Classification of diseases of cns

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  • As amazingly complex as the CNS is, even more amazing is the fact that its components are so remarkably simple----Neuron body, dendrites, axon.
  • Section from spinal cord. Is this grey matter or white matter?
  • Neurons with nucleus, nissl (Franz Nissl) granules, nerve fibers, glia. Glia are many times more common than neurons.
  • Blood vessel with endothelium and/or smooth muscle.
  • Various glia
  • This particular stain shows why the most common glial cell is called an “astro”cyte.
  • Oligodendrocytes, the CNS myelinators. Note the clear space around their nuclei, much in the same way myelin washed out from schwann glial calls as well.
  • Ependymal cells look exactly like ciliated columnar cells and like the ventricular spaced and choroid.
  • Choroid plexus is “papillary” in configuration.
  • Cluster of microglia, the macrophages of the CNS.
  • Neuronal loss and gliosis is a hallmark of more “chronic” CNS injury
  • A comparison of edema “compartments” the ECS (EXTRA Cellular Space) is vasogenic and the ICS (INTRA Cellular Space) is cytotoxic.
  • Flattened gyri often signify edema. Why? Ans: compression against the calvarium
  • 1) Falx, 2) Cingulate, and 3) Cereballar tonsillar levels of edema
  • “ Notching” of the cingulate gyrus.
  • Cerebellar tonsillar herniation
  • Basic pathophysiologic concepts about hydrocephalus which is defined as any major deviation from the normal physiology of CSF
  • Hydrocephalus on CT
  • Hydrocephalus on MRI
  • Hydrocephalus also showing cerebral edema, CT or MRI? Ans: CT Why? Ans: Bone is always very dense on CT, and water is always intense on T2 weighted MRI
  • Hydrocephalus, dilated ventricles
  • COMMON CNS malformations
  • Note the neural canal extends to the outside of the body. AFP, the same antigen found in hepatomas, is a good screening test for this.
  • Small gyri
  • Failure of the prosencephalon to develop, and separate, often leads to cyclops.
  • Normal corpus callosum
  • Absent corpus callosum
  • These are the three most common types of perinatal brain injuries
  • Differentiation between CNS trauma is crucial in medicolegal cases.
  • Know the correct definitions
  • Contusion
  • Skull fracture types
  • Epidural
  • Subdural
  • Three common sequelae of CNS trauma
  • You should recall cord injury level versus sensory and motor defects: “C5, still alive”
  • Histopathologic progression of CNS infarcts, parallels the general cellular progression of events in inflammation
  • Classical congenital “berry” aneurysm
  • Extensive basilar subarachnoid hemorrhage
  • Basal ganglia symptoms include tremors (rhythmic, involuntary, oscillatory movements), athetosis (slow, writhing movements of the fingers and hands, and sometimes of the toes), chorea (abrupt movements of the limbs and facial muscles), ballism (violent, flailing movements), and dystonia (a persistent posture of a body part which can result in grotesque movements and distorted positions of the body).
  • Meninges, purulent, at the base of the brain
  • Meninges, purulent, at the top of the brain
  • Meningitis vs. meningoencephalitis
  • Perhaps encephalo-meningitis would be a better term? Why? Ans: viruses primarilly involve CNS parenchyma, rather than meninges
  • Perivascular lymphocytic cuffing is the hallmark viral encephalitis, especially with respect to early, mild, or peripheral considerations.
  • Eosinophilic Negri body of Rabies, also basophilic inclusions of CMV
  • Demyelination is associated with gliosis and edema, therefore bright signals on T2 weighted images
  • Demyelination and gliosis
  • PR -oteinaceous I -nfectious particle = PRI -on
  • “ Replication” is felt to be due to the protein undergoing a conformational change to induce neighboring proteins to become like it.
  • Hence the term “spongiform.”
  • CJ has also been called JC, but the term “JC” makes it confusable with the JC polyoma virus, so CJ-D is probably the politically correct term
  • Demyelination, generically, is a NON-specific pattern of CNS reaction to injury of many types and usually goes hand in hand with edema and gliosis, If it wasn’t for the “edema” associated with demyelination, the “plaques” would not be seen on MRI.
  • The PLAQUE of MS is NOT like a plaque of skin diseases, i.e., it is not a raised lesion, but an area of demyelination.
  • MS gave MRI its first HUGE boom, by virtue of being able to detect these lesions, due to edema!
  • Myelinated white matter stains BLUE, and demyelination is loss of blue. Remember MS is a disease PRIMARILLY of WHITE matter.
  • Plaques grossly
  • Plaques microscopically. Demyelination, edema, gliosis, and, lower right, relative preservation of the actual nerve fibers
  • FOUR classical areas for brain degeneration, a decent anatomic classification.
  • ALZHEIMER disease is many times more common than all the other dementias put together.
  • Normal sulci.
  • Prominent sulci in cortical atrophy. Why are the sulci, NOT the gyri, prominent in atrophy? Ans: cortical LOSS
  • Plaques and tangles and beta-amyloid
  • Plaques and tangles, and central core of AMYLOID
  • Amyloid with congo red stain (LEFT), and Amyloid with congo red stain under polarization (RIGHT.
  • Neurons with tangles displacing nucleus, H & E
  • Neurons with TANGLES, often displacing NUCLEUS.
