Pathology of the central nervous system

1. Pathology of the central nervous system Jumphol Mitchai MD Department of pathology Khon kaen university

2. Review of the CNS(1) Scalp Skull � sutures and foramina Meninges : CNT Dura mater � fibrous double-layered membrane that separates at specific point to form dural sinuses Superior sagittal vanous sinus Etc.

6. Review of the CNS(2) Arachnoid � a loose weblike CNT Subarachnoid space � CSF Arachnoid granulation or villi Pia mater � very delicate CNT Partition of meninges Falx cerebri Tentorium cerebelli

8. Review of the CNS(3) Cerebrum Cerebral hemisphere Gyri and sulci Gray and white matter Major functional areas Motor cortex (precentral gyri) Sensory cortex (postcentral gyri) Broca�s area (left frontal) � expressive speech

11. Review of the CNS(4) Wernicke�s area � language integration center, both spoken and written Auditory area (temporal lobe) Visual area (occipital lobe) Diencephalon � central portion of the brain Thalamus � relay station for sensory impulses Hypothalamus � homeostasis, ANS and some endocrine system.

14. Review of the CNS(5) Brain stem Pons Medulla oblongata Respiratory center Cardiovascular center Cough reflex, swallowing, vomitting Pyramidal decussation Reticular formation � reticular activating system(RAS)

15. Review of the CNS(6) Cerebellum coordinate movement and maintain posture and equilibrium using input from propioceptors in joints and muscles, visual pathways and vestibular pathways from inner ear. Spinal cord Nerve fibers or tracts Spinal nerves

16. Review of the CNS(7) Ventricular system Lateral ventricles 3rd and 4th ventricles Choroid plexuses and CSF production Foramen of monro, aqueduct of Sylvius foramen of Luschka and Magendie Cranial nerves

18. Review of the CNS(8) Histology Neurons � axon Glias Astrocytes Oligodendroglias Ependymal cells Microglias � fixed macrophages

19. Common pathological features Increased intracranial pressure and brain herniation Cerebral edema Hydrocephalus

20. Increased ICP(1) Skull is rigid and nonexpandable. Increased fluid or additional tissue in intracranial space leads to increased ICP Causes of increased ICP Space-occupying mass : tumor, abscess, hematoma

21. Increased ICP(2) Diffuse lesions : brain edema, encephalitis, subarachnoid hemorrhage Increased volume of CSF : hydrocephalus

22. Increased ICP(3) Signs and symptoms Severe headache, (projectile) vomiting Decreased level of consciousness Cushing�s reflex : increased systolic BP, increasing pulse pressure, slowing heart rate and respiratory rate Papilledema

23. Brain herniation Subfalcine herniation Cingulate gyrus

25. Brain herniation Subfalcine herniation Transtentorial herniation Uncal gyrus Ipsilateral pupillary dilate (CN III compression) Contralateral hemiparesis or less common ipsilateral hemiparesis (Kernohan�s phenomenon)

26. Brain herniation Subfalcine herniation Transtentorial herniation Tonsillar herniation Cerebellar tonsils Medulla oblongata compression ? stop respiration

28. Brain herniation Subfalcine herniation Transtentorial herniation Tonsillar herniation Transcalvarial herniation Occur through skull and dura defect

29. Cerebral edema (1) Abnormal fluid accumulation in cerebral parenchyma Types Vasogenic edema - increased vascular permeability Tumor, inflammation Cytotoxic edema � altered cell regulation of fluid toxin

30. Cerebral edema (2) Interstitial edema � transudation of CSF through ependymal lining Hydrocephalus Pathology Increased brain weight Flat gyri Narrow sulci

31. Hydrocephalus (1) Enlargement of ventricles due to increase CSF volume Noncommunicating hydrocephalus = obstruction of CSF flow in ventricular system Congenital malformation : stenosis of aqueduct of sylvius, foramen of monro stenosis Tumor or hematoma

