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Paj 5103 clinical neuropahtophys ii hn10


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Paj 5103 clinical neuropahtophys ii hn10

  1. 1. Lecture II Ng, Hoikee PA-C, MPAS Nova Southeastern University
  2. 3. Learning Objectives <ul><li>Understand the mechanisms of brain injury </li></ul><ul><li>Understand how the brain components affect intracranial pressure </li></ul><ul><li>Define different types of tramatic brain injury </li></ul><ul><li>Understand different types of intracranial hematomas </li></ul><ul><li>Understand the epidemiology and etiology of cerebrovascular disease </li></ul><ul><li>Understand the epidemiology and etiology of different type of central nervous system infections </li></ul>
  3. 4. Acute brain injury <ul><li>Brain trauma </li></ul><ul><li>Cerebrovascular disease </li></ul><ul><li>Brain hemorrhage </li></ul><ul><li>Central nervous infections </li></ul>
  4. 5. Mechanisms of Brain Injury <ul><li>Primary brain injury occurs as a direct result of the initial insult (trauma, stroke) </li></ul><ul><li>Secondary injury refers to progressive damage resulting from the body’s physiologic response to the primary insult, (from days to weeks) </li></ul><ul><li>A critical factor in determining the neuronal cell fate after injury is the degree of adenosine triphosphate (ATP) depletion </li></ul>
  5. 6. Sequence of neuronal cell injury following acute ischemia Ischemia Cell hypoxia Mitochondrial failure Decreased ATP production Decreased Ca++ pumping Calcium overload Increased Glutamate release Open NMDA channels Free-radical production Reperfusion Immune cells Cell death
  6. 7. Mechanisms of Brain Injury (Cont.) <ul><li>Ischemia and Hypoxia </li></ul><ul><li>Ischemia is a contributing factor as the primary insult </li></ul><ul><li>Ischemia results in immediate neurologic dysfunction due to the inability of neurons to generate the ATP needed for energy-requiring processes </li></ul><ul><li>Ischemia sets the stage for secondary injury by oxygen free radicals, excitatory amino acids, and inflammatory cells. </li></ul>
  7. 8. Mechanisms of Brain Injury (Cont.) <ul><li>Cellular Energy Failure </li></ul><ul><li>Neuronal tissue is highly sensitive to oxygen deprivation because it has great ATP requirement </li></ul><ul><li>Lack of cellular oxygen results in mitochondrial dysfunction ; anaerobic glycotic pathways are initiated; pyruvate converted to lactate; hydrogen ions lead to cellular acidosis , which affects neuronal integrity; inadequate energy supply leads to deterioration of ion gradients ( Calcium overload ) </li></ul><ul><li>Calcium overload is thought to be a critical factor leading to activation of enzyme cascades, which disrupt function and cause irreversible damage to cell membranes </li></ul>
  8. 9. Mechanisms of Brain Injury (Cont.) <ul><li>Excitatory Amino Acids </li></ul><ul><li>Excessive glutamate may be released because of impaired membrane integrity </li></ul><ul><li>Reuptake mechanisms fail to remove excess glutamate because they are energy-dependent processes </li></ul><ul><li>Excess glutamate stimulates nearby neurons that then take up large amounts of injurious calcium ions; calcium overload , which results in cytotoxic edema, a rapid swelling of neurons </li></ul><ul><li>Gluatmate binds to NMDA receptors , stimulates nitric oxide production in neurons; in excess it may increase the production of reactive nitrogen species that function as free radicals to damage cellular components </li></ul>
