Week 1: Neurology I

What percentage of a person's body weight is made up by the brain?

2%

What percentage of cardiac output per minute is directed to the brain?

15%

What percent of all oxygen is sent to the brain?

20%

What substances does the brain not store?

• Oxygen

• Nutrition (E.g. Glycogen, glucose)

• Recovery nervous tissue (centrioles)

Why cant nervous tissue regenerate once destroyed?

Nervous tissue lack centrioles needed to direct survival for regeneration

How long can the CNS last without oxygen before it starts to shutdown?

10 seconds

How long can the CNS last without oxygen before apoptosis (cellular death) occurs?

4-6 minutes

When the brain is deprived of oxygen, how soon do deficits begin to occur?

After 10 minutes

Define neuromodulation

If one tissue has cell death, the other tissue will heighten and try make (ex: if one senses like sights goes away, other senses will make up)

What is state of consciousness dependent on?

Cerebral cortex (brain tissue) function and reticular formation

What is the reticular activating system (RAS)?

Located in the brain stem, and activates higher centres of cerebral cortex causing wakefulness

Low RAS activity =

Lower wakefulness/awareness (E.g. Sleep)

What is low RAS activity due to?

Pathology, which can alter consciousness (E.g. Decreased perfusion; altered metabolic state (e.g. metabolic acidosis) => altered consciousness (changed LOC))

Which ways can we assess consciousness?

-LOC

-GCS

-Neuro vital signs (PERRLA + Vital signs)

Outline the category of the glasgow coma scale (GCS) and the ranking for each category

Eye Opening Response:

1. No response

2. Response to pain

3. Response to speech

4. Spontaneous response

Verbal Response:

1. No response

2. Incomprehensible sounds

3. Inappropriate words

4. Confused

5. Oriented to person, place and time

Motor Response:

1. No response

2. Abnormal extension

3. Abnormal flexion

4. Flex to withdraw from pain

5. Moves to localized pain

6. Obeys commands

GCS of 6-8 =

Intubate

Define brain death

Brain death is characterized by no motor responses, no brainstem reflexes, and the presence of apnea (lack of breathing)

True or False: Is there a brain death criteria has been developed?

True

1 multiple choice option

Which brain stem reflexes are absent in brain death?

• Gag

• Cough

• Doll's eyes (oculocephalic)

What is the Doll's eyes (oculocephalic) reflex?

When the reflex is present, rotating the head to the right causes the eyes to move to the left. However, when the reflex is absent (abnormal), rotating the head to the right causes the eyes to move with the head

Define a vegetative state

Damage to the gray and white matter of the brain that does not meet brain death criteria due to presence of:

• Brainstem reflexes

• Sleep-wake cycle

• Hypothalamic functions adequate to meet basic demands (e.g. temperature regulation)

Does a person in a vegetative state have any form of awareness?

No awareness of self or surroundings, as well as the inability to voluntarily interact and reproduce behavioural responses (Some may have a minimally conscious state)

List the common causes of brain injury

• Cerebral vascular accident (CVA aka stroke) (thrombotic or hemorrhagic)

• Malformations (aneurysm, AVM)

• Hematomas/hemorrhage (Epidural, subdural, intracerebral)

• Blunt head injury/Concussion

• Infection

• Brain tumour

What is a hematoma?

Old blood that has pooled and is stagnant

What is a hemorrhage?

Active bleeding

The end result of brain injury =

Risk of increased ICP (intracranial pressure)

Both brain death + vegetative state are seen as results of

Recreational drug (toxicity)

What is the clinical focus in someone with a brain injury?

• Neuro vital signs (NVS)

• Assess deficits (related to area affected)

• Treatment to prevent further injury

How much blood flow (mL) does the brain receive every minute?

750ml (15% of CO)

What does CPP stand for?

Cerebral perfusion pressure

MOA of CPP

A pressure gradient between the internal carotid artery and subarachnoid vein; required to perfuse the brain

How do you calculate CPP? and what is considered normal CPP?

CPP = MAP - ICP

A minimum of 45mmHg (profound ischemia at less than 40 mmHg)

How do you calculate MAP?

(SBP + 2 x DBP)/3

Brain injuries are caused a __________ and a __________

Pathology, pathological sequelae

Outline the pathology of brain injuries

CVA (thrombus or bleed), infection (pathogen & toxin), tumour, trauma (hematoma, concussion etc.