32. Hydrocephalus (2) Communicating hydrocephalus = obstruction of subarachnoid flow of CSF Decreased reabsorption : SAH, meningitis Increased production : choroid plexus papilloma or carcinoma, ependymoma

33. Hydrocephalus (3) Pathology : dilated venticles, compressed white matter Clinical : Acute � increased ICP Chronic � weakness & incoordination, dementia, incontinence

35. Neural tube defect (1) Neural tube defect Commonest Defective closure of the midline structure over the neural tube Risk factor � folate def. in initial week of gestation

37. Neural tube defect (2) Anencephaly Absence of cranial vault and brain Fatal, spontaneous abortion Encephalocele Ossification defect in the skull Herniation of the brain & meninges Occipital, frontal, orbital & nasal

38. Neural tube defect (3) Spina bifida (spinal dysraphism) Defective development and closure of vertebral arch Most common in lumbar region 2 types Spina bifida occulta Spina bifida cystica

39. Neural tube defect (4) Spina bifida occulta Asymptomatic Normal spinal cord and meninges May have sinus tract of overlying skin Spina bifida cystica Meningomyelocele (myelomeningocele) Extension of CNS tissue through a defect Common in LS region

40. Neural tube defect (5) Meningocele Only meningeal extrusion Clinical Motor & sensory deficit in lower extremity Disturbances of bowel & bladder control Superimposed infection from overlying skin

41. Posterior fossa abn. (1) Arnold-Chiari malformation Small post. fossa with extension of cerebellar vermis through F. magnum Obstructive hydrocephalus Nearly always association with lumbar myelomeningocele.

42. Posterior fossa abn. (2) Dandy-Walker malformation Enlarged posterior fossa Absence or hypoplastic cerebellar vermis Enlarged fourth ventricle

43. Syringomyelia Cyst within spinal cord, usually posterior to central canal Lined by gliosis (astrocytes) Most common in cervical but may extend to medulla (syringobulbia)

44. Hydromyelia Dilated central canal containing CSF Lined by ependymal cells

45. Syringomyelia & hydromyelia Etiology of both Acquired (majority) : secondary to trauma or ischemia, tumor Congenital : may associated with Arnold-Chiari syndrome Clinical Muscle weakness & atrophy of upper limbs Loss of sensation of pain & temp.

46. Head injury Skull fracture Found 80% of fatal head injury Linear fractures of the cranial vault (62%) may extend to base of skull causing CN laceration Increased incidence of intracranial hematoma

47. Skull fracture Types of skull fracture Linear Penetrating � infection of CNS Compound � increased risk of infection Depressed � increased incidence of epilepsy Comminuted � increased incidence of massive brain damage

48. Brain parenchymal injury Parenchymal injury Concussion = clinical syndrome of alteration of consciousness secondary to head injury Transient neurologic dysfunction Loss of consciousness Temporary respiratory arrest Loss of reflexes Complete recovery Amnesia for the event Post concussion neuropsychiatric syndromes

49. concussion Pathogenesis � unknown (? RAS shock) Repeated concussion may result in brain damage

50. Contusion and laceration(1) Contusion and laceration Contusion = a bruise with extravasation of blood but with intact pia and arachnoid Laceration = tear of pia-arachnoid and brain parenchyma Both are focal brain damage caused by the brain against adjacent bone or direct impact

51. Contusion and laceration(2) Common sites Frontal lobe (inferior surface) Temporal lobe (tip) Less frequent � occipital lobe, brain stem, cerebellum Coup injury = contusion at the point of contact Contracoup injury = contusion at the point opposite to coup lesion

54. Contusion and laceration(3) Immobile head at the time of trauma, only coup injury is found Mobile head, there may be coup and contrecoup lesions Contrecoup lesion is thought to be caused by the brain strikes the opposite inner surface of the skull after sudden deceleration/acceleration (rebound of the brain)

55. Traumatic vascular injuries Epidural hematoma Subdural hematoma Subarachnoid hemorrhage Intraparenchymal hemorrhage

56. Epidural hematoma(1) Skull fracture at temporal bone may causes laceration of middle meningeal artery Recoil of the skull may be the cause