  9. 10. Mechanisms of Brain Injury (Cont.) <ul><li>Reperfusion Injury </li></ul><ul><li>Is the secondary injury that occurs after re-establishing blood flow </li></ul><ul><li>When oxygen reenters cells, erratic transfer of electrons to oxygen can produce reactive oxygen products that behave as free radicals (hydroxyl radicals, superoxide, peroxide) </li></ul><ul><li>Cell membranes may undergo lipid peroxidation in response to free radical damage with subsequent formation of arachidonic acid </li></ul><ul><li>Arachidonic acid cascade yields more oxygen free radicals and immune cells (interleukin, tumor necrosis factor, neurophils) </li></ul><ul><li>All this contributes to brain inflammation </li></ul>
  10. 11. Mechanisms of Brain Injury (Cont.) <ul><li>Abnormal Autoregulation </li></ul><ul><li>Autoregulation is normally influenced by the partial pressures of carbon dioxide and oxygen in the arterial blood </li></ul><ul><li>PaCO2 decreased: cerebral vessels constrict </li></ul><ul><li>PaCO2 increased: cerebral vessels dilate </li></ul><ul><li>Excessive cerebral blood volume can exacebrate cerebral edema </li></ul><ul><ul><li>Hyperventilation  low PaCO2  vasoconstriction  reduction of ICP </li></ul></ul>
  11. 12. Mechanisms of Brain Injury (Cont.) <ul><li>Injury can cause local or global impairment of autoregulation </li></ul><ul><li>Loss of matching between oxygen supply and demand occurs when autoregulatory mechanisms fail </li></ul>
  12. 13. Sequence of neuronal cell injury following acute ischemia Ischemia Cell hypoxia Mitochondrial failure Decreased ATP production Decreased Ca++ pumping Calcium overload Increased Glutamate release Open NMDA channels Free-radical production Reperfusion Immune cells Cell death Calcium overload is a key event in producing cellular damage
  13. 14. Mechanisms of Brain Injury (Cont.) <ul><li>Consequence of the mechanisms of brain injury </li></ul><ul><li>A. Increased Intracranial Pressure (ICP) </li></ul><ul><li>Volume of cranium composed of three elements: brain tissue, cerebrospinal fluid (CSF), blood </li></ul><ul><li>Monro-Kellie hypothesis: compensatory responses to change in volume in any of these components </li></ul><ul><li>Increased ICP can occur with space-occupying lesions, vasogenic or cytotoxic edema, or with obstruction or excessive production of CSF </li></ul>
  14. 15. Mechanisms of Brain Injury (Cont.) <ul><li>Cytotoxic edema (intracellular edema) </li></ul><ul><ul><li>Ischemic tissue swells because of cellular energy (ATP) failure. Calcium overload, Na inflow to the cell, creating an osmotic force to draw in water </li></ul></ul><ul><li>Vasogenic edema </li></ul><ul><ul><li>Increase capillary pressure  damage to the capillary endothelium  extravasation of electrolytes, proteins and fluid into the intracellular space  disrupt the blood brain barrier  brain swells  cerebral edema </li></ul></ul>
  15. 16. Mechanisms of Brain Injury (Cont.)
  16. 17. Mechanisms of Brain Injury (Cont.) <ul><li>Consequence of the mechanisms of brain injury </li></ul><ul><li>B. Brain Compression and Herniation </li></ul><ul><li>As intracranial pressure rises, it can compress neural tissue and blood vessels </li></ul><ul><li>Herniation: the protrusion of brain tissue through an opening in the supporting dura of the brain </li></ul><ul><li>Types of herniation syndromes include: </li></ul><ul><ul><li>Subfalcine </li></ul></ul><ul><ul><li>Tentorial </li></ul></ul><ul><ul><li>Uncal </li></ul></ul><ul><ul><li>Tonsillar </li></ul></ul>
  17. 18. Mechanisms of Brain Injury (Cont.)
