Week 6 - Neurological Diseases

Primary Brain Injury

direct physical damage occurring immediately at the precise moment of trauma

Primary Brain Injury examples

vessel rupture, cerebral contusions, shearing of axons during rotation

Secondary Brain Injury

evolving cellular damage resulting from subsequent pathological cascades initiated by the primary insult

Secondary Brain Injury example

delayed ischemic neuronal death around a contusion

Ischemic Injury

critical reduction of arterial blood flow to central nervous system tissue, depriving neurons of essential oxygen and glucose required for aerobic respiration

early stages of ischemic injury

neurons lack glucose/oxygen » cease oxidative phosphorylation and begin anaerobic glycolysis » quick depletion of ATP » accumulation of lactate » intracellular acidosis

what does failure of Na/K pump from ischemic injury cause

neurons lose resing membrane potential » sustained depolarization (less negative when Na rushes in) » ions and water passively enter cell by osmotic gradients » neuronal swelling (cytotoxic edema)

ischemic injury impact on glutamate

anoxic depolarization causes uncontrolled presynaptic release of the excitatory neurotransmitter glutamate into the synaptic cleft, while energy-starved glial transporters fail to reuptake excess glutamate

calcium influx from glutamate from ischemic injury

excess glutamate hyper-stimulates NMDA/AMPA receptors causing high Ca influx

impact of elevated Ca in ischemic injury (4)

hyper-activates destructive intracellular enzymes (proteases, phospholipases, endonucleases, and calpains), digest structural cell membranes, break down nuclear DNA, destroy active mitochondrial enzymes, and initiate necrotic or apoptotic cell death

what is Reperfusion Injury

blood supply is abruptly restored to previously ischemic brain tissue, initiates secondary destructive wave

explain reactive oxygen species (ROS) from reperfusion injury

reintroduction of O2 to ischemic cells with damaged mitochondrial transport triggers ROS release (unstable, reactive chemicals/free radicals)

impact of ROS in reperfusion injury (2)

extensive lipid peroxidation of neuronal/endothelial cell membranes, worsening structural cellular damage

mitochondrial membrane rupture, leading to the loss of ATP synthase and releasing pro-apoptotic factors into the cytoplasm

development of vasogenic edema (break of BBB) from reperfusion injury

inflammatory activation damaged capillary endothelial junction, degraded BBB, converts localized cytotoxic edema to widespread

Abnormal Autoregulation causing neuronal injury

usually maintains cerebral blood flow with BP changes

hypoperfusion: drop in BP and CBF also drops which extends infarction because lack of perfusion

hyperemia: vessels cannot control excessive blood flow into vulnerable tissue, causing it to be pushed into extracellular spaces > edema and increased ICP

3 non-compressible volumes within cranium, percentage

brain tissue ~80%

blood ~10%

CSF ~10%

Monro-Kellie hypothesis

total intracranial volume is constant

increase in volume of one compartment must offset by compensatory decrease in another, or ICP rises

what is considered elevated ICP

ICP > 20 mmHg

Etiologies that expand volumes and trigger elevated ICP (4)

space-occupying masses (hematomas, abscess, neoplasms)

cerebral edema (cytotoxic/vasogenic swelling)

vascular congestion (hypercapnia with PaCO2 > 45mmHg causing vasodilation or obstructed outflow)

abnormal CSF dynamics (hydrocephalus)

Hydrocephalus

progressive accumulation of excess CSF within the skull and ventricular system

Non-Communicating (Obstructive) Hydrocephalus

CSF flow through the ventricular system physically blocked

Non-Communicating (Obstructive) Hydrocephalus demographic (2)

Most common in neonates due to fetal developmental abnormalities (aqueductal stenosis, neural tube defects, myelomeningocele, or Arnold-Chiari malformation)

but happens at any age from intraventricular tumors, infections, or scar tissue

Communicating Hydrocephalus

CSF flows freely through the ventricular system, but absorption through the subarachnoid villi to dural sinuses is impaired

