Minarcik robbins 2013_ch28-cns


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  • Defined as brain and spinal cord. Nothing more.
  • What is the fifth type of “glial” cell?
  • The “13 questions” fit nicely into one of these categories, sorta.
  • As amazingly complex as the CNS is, even more amazing is the fact that its components are so remarkably simple----Neuron body, dendrites, axon.
    NB: Nissl goes into the dendrites but not the axons.
  • Section from spinal cord. Is this grey matter or white matter?
    CNS system, being regarded as the most complex physiologically, I contend is the easiest histologically!
    Tracts, nuclei, grey, white, etc.
  • 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.
    What are the “haloed” cells?
  • Oligodendrocytes, the CNS myelinators. Note the clear space around their nuclei, much in the same way myelin washed out from schwann glial cells as well.
  • Eppendymal cells look exactly like ciliated columnar cells and like the ventricular spaced and choroid. Ependymal cells are the only glial cells that look epithelial, i.e., “simple columnar”, like we see in glands, and in this case you may even think you see cilia, because they are!
  • Choroid plexus is “papillary” in configuration. Eppendymal cells like these papillae too. The only purpose is to pump out CSF! From these cells.
  • Cluster of microglia, the macrophages of the CNS.
    Ironic concept: MICRO-glia act like MACRO-phages!
  • Please rise and repeat after me: GLIOSIS, EDEMA, DEMYELINIZATION all go hand in hand!
    They are all NON-specific reactions to almost ANY type of injury.
  • Why red?
    Is this NON-specific due to ANY type of injury theoretically? Ans: YES
  • Neuronal loss and GLIOSIS is a hallmark of more “chronic” CNS injury, add to that edema and demyelination.
  • A comparison of edema “compartments”: The ECS (EXTRA Cellular Space) is vasogenic and the ICS (INTRA Cellular Space) is cytotoxic.
    Cerebral EDEMA is a NONSPECIFIC consequence of MANY types of acute and chronic brain pathologies, but chiefly acute!
  • What is the 4th obvious sign? Ans: flattening of gyri
  • Flattened gyri often signify edema. Why? Ans: compression against the calvarium. Are the sulci, ergo less prominent as well for purely a geometrical reason? ANS:YES
  • 1) Falx, 2) Cingulate, and 3) Cereballar tonsillar levels of edema
  • Do you think there might be hemorrhage here, as well as edema?
    Would you feel safe venturing an etiology of this lesion? Ans: NO
  • “Notching” of the cingulate gyrus. Is the cingulate gyrus part of the hippocampus?
  • Cerebellar tonsillar herniation. Do you think that this cerebellar tonsil is trying to get to the wrong side of the foramen magnum?
  • Is it logical that the symptoms are in increasing order of severity?
    Would you imagine the order of clinical severity might be related to the order of anatomic severity?
  • The 3-D visualization of the ventricular is enabled here.
  • Basic pathophysiologic concepts about hydrocephalus which is defined as any major deviation from the normal physiology of CSF
    Adjectives of hydrocephalus are shown here.
  • Fontanelle closure is the key factor whether hydrocephalus will result in any cranial enlargement
  • Hydrocephalus on CT can look as simple as merely dilated ventricles.
    How might you tell if this was normal pressure vs. increased pressure?
  • Hydrocephalus on MRI, due to aqueductal stenosis. Would you expect the space BEFORE the stenosis to be more dilated than the space AFTER the stenosis? Does the 4th ventricle look rather normal in size? Ans: YES
  • Hydrocephalus also showing cerebral edema, CT or MRI? Ans: MRI Why? Ans: Bone is always very dense on CT, and water is always intense on T2 weighted MRI.
    What is the arrow pointing to? Ans: periventricular damage.
    Do you think this would me more likely with a HIGH pressure hydrocephalus, than a NORMAL pressure hydrocephalus? ANS: YES
  • Hydrocephalus, dilated ventricles, autopsy.
  • COMMON CNS malformations. Like any other malformation, they can be generally explained as an error in normal embryological growth and development.
  • Anencephaly, not terribly rare.
  • 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. Most spina bifidas are caudally located, i.e., the bottom of the “zipper”. Sasdly, these are also associated with defects in the connec tive tissues and even skin POSTERIOR to the cord defects as well.