57. Epidural hematoma(2) �Lucid interval� ~ 4-8 hrs., when hematoma reach 30-50 ml. Emergency condition

58. Subdural hematoma(1) Potential space, subdural, contains bridging veins from cortical surface to empty into superior sagittal sinus Brain moves freely but venous sinus is fixed Brain displacement during trauma can tear the veins at the point they penetrate the dura

60. Subdural hematoma(2) Elderly person with brain atrophy, the bridging veins is stretched out Minor head trauma increase rate of subdural hematoma in these person

61. Subdural hematoma(3) Clinically manifest at first 48 hrs. Most-nonlocalising signs : headache, confusion May be focal signs : contralateral paralysis, seizures

62. Subdural hematoma(4) Lateral aspect of cerebral hemishere 10 % bilateral High rebleeding Chronic subdural hematoma = organizing hematoma

63. Spinal cord injury(1) Displacement of vertebral column causes by Stab wound Bullets Vertebral fracture with dislocation

64. Spinal cord injury(2)

65. Spinal cord injury(3) Neurologic manifestation � level of cord in injury Thoracic vertebra or below � paraplegia Cervical vertebra (below C4) � quadriplegia Cervical vertebra (upper C4) � respiratory arrest Interruption of pyramidal tract

67. Cerebrovascular diseases(1) Global cerebral ischemia (ischemic/hypoxic encephalopathy) Focal cerebral ischemia (cerebral infarction)

68. Cerebrovascular diseases(2) Brain is highly aerobic organ 20% of total body oxygen consumption 15% of resting cardiac output Autoregulation of cerebral blood flow Irreversible damage of the brain � 6-8 min.

69. Cerebrovascular diseases(3) Causes of oxygen deprivation Functional hypoxia Low inspire of oxygen Impaired oxygen carrying capacity Inhibit oxygen use by tissue Ischemia Decreased perfusion pressure � hypotension Occlusion of vessels

70. Global cerebral ischemia Ischemic/hypoxic encephalopathy Cause � profound systemic hypotension Transient � complete recovery Prolong � brain necrosis Vegetative state Brain death : diffuse cortical and brain stem damage ? cardiovascular failure

71. Cerebral infarction(1) �stroke� = sudden neurologic deficit caused by abnormal blood supply (including intracerebral hemorrhage) Clinical S&S � anatomic location of infarct Hemiplegia, sensory deficit, blindness, aphasia Fatal or slowly improve

72. Cerebral infarction(1) Etiology Thrombosis Atherosclerosis of bifurcation of carotid a., basilar a. � associated with HT, DM, coronary heart dis., hypercholesterolemia, gout Arteritis : infection (TB, syphilis), autoimmune(SLE, temporal arteritis) Others : polycythemia, dissecting aneurysm

73. Cerebral infarction(2) Embolism Mural thrombosis : MI, valvular dis., arial fibrillation, arterial mural thrombi Embolism from cardiac surgery Fat, tumor & air embolism

75. Intraparenchymal hemorrhage Most common cause of death in �stroke� Predisposing factors : hypertension(80%), AVM, tumor, hemorrhagic diathesis, amyloid angiopathy Hypertensive intracerebral hemorrhage is common

76. Hypertensive intracerebral hemorrhage(1) Site � 70% thalamic/basal ganglia region (ganglionic hemorrhage) HT result in blood vessel wall injury Found in areas supplied by middle, posterior cerebral a. or basilar a. with branching in acute angle from main vessels

77. Hypertensive intracerebral hemorrhage(2)

78. Hypertensive intracerebral hemorrhage(3)

79. Hypertensive intracerebral hemorrhage(4)

80. Hypertensive intracerebral hemorrhage(5) Clinical � up to size and position of lesion, increased ICP with herniation, reabsorption of hematoma

81. Subarachnoid hemorrhage(1) Berry aneurysm is the most common cause Other aneurysm � atherosclerotic aneurysm, mycotic and traumatic dissecting aneurysm Most common site � anterior circulation of circle of Willis at branch points

