CNS TRAUMA CEREBROVASCULAR DISORDERS DEGENERATIVE DISORDERS CNS Injury
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
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
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