  • Small gyri
  • Failure of the prosencephalon to develop, and separate, often leads to “cyclops”. What is the prosecephalon? ANS: The most anterior/superior portion of the neural tube (forebrain).
  • Normal corpus callosum. The very limiting factor of the falx. Often these are relatively asymptomatic, relatively speaking.
  • Absent corpus callosum. Mild or partial cases can be asymptomatic. Severe cases can result in severe retardation, or even be fatal.
  • Know what a “syrinx” is: Dilation of the central canal of the spinal cord.
  • These are the three most common types of perinatal brain injuries
  • Various patterns of CNS injury in newborns, intraventricular bleeding, intraparenchymal bleeding, periventricular infarcts in basal ganglia.
    Can intracerebral hemorrhage extend intraparenchymally and vice versa? YES!
  • Differentiation between CNS trauma is crucial in medicolegal cases.
  • Know the correct definitions
  • Contusion. Hemorrhage is the hallmark!
  • Skull fracture types
  • Probably the most common terms in medicine used before the phrase “brain hemorrhage”.
  • Does the most superficial layer of the dura blend in with the periosteum?
  • Epidural
  • Subdural
    Understand: coup/contre-coup
  • Subarachnoid hemorrhage occurs where the BIG intracranial arteries are, i.e., subarachnoid space.
    What 2 things commonly cause Subarachnoid Hemorrhage: 1) “Hemorrhagic” CVA’s due to arterial wall rupture, and 2) ruptured aneurysms
    Could hypertension be a risk factor for subarachnoid hemorrhage? Ans: YES
  • Could intraparenchymal extend (i.e., dissect) both ways if it is big enough, i.e., ventricular and subarachnoid?
  • Intraparenchymal extending (i.e., “dissecting”) intraventricularly
  • Could this dissect intraparenchymally as well? Ans: YES
  • Three common sequelae of CNS trauma
  • Use the logical symmetry rule!
  • You should recall cord injury level versus sensory and motor defects: “C5, still alive”
  • “C-5, still alive” principle.
    Nice chart to remember, even memorize if you feel you have to!
  • Definition should be clear: CVA = “STROKE”
  • Histopathologic progression of CNS infarcts, parallels the general cellular progression of events in inflammation. No exception here.
    The only exception is brain infarcts do NOT usually result in fibrosis.
  • Do you remember the LENTICULOSTRIATE arteries?
  • Why can brains sometimes be better examined blindfolded?
    Edema can be FELT better than SEEN better on gross brain cutting sessions.
  • Often asymptomatic, because of very small pinpoint size.
  • LacunarSlitMAJOR
  • Young woman dropping dead instantly for no reason is usually regarded as a ruptured berry aneurysm until proven otherwise!
    Would you imagine atherosclerotic aneurysms are far more common than congenital berry aneurysms? ANS:YES
  • Classical congenital “berry” aneurysm, Even LOOKS like a blueberry to me!
  • Extensive basilar subarachnoid hemorrhage. Would you expect aneurysm subarachnoid bleeds to involve (i.e., “dissect” through) the BASILAR subarachnoid space primarily? OF COURSE!!!
  • 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). Nice things to see demonstrated on you youtube!
  • Question #7
  • Meninges, purulent, at the base of the brain. Does a neuropathologist always look for “cloudiness” of the (lepto) meninges? YES
  • Meninges, purulent, occipital.
    CLOUDINESS of LEPTOMENINGES is what is looked for at autopsy.
  • Meningitis vs. meningoencephalitis
  • Logical explanations for various types of brain abscesses?
  • Abscesses, some with satellites.
    Often very hard to differentiate from GBM, but isn’t a GBM like an abscess? Ans: YES!, in fact, a GBM might even cause one!
  • Caspsule, or pseudocapsule. What is the difference? ANS: True capsules are epithelial lined.
  • No big surprise here.
  • Sinusoiditis, mastoiditis?
  • Many epidural abscesses are in the spinal cord, often secondary to surgery. Why? BONE TRAUMA.
  • Can a large granuloma look like a TUMOR? Ans: YES, that is why it is called a tuberculoma.
  • LYME DISEASE (Neuro-Borreliosis), one exception to the thumbnail rule that encephalitis is viral. Tick usually of Ixodes genus.
  • 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.
    An ACUTE clinical syndrome, may show cuffing by characteristically CHRONIC (lymphs macs) inflammatory cells.