  • A “tangle” in proximity to a nucleus. A “tangle” is hyperphosphorylation of a neuron microtubule protein called “tau”, causing it to precipitate
  • Tau is a gene, Tau protein is a microtubule protein associated with hyperphosphorylation in tau-opathies. MANY cortical dementias are associated with this.
  • How would one differentiate MID from MS? Ans: MS is purely white matter. In this MRI we see grey matter lesions, so it is more likely MID rather than MS
  • NORMALLY BLACK substantia nigra due to adequate dopamine.
  • PALE substantia nigra in Parkinson’s disease (on LEFT) due to inadequate dopamine.
  • The locus ceruleus is also pale in Parkinson’s disease, which is another pigmented area due to abundant dopamine.
  • Which patient has Parkinson’s disease? Ans: the RIGHT Why? Ans: decreased dopamine
  • Lewy bodies are commonly regarded as diagnostic of Parkinson’s disease also. The main substance of the eosinophilic inclusion is alpha-synuclein .
  • Alpha synuclein stains.
  • Vitamin B1 deficiency (Wernicke-Korsakoff), hemorrhagic mamillary bodies are the most classic finding. B1 deficiency is the culprit here.
  • Posterior column demyelination in B12 deficiency, this is also called SUBACUTE COMBINED DEGENERATION
  • Gliosis vs. Glioma?
  • Glioma, intermediate grade
  • Glioma, high grade, Note NECROSIS. NECROSIS (orangophilia and granularity) is needed for the diagnosis of a HIGH grade glioma.
  • Glioblastoma (multiforme). Why is it called “multiforme”? Note the 1) palisading (two arrows) and 2) necrosis (ovals) which are hallmarks of GBM.
  • Central necrosis is a sign of rapid growth. It outgrows its blood supply.
  • Normal oligodendrocytes on the left.
  • What is this? (Hint: note rosettes) Ans: neuroblastoma
  • Any midline cerebellum tumor in a child is a medulloblastoma till proven otherwise!
  • Midline cerebellum tumor in a kid. What is it? Ans: medulloblastoma
  • Arts of this meningioma are denser than bone.
  • Note cortical compression from this meningioma.
  • Psammoma bodies are diagnostic of meningiomas in brain tumors! What other kinds of tumors have psammoma bodies? Ans: papillary carcinomas, classically in thyroid
  • Toxoplasmosis and lymphomas and encephalitis are very common in AIDS. Might you cal the MRI lesion a “toxoplasmoma”? Ans: Sure
  • A solitary brain mass is statistically just as likely to be metastatic than primary
  • Classification of diseases of cns

    1. 1. CNS www.freelivedoctor.com
    2. 2. CNS <ul><li>Normal </li></ul><ul><ul><li>Neurons </li></ul></ul><ul><ul><li>Glia </li></ul></ul><ul><ul><ul><li>Astrocytes </li></ul></ul></ul><ul><ul><ul><li>Oligodendrocytes </li></ul></ul></ul><ul><ul><ul><li>Ependymal Cells </li></ul></ul></ul><ul><ul><ul><li>Microglia </li></ul></ul></ul>www.freelivedoctor.com
    3. 3. Classical Disease Patterns <ul><li>Degenerative </li></ul><ul><li>Inflammatory </li></ul><ul><li>Neoplastic </li></ul>www.freelivedoctor.com
    4. 4. Classical CNS Disease Patterns <ul><li>Degenerative </li></ul><ul><li>Inflammatory </li></ul><ul><li>Neoplastic </li></ul><ul><li>Traumatic </li></ul>www.freelivedoctor.com
    5. 5. www.freelivedoctor.com
    6. 6. www.freelivedoctor.com
    7. 7. www.freelivedoctor.com
    8. 8. www.freelivedoctor.com
    9. 9. www.freelivedoctor.com
    10. 10. www.freelivedoctor.com
    11. 11. www.freelivedoctor.com
    12. 12. www.freelivedoctor.com
    13. 13. www.freelivedoctor.com
    14. 14. www.freelivedoctor.com
    15. 15. CELLULAR REACTIONS <ul><li>Neurons </li></ul><ul><ul><li>Acute (RED neuron, karyolysis) </li></ul></ul><ul><ul><li>Subacute, chronic, cell loss, gliosis </li></ul></ul><ul><ul><li>Axonal </li></ul></ul><ul><ul><li>Inclusions (lipid, prot., carb., viruses) </li></ul></ul><ul><li>Glia, “gliosis” </li></ul><ul><ul><li>Swelling </li></ul></ul><ul><ul><li>Fibers </li></ul></ul><ul><ul><li>Inclusions </li></ul></ul>www.freelivedoctor.com