  18. 19. Mechanisms of Brain Injury (Cont.) <ul><li>From the ischemia injury, if not treat promptly, will result in focal cell death, cascade event causes cerebral edema, increase ICP, brain herniation, result in permanent neurologic damage </li></ul>
  19. 20. Traumatic Brain Injury <ul><li>TBI is a major cause of death and a leading cause of disability among young adults </li></ul><ul><li>Most head injuries are incurred in motor vehicle accidents, falls, and sports accidents </li></ul><ul><li>The severity of TBI is classified by the GCS (Glasgow Coma Scale) score as: </li></ul><ul><ul><li>Mild GCS score 13-15 </li></ul></ul><ul><ul><li>Moderate GCS score 9-12 </li></ul></ul><ul><ul><li>Severe GCS score 8 or below </li></ul></ul>
  20. 21. Epidemiology <ul><li>1.5 million cases of TBI diagnosed annually; 50,000 result in death </li></ul><ul><li>Males are more likely to sustain a TBI and have a higher risk of death from TBI than females </li></ul><ul><li>Those at lowest socioeconomic levels have the highest per capita rate of TBI </li></ul>
  21. 22. Types of Brain Injury <ul><li>Tramatic brain injury: Primary injury </li></ul><ul><ul><li>Focal </li></ul></ul><ul><ul><li>Polar </li></ul></ul><ul><ul><li>Diffuse </li></ul></ul><ul><li>Intracranial hematomas </li></ul><ul><ul><li>Epidural </li></ul></ul><ul><ul><li>Subdural </li></ul></ul><ul><ul><li>Subarachnoid </li></ul></ul>
  22. 23. Primary Injury <ul><li>Focal injuries localized to site of impact </li></ul><ul><li>Polar injuries are due to acceleration-deceleration movement of the brain within the skull, resulting in double injury </li></ul><ul><li>Diffuse injury is due to movement of the brain within the skull, resulting in widespread axonal injury </li></ul>
  23. 24. Types of Tramatic Brain Injury <ul><li>Concussion </li></ul><ul><ul><li>Head injury produces an alternation on consciousness, but no evidence of brain damage is found on physical and radiologic exam </li></ul></ul><ul><ul><li>Common consequence of sports related head injury </li></ul></ul><ul><li>Contusion </li></ul><ul><ul><li>When CT or MRI reveals an area of brain tissue damage (necrosis, laceration, bruising) </li></ul></ul>
  24. 25. Primary Injury (Cont.) <ul><li>Intracranial Hematomas </li></ul><ul><li>Disruption of the vasculature can result in intracranial hemorrhage </li></ul><ul><li>May expand slowly or rapidly, progressively compressing brain structures and increasing ICP </li></ul><ul><li>Three types of hematoma can develop: </li></ul><ul><ul><li>Epidural </li></ul></ul><ul><ul><li>Subdural </li></ul></ul><ul><ul><li>Subarachnoid </li></ul></ul>
  25. 26. Primary Injury (Cont.) 05/18/10
  26. 27. Primary Injury (Cont.) <ul><li>Epidural Hematoma </li></ul><ul><li>Collection of blood between dura and skull </li></ul><ul><li>Typically involves arterial injury thus rapid onset of symptoms </li></ul><ul><li>Often involves a fracture of the temporal bone with disruption of the middle meningeal artery </li></ul>
  27. 28. Primary Injury (Cont.) <ul><li>Subdural Hematoma </li></ul><ul><li>Collection of blood between dura and outer layer of the arachnoid membrane </li></ul><ul><li>Typically involves bridging veins, thus symptom onset may be slower </li></ul><ul><ul><li>Bridging veins drain venous blood from the surface of the brain, crossing the arachnoid and subdural spaces before emptying into the venous sinuses </li></ul></ul><ul><li>Chronic subdural hematomas may be prone to rebleeding </li></ul>
  28. 29. Primary Injury (Cont.) <ul><li>Subarachnoid Hemorrhage </li></ul><ul><li>Collection of blood between arachnoid membrane and the pia mater </li></ul><ul><li>Due to rupture of bridging veins (tramatic brain injury) that pass through the subarachnoid space </li></ul><ul><li>Can also be caused by rupture of cerebral aneurysm, arteriovenous malformations </li></ul><ul><li>Blood spreads throughout CSF, causing meningeal irritation </li></ul>
  29. 30. Primary Injury (Cont.) <ul><li>Cerebral Aneurysm and Arteriovenous Malformation </li></ul><ul><ul><li>Structural abnormalities of the cerebral arteries predispose to intracerebral bleeding and hemorrhage </li></ul></ul><ul><ul><li>Cerebral aneurysms and AVMs are the most common causes of subarachnoid hemorrhage </li></ul></ul>