Communicating Hydrocephalus cause

commonly by post-meningitic adhesions, subarachnoid hemorrhage blood clogging the villi, or developmental aplasia of subarachnoid villi

hydrocephalus in infants by cranial mechanics

Unfused cranial sutures and open fontanelles allow physical expansion of the skull

cranial mechanics of hydrocephalus in children/adults

Fused cranial sutures create a fixed, rigid volume; skull cannot expand to relieve pressure

Head Circumference changes with hydrocephalus

Abnormal, rapid head enlargement; bulging, tense fontanelles; dilated scalp veins

adults circumference unchanged because rigid

ocular findings for neonates with hydrocephalus

sunset signs, sluggish pupillary light response

sunset signs

eyes deviate downward so sclera is visible above pupil

ocular findings for adults with hydrocephalus

Papilledema (optic disc swelling); diplopia; abducens (CN VI) nerve palsy

signs for neonates with hydrocephalus

High-pitched, shrill cry; lethargy; irritability; poor feeding and difficulties.

signs for adults with hydrocephalus

Severe headache; nausea and projectile vomiting; cognitive decline; ataxia (lack muscle coordination); rapid rise in ICP.

decreased LOC - type of ICP sign + rationale

early, direct pressure on RAS in brainstem impairs cortical arousal

severe headache - type of ICP sign + rationale

early, increased pressure stretches/distorts pain-sensitive dura mater and walls of large BVs

projectile vomiting - type of ICP sign + rationale

early, elevated pressure stimulates emetic center in medulla independent of food intake

papilledema - type of ICP sign + rationale

early, elevated CSF pressure along optic nerve compresses central retinal vein > optic nerve swelling

ipsilateral pupillary abnormalities - type of ICP sign + rationale

early, compression of CN III on same side as lesion causes sluggishness, ptosis, and eventual fixed pupil dilation

Cushing’s reflex - type of ICP sign + rationale

late, ischemia stimulates medullary vasomotor centres to increase arterial blood supply to brain via systemic vasoconstriction to restore cerebral perfusion pressure

Systolic Hypertension & Widened Pulse Pressure - type of ICP sign + rationale

late, systemic BP surge to force blood into ischemic brain: elevated systolic while diastolic rises minimally

ICP relation to pulse pressure

increased PP

reflex bradycardia - type of ICP sign + rationale

late

elevated systemic BP stimulates baroreceptors in carotid and aortic arch, vagal output triggered to slow HR

bradypnea - type of ICP sign + rationale

late, compressed brainstem/pons cannot compensate to increase breathing by CO2 buildup from ineffective ventilation, disrupted breathing signals > brady/irregular

Cushing’s Triad components

late sign

systemic HTN with WIDENDED PP

bradycardia

bradypnea

where is lumbar puncture performed

needle between L3-L4 subarachnoid space

Pinkish / Reddish Fluid CSF indication

contains erythrocytes, indicating CNS hemorrhage or traumatic tap

Cloudy / Yellowish Fluid CSF indication

contains excess white blood cells (WBCs), indicating active infection or inflammation

Abnormal Protein Elevation CSF indication (3)

Indicates blood-brain barrier breakdown, tissue necrosis, or neoplasm

Transtentorial Herniation

cerebral hemispheres, diencephalon, and midbrain are displaced downward through the tentorial notch

Transtentorial Herniation outcome

brainstem, RAS, BVs, CSF flow is compressed » coma + decerebrate posturing

Uncal Herniation

Uncus of the temporal lobe is displaced downward over the tentorial edge

what is compressed with uncal herniation

CN III, posterior cerebral artery, midbrain/RAS

CN III compression impact from uncal herniation

ipsilateral fixed, dilated pupil and ptosis

posterior cerebral artery compression impact from uncal herniation

occipital lobe ischemia and visual field loss

midbrain and RAS compression impact from uncal herniation (2)

rapid loss of consciousness and motor deficits

Infratentorial (Tonsillar) Herniation

cerebellar tonsils are pushed downward through the foramen magnum

Infratentorial (Tonsillar) Herniation impact

compression of the medulla oblongata compresses vital respiratory and cardiovascular control centers » rapid infarction and death

stupor

unresponsive except to repeated painful stimuli

GCS assessment parameter

eye opening, verbal response, motor response

Decorticate Posturing score and manifestation

3 - flexion to chest, internal rotation

decerebrate Posturing score and manifestation

2 - rigidity and extension, rigid legs

Consciousness in locked-in syndrome

conscious and capable of thinking; aware of surroundings

Consciousness in vegetative state

loss of awareness and mental capabilities (diffuse brain damage)