    16. 16. ACUTE NEURONAL INJURY “ RED ” NEURONS www.freelivedoctor.com
    17. 17. www.freelivedoctor.com
    18. 18. CEREBRAL EDEMA (normal weight 1200-1300 grams) <ul><li>Vasogenic (disrupted BBB) </li></ul><ul><ul><li>Intravascular  INTER-cellular </li></ul></ul><ul><li>Cytotoxic </li></ul><ul><ul><li> INTRA-cellular </li></ul></ul>www.freelivedoctor.com
    19. 19. CEREBRAL EDEMA <ul><li>Subfalcine (SUPRA-tentorial) </li></ul><ul><li>Cingulate (TENTORIAL) </li></ul><ul><li>Cerebellar tonsilar (SUB-tentorial, or INFRA-tentorial) </li></ul>www.freelivedoctor.com
    20. 20. www.freelivedoctor.com
    21. 21. www.freelivedoctor.com
    22. 22. www.freelivedoctor.com
    23. 23. www.freelivedoctor.com
    24. 24. www.freelivedoctor.com
    25. 25. <ul><li>DDX: </li></ul><ul><ul><li>EVERYTHING </li></ul></ul><ul><li>SYMPTOMS </li></ul><ul><ul><li>HEADACHE </li></ul></ul><ul><ul><li>HALLUCINATIONS </li></ul></ul><ul><ul><li>COMA </li></ul></ul><ul><ul><li>DEATH </li></ul></ul>CEREBRAL EDEMA www.freelivedoctor.com
    26. 26. HYDROCEPHALUS www.freelivedoctor.com
    27. 27. HYDROCEPHALUS <ul><li>Impaired RESORPTION </li></ul><ul><li>Increased PRODUCTION </li></ul><ul><li>OBSTRUCTION </li></ul><ul><li>COMMUNICATING (entire) </li></ul><ul><li>NON-COMMUNICATING (part) </li></ul><ul><li>HIGH Pressure </li></ul><ul><li>NORMAL Pressure </li></ul>www.freelivedoctor.com
    28. 28. www.freelivedoctor.com
    29. 29. www.freelivedoctor.com
    30. 30. www.freelivedoctor.com
    31. 31. www.freelivedoctor.com
    32. 32. CNS MALFORMATIONS <ul><li>Neural Tube </li></ul><ul><ul><li>Anencephaly, Encephalocele, Spina Bifida </li></ul></ul><ul><li>Forebrain </li></ul><ul><ul><li>Polymicrogyria, Holoprosencephaly, Agenesis of Corpus Callosum </li></ul></ul><ul><li>Posterior Fossa (Infratentorial) </li></ul><ul><ul><li>Arnold Chiari (infratentorial herniation, SMALL PF), Dandy-Walker (cerebellar cyst, LARGE PF) </li></ul></ul><ul><li>Syringomyelia/Hydromyelia </li></ul>www.freelivedoctor.com
    33. 33. SPINA BIFIDA www.freelivedoctor.com
    34. 34. POLYMICROGYRIA www.freelivedoctor.com
    35. 35. HOLOPROSENCEPHALY www.freelivedoctor.com
    36. 36. www.freelivedoctor.com
    37. 37. www.freelivedoctor.com
    38. 38. SYRINGOMYELIA (note “SYRINX”) www.freelivedoctor.com
    39. 39. PERINATAL Brain Injuries <ul><li>Intraparenchymal Hemorrhage </li></ul><ul><li>Intraventricular hemorrhage (premies) </li></ul><ul><li>Periventricular “leukomalacia” (i.e., infarcts) </li></ul><ul><li>Cerebral “Palsy” refers to nonprogressive diffuse cerebral pathology apparent at childbirth </li></ul>www.freelivedoctor.com
    40. 40. CNS TRAUMA <ul><li>Skull Fractures </li></ul><ul><li>Parenchymal Injuries </li></ul><ul><li>Traumatic Vascular Injury </li></ul><ul><li>Sequelae </li></ul><ul><li>Spinal Cord Trauma </li></ul>www.freelivedoctor.com
    41. 41. BRAIN TRAUMA <ul><li>Contusion (bruise) </li></ul><ul><li>Laceration (tear) </li></ul><ul><li>Coup/Contre-Coup </li></ul><ul><li>Concussion </li></ul>www.freelivedoctor.com
    42. 42. www.freelivedoctor.com
    43. 43. “ HAIRLINE” “ DEPRESSED”, aka “ DISPLACED” www.freelivedoctor.com
    44. 44. HEMATOMAS/HEMORRHAGE <ul><li>EPIDURAL (fx) </li></ul><ul><li>SUBDURAL (trauma NO fx) </li></ul><ul><li>SUBARACHNOID (arterial, no trauma) </li></ul><ul><li>INTRAPARENCHYMAL (any) </li></ul><ul><li>INTRAVENTRICULAR (no trauma, rare in adults, common in premies) </li></ul>www.freelivedoctor.com
    45. 45. www.freelivedoctor.com
    46. 46. EPIDURAL HEMATOMA www.freelivedoctor.com
    47. 47. SUBDURAL HEMATOMA www.freelivedoctor.com
    48. 48. SUBARACHNOID www.freelivedoctor.com
    49. 49. INTRAPARENCHYMAL www.freelivedoctor.com
    50. 50. INTRAPARENCHYMAL www.freelivedoctor.com
    51. 51. INTRAVENTRICULAR www.freelivedoctor.com
    52. 52. CNS TRAUMA SEQUELAE <ul><li>Hydrocephalus (WHY?) </li></ul><ul><li>Dementia (Punch Drunk Syndrome) </li></ul><ul><li>Diffuse Axonal Injury (white matter) </li></ul>www.freelivedoctor.com