  30. 31. Primary Injury (Cont.) <ul><li>Cerebral Aneurysm </li></ul><ul><li>Lesion of an artery that results in dilation and ballooning of a segment of the vessel </li></ul><ul><li>Congenital defect of the medial layer of the artery weakens to arterial pressure, allowing the dilated portion to fill with blood and eventually burst causing SAH </li></ul><ul><li>90%of cerebral aneurysms are located in the circle of Willis </li></ul><ul><li>Typical presentation is severe HA with meningismus: worst headache in his/her life </li></ul><ul><li>Treatment involves surgical stabilization with aneurysm clipping or embolization </li></ul>
  31. 32. Primary Injury (Cont.) <ul><li>Arteriovenous Malformation </li></ul><ul><li>Capillary system fails to develop appropriately with arterial blood shunted directly into the venous system; causes the vessels to progressively enlarge; becomes a congested mass of enlarged vessels that can burst </li></ul><ul><li>The majority of AVMs are diagnosed in 20-40 yrs of age </li></ul><ul><li>90% of AVMs are found in the cerebral hemispheres </li></ul><ul><li>Patients typically present with seizure and neurologic dysfunction </li></ul>
  32. 33. Secondary Injury <ul><li>Ischemic and hypoxic events, subsequent vasogenic/ cytotoxic edema and other processes that lead to increased ICP, and altered vascular regulation may affect patient outcomes to a greater extent than the primary injury </li></ul><ul><ul><li>Vasogenic, cytotoxic edema may increase for 48 to 72 hrs after injury </li></ul></ul>
  33. 34. Cerebrovascular Disease and Stroke <ul><li>Stroke is a sudden onset of neurologic dysfunction due to cardiovascular disease that results in an area of brain infarction </li></ul><ul><li>Stroke is the third leading cause of death in the United States </li></ul><ul><li>Most common form of stroke is ischemic </li></ul>
  34. 35. Epidemiology <ul><li>Females affected more often than males </li></ul><ul><li>Most stroke victims are >65 years of age </li></ul><ul><li>Risk factors are similar to those for other atherosclerotic vascular diseases (hypertension, DM, hyperlipidemia, smoking) </li></ul>
  35. 36. Ischemic Stroke <ul><li>Result from sudden occlusion of cerebral artery secondary to thrombus formation or emboli </li></ul><ul><li>Thrombotic strokes associated with atherosclerosis and coagulopathies </li></ul><ul><li>Embolic strokes associated with cardiac dysfunction or dysrhythmias (atrial fibrillation) </li></ul><ul><li>Penumbra: a much larger area of ischemic but viable cells that is surrounding the infarct. The penumbra receives some partial or collateral flow and may recover if the ischemia is mild or perfusion is restored in a timely manner. </li></ul><ul><li>Salvaging the penumbra is the aim of early thrombotic therapy; however, treatment must be instituted within 3 hours of symptom onset to be maximally effective </li></ul>
  36. 37. Ischemic Stroke <ul><li>Transient ischemic attack (TIA) </li></ul><ul><ul><li>Neurologic symptoms typically last only minutes, but may last as long as 24 hrs. Symptoms resolve completely without evidence of neurologic dysunction </li></ul></ul><ul><li>Lacunar infarcts </li></ul><ul><ul><li>Occlusion of the small penetrating arterioles can produce small lesions. The basal ganglia, pons, cerebellum and internal capsule are common sites for lacunar infarcts </li></ul></ul>
  37. 38. Hemorrhagic Stroke <ul><li>Hemorrhage within the brain parenchyma </li></ul><ul><li>Usually occurs secondary to severe, chronic, hypertension </li></ul><ul><li>Most occur in basal ganglia or thalamus </li></ul><ul><li>Degree of secondary injury and associated morbidity and mortality is much higher in hemorrhagic stroke than ischemic stroke </li></ul>
  38. 39. Central Nervous System Infections <ul><li>Organisms may gain access to the CNS through the bloodstream, direct extension from a primary site or along peripheral and cranial nerves, or through maternal-fetal exchange </li></ul><ul><li>Meningitis and cerebral abscess commonly associated with bacterial infections; encephalitis is usually viral </li></ul><ul><li>A frequent consequence of bacterial infections is hydrocephalus, as the bacterial, WBCs block CSF resorption in the arachnoid villi </li></ul>
