Neuroscience Quiz on Cerebral Edema

Lecture Hall Timeline

• 1:30-2:15: PollEv questions and focused review
• 2:20-3:05: Group meeting, work on case/questions
• 3:05-3:15: Break
• 3:15-4:15: Review case/questions, submit assignment
• 4:20: Class ends

Questions & Review

• A&P: Brain & Spinal Cord, Cerebral hemodynamics, CSF & ICP, Delirium & Dementia, Brain Injury (CVA, TBI), Seizures
• Group Work: Spinal Cord Injury (neurogenic & spinal shock, autonomic dysreflexia), Intracerebral hypertension (cerebral edema, ICP)

Cerebral Hemodynamics

• Monroe-Kellie Doctrine: The brain, blood, and cerebrospinal fluid are contained within the rigid skull. Increasing the volume of any one component results in increased intracranial pressure (ICP). To maintain normal ICP, the volume of one component must decrease.
• Brain: 80%
• Blood: 10%
• CSF: 10%

Cerebrospinal Fluid (CSF)

• CSF provides buoyancy to protect the brain and spinal cord.
• Approximately 125-150 cc of CSF circulates around brain and spinal cord, with 75 cc inside intracranial space.
• Produced in the choroid plexus in ventricles of the brain.
• CSF flows from the lateral ventricles, through the cerebral aqueduct, and into fourth ventricle.

CSF exerts pressure

• CSF flow results from pressure gradient between the arterial system and CSF-filled cavities.
• CSF flows from lateral ventricles through third ventricle, cerebral aqueduct, fourth ventricle, pontine cisterns, and cerebromedullary cistern & into subarachnoid space of brain and spinal cord.
• A cistern is an opening of subarachnoid space, created by a separation of arachnoid and pia mater.

Arachnoid villi

• Arachnoid villi are one-way valves that open at a pressure gradient of 5 mmHg; closer and stop allowing flow backward.
• Flow stops when the pressure gradient is less than 5 mmHg.
• CSF ultimately drains into jugular system for return to the heart.

Lumbar Puncture

• CSF samples can be taken using lumbar puncture, into the space between third & fourth lumbar vertebrae.
• Sample evaluation: discolouration (3 hours after SAH), WBC (0-5 cells/mm3 normal), protein (15-45mg/100 ml normal), glucose (60-100mg/100 ml or 80% of blood glucose normal)

Intracranial Pressure (ICP)

• Normal ICP is 5-15 mmHg.
• Can be increased by: increased brain volume (tumor, hematoma, edema, abscess, infection), increased blood volume (increased arterial flow, decreased venous drainage), increased CSF volume (hydrocephalus from increased production, obstruction to flow)
• If autoregulation is overwhelmed, ICP rises more rapidly, causing brain herniation into the brainstem and inevitable brain death.

Cerebral Edema

• Vasogenic: Increased capillary permeability, water and proteins move from intravascular space to extravascular space; blood brain barrier disrupted by direct injury, tumor, or inflammation.
• Cytotoxic: Neuronal, glial, & endothelial cellular swelling due to loss of Na⁺ and K⁺ pump function; usually from ischemia.
• Interstitial: Increased fluid in periventricular white matter due to increased CSF and hydrostatic pressure.

Cerebral Autoregulation

• Stage 1: Vasoconstriction to decrease blood flow into the brain.
• Stage 2: ICP becomes too high to compensate with vasoconstriction; systemic hypertension occurs to force adequate blood upward.
• Stage 3: ICP rises to almost equal arterial pressure, leading to brain tissue ischemia, inflammation, and edema.
• Stage 4: Increased pressure in the cranial vault causes brain herniation, with increased ischemia, obstructive hydrocephalus, and cessation of systemic and cerebral blood flow.

Clinical Signs & Symptoms of Increased ICP

• Infants: Tense/bulging fontanel, separated cranial sutures, increased occipital circumference, tense scalp veins, changes in feeding, crying when disturbed, setting-sun sign
• Children: headache, nausea, vomiting, diplopia, blurred vision, seizures

Delirium vs. Dementia

• Delirium: Acute, often dramatic onset; global amnesia; waxing and waning severity; often reversible
• Dementia: Gradual onset; selective amnesia; sun-downing; often irreversible; EEG shows normal baseline unless advanced.

Alzheimer's Disease

• First diagnosed in 1906 by Dr. Alzheimer.

• Characterized by:

  • Extraneuronal Beta-amyloid plaques: cluster of beta-amyloid protein due to enzyme deficiency or genetic mutation
  • Intraneuronal Tau protein neurofibrillary tangles: due to lack of enzyme or genetic defect, causes overproduction of tau protein.
  • Acetylcholine deficit

• Most likely a combination of 3 factors: neuron death & inflammation, brain atrophy (esp. cortex & hippocampus), and enlargement of ventricles.

• Stages of Alzheimer's progress over 12+ years: Stage 1 (no deficits), 2 (mild cognitive deficits), 3 (mild confusion), 4 (inability to do financial work), 5 (requires assistance), 6 (lacks past & present awareness), 7 (limited speech & movement)

Alzheimer's Disease Management

• Initial treatments (anticholinesterases) only cause a temporary change in the disease's progression.
• New treatments are examining critical steps in plaque and tangle formation.