    53. 53. www.freelivedoctor.com
    54. 54. SPINAL CORD TRAUMA <ul><li>Parallels BRAIN patterns of injury on a cellular basis </li></ul><ul><li>Usually secondary to spinal column displacement </li></ul><ul><li>Level of injury mirrors motor loss: Death  Quadriplegia  Paraplegia </li></ul>www.freelivedoctor.com
    55. 55. www.freelivedoctor.com
    56. 56. Cerebrovascular Diseases (CVA, “Stroke”) <ul><li>Ischemic ( ↓ blood and 02) </li></ul><ul><ul><li>Global </li></ul></ul><ul><ul><li>Focal (regional): </li></ul></ul><ul><ul><li>ACUTE: edema  neuronal microvacuolization  pyknosis  karyorrhexis  neutrophils </li></ul></ul><ul><ul><li>CHRONIC: macrophages  gliosis </li></ul></ul><ul><li>Hemorrhagic (rupture of artery/aneurysm) </li></ul>www.freelivedoctor.com
    57. 57. www.freelivedoctor.com
    58. 58. THROMBOTIC MCA www.freelivedoctor.com
    59. 59. HEMORRHAGIC ACA www.freelivedoctor.com
    60. 60. <ul><li>EDEMA </li></ul><ul><li>“ RED” NEURONS </li></ul><ul><li>POLYs </li></ul><ul><li>MONO’s (MACs) </li></ul><ul><li>GLIOSIS </li></ul>Histopathologic progression of CNS infarcts www.freelivedoctor.com
    61. 61. HYPERTENSIVE CVA <ul><li>Intracerebral </li></ul><ul><li>Basal Ganglia Region </li></ul><ul><li>(lenticulostriate arteries of internal capsule, putamen) </li></ul>www.freelivedoctor.com
    62. 62. www.freelivedoctor.com
    63. 63. HYPERTENSIVE CVA www.freelivedoctor.com
    64. 64. LACUNAR INFARCTS www.freelivedoctor.com
    65. 65. “ SLIT” HEMORRHAGE(s) www.freelivedoctor.com
    66. 66. SUBARACHNOID HEMORRHAGE <ul><li>Rupture of large intracerebral arteries which are the primary branches of the anatomical circle (of Willis) </li></ul><ul><li>Congenital (“berry” aneurysms) </li></ul><ul><li>Atherosclerotic (atherosclerotic aneurysms, or direct wall rupture) </li></ul>www.freelivedoctor.com
    67. 67. www.freelivedoctor.com
    68. 68. www.freelivedoctor.com
    69. 69. www.freelivedoctor.com
    70. 70. HYPERTENSIVE ENCEPHALOPATHY <ul><li>ACUTE </li></ul><ul><ul><li>Headaches </li></ul></ul><ul><ul><li>Confusion </li></ul></ul><ul><ul><li>Anxiety </li></ul></ul><ul><ul><li>Convulsions </li></ul></ul><ul><li>CHRONIC </li></ul><ul><ul><li>Dementia (MID, Multi-Infarct-Dementia) </li></ul></ul><ul><ul><li>Gait Disturbances </li></ul></ul><ul><ul><li>Basal Ganglia symptoms </li></ul></ul>www.freelivedoctor.com
    71. 71. CNS INFECTIONS <ul><li>ACUTE MENINGITIS </li></ul><ul><li>ACUTE FOCAL SUPPURATIVE </li></ul><ul><li>CHRONIC BACTERIAL </li></ul><ul><li>VIRAL </li></ul><ul><li>FUNGAL </li></ul><ul><li>OTHER </li></ul>www.freelivedoctor.com
    72. 72. INFECTIONS <ul><li>Meningitis (generally* bacterial) </li></ul><ul><ul><li>E. coli, Strep B (neonates) </li></ul></ul><ul><ul><li>H. influenzae (children) </li></ul></ul><ul><ul><li>Neisseria meningitidis (adults) </li></ul></ul><ul><ul><li>Strep. pneumoniae, Listeria (elderly) </li></ul></ul><ul><ul><li>PMNs in CSF, INCREASED protein, REDUCED glucose </li></ul></ul><ul><li>Encephalitis (generally viral) </li></ul><ul><ul><li>Arboviruses, HSV, CMV, V/Z, polio, rabies, HIV </li></ul></ul><ul><ul><li>Lymphs and macrophages in perivascular “Virchow-Robbins” spaces </li></ul></ul><ul><li>Meningoencephalitis </li></ul>www.freelivedoctor.com
    73. 73. www.freelivedoctor.com
    74. 74. www.freelivedoctor.com
    75. 75. www.freelivedoctor.com
    76. 76. ACUTE FOCAL SUPPURATIVE CNS INFECTIONS <ul><li>CEREBRAL ABSCESSES </li></ul><ul><ul><li>Local (mastoiditis, sinusitis) </li></ul></ul><ul><ul><li>Hematogenous (tooth extraction, sepsis) </li></ul></ul><ul><ul><li>Staph, Strep </li></ul></ul><ul><ul><li>Often fibrous capsule, liquid center </li></ul></ul><ul><li>SUBDURAL EMPYEMA (IN SINUSITIS) </li></ul><ul><li>EXTRADURAL ABSCESS </li></ul><ul><li>(IN OSTEOMYELITIS) </li></ul>www.freelivedoctor.com
    77. 77. www.freelivedoctor.com
    78. 78. www.freelivedoctor.com
    79. 79. www.freelivedoctor.com