    The space is termed the Virchow-Robin space often.
  • Are the temporal lobes showing increased MRI signals, i.e., water, i.e., protons, i.e., edema?
  • Eosinophilic Negri body of Rabies, also basophilic inclusions of CMV
  • This is NOT opportunistic pathogen, it is HIV itself!
  • Usually in immunologically impaired patients.
  • Demyelination is associated with gliosis and edema, therefore bright signals on T2 weighted images.
    Demyelination is associated with gliosis and edema.
    Gliosis is associated with demyelinization and edema.
    Edema is associated with demyelinization and gliosis.
  • The edema enable MRI, visualization, the gliosis is demonstrative of the cellular histopathologic reaction.
  • Myelin (fat) stain.
  • Mostly a historical note, but doesn’t it still follow the rule of lymphocytic perivascular cuffing? ANS: YES
  • Simple India Ink prep, showing the capsule.
  • What simple fungal stain might you use for the abnormal areas? ANS: PAS
  • Parasites! Most of which are protozoans!
  • The last six questions are more exotic than the first seven
  • Question #8:
    PR-oteinaceous I-nfectious particle = PRI-on
  • Prion diseases in animals and Humans cause “spongiform” changes in the CNS.
  • “Replication” is felt to be due to the protein undergoing a conformational change to induce neighboring proteins to become like it.
    THIS is finally the answer to the age-old question: How can a pathogenic protein replicate without DNA or RNA!!!
    Please watch this UCSF video http://www.youtube.com/watch?v=w5aAPEYIL9A
    Prion Protein is NORMAL, Prions are AB-Normal!
  • 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
  • Question #9:
    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 gliosis is the usual non specific cellular response to damaged tissue.
  • The PLAQUE of MS is NOT like a plaque of skin diseases or Alzheimer disease. In MS the plaque is a demyelinated area.
  • MS gave MRI its first HUGE boom, by virtue of being able to detect these lesions, due to edema!
    Where do you see MS in the brain? Ans: Wherever there is white matter!
    Do you think DEMYELINATION ALONE might cause increased MRI signals?
  • Myelinated white matter stains BLUE, and demyelination is loss of blue. Remember MS is a disease PRIMARILLY of WHITE matter.
    If you have a good sense of symmetry, you done need to go to neuropathologist school.
  • Plaques grossly, do some areas in the brain white matter look “less” white?
  • Plaques microscopically. Demyelination, edema, gliosis, and, lower right, relative “preservation” of the actual nerve fibers, usung a nerve fiber stain, like wires without insulation!
  • Question #10
    FOUR classical areas for brain degeneration, a decent anatomic classification.
  • ALZHEIMER disease is many times more common than all the other dementias put together, except for MID.
    Progressive supranuclear palsy (PSP) is a rare degenerative tauopathy involving the gradual deterioration and death of selected areas of the brain, chiefly basal ganglia and cortex. CBD is a similar tauopathy. Pick Disease is another tauopathy. Do you see a pattern here?
    Are “tau”-opathies (i.e., tau protein buildups) generally synonymous with CNS degenerative diseases? YES.
    CNS degenerative diseases were generally regarded as the same as “senility” until the PC police disallowed this word.
  • * NB: NOT at all like MS plaques.
  • 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 of Alzheimer’s diaease
  • 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). Remember the amyloid of Alzheimer’s disease is BETA amyloid, NOT the usual kind of ALPHA amyloid seen with immunoglobulinproliferative diseases such as myelomas.
  • 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, causing it to precipitate
  • Tau is a gene, Tau protein is a microtubule protein associated with hyperphosphorylation in tau-opathies. MANY cortical dementias are TAU protein, and therefore most cortical dementias are known as TAUOPATHIES.
  • 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 due to inadequate dopamine, normal on right.
  • 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.
  • Please understand ataxia http://www.youtube.com/watch?v=5eBwn22Bnio
  • Kennedy's disease (KD) or X-linked spinal and bulbar muscular atrophy (SBMA) or spinobulbar muscular atrophy or X-Linked bulbo-spinal atrophy is a neuromuscular disease associated with mutation of the androgen receptor (AR). Because of its endocrine manifestations related to the impairment of the AR, it can be viewed as a variation of the disorders of the androgen insensitivity syndrome. It is also related to other neurodegenerative diseases caused by similar mutations, such as Huntington's disease and the spinocerebellar ataxias. Kennedy's disease is named after W. R. Kennedy, a neurologist who was among the first to describe this disease.