Outline the pathological sequelae of brain injuries

• Ischemia

• Inflammation (cerebral edema)

• Increased ICP

• Electrolyte imbalances/neurotransmitter imbalance (Na, K, Ca)

Brain injury can caused the

BBB to be compromised

Significance of BBB compromise

This is significant b/c BBB is a glycoproteins that is selectively permeable but once its compromised the fx is compromised as well (can cause toxicity) 

The higher severity of a brain injury =

The more pronounced the neurological dysfunction (S&S)

Sudden increased in ICP tx

• On tx: surgical (evacuation of fluid)

• 3 % NaCI solution

Define hypoxia

Deficient delivery of oxygen to tissues

What is hypoxia the result of?

• Hypoxemia (E.g. anemia)

• Decreased oxygen delivery to all brain tissue (E.g. low CO)

Define hypoxemia

Low oxygen in the blood

List the signs and symptoms of hypoxia

• Agitation/irritability

• Decreased LOC

• Seizures (Seizures are usually sign of something else happening in the brain, usually symptomatic)

S&S are also depend on severity and suddenness of onset

Define ischemia

The lack of oxygen/removal of waste within a tissue

What are the two types of ischemia?

Focal and global ischemia

What is focal ischemia?

A localized deficit (E.g. cerebral tumour = deficit in the affected brain region, e.g. hearing, tinnitus,... (vestibulocochlear CN))

What can happen if focal ischemia is not resolved?

If not resolved, the sequelae will result in more global signs and symptoms

What is global ischemia?

All brain tissue affected

Example of global ischemia

Low CO (MI, severe arrhythmia); metabolic acidosis (lactate - electrolyte imbalance) (e.g. severe asthma attack; DKA)

What global deficits are observed in global ischemia?

• Altered consciousness (stupor/coma)

• Declining autoregulation (altered VS, loss of protective reflexes)

Cushing triad - sign of increased ICP (d/t brain injury)

• Increased pulse pressure (difference btw systolic and diastolic BP)

  • 120 - 80 => 40 usually

• Low heart rate  (<60bpm) - see if they are on beta blockers

• Irregular respirations

*Compensation for bradycardia & loss of auto regulation

Outline ischemia brain injury sequelae

No nutrient & O2 delivery => depletion of resources within 5 minutes => brain injury 

Outline inflammation brain injury sequelae

Cerebral edema, increased ICP

Outline electrolyte imbalance brain injury sequelae

• E.g. causes excess intracellular calcium => ‘calcium cascade’ injury: protein lysis, lipid lysis (oxidation), free radical formation => DNA injury & mitochondrial injury = cell death

• E.g. causes abnormal CNS neurotransmitter secretion/recycling => accumulation/depletion of neurotransmitters

  • Issue with NTs -> we can't assess them (no serum check or anything), mostly relies on symptoms and observations

List the compounding issues associated with the brain injury sequelae

• Watershed infarcts

• Reperfusion injury

Define watershed infarcts

Heightened focal damage to lowered-blood flow regions such as the hippocampus (More perfusion is directed to areas of the brain that are seen as more important (like brainstem) and less perfusion to areas that are seen as less important causing damage to the less perfused areas in an attempt to save the more important areas)

Define reperfusion injury

Injury due to sudden re-perfusion after a period of ischemia => O2 induced vasodilation, enzyme release (e.g. nitric oxide), inflammation, electrolyte imbalances (& sequelae as per ‘electrolyte imbalances’)

Reperfusion injury compounds ________

The original injury (as reperfusion needs to be done slowly)

Cerebral edema =

High ICP

What are two types of cerebral edema?

• Vasogenic

• Cytotoxic

What is the etiology of vasogenic cerebral edema?

• Head injury

• Hematoma/hemorrhage

• CNS infection

What adverse events are present in vasogenic cerebral edema?

• Inflammation causing increased vascular permeability resulting in high ICP

• BBB is compromised, when compromised we lose the proactive barrier that normally safeguards the brain (E.g. more drugs will be able to pass through to the brain)

What is the etiology of cytotoxic cerebral edema?

• Hypo-osmotic states

• Electrolyte imbalance

What adverse events are present in cytotoxic cerebral edema?

Increased water shift into cells (intracellular fluid shift) causing high ICP (too much solvent and not enough solute)

How do you treat cerebral edema?

Treat the underlying cause to decrease further injury

What are the cranial cavity contents surrounded by?

The rigid skull

List the contents of the cranial cavity?

• Brain tissue (80%)

• Blood (10%)

• Cerebral Spinal Fluid (CSF) (10%)

What is considered normal ICP?

0-15 mmHg

How does the body compensate for increased ICP?