    80. 80. SUBDURAL EMPYEMA www.freelivedoctor.com
    81. 81. CHRONIC BACTERIAL Meningo-encephalits <ul><li>TB, brain and meninges </li></ul><ul><li>SYPHILIS, gummas in brain </li></ul><ul><li>LYME DISEASE (Neuro-Borreliosis) </li></ul>www.freelivedoctor.com
    82. 82. TUBERCULOMA www.freelivedoctor.com
    83. 83. VIRAL Meningo-encephalitis <ul><li>ARBO VIRUSES (West Nile, Equines, Venez., many more) </li></ul><ul><li>HSV1 </li></ul><ul><li>HSV2 </li></ul><ul><li>V/Z </li></ul><ul><li>CMV </li></ul><ul><li>POLIO </li></ul><ul><li>RABIES </li></ul><ul><li>HIV </li></ul><ul><li>Progressive Multifocal Leukoencephalopathy (JC) </li></ul><ul><li>Subacute Sclerosing Panencephalitis (Measles) </li></ul>www.freelivedoctor.com
    84. 84. VIRAL ENCEPHALITIS PERIVASCULAR LYMPHOCYTIC “ CUFFING” www.freelivedoctor.com
    85. 85. Bitemporal encephalitis is HSV until proven otherwise! www.freelivedoctor.com
    86. 86. HSV = TEMPORAL lobe(s) www.freelivedoctor.com
    87. 87. www.freelivedoctor.com
    88. 88. PERIVASCULAR GIANT CELLS in WHITE MATTER in HIV ENCEPHALITIS www.freelivedoctor.com
    89. 89. P ROGRESSIVE M ULTIFOCAL L EUKOENCEPHALOPATHY (PML) <ul><li>JC Polyoma virus is the cause </li></ul><ul><li>Primarilly affects oligodendocytes </li></ul><ul><li>Ergo, demyelination is the main feature </li></ul>www.freelivedoctor.com
    90. 90. www.freelivedoctor.com
    91. 91. www.freelivedoctor.com Demyelination and gliosis
    92. 92. PML www.freelivedoctor.com
    93. 93. SUBACUTE SCLEROSING PANENCEPHALITIS (SSPE) <ul><li>VERY rare since measles eradicated </li></ul><ul><li>Thought to be caused by measles virus </li></ul>www.freelivedoctor.com
    94. 94. FUNGAL MENINGO-ENCEPHALITIS <ul><li>CRYPTOCOCCUS </li></ul><ul><li>CANDIDA </li></ul><ul><li>ASPERGILLIS </li></ul><ul><li>MUCOR </li></ul>(Mostly in immunocompromised hosts) www.freelivedoctor.com
    95. 95. www.freelivedoctor.com
    96. 96. CRYPTOCOCCUS MICROABSCESSES www.freelivedoctor.com
    97. 97. OTHERS <ul><li>MALARIA </li></ul><ul><li>TOXOPLASMOSIS (in HIV) </li></ul><ul><li>AMEBIASIS </li></ul><ul><li>TRYPANOSOMES </li></ul><ul><li>RICKETTSIAE </li></ul><ul><li>ECHINOCOCCUS </li></ul>www.freelivedoctor.com
    98. 98. CNS II www.freelivedoctor.com
    99. 99. PRION DISEASES <ul><li>Creutzfeldt-Jakob Disease (CJD) </li></ul><ul><li>Gerstmann-Straussler-Scheinker syn. (GSS) </li></ul><ul><li>Fatal familial insomnia </li></ul><ul><li>Kuru, human variety </li></ul><ul><li>Scrapie (sheep and goats) </li></ul><ul><li>Mink transmissible encephalopathy </li></ul><ul><li>Chronic wasting disease (deer and elk) </li></ul><ul><li>Bovine Spongiform Encephalopathy (BSE) </li></ul>www.freelivedoctor.com
    100. 100. PRION DISEASES: common features <ul><li>Infectious agents with apparently no DNA </li></ul><ul><li>DEMENTIA </li></ul><ul><li>Prion Protein ( PrP ) accumulation </li></ul><ul><li>“ SPONGIFORM” changes in neurons and glia </li></ul><ul><li>TRANSMISSIBLE, FATAL, NO Rx </li></ul>www.freelivedoctor.com
    101. 101. PRION PROTEIN Normally found in humans Exact structure known, 208 amino acids Specific chromosome, #20, specific genes also known Requires a conformational change to accumulate and do damage www.freelivedoctor.com
    102. 102. www.freelivedoctor.com
    103. 103. CJD (Creutzfeldt-Jakob) <ul><li>1 per million incidence, 7 th decade </li></ul><ul><li>Sporadic cases, not epidemic </li></ul><ul><li>Transmitted! </li></ul><ul><li>Familial cases well documented </li></ul><ul><li>Rapidly progressive dementia </li></ul><ul><li>Grey Matter </li></ul><ul><li>Cerebellar ataxia also, usually </li></ul><ul><li>FATAL, no treatment known, like ALL prion diseases </li></ul>www.freelivedoctor.com
    104. 104. DEMYELINATING DISEASES <ul><li>MS (MULTIPLE SCLEROSIS) </li></ul><ul><li>MS variants </li></ul><ul><li>ACUTE DISSEMINATED ENCEPHALOMYELITIS (ADEM) </li></ul><ul><li>ACUTE NECROTIZING HEMORRHAGIC ENCEPHALOMYELITIS (ANHE) </li></ul><ul><li>Many, many, many others. Remember: DEMYELINATION is a NON-SPECIFIC reaction to MANY types of CNS injury </li></ul>www.freelivedoctor.com