  • Question #11
  • Leukodystrophy refers to a group of disorders characterized by progressive degeneration of the myelinated white matter (“leuko” means white) of the brain. The leukodystrophies are caused by imperfect growth or development of myelin due to genetic defects in the enzymes required for proper myelin production and maintenance.
  • Question #12
  • 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. This is why you carry a tuning fork in your black bag, the detect the earliest clinical symptoms, i.e., the loss of vibratory sense.
  • Final Question #13/13
  • Usually very slow and subtle onset.
    Most of these presenting symptoms occur after tumor is sizeable.
  • Routine workup of CNS tumors.
  • The differential between gliosis and a well differentiated glioma can be gruelingly difficult.
  • Gliosis vs. Glioma?
    To tell you the truth, I kinda forgot what it was.
    Every pathologist’s nightmare! Why?
  • Glioma, intermediate grade
  • Glioma, high grade, Note NECROSIS. NECROSIS is needed for the diagnosis of a HIGH grade glioma.
    The higher grade gliomas merit the term GBM (GlioBlastome Multiforme), which need the presence of NECROSIS for a correct diagnosis, but pleormorphism and palisading usually can be easily demonstrated as well. Often, a PERIVASCULAR growth pattern is also seen.
  • Glioblastoma (multiforme). Why is it called “multiforme”? Note the 1) palisading and 2) necrosis which are hallmarks of GBM.
  • Central necrosis is a sign of rapid growth. It outgrows its blood supply, and therefore liquefies centrally, like an abscess. This is NOT a T2 weighted image because the abscess material is usually liquid, but is probably a Ti weighted image.
  • What kinds of glial cells are these?
  • What is this? Could it be a TUMOR of glial cells that look like oligodendrocytes?
  • YES it is
  • What kinds of glial cells are these?
  • Could this be a tumor of glial cells that look like ependymal cells?
    Might this “glioma” look like an adenocarcinoma, or even a papillary adenocarcinoma?
  • Normal ependyma on the left. Where would most ependymomas have to me located? Would a choroid plexus tumor be a type of ependymoma? Ans: Sure
    Could this result in an overproduction of CSF? ANS: SURE
  • Do you think that of all the brain tumors, the ependymomas look the most like adenocarcinomas. Ans: YES
    Do you think they would be more likely to arise where ependyma is abundant such as in choroid plexus? Ans: YES
  • What is this? (Hint: note rosettes) Ans: neuroblastoma. Neuroblastomas of the CNS are classically neoplasms of NEURONS, NOT mature neurons but neuron precursors.
  • Any midline cerebellum tumor in a child is a medulloblastoma till proven otherwise!
    Are medulloblastomas PNET tumors? Answer: YES!
    So does that mean the will look like a small cell carcinoma, or Ewings, or lymphoma, or any other “small round blue” cell tumor? Ans: Yes!
  • Quiz: Midline cerebellum tumor in a kid. What is it? Ans: medulloblastoma, always, unless proven otherwise.
  • Tell story about surgeon.
  • Parts 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
  • Toxoplasmosis and lymphomas and encephalitis are very common in AIDS. Might you call the MRI lesion a “toxoplasmoma”? Ans: Sure, why not?
  • A solitary brain mass is statistically just as likely to be metastatic than primary
  • Occasionally these symptoms of para-neoplastic syndromes are warnings that a malignancy is present.
    Whys is “prophylactic” brain radiation given to patients with small cell carcinomas, and no radiologic evidence for CNS invlvement?
  • Important quick facts not worth going into too much at this time.
  • Minarcik robbins 2013_ch28-cns

    1. 1. CNS
    2. 2. CNS • Normal – Neurons – Glia • Astrocytes • Oligodendrocytes • Ependymal Cells • Microglia • Pathology (13 Questions)
    3. 3. Classical Disease Patterns • Degenerative • Inflammatory • Neoplastic
    4. 4. Classical CNS Disease Patterns • Degenerative • Inflammatory • Neoplastic • Traumatic
    5. 5. • 1) What are general patterns of CNS cell pathology? • 2) • 3) • 4) • 5) • 6) • 7) What are the consequences of ↓↑ CNS pressure? What are common patterns of CNS malformations? What are common perinatal CNS injuries? What are the patterns of CNS trauma? What are the patterns of CNS vascular disease? What are the patterns of CNS infection? ___________________________________________________ • 8) What are the patterns of CNS prion disease? • 9) What are the patterns of CNS demyelinating disease? • 10) What are the patterns of CNS degenerative disease? • 11) What are the CNS genetic metabolic diseases? • 12) What are the CNS acquired metabolic/toxic diseases? • 13) What are the CNS tumors?
