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
    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>
    3. 3. Classical Disease Patterns <ul><li>Degenerative </li></ul><ul><li>Inflammatory </li></ul><ul><li>Neoplastic </li></ul>
    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>
    5. 5.
    6. 6.
    7. 7.
    8. 8.
    9. 9.
    10. 10.
    11. 11.
    12. 12.
    13. 13.
    14. 14.
    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>
    17. 17.
    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>
    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>
    20. 20.
    21. 21.
    22. 22.
    23. 23.
    24. 24.
    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
    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>
    28. 28.
    29. 29.
    30. 30.
    31. 31.
    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>
    33. 33. SPINA BIFIDA
    36. 36.
    37. 37.
    38. 38. SYRINGOMYELIA (note “SYRINX”)
    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>
    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>
    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>
    42. 42.
    43. 43. “ HAIRLINE” “ DEPRESSED”, aka “ DISPLACED”
    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>
    45. 45.
    48. 48. SUBARACHNOID
    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>
    53. 53.
    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>
    55. 55.
    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>
    57. 57.
    58. 58. THROMBOTIC MCA
    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
    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>
    62. 62.
    65. 65. “ SLIT” HEMORRHAGE(s)
    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>
    67. 67.
    68. 68.
    69. 69.
    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>
    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>
    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>
    73. 73.
    74. 74.
    75. 75.
    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>
    77. 77.
    78. 78.
    79. 79.
    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>
    82. 82. TUBERCULOMA
    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>
    85. 85. Bitemporal encephalitis is HSV until proven otherwise!
    86. 86. HSV = TEMPORAL lobe(s)
    87. 87.
    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>
    90. 90.
    91. 91. Demyelination and gliosis
    92. 92. PML
    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>
    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)
    95. 95.
    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>
    98. 98. CNS II
    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>
    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>
    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
    102. 102.
    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>
    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>
    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>
    106. 106.
    107. 107.
    108. 108. PLAQUES, MS
    109. 109.
    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>
    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>
    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>
    113. 113.
    114. 114.
    115. 115. Neuritic plaques Neuritic plaques, stained with anti- beta amyloid immunostain
    116. 116.
    117. 117.
    118. 118.
    119. 119.
    120. 120.
    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>
    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>
    123. 123.
    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>
    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>
    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>
    127. 127.
    128. 128.
    130. 130.
    131. 131.
    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>
    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>
    134. 134.
    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
    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>
    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>
    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>
    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>
    140. 140. ALS, DEMYELINATION IN CORTICOSPINAL TRACTS ALS, pathologic changes in anterior horn cells
    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>
    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>
    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>
    144. 144.
    145. 145. 128 Hz
    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>
    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>
    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>
    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>
    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>
    151. 151.
    152. 152.
    153. 153.
    154. 154.
    155. 155.
    156. 156.
    157. 157.
    158. 158.
    159. 159.
    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>
    161. 161.
    162. 162.
    163. 163.
    164. 164. HIV
    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>
    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>
    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>