Focal Brain Injury

• Contusion: Injury at the point of impact and rebound sites, injured blood vessels in the area causing hemorrhage, infarction, necrosis, and edema. Symptoms vary with severity. Can include loss of consciousness, brief loss of reflexes, loss of respiration, bradycardia, and hypotension.
• Hematoma: Bleeding between dura and skull (epidural), between dura & arachnoid (subdural), within brain parenchyma (intracerebral).
• Severity of hematoma and secondary injury impacts symptoms.

Diffuse Axonal Brain Injury (DAI)

• Widespread damage to axons with associated tissue tears due to shearing forces from deceleration.
• Not immediately visible on CT, but may be visible on MRI 12 hours to several days later.
• Severity levels based on coma duration and brainstem function: Mild (coma 6-24 hours), moderate (coma > 24 hours), severe (impaired brainstem function, high mortality).

Primary vs. Secondary Injury

• Primary: immediate injury from direct impact (focal, diffuse)
• Secondary: delayed damage from ischemia, edema, inflammation, neuronal loss, resulting in longer-term consequences.

Cerebrovascular Accidents (CVAs)

• Classified as ischemic or hemorrhagic
• Ischemic: Thrombotic (clot), Embolic (traveling clot), global hypoperfusion/anoxia; treatment focuses on restoring perfusion.
• Hemorrhagic: Intracerebral hemorrhage, intracranial, subarachnoid; treatment manages pressure and secondary tissue injury.

Ischemic Stroke

• No matter the cause, the initial injury leads to an 'ischemic core' and a 'penumbra' (surrounding tissue at risk).
• Treatment: Thrombolytic therapy (like t-PA), or mechanical clot removal.

Hemorrhagic Stroke

• Hemorrhage can arise due to: Spontaneous, hemorrhagic conversion of an ischemic stroke, vascular malformation.
• Increased pressure and secondary tissue injury are a major concern.

Seizures

• Abrupt excessive discharge of impulses in cortical neurons, disturbing excitation/inhibition of impulses.
• Focal vs. generalized
  • Focal: originate within one hemisphere and remain confined. Different focal areas can lead to different symptoms
  • Generalized: involve multiple subcortical foci from both hemispheres.

Types of Seizures

• Simple Partial: Awareness retained, sensory/motor/autonomic symptoms
• Complex Partial: Altered awareness, may involve autonomic symptoms and/or psychomotor phenomena
• Absence: brief, staring episode
• Tonic-Clonic (Grand Mal): Loss of consciousness, stiffness (tonic), jerking movements (clonic)
• Myoclonic: sudden, brief muscle jerks
• Atonic: sudden loss of muscle tone.

Causes of Seizures

• Neurodegenerative disorders
• Genetic factors
• Hypoxic-ischemic causes
• Metabolic issues
• Conditions leading to space-occupying lesions (e.g. tumors, trauma, infection)
• Brain trauma

Spinal Cord Injury

• Results in both primary (immediate) and secondary (delayed) injury.
• Primary: impact that directly damages the spinal cord tissue
• Secondary: ischemia, edema, inflammation, and neuronal loss.
• Increased pressure within the spinal canal plays a destructive role.

Level of Injury: Sensory & Motor Deficits

• Myotomes: muscle groups controlled by specific segments of spinal cord
• Dermatomes: areas of skin innervated by specific spinal nerves

Incomplete Spinal Cord Injuries

• Different types result in variable degrees of sensory and motor loss.
  • Brown-Sequard Syndrome: paralysis/weakness on one side of the body with loss of sensation on opposite side
  • Anterior Cord Syndrome: loss of motor function and pain and temperature sensation. Often from compression.
  • Posterior Cord Syndrome: loss of pain, temperature, vibration, and position sense. Often from compression.
  • Central Cord Syndrome: greater motor impairment in the upper body, with variable sensory loss; common in cervical spine injures

Neurogenic vs. Spinal Shock

• Spinal Shock: Complete loss of reflexes and flaccidity. May persist for days to 3 months, then hyperreflexia and spasms.
• Neurogenic Shock: Occurs in cervical or upper thoracic injuries. Loss of sympathetic tone, causing parasympathetic predominance: bradycardia, hypotension, and hypothermia

Autonomic Dysreflexia (AD)

• Life-threatening hypertensive crisis.
• Stimuli from below injury level (e.g. pain, full bladder/bowel) triggers massive sympathetic response: widespread vasoconstriction, causing dangerous hypertension.

Intracranial Hypertension (ICH)

• Increased pressure inside the cranial vault by a variety of events
• Manifests clinically through a number of symptoms relating to the pressure on the underlying brain structure and/or its vessels

Group Work Part II & III Questions

• The provided cases are clinical scenarios, and the specific answers require analysis of medical information. The notes provided will be helpful to formulate accurate responses to the questions.

Test your knowledge on cerebral edema and its mechanisms in this neuroscience quiz. Delve into the intricacies of Alzheimer's disease, cerebral autoregulation stages, and the symptoms of increased intracranial pressure. Perfect for students studying advanced neurobiology concepts.