    6. 6. CELLULAR REACTIONS • Neurons – Acute (RED neuron, karyolysis) – Subacute, chronic, cell loss, gliosis – Axonal – Inclusions (lipid, prot., carb., viruses) • Glia, “gliosis” – Swelling – Fibers – Inclusions
    8. 8. CEREBRAL EDEMA (normal weight 1200-1300 grams) • Vasogenic (disrupted BBB) Intravascular INTER-cellular • Cytotoxic  INTRA-cellular
    9. 9. CEREBRAL EDEMA • Subfalcine (SUPRA-tentorial) • Cingulate (TENTORIAL) • Cerebellar tonsilar (SUB-tentorial, or INFRA-tentorial)
    13. 13. CNS MALFORMATIONS • Neural Tube – Anencephaly, Encephalocele, Spina Bifida • Forebrain – Polymicrogyria, Holoprosencephaly, Agenesis of Corpus Callosum • Posterior Fossa (Infratentorial) – Arnold Chiari (infratentorial herniation), DandyWalker (cerebellar cyst) • Syringomyelia/Hydromyelia
    14. 14. SPINA BIFIDA
    17. 17. SYRINGOMYELIA (note “SYRINX”)
    18. 18. PERINATAL Brain Injuries • Intraparenchymal Hemorrhage • Intraventricular hemorrhage (premies) • Periventricular “leukomalacia” (i.e., infarcts) • Cerebral “Palsy” refers to nonprogressive diffuse cerebral pathology apparent at childbirth
    19. 19. CNS TRAUMA • Skull Fractures • Parenchymal Injuries • Traumatic Vascular Injury • Sequelae • Spinal Cord Trauma
    20. 20. BRAIN TRAUMA • Contusion (bruise) • Laceration (tear) • Coup/Contre-Coup • Concussion
    22. 22. HEMATOMAS/HEMORRHAGE • • • • • EPIDURAL (fx) SUBDURAL (trauma NO fx) SUBARACHNOID (arterial, no trauma) INTRAPARENCHYMAL (any) INTRAVENTRICULAR (no trauma, rare in adults, common in premies)
    25. 25. SUBARACHNOID
    29. 29. CNS TRAUMA SEQUELAE • Hydrocephalus (WHY?) • Dementia (Punch Drunk Syndrome) • Diffuse Axonal Injury (white matter)
    30. 30. SPINAL CORD TRAUMA • Parallels BRAIN patterns of injury on a cellular basis • Usually secondary to spinal column displacement • Level of injury mirrors motor loss: Death Quadriplegia  Paraplegia
    31. 31. Cerebrovascular Diseases (CVA, “Stroke”) • Ischemic (Thrombotic) (↓ blood and 02) – Global – Focal (regional): – ACUTE: edema  neuronal microvacuolization  pyknosis  karyorrhexis  neutrophils – CHRONIC: macrophages  gliosis • Hemorrhagic (rupture of artery/aneurysm)
    32. 32. THROMBOTIC MCA
    34. 34. A) EDEMA B) “RED” NEURONS C) POLYs D) MONO’s (MACs) E) GLIOSIS Histopathologic progression of CNS infarcts
    35. 35. HYPERTENSIVE CVA • Intracerebral • Basal Ganglia Region (lenticulostriate arteries of internal capsule, putamen)
    38. 38. “SLIT” HEMORRHAGE(s)
    39. 39. SUBARACHNOID HEMORRHAGE • Rupture of large intracerebral arteries which are the primary branches of the anatomical circle (of Willis) • Congenital (“berry” aneurysms) • Atherosclerotic (atherosclerotic aneurysms, or direct wall rupture)
