CNS TRAUMA; CEREBROVASCULAR

DISORDERS; DEGENERATIVE

DISORDERS

CNS Injury

• Increased intracranial pressure (i.c.p.)– Due to

• Tumor growth

• Edema

• Excess csf

• Hemorrhage

Pathophysiology of CNS Trauma

• Example: trauma of head breakdown of the blood-brain barrier

• CSF most readily displaced content • As much as possible reabsorbed Relieves building fluid pressures

• Where does it go?

• Alteration of cerebral blood volume– Controlled by incr’d venous return from brain– Also to decr’d fluid pressures in brain

• If fluid displacement doesn’t relieve pressures, fluid continues to accumulate, and

• Edema increased tissue pressure– As fluids expand, pressures build

• Compensations of fluid displacement (csf and blood) may be overwhelmed– I.c.p. continues to incr, cranial content continues

expanding. Next:

• Systemic b.p. changes– Arterial vasoconstriction to decr fluid toward brain

• BUT: Now another problem:

• This condition

• Oxygenation of brain tissue compromised– Remember: ischemia hypoxia

• Brain tissues hypoxic; hypercapnia, acidosis deterioration of brain cells

• Brain tissue shifts (herniates) from compartment of higher pressure to compartment(s) of lower pressure (Fig.14-9)

• Blood supply to herniated tissue now further decr’d – Now pressing against arterial vasculature

further ischemia, hypoxia to brain tissues

• Increased pressure builds in adjoining compartment(s) further pressure on blood vessels leading to healthy tissue– Now have generated ischemia, hypoxia of

adjoining region(s), so– Formerly healthy tissue begins to degenerate

• Finally, small hemorrhages begin; blood supply ceases

Head Injury • Highest risk populations

– Young people 15-24 years old – Children 6 months – 2 years– Children 5-8 years – Elderly– Also, males at higher risk than females by 2:1

• Most likely causes of head injury– Transportation accidents– Falls– Sports related events– Crime

• Penetrating trauma– Causes focal injuries

• Blunt trauma common– Head strikes hard surface or is struck – Dura intact, so no brain tissue is exposed– Focal or diffuse injury

• Mild concussion, cerebral concussion most common

• About 75-90% of all head injuries– Not severe– Survival rate increased due to

• Reduced severity

• Improved management at accident scenes

• Contusion = impact hemorrhage, possibly hematoma– Coup (strike) – impact against object at front or

back of head (Fig.15-1)• Causes direct brain trauma, shearing forces through

brain Tearing of subdural veins and trauma

– Contrecoup (rebound) – impact within skull from injury to back of head, so

• Brain hits opposite side of skull Shearing forces

• Epidural hematomas – often caused by temporal fracture – Source of bleeding often artery Herniation (shift) of temporal lobe

• Subdural hematomas (Fig.15-2)– Acute – develop rapidly after trauma– Usually at top of head– Often due to vein tearing– Expanding mass incr’d i.c.p. herniation of

brain tissue

• Clinical (contusion)– Loss consciousness, reflexes– Transient cessation of breathing– Brief bradycardia– Decr’d blood pressure

• Treatment– Contusions

• Control i.c.p.– Drugs to relieve fluid pressures

» Some alter Na+ concentration in brain fluids

• Manage symptoms

– Hematomas• Surgically ligate, remove bleeding vessels

Cerebrovascular Disease

• Due to blood vessel pathology– Lesions on walls of vessels– Occlusions of vessel lumen– Vessel rupture– Alteration of vessel permeability

• Two types of brain abnormalities– Ischemia (with or without brain infarct)– Hemorrhage

Cerebrovascular accident (CVA; stroke)

• Incidence– Third leading cause of death in the U.S.– Highest risk in the population > 65 years old– BUT about 1/3 of patients are < 65 years old– Evidence of familial patterns– More often in

• Females

• Blacks

Three types of CVA based on pathophysiology

• Thrombotic –from arterial occlusions– Thrombi in arteries to the brain– Risk factors – same as for thrombus formation in other vessels as

well as:• Oral contraceptive use• Dehydration• Sickle cell disease• Chronic hypoxia