  39. 40. Meningitis <ul><li>Bacteria usually reach the CNS via the bloodstream or extension from cranial structures </li></ul><ul><li>Most common bacteria are Streptococcus pneumoniae and Neisseria meningitidis </li></ul><ul><li>Bacteria invade leptomeninges (pia mater & the arachnoid space) accumulation of inflammatory exudate can result in hydrocephalus </li></ul>
  40. 41. Encephalitis <ul><li>Inflammation of the brain commonly caused by West Nile virus, western equine encephalitis, and herpes simplex </li></ul><ul><li>Typical presentation includes fever, HA, malaise, muscle pain, and/or rash </li></ul>
  41. 42. Brain Abscess <ul><li>Localized collection of pus within the brain parenchyma </li></ul><ul><li>Pyogenic (pus-producing) pathogens reach the brain by </li></ul><ul><ul><li>Penetrating wounds </li></ul></ul><ul><ul><li>Direct extension or retrograde thrombophlebitis of an infected neighboring structure (mastoiditis) </li></ul></ul><ul><ul><li>Blood borne dissemination for a distant infected site (lungs) </li></ul></ul>
  42. 43. Brain Abscess <ul><li>Most common infective organisms: streptococci, staphylococci, and anaerobes </li></ul><ul><li>The abscess has a focal infected core: central portion contains neurtrophils and pus </li></ul><ul><li>The peripheral portion of the abscess: made up of inflammatory granulation tissue </li></ul><ul><li>Around the brain abscess is perifocal edema with proliferation of surviving astrocytes. </li></ul><ul><li>In chronic phase, the core is liquefied & the peripheral portion forms a collagenous capsule & is surrounded by fibrous gliosis </li></ul>
  43. 44. Brain Abscess
  44. 45. Chronic Disorders of Neurologic Function
  45. 46. Learning objectives <ul><li>Understand the etiology and pathogenesis of cerebral and cerebellar disorder: Seizure disorder, Dementia, Parkinson disease, Cerebral Palsy, hydrocephalus, cerebellar disorders. </li></ul><ul><li>Understand the etiology and pathogenesis of certain spinal cord and peripheral nerve disorders: Multiple Sclerosis, Spina Bifida, Amyotrophic Lateral Sclerosis, Spinal Cord Injury, Guillain-Barre Syndrome </li></ul>
  46. 47. Brain and cerebellar disorders <ul><li>Seizure Disorder </li></ul><ul><li>Dementia </li></ul><ul><li>Parkinson Disease </li></ul><ul><li>Cerebral Palsy </li></ul><ul><li>Hydrocephalus </li></ul><ul><li>Cerebellar Disorders </li></ul>
  47. 48. Seizure Disorder <ul><li>Transient neurologic event of paroxysmal abnormal or excessive cortical electrical discharges that are manifested by disturbances of skeletal motor function, sensation, autonomic visceral function, behavior, or consciousness </li></ul><ul><li>Epilepsy or seizure disorder refers to recurrent seizures </li></ul><ul><li>Seizures are a component of many diseases </li></ul>
  48. 49. Seizure Disorder <ul><li>Etiology </li></ul><ul><ul><li>Acquired event as a consequence of cerebral injury or other pathologic process such as tumors, blood clots, infection, metabolic disorders, head injury, stroke, medication overdose, medication adverse effect, exposure to toxins </li></ul></ul><ul><ul><li>In some cases, no explanation for the seizure disorder: idiopathic seizures. </li></ul></ul>
  49. 50. Seizure Disorder <ul><li>Pathogenesis </li></ul><ul><ul><li>Due to an alteration in membrane potential that makes certain neurons abnormally hyperactive and hypersensitive to changes in their environment </li></ul></ul><ul><ul><li>Abnormal neurons form an epileptogenic focus. This focus functions autonomously, emitting excessively large numbers of paroxysmal electrical discharges. Nerve cells can recruit neurons in adjacent areas and synaptically related neurons in distant areas of the brain; thus, greatly increasing the number of neurons involved in seizure activity </li></ul></ul>
  50. 51. Seizure Disorder
  51. 52. Seizure Disorder (Cont.) <ul><li>Generalized seizures involve the entire brain from the onset of the seizure </li></ul><ul><li>Partial seizures are those in which abnormal electrical activity is restricted to one brain hemisphere </li></ul><ul><li>Status epilepticus is a continuing series of seizures without a period of recovery between seizure episodes and can be life-threatening </li></ul>