    40. 40. HYPERTENSIVE ENCEPHALOPATHY • ACUTE – Headaches – Confusion – Anxiety – Convulsions • CHRONIC – Dementia (MID, Multi-Infarct-Dementia) – Gait Disturbances – Basal Ganglia symptoms
    42. 42. INFECTIONS • Meningitis (generally* bacterial) – – – – – E. coli, Strep B (neonates) H. influenzae (children) Neisseria meningitidis (adults) Strep. pneumoniae, Listeria (elderly) PMNs in CSF, INCREASED protein, REDUCED glucose • Encephalitis (generally viral) – Arboviruses, HSV, CMV, V/Z, polio, rabies, HIV – Lymphs and macrophages in perivascular “VirchowRobbins” spaces • Meningoencephalitis * viral, chemical, tumoral
    43. 43. ACUTE FOCAL SUPPURATIVE CNS INFECTIONS • CEREBRAL ABSCESSES – Local (mastoiditis, sinusitis) – Hematogenous (tooth extraction, sepsis) – Staph, Strep – Often fibrous capsule, liquid center • SUBDURAL EMPYEMA (IN SINUSITIS) • EXTRADURAL ABSCESS (IN OSTEOMYELITIS)
    45. 45. CHRONIC BACTERIAL Meningo-encephalits • TB, brain and meninges • SYPHILIS, gummas in brain • LYME DISEASE (Neuro-Borreliosis)
    46. 46. TUBERCULOMA
    47. 47. VIRAL Meningo-encephalitis • • • • • • • • • • ARBO VIRUSES (West Nile, Equines, Venez., many more) HSV1 HSV2 V/Z CMV POLIO RABIES HIV Progressive Multifocal Leukoencephalopathy (JC) Subacute Sclerosing Panencephalitis (Measles)
    49. 49. Bitemporal encephalitis is HSV until proven otherwise!
    50. 50. HSV = TEMPORAL lobe(s)
    52. 52. PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) • JC Polyoma virus is the cause (JCV) • Primarilly affects oligodendocytes • Ergo, demyelination is the main feature
    53. 53. PML
    54. 54. SUBACUTE SCLEROSING PANENCEPHALITIS (SSPE) • VERY rare since measles eradicated • Thought to be caused by measles virus
    55. 55. FUNGAL MENINGO-ENCEPHALITIS • CRYPTOCOCCUS • CANDIDA • ASPERGILLIS • MUCOR (Mostly in immunocompromised hosts)
    58. 58. CNS II
    59. 59. • 1) What are general patterns of CNS cell pathology? • 2) 3) 4) 5) 6) 7) • • • • • What are the consequences of ↓↑ CSF pressure? What are common patterns of CNS malformations? What are common perinatal CNS injuries? What are the patterns of CNS trauma? What are the patterns of CNS vascular diseases? What are the patterns of CNS infection? • 8) What are the patterns of CNS prion diseases? • 9) What are the patterns of CNS demyelinating diseases? • 10) What are the patterns of CNS degenerative diseases? genetic metabolic diseases? 12) What are the CNS acquired metabolic/toxic • 11) What are the CNS • diseases? • 13) What are the CNS tumors?