– Development of disease• Often arteriosclerosis and inflammation of vessels • Arterial wall damage• Over time, plaques form • Clots in cerebral circulation

– Thrombotic strokes further subdivided clinical types:• Transient Ischemic Attacks (TIAs)

– Due to thrombotic particles intermittent blockage of cerebral circulation or vessel spasm

– No residual dysfunction

– Any neurological deficits cleared within 24 hrs

– BUT often precedes completed stroke

• Stroke-in-Evolution (Progressive Stroke)– May evolve over minutes/hours

– Gradual progression of neurological deficit (over days)

• Completed Stroke– Maximal destruction of neurological tissues Neurological defects

• All cause decr’d blood supply to brain– Ischemia hypoxia necrosis, swelling of brain tissue neuron

disintegration

• Embolic – second type of CVA– Fragments of thrombus from outside brain (ex: heart, aorta,

common carotid) travel

– Obstruction often at bifurcations, points of narrowing of vasculature

– Causes ischemia• Lumen of brain vasculature entirely plugged and embolus remains in place

• OR embolus may break again fragments travel to other brain areas

– Associated conditions• Risk factors are same as for thrombus formation, arteriosclerosis elsewhere

in body, as well as– Patients with atrial defibrillation

– Patients with myocardial infarct

– Patients with disorders of cardiac circulation

– Also leads to loss of blood supply to brain, and ischemic/hypoxic conditions

• Hemorrhagic CVA – third type of CVA– May be due to:

• Hypertensive hemorrhage– If incr’d blood pressure over several years

– Occurs within brain tissue

– Mass of blood forms incr’d volume in cranium

– Blood mass displaces, compresses adjacent brain tissue

– Rupture or seepage can occur

• Ruptured aneurisms (Fig.15-12)

• Bleeding disorders

– Pathophysiology not fully understood• Mass of blood causes compression ischemia of surrounding

brain tissue

• Get incr’d i.c.p. edema, other sequential steps

• Resolves through reabsorption of blood from cranial cavity

• Clinical – Thrombotic/embolic

• Maximal cerebral edema in 72 hours of obstruction

• Commonly subsides within 2 weeks

• Ischemic stroke survived by most, unless massive cerebral edema

• Symptoms depend on site of obstruction– Different arteries supply different brain regions, which control different

body functions

– BUT massive brainstem infarct death

– Why? What functions are controlled by the brainstem?

– Hemorrhagic – also depends on location, size of bleeding• Aneurism can symptoms from excruciating headache

unconsciousness

• Treatment– Stabilize vital signs– Detect/correct any cardiac arrhythmias– Proper positioning– Platelet anti-aggregants– Surgery to ligate aneurisms, improve blood flow– Preventive – hypertension is a most important risk

factor, so• Decrease salt intake• Increase exercise• NO SMOKING• No oral contraceptives

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Degenerative Disorders• Alzheimer’s Disease – intellectual dysfunction

– Incidence – common – Probable causes

• Both familial and non-inherited forms

• Evidence for several, varied causes, including– Aluminum toxicity

– Autoimmune dysfunction

– Prions

– Involvement of CNS neurons

– Aggregation of amyloid glycoprotein develops • Proteins in neurons become distorted, twisted

“neurofibrillary tangle” (Fig.15-14,15)

• Groups of nerve cells degenerate, coalesce around amyloid core

– Now “plaque”

• Disrupt transmission of nerve impulses– Number of plaques corresponds with amount dysfunction

• Memory loss may be due to decr’d ACh – ACh needed for recent memory

– Clinical• Progressive forgetfulness disorientation, confusion

• Behavioral changes– Anxiety, depression, hostility

• Motor changes possible, depending on site(s) of plaque(s)

– Treatment• Maintain general health

• Maintain any unaffected cognitive function

• Parkinson’s Disease – a movement disorder– Incidence: 130/100,000 population

• Onset commonly after age 40; peak age of onset is early 60’s

• About same male:female ratio• Apparently not familial

– Probable cause(s) –unknown, but several theories exist:

• Vascular disorder• Viral infection• Metabolic disorder• May be age predisposes neurons to damage by toxins,

viruses

– Involvement of dopaminergic neurons degeneration of basal ganglia (Fig.15-16)

• Degeneration dopaminergic neurons loss of neurons that produce dopamine as well as loss of receptors for dopamine

Imbalance of dopaminergic to cholinergic activity– Dopamine mostly inhibitory, ACh mostly excitatory for motor

function

– As dopaminergic neurons decr, inhibitory effects are lost Relatively more ACh neurons (excitatory) Patient dev’s movement disorders -- muscles are more active

– Clinical• Syndrome of abnormal movement = Parkinson’s

syndrome (Fig.15-17)– Tremor at rest

– Regidity

– Akinesia – decr’d voluntary movement or incr’d time nec to perform voluntary movement

– Dementia possible later

– Treatment• Need to incr brain dopamine

– Dopamine can’t cross blood-brain barrier

• Give L-dopa -- precursor to dopamine– Crosses blood brain barrier

– In brain tissue, converted to usable dopamine

• BUT L-dopa has many side-effects

• Multiple Sclerosis – demyelinating disease– Myelin = lipid covering over axons

• Needed for proper action potentials and nerve conduction in correct path along axon

– Previously healthy myelin degenerates (Fig.15-18) • Patients do not form successful action potentials

movement disorders

– Incidence• 30-80/100,000 population

• Common time of onset 20-40 years old

• Mostly female, White

• Most prevalent -- those who live away from equator

• Some familial patterns but no clear genetic pattern

– Probable cause(s) – unknown; several theories exist including

• Exposure to environmental agent in childhood

• Most MS patients have a specific histocompatibility Ag in bloodstream

– Increasing Ag concentration correlates with incr’d susceptibility

– Believe Ag may alter immune response toward viruses

– Involvement of only CNS neurons (NOT PNS)– Causes degeneration of previously normal myelin

• Axons seem well-preserved

• BUT impulses do not pass smoothly

• Demyelinization plaque formation along axon

• Also gliosis glial scarring

• Lesions form; diffuse, small, widespread

– Clinical• Symptoms remit following inflammatory edema near

plaques– Sensory/visual problems

– Limb weakness

– Cerebellar signs

– Bladder dysfunction

– Mood disorders

– Treatment• Prednisone, glucocorticoids to decr inflam’n with acute

attacks

• Manage symptoms

• Supportive rehabilititative management

• Myasthenia gravis – disorder of the neuromuscular junction– “Grave muscle weakness”

– Probable cause – autoimmune dysfunction• Assoc’d with development of other autoimmune diseases

– At neuromuscular junctions, get defect in transmission of impulse to a muscle cell

– Causes decr’d binding of ACh at its postsynaptic receptors on muscle cells

• Ab’s prod’d by patient’s body against its own postsynaptic receptors

– Ab’s bind ACh receptors on muscle cells at synapse

– Receptor therefore blocked from binding ACh from impinging neuron

– So neuron’s signal is not received by the muscle cell

• Finally receptors destroyed– Diminished transmission of impulses across neuromuscular junction

– No muscle depolarization

– Clinical – “insidious onset”• Fatigue, recurrent upper respiratory infections• Muscles of eyes, face, mouth, throat, neck first affected

– Facial droop– Difficulty swallowing– Choking, drooling

• Respiratory muscles weaken impaired ventilation respiratory arrest – Treatment

• Anticholinesterases– Cholinesterase -- enzyme present in synapse; breaks down ACh

» Needed as body’s mechanism to stop ACh signal after time, once transmission is complete

– Anticholinesterases stop the activity of cholinesterase enzyme Less ACh broken down More ACh available to bind to any remaining healthy receptors on muscle

cells– BUT these agents have side effects

• Steroids• Immunosuppressants to decrease Ab synthesis