The content compartments compensate to maintain homeostasis through Monroe-Kellie hypothesis

Define Monroe-Kellie hypothesis

Reduction of blood flow/reduction of CS

• Decreases one compartment that’s moveable to make more room for the expanding compartment

  • This can increase the severity of brain injury - d/t low perfusion

  • We can compensate short term

The Monro-Kellie hypothesis (or doctrine) states that the total volume within the rigid skull (brain tissue, blood, and cerebrospinal fluid (CSF)) is constant, meaning an increase in one component must be offset by a decrease in another to maintain stable intracranial pressure (ICP)

What does increased ICP obstruct?

• CSF and blood flow causing injures to the brain (tissue compression injury)

• Maximum impact can also cause 'brain herniation' (pressure displacement & necrosis of brain tissue)

List the signs and symptoms of life threatening ICP

Cushing’s triad:

• Hypertension and wide pulse pressure (A significant difference between SBP and DBP)

• Bradycardia

• Irregular respirations

What are the two types of cerebral vascular accident (CVA)?

• Ischemic CVA

• Hemorrhagic CVA

How can we determine if a CVA is ischemic or hemorrhagic?

Conduct a CT scan

What causes an ischemic CVA?

Blockage from a thrombus or embolus

Ischemic CVA makes up_______% of all CVA's

80

List the risk factors associated with Ischemic CVA

• Hypertension

• Atherosclerosis

• Smoking

• Dyslipidemia

• Stenosis (narrowing)

• DM

• Atrial fibrillation (embolus!)

• Drug side effects

• Age

• Genetics

Hypoxia → _______ → _______

Ischemia, injury

What is a hemorrhagic CVA?

Vessel rupture causing blood to escape instead of reach it's target tissue

Between ischemic and hemorrhagic CVA which one is less common and more fatal?

Hemorrhagic CVA

1 multiple choice option

List the risk factors associated with hemorrhagic CVA

• Hypertension

• Medications (ex: anticoagulants)

• Age

• Arterial deficits (E.g. AVM, aneurysm)

• Bleeding disorders (inability to clot, hemophilia)

What are the first signs and symptoms of a hemorrhagic CVA?

• Headache

• Vomiting

• Affected area S&S

Outline the sequelae of a hemorrhagic CVA?

• Hemorrhage

• Ischemia

• High ICP

• Edema

• Necrosis

• Death

Does a hemorrhagic CVA have a sudden or slow onset?

Sudden onset, with no TIA

1 multiple choice option

What the is ER treatment for a hemorrhagic CVA?

• Stabilize (intubate/02, sedate, e.g. reverse anticoagulation)

• Osmotic diuretics/hypertonic NS

• Optimize perfusion (e.g. htn tx)

• Surgical evacuation

What is a transient ischemic attack (TIA)?

Transient occlusions that act as a CVA warning sign (Angina of the brain)

When TIAs occur, what prevention strategies should be initiated?

CVA prevention

How do you treat TIA's?

Anticoagulants and antiplatelets

List the anticoagulants and antiplatelets used in the treatment of TIA's

• Apixaban (Eliquis): Factor Xa inhibitor (anticoagulant)

• Dabigatran (Pradaxa): Factor IIa inhibitor (anticoagulant)

• ASA (81mg): Thromboxane A2 inhibitor (antiplatelet)

What is the FAST acronym stand for and what is it used for?

Used to identity stroke

Face: Is it drooping?

Arms: Can they raise both arms?

Speech: Is their speech slurred or jumbled?

Time: Call 9-1-1 STAT

Where is the most common area for strokes?

The middle cerebral artery (MCA) 50% - 60% stroke are from here

What areas of the middle cerebral artery are affected during a stroke?

• Upper limbs and face

• Broca's area of speech (the area of CNS tissue supplied by MCA)

Define collateral circulation

A network of alternate blood vessels that form (angiogenesis) or become functional to maintain blood flow to an area when the primary pathway is obstructed. These vessels can develop naturally over time or become activated during times of arterial blockages or ischemia

How do you treat Ischemic CVA less than 4 and a half hours from onset?

Thrombolytics (tPA)

How do you treat Ischemic CVA less than 24 hours since onset?

Thrombectomy (catheter aspiration or mechanical)

What are the other associated Ischemic CVA treatment methods?

• Carotid endarterectomy (CEA) or angioplasty

• Drugs: Anticoagulants and antiplatelets

• + Treat hypertension, dyslipidemia, etc.

Define dysarthria

Weak muscle control (slurred speech)

Define dysphagia

Difficulty swallowing, including problems with coughing or choking when eating or drinking

Define aphasia

Impairment of language and speaking, including speaking any words, saying the correct word (expressive aphasia), and comprehension of speech (receptive aphasia)