    60. 60. PRION DISEASES • Creutzfeldt-Jakob Disease (CJD) • • • • • • • Gerstmann-Straussler-Scheinker syn. (GSS) Fatal familial insomnia Kuru, human variety (cannibalism) Scrapie (sheep and goats) Mink transmissible encephalopathy Chronic wasting disease (deer and elk) Bovine Spongiform Encephalopathy (BSE)
    61. 61. PRION DISEASES: common features • Infectious agents with apparently no DNA • DEMENTIA • Prion Protein (PrP) accumulation • “SPONGIFORM” changes in neurons and glia • TRANSMISSIBLE, FATAL, NO Rx
    62. 62. 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
    63. 63. CJD (Creutzfeldt-Jakob) • 1 per million incidence, 7th decade • Sporadic cases, not epidemic • Transmitted! • Familial cases well documented • Rapidly progressive dementia • Grey Matter • Cerebellar ataxia also, usually • FATAL, no treatment known, like ALL prion diseases
    65. 65. MS • Cause: ? • USA prevalence: 1:1000 • F>>M, Ages: 30’s, 40’s • Immune response primarily against CNS myelin (white matter) • Regional area of white matter demyelination is called “PLAQUE” • Increased CSF gamma globulin, i.e., oligoclonal bands • Often presents with VISUAL problems • EXACERBATIONS/REMISSIONS
    66. 66. PLAQUES, MS
    67. 67. CNS DEGENERATIVE DISEASES • CORTEX (dementias) • BASAL GANGLIA and BRAIN STEM (parkinsonian) • SPINOCEREBELLAR (ataxias) • MOTOR NEURONS (muscle atrophy)
    68. 68. CNS DEGENERATIVE DISEASES • CORTEX (dementias) –ALZHEIMER DISEASE – Frontotemporal – Pick Disease (also primarily frontal) – Progressive Supranuclear Palsy (PSP) – CorticoBasal Degeneration (CBD) – Vascular Dementias (MID)
    69. 69. ALZHEIMER DISEASE • Commonest cause of dementias (majority) • Sporadic, 5-10% familial • CORTICAL (grey matter) ATROPHY • NEURITIC PLAQUES* (extraneuronal) • NEUROFIBRILLARY TANGLES (intraneuronal) • AMYLOID!!! (i.e., “BETA” amyloid)
    70. 70. Neuritic plaques Neuritic plaques, stained with anti- beta amyloid immunostain
    72. 72. VASCULAR DEMENTIA • Associated with multiple infarcts, hence the name MID (Multiple Infarct Dementia) – Lacunar infarcts – Cortical microinfarcts – Multiple embolic infarcts • SECOND commonest form of dementia after Alzheimer
    73. 73. CNS DEGENERATIVE DISEASES • BASAL GANGLIA and BRAIN STEM –Parkinsonism – Parkinson Disease – Multiple System Atrophy – Huntington Disease
    74. 74. Parkinsonism • Is a clinical “syndrome”, NOT a disease – Diminished facial expression – Stooped posture – Slowness of voluntary movement – “Festinating” gate (short, fast) – Rigidity (cogwheel) – “Pillrolling” tremor • The above clinical findings involve pathology of the SUBSTANTIA NIGRA, and include: – PARKINSON DISEASE – MULTIPLE SYSTEM ATROPHY – POSTENCEPHALIC PARKINSONISM – Progr. Supranuc. Palsy, Cort. Basal Degen. (cortical disorders)
    75. 75. PARKINSON DISEASE • PALLOR of the SUBSTANTIA NIGRA (and LOCUS COERULEUS) • LEWY BODIES (alpha-synuclein protein)
    76. 76. LOCUS COERULEUS* in PONS (CERULEUS**) * 254,000 ** 76,000
    77. 77. PARKINSON DISEASE • Parkinsonism symptoms, i.e., – cogwheel rigidity – intention tremor • • • • Progressive Hallucinations Dementia Symptomatic response to L-DOPA
    78. 78. MULTIPLE SYSTEM ATROPHY • MSA • WIDE SPECTRUM of diseases • GLIAL CYTOPLASMIC INCLUSIONS (GCIs) in oligodendrocytes (alpha synuclein) • Clinically, – parkinsonism symptoms – autonomic dysfunction
    79. 79. HUNTINGTON DISEASE • Classical familial, genetic disease • Progressive motor loss and dementia • “chorea”, i.e. “jerky” movements • Progressive, fatal • Atrophy of basal ganglia, i.e., corpus striatum Cortical (basal ganglia) atrophy Ventricular enlargement
    80. 80. CNS DEGENERATIVE DISEASES • SPINOCEREBELLAR DEGENERATIONS (ATAXIAS) – Spinocerebellar ataxias – Friedrich Ataxia – Ataxia-Telangiectasia
    81. 81. SPINOCEREBELLAR DEGENERATIONS • Cerebellar cortex • Spinal cord • Peripheral nerves • FEATURES: –ATAXIA (loss of extremity muscle coordination) – SPASTICITY – NEUROPATHIES