    105. 105. MS <ul><li>Cause: ? </li></ul><ul><li>USA prevalence: 1:1000 </li></ul><ul><li>F>>M, Ages: 30’s, 40’s </li></ul><ul><li>Immune response primarily against CNS myelin (white matter) </li></ul><ul><li>Regional area of white matter demyelination is called “PLAQUE” </li></ul><ul><li>Increased CSF gamma globulin, i.e., oligoclonal bands </li></ul><ul><li>Often presents with VISUAL problems </li></ul><ul><li>EXACERBATIONS/REMISSIONS </li></ul>www.freelivedoctor.com
    106. 106. www.freelivedoctor.com
    107. 107. www.freelivedoctor.com
    108. 108. PLAQUES, MS www.freelivedoctor.com
    109. 109. www.freelivedoctor.com
    110. 110. CNS DEGENERATIVE DISEASES <ul><li>CORTEX (dementias) </li></ul><ul><li>BASAL GANGLIA and BRAIN STEM (parkinsonian) </li></ul><ul><li>SPINOCEREBELLAR (ataxias) </li></ul><ul><li>MOTOR NEURONS (muscle atrophy) </li></ul>www.freelivedoctor.com
    111. 111. CNS DEGENERATIVE DISEASES <ul><li>CORTEX (dementias) </li></ul><ul><ul><li>ALZHEIMER DISEASE </li></ul></ul><ul><ul><li>Frontotemporal </li></ul></ul><ul><ul><li>Pick Disease (also primarily frontal) </li></ul></ul><ul><ul><li>Progressive Supranuclear Palsy (PSP) </li></ul></ul><ul><ul><li>Corticobasal Degeneration (CBD) </li></ul></ul><ul><ul><li>Vascular Dementias (MID) </li></ul></ul>www.freelivedoctor.com
    112. 112. ALZHEIMER DISEASE <ul><li>Commonest cause of dementias (majority) </li></ul><ul><li>Sporadic, 5-10% familial </li></ul><ul><li>CORTICAL (grey matter) ATROPHY </li></ul><ul><li>NEURITIC PLAQUES (extraneuronal) </li></ul><ul><li>NEUROFIBRILLARY TANGLES (intraneuronal) </li></ul><ul><li>AMYLOID!!! </li></ul>www.freelivedoctor.com
    113. 113. www.freelivedoctor.com
    114. 114. www.freelivedoctor.com
    115. 115. Neuritic plaques Neuritic plaques, stained with anti- beta amyloid immunostain www.freelivedoctor.com
    116. 116. www.freelivedoctor.com
    117. 117. www.freelivedoctor.com
    118. 118. www.freelivedoctor.com
    119. 119. www.freelivedoctor.com
    120. 120. www.freelivedoctor.com
    121. 121. OTHER CORTICAL DEMENTIAS (tau gene/protein, tau-opathies) <ul><li>FRONTOTEMPORAL </li></ul><ul><li>PICK DISEASE (LOBAR ATROPHY) </li></ul><ul><li>PROGRESSIVE SUPRANUCLEAR PALSY (PSP) </li></ul><ul><li>CORTICOBASAL DEGENERATION (CBD) </li></ul><ul><li>VASCULAR DEMENTIA (MID) </li></ul>www.freelivedoctor.com
    122. 122. VASCULAR DEMENTIA <ul><li>Associated with multiple infarcts, hence the name MID (Multiple Infarct Dementia) </li></ul><ul><ul><li>Lacunar infarcts </li></ul></ul><ul><ul><li>Cortical microinfarcts </li></ul></ul><ul><ul><li>Multiple embolic infarcts </li></ul></ul><ul><li>SECOND commonest form of dementia after Alzheimer </li></ul>www.freelivedoctor.com
    123. 123. www.freelivedoctor.com
    124. 124. CNS DEGENERATIVE DISEASES <ul><li>BASAL GANGLIA and BRAIN STEM </li></ul><ul><ul><li>Parkinsonism </li></ul></ul><ul><ul><li>Parkinson Disease </li></ul></ul><ul><ul><li>Multiple System Atrophy </li></ul></ul><ul><ul><li>Huntington Disease </li></ul></ul>www.freelivedoctor.com
    125. 125. Parkinsonism <ul><li>Is a clinical “syndrome”, NOT a disease </li></ul><ul><ul><li>Diminished facial expression </li></ul></ul><ul><ul><li>Stooped posture </li></ul></ul><ul><ul><li>Slowness of voluntary movement </li></ul></ul><ul><ul><li>“ Festinating” gate (short, fast) </li></ul></ul><ul><ul><li>Rigidity (cogwheel), intention tremor </li></ul></ul><ul><ul><li>“ Pillrolling” tremor </li></ul></ul><ul><li>The above clinical findings involve pathology of the SUBSTANTIA NIGRA, and include: </li></ul><ul><ul><li>PARKINSON DISEASE </li></ul></ul><ul><ul><li>MULTIPLE SYSTEM ATROPHY </li></ul></ul><ul><ul><li>POSTENCEPHALIC PARKINSONISM </li></ul></ul><ul><ul><li>PSP, CBD (cortical disorders) </li></ul></ul>www.freelivedoctor.com