Consciousness in coma

deep state of unarousable unconsciousness

Motor & Brainstem Function in locked-in syndrome

paralyzed and unable to communicate verbally

*eye movements/blinking retained

Motor & Brainstem Function in vegetative state

Unresponsive to external stimuli; involuntary brainstem functions continue

Motor & Brainstem Function in coma

absent voluntary/reflex motor responses

Sleep-Wake Cycles in locked-in syndrome

Normal sleep-wake cycles present

Sleep-Wake Cycles in vegetative state

cycle appearance present

Sleep-Wake Cycles in coma

completely absent

characteristics of brain dead

ceased brain function, absent respirations, no sleep-wake cycle

diagnostic criteria of brain death (6)

complete cessation of all brain function, flat EEG, absent brainstem reflex, absent spontaneous resp with ventilator removed, certainty of cause of brain damage, evaluation by 2 physicians

Epidemiology of traumatic brain injury

peaks around 15-24, and elderly >65

males 2x more affected than females

TBI severity distribution

mild- concussions ~80%

moderate- structural injuries with GCS 9-12 ~10%

severe- comas with GCS<8 ~10%

focal injury - brain injury pattern

Localized to the specific site of impact (e.g., contusion, laceration, hematoma), manifesting with focal neurological deficits

polar injury - brain injury pattern

by acceleration-deceleration forces; injury occurs at the poles of the brain (commonly frontal and temporal lobes)

Often bilateral with cognitive and behavioral alterations

Diffuse Axonal Injury - brain injury pattern

by rotational or shearing forces

Widespread axonal damage, especially at gray-white matter junctions » prolonged coma without large focal mass lesions on imaging

Concussion pathology

minimal brain trauma; reversible interference with brain function without structural rupture

Concussion mechanism

Mild blow to the head or whiplash-type sudden excessive brain movement

Concussion clinical course

transient confusion, amnesia, and headache; recovery usually within 24 hours without permanent damage

cerebral contusion pathology and mechanism

bruising of brain tissue, rupture of small blood vessels, and edema by blunt blow to head

cerebral contusion clinical course

focal neurological deficits, persistent edema; possible residual permanent damage

Closed Head Injury

Skull is not fractured; brain tissue and blood vessels may be injured, with extensive damage if head is rotated

Open Head Injury

Involves fractures or penetration of the brain

Depressed Skull Fracture

Involves displacement of a piece of bone below the level of the skull surface, compressing brain tissue and impairing local blood supply

Basilar Skull Fracture

Fracture occurring at the base of the skull (ex. forehead hitting windshield)

Basilar Skull Fracture indication (3)

leakage of CSF through ears or nose

periorbital/mastoid ecchymosis

formation of halo sign when CSF drainage is on gauze

otorrhea

leakage through ear

rhinorrhea

leakage from nose

Periorbital ecchymosis

raccoon eyes

mastoid ecchymosis

Battle’s sign, bruising behind ear at mastoid process

optic nerve Lesion Resulting Visual Field Deficit

Complete blindness in affected eye

optic chiasm Lesion Resulting Visual Field Deficit

Bitemporal hemianopia (loss of temporal visual fields in both eyes)

optic tract Lesion Resulting Visual Field Deficit

Contralateral homonymous hemianopia

Optic Radiations (Temporal Lobe - Meyer's Loop) Lesion Resulting Visual Field Deficit

Contralateral superior quadrantanopia ("pie in the sky")

Optic Radiations (Parietal Lobe) Lesion Resulting Visual Field Deficit

Contralateral inferior quadrantanopia

Occipital Cortex Lesion Resulting Visual Field Deficit

Contralateral homonymous hemianopia with macular sparing

damage to CN I olfactory

Loss of smell (anosmia)

damage to CN II optic

Visual field deficits (e.g., hemianopia)

damage to CN III oculomotor

Ptosis, dilated pupil, eye deviated "down and out"

damage to CN V trigeminal

Loss of facial sensation, weak jaw movement