  52. 53. Dementia <ul><li>A syndrome associated with many pathologic processes and characterized by progressive deterioration and continuing decline of memory and other cognitive changes </li></ul><ul><li>Patients may initially appear uninterested or lacking initiative, many have agnosia (lack of ability to interpret sensory stimulation) or lack of insight into their cognitive deficiencies </li></ul><ul><li>Important to first rule out manageable causes of dementia; often cause unknown </li></ul>
  53. 54. Dementia <ul><li>Etiology </li></ul><ul><li>50-60% Alzhemier ‘sdisease </li></ul><ul><li>15-20% vascular dementia </li></ul><ul><li>Dementia-causing illness: alcoholism, intracranial tumor, normal pressure hydrocephalus, Parkinson disease, Lewy Body disease, Huntington disease, multiple sclerosis, Creutzfeldt-Jakob disease </li></ul>
  54. 55. Dementia <ul><li>Delirium </li></ul><ul><ul><li>A global mental dysfunction includes disturbed consciousness, decreased awareness of the environment, inability to maintain attention, disrupted sleep wake cycles, drowsiness, restlessness, emotional lability, incoherence, hallucinations </li></ul></ul><ul><ul><li>Abrupt onset, fluctuate often, worse at night </li></ul></ul><ul><ul><li>Causes: polypharmacy, metabolic abnormalities, nutritional deficiencies, infection </li></ul></ul>
  55. 56. Dementia <ul><li>Pathogenesis of Alzheimer’s disease </li></ul><ul><ul><li>1. Intracellular neurofibrillary tangles </li></ul></ul><ul><ul><li>2. Extracellular amyloid (senile) plaques </li></ul></ul><ul><ul><li> diffuse neuronal damage & brain atrophy occurs </li></ul></ul><ul><ul><li>The brain of Alzheimer disease often weighs less than a normal person </li></ul></ul><ul><ul><li>The temporoparietal and anterior frontal regions of the brain are affected the most </li></ul></ul>
  56. 57. Dementia <ul><li>Pathogenesis of Alzheimer’s Disease </li></ul><ul><ul><li>3. Neurotransmitter system: abnormalities in cholinergic system </li></ul></ul><ul><ul><ul><li>Reduced activity of choline acetyltransferase(the enzyme necessary for acetylcholine synthesis), and decreased ACH synthesis </li></ul></ul></ul>
  57. 58. Dementia <ul><li>Conclusion: </li></ul><ul><li>The dementia of Alzheimer disease is characterized by degeneration of neurons in temporal and frontal lobes, brain atrophy, amyloid plaques, and neurofibrillary tangles </li></ul><ul><li>Cause remains unknown, although genetic and environmental triggers are suggested </li></ul><ul><li>Synthesis of brain acetylcholine is deficient and treatment is aimed at increasing acetylcholine levels by reducing acetylcholine reuptake </li></ul>
  58. 59. Parkinson’s disease <ul><li>The basal ganglia includes the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, and substantia nigra. </li></ul>
  59. 60. Parkinson disease <ul><li>The basal ganglia and the cerebellum transmit information via the thalamus to the cerebral cortex in order to regulate movement. In a healthy brain, the neurons based in the substantia nigra extend into the putamen and caudate (which both comprise the striatum). These cells release dopamine in the striatum, which modulates neuronal activity. As a result, this affects the performance of movement. </li></ul>
  60. 61. Basal Ganglia
  61. 62. Parkinson disease <ul><li>In Parkinson’s disease, there is a breakdown in the connection between the neuron in the substantia nigra and the putamen portion of the striatum. Symptoms of Parkinson’s disease appear after 60-80% of these cells become impaired or die. It is not specifically the loss of the cells that causes the disease, but rather the decrease in the dopamine, which occurs with the decreased number of substantia nigra neurons. </li></ul>
  62. 63. Parkinson disease <ul><li>Typically, symptoms appear after striatal dopamine levels have decreased by 20-50% of normal levels. </li></ul><ul><li>When Substantia nigra projections to the putamen have been impaired, the globus pallidus interna and subthalamic nucleus begin to function abnormally. The result is that the brain is no longer able to sufficiently control motor function. </li></ul>
  63. 64. Parkinson Disease (Cont.) <ul><li>These signals could overly excite many of the muscles of the body, leading to rigidity. Symptoms include lead-pipe rigidity, tremor, pill-rolling movements, and reduced voluntary movement , loss of facial expression, drooling, propulsive gait, and absent arm swing </li></ul>
  64. 65. Parkinson Disease (Cont.)