    126. 126. PARKINSON DISEASE <ul><li>PALLOR of the SUBSTANTIA NIGRA (and LOCUS COERULEUS) </li></ul><ul><li>LEWY BODIES (alpha-synuclein protein) </li></ul>www.freelivedoctor.com
    127. 127. www.freelivedoctor.com
    128. 128. www.freelivedoctor.com
    129. 129. LOCUS COERULEUS in PONS (CERULEUS) www.freelivedoctor.com
    130. 130. www.freelivedoctor.com
    131. 131. www.freelivedoctor.com
    132. 132. PARKINSON DISEASE <ul><li>Parkinsonism symptoms, i.e., </li></ul><ul><ul><li>cogwheel rigidity </li></ul></ul><ul><ul><li>intention tremor </li></ul></ul><ul><li>Progressive </li></ul><ul><li>Hallucinations </li></ul><ul><li>Dementia </li></ul><ul><li>Symptomatic response to L-DOPA </li></ul>www.freelivedoctor.com
    133. 133. MULTIPLE SYSTEM ATROPHY <ul><li>MSA </li></ul><ul><li>WIDE SPECTRUM of diseases </li></ul><ul><li>GLIAL CYTOPLASMIC INCLUSIONS (GCIs) in oligodendrocytes (alpha synuclein) </li></ul><ul><li>Clinically, </li></ul><ul><ul><li>parkinsonism symptoms </li></ul></ul><ul><ul><li>autonomic dysfunction </li></ul></ul>www.freelivedoctor.com
    134. 134. www.freelivedoctor.com
    135. 135. HUNTINGTON DISEASE <ul><li>Classical familial, genetic disease </li></ul><ul><li>Progressive motor loss and dementia </li></ul><ul><li>“ chorea”, i.e. “jerky” movements </li></ul><ul><li>Progressive, fatal </li></ul><ul><li>Atrophy of basal ganglia, i.e., corpus striatum </li></ul>Cortical (basal ganglia) atrophy Ventricular enlargement www.freelivedoctor.com
    136. 136. CNS DEGENERATIVE DISEASES <ul><li>SPINOCEREBELLAR DEGENERATIONS (ATAXIAS) </li></ul><ul><ul><li>Spinocerebellar ataxias </li></ul></ul><ul><ul><li>Friedrich Ataxia </li></ul></ul><ul><ul><li>Ataxia-Telangiectasia </li></ul></ul>www.freelivedoctor.com
    137. 137. SPINOCEREBELLAR DEGENERATIONS <ul><li>Cerebellar cortex </li></ul><ul><li>Spinal cord </li></ul><ul><li>Peripheral nerves </li></ul><ul><li>FEATURES: </li></ul><ul><ul><li>ATAXIA (loss of extremity muscle coordination) </li></ul></ul><ul><ul><li>SPASTICITY </li></ul></ul><ul><ul><li>NEUROPATHIES </li></ul></ul>www.freelivedoctor.com
    138. 138. CNS DEGENERATIVE DISEASES <ul><li>MOTOR NEURONS </li></ul><ul><ul><li>ALS (Amyotrophic Lateral Sclerosis, i.e., Lou Gehrig’s disease) </li></ul></ul><ul><ul><li>BulboSpinal Atrophy (Kennedy Syndrome) </li></ul></ul><ul><ul><li>Spinal Muscular Atrophy </li></ul></ul>www.freelivedoctor.com
    139. 139. Amyotrophic Lateral Sclerosis <ul><li>Unknown etiology </li></ul><ul><li>Progressive muscle atrophy due to motor neuron loss (lower, upper) </li></ul><ul><li>5-10% familial </li></ul><ul><li>Lou Gehrig had it, so does Steven Hawking </li></ul><ul><li>Hand weakness  diaphragm </li></ul><ul><li>Anterior horn cells reduced and gliotic </li></ul>www.freelivedoctor.com
    140. 140. ALS, DEMYELINATION IN CORTICOSPINAL TRACTS ALS, pathologic changes in anterior horn cells www.freelivedoctor.com
    141. 141. GENETIC METABOLIC DISEASES <ul><li>NEURONAL STORAGE DISEASES </li></ul><ul><ul><li>(classical autosomal recessive enzyme deficiencies) </li></ul></ul><ul><li>“ LEUKO”-DYSTROPHIES </li></ul><ul><ul><li>(abnormal “myelin” synthesis) </li></ul></ul><ul><li>MITOCHONDRIAL ENCEPHALOPATHIES </li></ul><ul><ul><li>(mitochondrial gene mutations) </li></ul></ul>www.freelivedoctor.com
    142. 142. LEUKODYSTROPHIES <ul><li>Krabbe </li></ul><ul><li>Metachromatic- </li></ul><ul><li>Adreno- </li></ul><ul><li>Pelizaeus-Merzbacher </li></ul><ul><li>Canavan </li></ul>www.freelivedoctor.com
    143. 143. ACQUIRED TOXIC/METABOLIC CNS DISEASES <ul><li>Vitamin B1 deficiency (Wernicke-Korsakoff) </li></ul><ul><li>Vitamin B12 deficiency (vibratory sense) </li></ul><ul><li>Diabetes Increased/Decreased GLUCOSE </li></ul><ul><li>Hepatic Failure (NH4+) </li></ul><ul><li>CO (Cortex, hippocampus, Purkinje cells) </li></ul><ul><li>CH3-OH, Methanol (Retinal ganglion cells) </li></ul><ul><li>CH3-CH2-OH (acute/chronic, direct/nutrit’l) </li></ul><ul><li>Radiation (Brain MOST resistant to Rad. Rx.) </li></ul><ul><li>Chemo (Methotrexate + Radiation) </li></ul>www.freelivedoctor.com
