CNS TRAUMA; CEREBROVASCULAR DISORDERS; DEGENERATIVE DISORDERS

1. CNS TRAUMA; CEREBROVASCULAR DISORDERS; DEGENERATIVE DISORDERS

2. CNS Injury • Increased intracranial pressure (i.c.p.) • Due to • Tumor growth • Edema • Excess csf • Hemorrhage

3. 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?

4. 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:

5. 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)

6. 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

8. 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

9. 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

10. 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

11. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

21. 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

22. 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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24. 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

25. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

35. 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

36. 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

38. 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