  65. 66. Cerebral Palsy <ul><li>Diverse group of crippling syndromes that appear during childhood and involve permanent, nonprogressive damage to motor control areas of the brain </li></ul><ul><li>Classified on the basis of neurologic signs and symptoms, with the major types involving spasticity, ataxia, dyskinesia, or a mix of one or more of the three </li></ul>
  66. 67. Cerebral Palsy (Cont.) <ul><li>Etiology may include prenatal infections, or diseases of the mother; mechanical trauma to the head before, during, or after birth; exposure to nerve-damaging poisons or reduced oxygen supply to the brain </li></ul>
  67. 68. Hydrocephalus <ul><li>Characterized by abnormal accumulation of fluid in the cerebroventricular system </li></ul><ul><li>1. Normal pressure hydrocephalus is due to an increased volume of CSF without change in ICP </li></ul><ul><ul><li>Ventricles become distended, compressing brain tissue & cerebral vessels </li></ul></ul><ul><ul><li>NPH triad of symptoms: gait instability, urinary incontience, dementia </li></ul></ul>
  68. 69. Hydrocephalus <ul><li>2. Obstructive hydrocephalus is due to an obstruction to the flow of CSF </li></ul><ul><ul><li>There is an obstruction at some point in either the intraventricular or extraventricular pathways of the ventricular system. </li></ul></ul><ul><ul><li>Usually congential abnormality, such as stenosis of the foramina of the 4 th ventricle, aqueduct stenosis or spina bifida cystica </li></ul></ul>
  69. 70. Hydrocephalus <ul><li>3. Communicating hydrocephalus occurs due to abnormal absorption of CSF </li></ul><ul><ul><li>Also called acquired communicating hydrocephalus </li></ul></ul><ul><ul><li>Abnormality in CSF absorption from the subarachnoid space. There is no obstruction to the flow of the fluid between the ventricles and subarachnoid space </li></ul></ul><ul><ul><li>Causes: Infections, trauma, tumors </li></ul></ul>
  70. 71. Hydrocephalus (Cont.)
  71. 72. Hydrocephalus <ul><li>Medical treatment is limited </li></ul><ul><li>Obstructions may be corrected surgically </li></ul><ul><li>The most effective treatment for management of hydrocephalus is surgical correction employing a shunt </li></ul>
  72. 73. Hydrocephalus (Cont.)
  73. 74. Cerebellar Disorders <ul><li>Cerebellum is responsible for coordinated control of muscle action, excitation and inhibition of postural reflexes, and maintenance of balance </li></ul><ul><li>Etiology of cerebellar disorders includes abscess, hemorrhage, tumors, trauma, viral infection, or chronic alcoholism </li></ul><ul><li>Clinical manifestations include ataxia, hypotonia, intention tremors, and disturbances in gait and balance </li></ul>
  74. 75. Spinal cord & peripheral nerve disorders <ul><li>Multiple sclerosis </li></ul><ul><li>Spina bifida </li></ul><ul><li>Amyotrophic lateral sclerosis </li></ul><ul><li>Spinal cord injury </li></ul><ul><li>Guillain barre syndrome </li></ul>
  75. 76. Multiple Sclerosis <ul><li>Chronic inflammation, demyelination, & gliosis (scarring) </li></ul><ul><ul><li>“ Disseminated in time & space” </li></ul></ul><ul><li>Affects 400,000 Americans </li></ul><ul><ul><li>Most frequent cause of neurologic disability early/middle adulthood (excluding trauma) </li></ul></ul><ul><li>? autoimmune etiology </li></ul><ul><ul><li>environmental trigger in genetically susceptible </li></ul></ul><ul><li>Name from plaques in white matter </li></ul><ul><ul><li>Occasionally - gray matter </li></ul></ul>
  76. 77. Multiple Sclerosis <ul><li>Epidemiology: </li></ul><ul><ul><li>Female:Male = 2:1 </li></ul></ul><ul><ul><li>Onset of age: 20-50 yrs </li></ul></ul><ul><ul><li>Orkney islands - Scandinavia - northern European descent </li></ul></ul><ul><ul><li>US - Caucasians > other races </li></ul></ul><ul><ul><li>Rare in Japan; unknown in black Africans; </li></ul></ul><ul><ul><ul><li>Japanese Americans/African Americans  risk </li></ul></ul></ul><ul><ul><li>Disease of temperate climates </li></ul></ul>
  77. 78. Multiple Sclerosis <ul><li>Etiology </li></ul><ul><ul><li>A viral infection or environmental toxin intitates the autoimmune attack in a genetrically predisposed individual </li></ul></ul><ul><ul><li>Both humoral and cellular immune factors have been implicated in demyelination </li></ul></ul><ul><ul><li>T-cell lymphocyte-mediated damage to the myelin has also been implicated in causing the autoimmune damage and sustaining inflammation </li></ul></ul>