    144. 144. www.freelivedoctor.com
    145. 145. 128 Hz www.freelivedoctor.com
    146. 146. CNS TUMORS <ul><li>GLIOMAS </li></ul><ul><ul><li>Astrocytes ( I , II, III, IV ) </li></ul></ul><ul><ul><li>Oligodendroglioma </li></ul></ul><ul><ul><li>Ependymoma </li></ul></ul><ul><li>NEURONAL (neuroblastoma) </li></ul><ul><li>POORLY DIFFERENTIATED (medulloblastoma) </li></ul><ul><li>MENINGIOMAS </li></ul><ul><li>LYMPHOMAS </li></ul><ul><li>METASTATIC </li></ul>www.freelivedoctor.com
    147. 147. CNS TUMORS <ul><li>SYMPTOMS? </li></ul><ul><ul><li>Headache </li></ul></ul><ul><ul><li>Vomiting </li></ul></ul><ul><ul><li>Mental Changes </li></ul></ul><ul><ul><li>Motor Problems </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Increased Intracranial Pressure </li></ul></ul><ul><ul><li>ANY localizing CNS abnormality </li></ul></ul>www.freelivedoctor.com
    148. 148. CNS TUMORS <ul><li>History </li></ul><ul><li>Physical </li></ul><ul><li>Neurologic exam </li></ul><ul><li>LP (including cytology) </li></ul><ul><li>CT </li></ul><ul><li>MRI </li></ul><ul><li>Brain angiography </li></ul><ul><li>Biopsy </li></ul>www.freelivedoctor.com
    149. 149. CNS TUMORS <ul><li>Benign? Malignant?, Primary vs. met? </li></ul><ul><li>Location? </li></ul><ul><li>Age? </li></ul><ul><li>X-ray Density? MIR signals? </li></ul><ul><li>Calcifications? </li></ul><ul><li>Vascularity? </li></ul><ul><li>Necrosis? </li></ul><ul><li>Liquefaction? </li></ul><ul><li>Edema? </li></ul><ul><li>Compression of neighbors? </li></ul>www.freelivedoctor.com
    150. 150. GLIOSIS vs. GLIOMA <ul><li>Age? </li></ul><ul><li>White vs. Grey Matter? </li></ul><ul><li>Gross texture? </li></ul><ul><li>Vascularity? </li></ul><ul><li>Mitoses? </li></ul><ul><li>(N/C, Pleomorphism, Hyperchromasia) </li></ul><ul><li>Calcifications? </li></ul><ul><li>Cysts? </li></ul><ul><li>Satellitosis? </li></ul><ul><li>Delineation? </li></ul>www.freelivedoctor.com
    151. 151. www.freelivedoctor.com
    152. 152. www.freelivedoctor.com
    153. 153. www.freelivedoctor.com
    154. 154. www.freelivedoctor.com
    155. 155. www.freelivedoctor.com
    156. 156. www.freelivedoctor.com
    157. 157. www.freelivedoctor.com
    158. 158. www.freelivedoctor.com
    159. 159. www.freelivedoctor.com
    160. 160. MENINGIOMAS <ul><li>Occur where dura is </li></ul><ul><li>Very vascular </li></ul><ul><li>BENIGN, but…. </li></ul><ul><li>Can invade skull, etc. </li></ul><ul><li>Only invade (displace) brain in areas adjacent to dura, i.e., parasagittal, falx, tentorium, venous sinuses </li></ul><ul><li>Small, firm, and well defined like a SUPERBALL </li></ul><ul><li>Often (usually?) have PSAMMOMA bodies </li></ul>www.freelivedoctor.com
    161. 161. www.freelivedoctor.com
    162. 162. www.freelivedoctor.com
    163. 163. www.freelivedoctor.com
    164. 164. HIV www.freelivedoctor.com
    165. 165. METASTATIC CNS TUMORS <ul><li>LUNG </li></ul><ul><li>BREAST </li></ul><ul><li>MELANOMA </li></ul><ul><li>KIDNEY </li></ul><ul><li>GI </li></ul>www.freelivedoctor.com
    166. 166. “ PARA”NEOPLASTIC SYNDROMES <ul><li>SMALL CELL, LUNG </li></ul><ul><li>LYMPHOMAS </li></ul><ul><li>BREAST CA </li></ul><ul><li>Purkinje Cell Degeneration </li></ul><ul><li>Encephalitis, Limbic System </li></ul><ul><li>Sensory Neuron Degeneration, DRG </li></ul><ul><li>Eye Movement Disorders </li></ul>www.freelivedoctor.com
    167. 167. FAMILIAL TUMOR SYNDROMES <ul><li>NF1 </li></ul><ul><ul><li>Neurofibromas </li></ul></ul><ul><ul><li>Gliomas </li></ul></ul><ul><li>NF2 </li></ul><ul><ul><li>Schwannomas </li></ul></ul><ul><ul><li>Meningiomas </li></ul></ul><ul><li>Tuberous Sclerosis , i.e., CNS and somatic “hamartomas” </li></ul><ul><li>Von-Hippel-Lindau , CNS hemangioblastomas, chiefly cerebellar </li></ul>www.freelivedoctor.com

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