (below 12 mL/100g/min) resulting in neurons dying

Penumbra Stroke Zone

Hypoperfused ischemic region peripheral to the core that may be reversible. Time is essence with saving neurons here

Penumbra Stroke Zone Blood Flow Limit

(12-22mL/100g/min).

Oligemia Stroke Zone

Hypoperfused area not at risk for damage, flow is reduced but not enough to cause damage, no infarction risk unless stress increases

Oligemia Stroke Zone Blood Flow Limit

22-35mL/100g/min

What is normal perfusion ratio of the brain?

50-55mL/100g/min

Acute Phase of Stroke lasts how long?

Minutes to hours

Acute Phase of Stroke Events

1. Blood Flow Decreases (ATP begins to deplete)

2. Ionic Homeostasis Disturbance (Loss of Na⁺/K⁺ pump function due to ATP depletion)

3. Intracellular Calcium Increase (Too much Ca²⁺ = cell death signal)

4. Glutamate release increases and excitotoxicity (Excitotoxicity = neuron death from overstimulation.)

5. Cytotoxic Oedema (Cellular swelling induces cell rupture)

6. Membrane, Mitochondrial and DNA Damage

7. Misfolding of Proteins and enzyme dysfunction (enzymes lose structure)

8. Necrosis (Unregulated cell death)

Subacute Phase of Stroke lasts how long?

Hours to Days

Subacute Phase of Stroke Events

1. Apoptosis (Programmed cell death or random)

2. Inflammation by neutrophils, monocytes, microglia (BBB gets disrupted by pro-inflammatory cytokines)

3. Cytokine production (IL-1, IL-6, TNF-α → amplify inflammation. Promote BBB breakdown)

4. Proteolytic enzyme activation

(MMPs) degrade BBB, extracellular matrix

5. Vasogenic edema

BBB permeability ↑ → fluid leaks into extracellular space.

↑ intracranial pressure (ICP)

6. Reactive oxygen species production

Mitochondrial and immune cell ROS → Oxidative stress and DNA damage.

7. Stimulation of neurogenesis and angiogenesis

Some regenerative signaling begins (VEGF, BDNF) through synaptogeneis

Which areas in the brain only grow through synaptogeneis?

Entorhinal Area and Hippocampus

Chronic Phase of Stroke lasts how long?

Weeks to months

Chronic Phase of Stroke Events

1. Necrotic debris removal

2. Stem cell proliferation, differentiation, and maturation

3. Angiogenesis

Formation of new blood vessels to restore perfusion.

4. Gliosis

Astrocyte proliferation → form glial scar.

Restores BBB but may hinder axon regrowth.

5. Reconnection of lost circuits

Plasticity allows surviving neurons to form new synaptic connections. (Disinhibition of Silent Synapses)

6. Neurovascular remodeling and functional recovery (Cortical Reorganization)

Within hemorrhagic strokes, what is toxic to neural tissue?

BLOOD, has a direct correlation to injury of neurons

You want to monitor ___ after hemorrhagic stroke?

ICP

Blood in the cranial cavity increases?

ICP, due to blood raising pressure and compresses surrounding brain tissue and can result in a herniation if pressure becomes severe

Hemorrhagic stroke can also block?

Block CSF flow, causing hydrocephalus.

Stats of TBI

147,815 mild TBIs/year (2008–2016 data).

In 2017:

224,000 hospitalizations

61,000 deaths from TBI.

Economic burden of moderate to severe TBI = $76.5 billion.

Who has a higher chance of TBI?

Radical and ethnic minority status, military service, incarceration, homelessness, intimate partner violence

Who has a higher chance of Mortality-TBI death?

Lower socioeconomic status and rural location

Most common MOIs of TBI?

MVA and Unintentional falls

MOI of TBI

Closed head injuries, Penetrating injuries and Blast Injuries

Closed Head Injuries

Brain hits skull (e.g., in MVAs, falls, sports).

Results in coup-contrecoup injuries.

Can be focal or cause diffuse axonal injury (DAI) due to shearing of white matter.

Coup-Contrecoup Injuries

Damage at two sites in the brain: one at the site of initial impact (coup) and another on the opposite side (contrecoup), due to the brain rebounding within the skull.

Penetrating Injuries

Gunshot wounds or Shrapnel

Blast Injuries

Explosions, pressure waves cause TBI that penetrate skull

Pathophysiology of TBI

Altered brain function caused by external force resulting in cellular dysfunction

Primary Injury of TBI

Mechanical trauma resulting in focal or diffuse axonal injury = neuronal dysfunction and cell death

Phase 1 of TBI Events

Impaired blood flow, metabolic imbalance, tissue damage and membrane permeability

Primary Injury is analogous to?

"Core Zone" in Stroke

Secondary Injury of TBI

Delayed or prolonged biochemical, cellular, physiological events = additional neuronal dysfunction and cells death

Between Phase 1 and Phase 2 of TBI events

Cytotoxic or vasogenic edema formation, inflammation (cytokines) and BBB breakdown

Phase 2 of TBI Events

Axon terminal depolarization, intracellular breakdown, apoptosis, necrosis, free radical generation, release of glutamate (excitotoxic) = cell death

Mild TBI

LOC: 0-30 mins

Altered Consciousness: Brief <24 hrs, may be dazed or confused

Post-Traumatic Amnesia: 0-1 day

GCS: 13-15

Imaging: Normal

Moderate TBI

LOC: >30 minutes but <24 hours.

AOC: >24 hours.

PTA: lasts between 1 and 7 days (More prominent memory issues)

GCS: 9–12

Imaging: Normal or abnormal

Severe TBI

LOC: >24 hours.

AOC: >24 hours. Minimal consciousness or coma

PTA: >7 days (often profound amnesia).

GCS: ≤9

Imaging: Abnormal — hemorrhage, contusions, herniation, edema, skull fractures.

Severe TBI can have what kind of posturing?

May have decorticate or decerebrate posturing.

TBI severity is measured by 2 main things. What are they?

GCS and Post-Traumatic Amnesia

GCS is out of how many points?

15

Eye opening (4)

Verbal response (5)

Motor Response (6)

GCS Eye Opening Questions

Spontaneous: 4

To verbal stimuli or command: 3

To pain: 3

No response: 1

GCS Verbal Response Questions

Oriented: 5 points

Confused, but able to answer: 4 points

Inappropriate Words: 3 points

Incomprehensible Speech: 2 points

No response: 1 point

GCS Motor Response Questions

Obeys commands for Movement: 6

Purposeful movement to pain: 5

Withdraws in response to pain: 4

Decorticate Posturing in response to pain: 3

Decerebrate Posturing in response to pain: 2

No response: 1

Decorticate Posturing

UE in Flexion and LE in extension, which indicates a lesion above the red nucleus

Rubrospinal intact, lesions above it disconnect cortical inhibition, so the red nucleus becomes relatively overactive, leading to UE flexion.

Decerebrate Posturing

UE and LE in extension, lesion below the red nucleus

Disrupts both cortical input and the red nucleus, eliminating flexor influence.

Vestibulospinal tract and Pontine reticulospinal tract

Which is worse, Decorticate or Decerebrate?

Decerebrate