  78. 79. Multiple Sclerosis <ul><li>Pathogenosis </li></ul><ul><ul><li>Demyelination can occur throughout the CNS but often affects the optic and oculomotor nerves, the corticospinal, cerebellar, and posterior column systems </li></ul></ul><ul><ul><li>Myelin facilitates nerve conduction, inflammation and scarring of the myelin slows or interrupts the conduction of nerves impulses </li></ul></ul>
  79. 80. Spinal Cord and Peripheral Nerve Disorders
  80. 81. Spina Bifida <ul><li>Developmental anomaly characterized by defective closure of the bony encasement of the spinal cord (neural tube) through which the spinal cord and meninges may or may not protrude </li></ul><ul><li>If anomaly not visible, condition is called spina bifida occulta </li></ul><ul><li>If there is an external protrusion of the saclike structure, the condition is called spina bifida cystica, and further classified according to the extent of neural involvement </li></ul>
  81. 82. Amyotrophic Lateral Sclerosis <ul><li>ALS is a progressive degenerative disease affecting both the upper and lower motor neurons </li></ul><ul><li>Cause remains unknown, environmental factors, and genetic predisposition </li></ul><ul><li>Weakness and wasting of the upper extremities usually occur, followed by impaired speech, swallowing, and respiration </li></ul><ul><li>Typically occurs between the ages of 40-60 years and affects men more than women </li></ul>
  82. 83. Amyotrophic Lateral Sclerosis <ul><li>Pathologic changes in the spinal cord include degeneration of the lateral columns where the corticospinal tracts are located </li></ul><ul><li>ALS is also known as Lou Gehrigh disease </li></ul>
  83. 84. Spinal Cord Injury <ul><li>Etiology </li></ul><ul><ul><li>Usually traumatic, a result of motor vehicle accidents, falls, penetrating wounds, or sports injuries </li></ul></ul>
  84. 85. Spinal Cord Injury <ul><li>Pathogenesis </li></ul><ul><ul><li>The major mechanisms of injury: hyperflexion, hyperextension, and compression </li></ul></ul><ul><ul><li>Primary injury: The cord may be compressed, transected, or contused </li></ul></ul><ul><ul><li>Secondary injury: edema, ischemia, excitotoxicity, inflammation (neutrophils, macrophages, pro-inflammatory cytokines, T-lymphocytes), causing increased cell death, disruption of blood brain barrier, and demyelination </li></ul></ul>
  85. 86. Spinal Cord Injury (Cont.)
  86. 87. Spinal Cord Injury (Cont.) <ul><li>Spinal shock occurs immediately following SCI and is characterized by temporary loss of reflexes below the level of injury </li></ul><ul><ul><li>Muscles are flaccid; skeletal and autonomic reflexes are lost </li></ul></ul><ul><li>Neurogenic shock may occur after SCI due to peripheral vasodilation </li></ul><ul><ul><li>Hypotension and circulatory collapse can occur; high spinal cord injuries can affect respiratory muscles, leading to ventilatory failure </li></ul></ul>
  87. 88. Guillain-Barré Syndrome <ul><li>Acute Inflammatory Demyelinating Polyneuropathy (AIDP) </li></ul><ul><ul><li>Axonal degeneration </li></ul></ul><ul><li>Disease of the peripheral nervous system or a lower motor neuron disorder </li></ul><ul><li>Immune-mediated - ? immunopathogenesis </li></ul><ul><li>~ 75% - antecedent infection (prior 1-3 wks acute infection process) </li></ul><ul><ul><li>CMV& EBV, Campylobacter jejuni gastroenteritis, herpesvirus, mycoplasma, surgical procedure </li></ul></ul>
  88. 90. Guillain-Barré Syndrome (GBS) <ul><li>Occurs: 0.6-1.9 cases/100,000/yr </li></ul><ul><li>All parts of world; all seasons; children & adults; both sexes; all ages (  d 50-81 yoa) </li></ul><ul><li>Life-threatening </li></ul><ul><ul><li>respiratory insufficiency, swallowing difficulties, & autonomic dysregulation </li></ul></ul><ul><li>Mortality < 5% in optimal settings </li></ul><ul><li>Ascending, primarily motor paralysis </li></ul>
  89. 91. References <ul><li>Pathophysiology by Copstead & Banasik </li></ul><ul><ul><li>Ch 44, 45 </li></ul></ul>