82. Subarachnoid hemorrhage(2) Clinical 40-50 yrs. Multiple During increased ICP : straining at stool, sexual orgasm Sudden excruciated headache with rapid unconscious Common rebleeding 25-50% death

83. Subarachnoid hemorrhage(3)

84. Subarachnoid hemorrhage(4)

85. Acute hypertensive encephalopathy Emergency condition Occur when diastolic BP>130 mmHg Diffuse cerebral dysfunction : headache, confusion, vomiting, convulsion, coma Patho : brain edema, herniation, petechial hemorrhage, necrotizing arteritis

86. Infections Routes of entry Hematogenous : common Direct implantation : trauma, iatrogenic Local extension : mastoid, infected tooth Peripheral nervous system : rabies, herpes simplex

87. Acute pyogenic meningitis(1) Organism : bacteria Neonate : E. coli, strep gr. B Infant & children : H. influ Adolescents & young adult : N. meningitidis Elderly : strep. pneumo, L. mono.

88. Acute pyogenic meningitis(2) Clinical : S&S of infection with meningeal irritation Headache, photophobia, irritability, clouding of consciousness, stiffneck CSF : purulent, increased protein, decreased glucose Heal � fibrosis, hydrocephalus

89. Acute pyogenic meningitis(3)

90. Aseptic (viral) meningitis Less fulminant course Self limited CSF : lymphocytic pleocytosis, increased protein, normal glucose Cause : entero virus (ECHO, coxsackies virus), HIV

91. Brain abscess(1) Organism : strep., staph Predisposing conditions Acute bacterial endocarditis Cyanotic heart diseases Chronic pulmonary sepsis Clinical : progressive focal deficits, increased ICP

92. Brain abscess(2) CSF : pleocytosis, increased protein, normal glucose Course : may rupture causing ventriculitis, meningitis, sinus thrombosis

93. Brain abscess(3)

94. Tuberculous meningitis(1) Headache, malaise, mental confusion, vomiting CSF : pleocytosis � mononuclear or PMN + mono, increased protein, normal or slightly lower glucose Site : base of skull

95. Tuberculous meningitis(2) Complications : arachnoid fibrosis(hydrocephalus), art.occlusion(infarct of brain) Tuberculoma : mass effect Agents : M. tuberculosis, M. avium-intracellulare (AIDS)

96. Fungal infection Immunocompromised host Disseminated fungal infection � late involvement to the brain Organism : Candida, Mucor, Aspergillus, Cryptococcus, Histoplasmosis Pathology : Vasculitis � brain infarct Abscess and granuloma Chronic meningitis � Crypto. in AIDS

97. Viral encephalitis Meningoencephalitis, meningomyelitis Agents : HSV, VZV, CMV, Poliomyelitis virus, Rabies, HIV

98. ARBO virus encephalitis(1) Epidemic Far east region : Japanese B encephalitis virus Mosquito vector Generalized neurologic deficits : seizure, confusion, delirium, stupor or coma

99. ARBO virus encephalitis(2) CSF : Pleocytosis � PMN ? mono Increased protein, normal sugar Pathology Necrotizing vasculitis Perivascular cuffing Neuronal necrosis

100. Tumors Unique characteristics Histological benign but malignant behavior Restrict surgical removal Spreading via subarachnoid space Primary = metastasis Progressive headache, seizure, focal neurologic deficits

101. Primary brain tumors(1) Gliomas Astrocytoma : well differentiated, anaplastic astrocytoma, glioblastoma multiforme Oligodendroglioma Ependymoma � choroid plexus papilloma

102. Primary brain tumors(2) Neuroectodermal tumor Medulloblastoma Primitive neuroectodermal tumor (PNET) Meningioma

103. Primary brain tumors(3)

104. Primary brain tumors(4)

105. Metastatic tumors Lung, breast, skin(malignant melanoma), kidneys, GI tract Pathology Well demarcated, multiple Gray-white matter junction