    82. 82. CNS DEGENERATIVE DISEASES • MOTOR NEURONS –ALS (Amyotrophic Lateral Sclerosis, i.e., Lou Gehrig’s disease) – BulboSpinal Atrophy (Kennedy Syndrome) – Spinal Muscular Atrophy
    83. 83. Amyotrophic Lateral Sclerosis • Unknown etiology • Progressive muscle atrophy due to motor neuron loss (lower, upper) • 5-10% familial • Lou Gehrig had it, so does Steven Hawking • Hand weakness diaphragm • Anterior horn cells reduced and gliotic
    84. 84. A.L.S., DEMYELINATION IN CORTICOSPINAL TRACTS ALS, pathologic changes in anterior horn cells
    85. 85. GENETIC METABOLIC DISEASES • NEURONAL STORAGE DISEASES – (classical autosomal recessive enzyme deficiencies) • “LEUKO”-DYSTROPHIES – (abnormal “myelin” synthesis) • MITOCHONDRIAL ENCEPHALOPATHIES – (mitochondrial gene mutations)
    86. 86. LEUKODYSTROPHIES • • • • • Krabbe MetachromaticAdrenoPelizaeus-Merzbacher Canavan
    87. 87. ACQUIRED TOXIC/METABOLIC CNS DISEASES • • • • • • • • • Vitamin B1 deficiency (Wernicke-Korsakoff) Vitamin B12 deficiency (vibratory sense) Diabetes Increased/Decreased GLUCOSE Hepatic Failure (NH4+) CO (Cortex, hippocampus, Purkinje cells) CH3-OH, Methanol (Retinal ganglion cells) CH3-CH2-OH (acute/chronic, direct/nutrit’l) Radiation (Brain MOST resistant to Rad. Rx.) Chemo (Methotrexate + Radiation)
    88. 88. 128 Hz
    89. 89. CNS TUMORS • GLIOMAS (do not metastasize out of the CNS) – • • • • • III, IV) Astrocytes (I, II, – Oligodendroglioma – Ependymoma NEURONAL (neuroblastoma) POORLY DIFFERENTIATED (medulloblastoma) MENINGIOMAS LYMPHOMAS METASTATIC
    90. 90. CNS TUMORS • SYMPTOMS? – Headache – Vomiting – Mental Changes – Motor Problems – Seizures – Increased Intracranial Pressure –ANY localizing CNS abnormality
    91. 91. CNS TUMORS • History • Physical • Neurologic exam • LP (including cytology) • CT • MRI • Brain angiography • Biopsy
    92. 92. CNS TUMORS • Benign? Malignant?, Primary vs. met? • • • • • • • • • Location? Age? X-ray Density? MRI signals? Calcifications? Vascularity? Necrosis? Liquefaction? Edema? Compression of neighbors?
    93. 93. GLIOSIS vs. GLIOMA • • • • • • • • • • Age? White vs. Grey Matter? Gross texture? Vascularity? Mitoses? (N/C, Pleomorphism, Hyperchromasia) Calcifications? Cysts? Satellitosis? Delineation?
    95. 95. OLIGODENDROGLIOMA Occurs frequently in the frontal or temporal lobes Can be classified as low grade or high grade Common among men and women in their 20s-40s, but can occur in children More common in men than women Accounts for two percent of all brain tumors May be associated with 1p or 19q chromosomal losses
    96. 96. EPPENDYMOMA Usually localized to one area of the brain Develops from cells that line the hollow cavities at the bottom of the brain and the canal containing the spinal cord Can be slow growing or fast growing May be located in the ventricles (cavities in the center of the brain) May block the ventricles, causing hydrocephalus (water on the brain) Sometimes extends to the spinal cord Common in children, and among men and women in their 40s and 50s Occurrence peaks at age five and again at age 34 Accounts for two percent of all brain tumors
    97. 97. Zoom Me!
    98. 98. • • • • • MENINGIOMAS Occur where dura is Very vascular BENIGN, but………….(can be damned invasive) Can invade skull, etc. Only invade (displace) brain in areas adjacent to dura, i.e., parasagittal, falx, tentorium, venous sinuses • Small, firm, and well defined like a SUPERBALL • Often (usually?) have PSAMMOMA bodies
    99. 99. HIV
    101. 101. “PARA”NEOPLASTIC SYNDROMES • SMALL CELL, LUNG • LYMPHOMAS • BREAST CA • Purkinje Cell Degeneration • Encephalitis, Limbic System • Sensory Neuron Degeneration, DRG • Eye Movement Disorders
    102. 102. FAMILIAL TUMOR SYNDROMES • NF1 – Neurofibromas – Gliomas • NF2 – Schwannomas – Meningiomas • Tuberous Sclerosis, i.e., CNS and somatic “hamartomas” • Von-Hippel-Lindau, CNS hemangioblastomas, chiefly cerebellar