<ul><li>Demyelinating Diseases </li></ul><ul><li>Selective loss of myelin </li></ul><ul><li>a)  MS is demyelinating, where...
-  characterized by   of a  cerebroside (galactosyl  sulfatide) in white matter of  brain and PNS iii)  predominates in i...
iv)  almost complete loss of    oligodendroglia and myelin v)  presence of gobloid cells    found around blood vessels c) ...
iv)  enzyme mutation - impairs capacity to degrade    VLCFA’s v)  more severe demyelination in    cortical white matter - ...
v)  psychomotor retardation,    progressive dementia,    paralysis    death vi)  mutation of gene encoding    GFAP    Ro...
c)  affects sensory and motor      functions d)  acquired disease, mean age ~    30yrs i)  women 2:1  e)  etiology remains...
h)  infectious agents i)  wide variety of viruses -  mumps, rubella, herpes      simplex and measels (via    vaccination) ...
iii)  neurons are spared, while    axons degenerate when next    to plaque! iv)  MS has “focal” areas of injury v)  demyel...
J)  clinical i)  onset 30-40 yrs ii)  PNS are uniformly spared iii)  usually begins with symptoms    in optic nerves, brai...
<ul><li>v)  disease usually follows chronic    relapsing and remitting course      develop permanent lesions  </li></ul><...
ii)  present as bilateral optic    neuritis and spinal cord    involvement iii)  lesions similar to MS but    more destruc...
<ul><li>Acute disseminated encephalomyelitis </li></ul><ul><li>a)  follow either </li></ul><ul><li>i)  viral infection or ...
<ul><li>v)  symptoms progress rapidly       fatal in 20% and remaining    cases    complete recovery </li></ul><ul><li>A...
<ul><li>iii)  highly fatal </li></ul><ul><li>Central pontine myelinolysis </li></ul><ul><li>a)  loss of myelin </li></ul><...
<ul><li>iii)  can occur during setting of: </li></ul><ul><li>-  alcoholism </li></ul><ul><li>-  severe electrolyte/osmolar...
<ul><li>Degenerative Diseases </li></ul><ul><li>Parkinson Disease </li></ul><ul><li>a)  Common movement disorder </li></ul...
<ul><li>Epidemiology </li></ul><ul><li>a)  6-8 decades </li></ul><ul><li>b)  more than 2% in North America    develop dise...
ii)  toxin intake -  MPTP (1-methyl-4-phenyl-   1,2,3,6-tetrahydropyridine) f)  substantia nigra relays information    to ...
iv)  oxidative stress (of    catecholamines) during melanin    formation injures neurons in    substantia nigra g)  loss o...
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ii)  coarse tremor of distal    extremities -  at rest iii)  face is expressionless    (mask-like) -  reduced rate of swal...
<ul><li>v)  early PD tx with L-dopa </li></ul><ul><li>-  after several years      becomes ineffective </li></ul><ul><li>vi...
c)  less severe changes in substantia    nigra and locus ceruleus  d)  associated with Shy-Drager      disease and   olivo...
<ul><li>ii)  Autonomic dysfunction </li></ul><ul><ul><li>  orthostatic hypotension </li></ul></ul><ul><li>f)  when present...
<ul><li>Amyotrophic lateral sclerosis (ALS) </li></ul><ul><li>a)  leads to profound weakness and    death </li></ul><ul><l...
<ul><li>i)  Chomoro people in Guam </li></ul><ul><ul><li>  disease is rich in tau NFT </li></ul></ul><ul><li>    now class...
<ul><li>h)  affects motor neurons (3        locations) </li></ul><ul><li>i)  anterior horn cells of cord </li></ul><ul><li...
<ul><li>v)  loss of pyramidal “Betz” cells in    motor cortex </li></ul><ul><li>vi)  loss of myelinated fibers in    later...
<ul><ul><li>-  irregular rapid contractions of    muscles that do not move limbs    (fasciculations) </li></ul></ul><ul><u...
<ul><li>Huntinton disease </li></ul><ul><li>a)  inherited autosomal dominant     disease </li></ul><ul><li>b)  progressive...
e)  progressive i)  course ~ 15 years f)  HD gene    4p16.3 encodes a      protein i)  huntingtin ii)  repeat mutation   ...
<ul><li>g)  clinical </li></ul><ul><li>i)  4-5th decade at onset </li></ul><ul><li>ii)  motor symptoms usually    precede ...
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<ul><li>Spinocebellar ataxias </li></ul><ul><li>loss of neurons and neural tracts in </li></ul><ul><li>cerebellum, brainst...
<ul><li>Friedreich ataxia </li></ul><ul><li>a)  most common inherited ataxia </li></ul><ul><li>b)  autosomal recessive </l...
<ul><ul><li>-  hypertrophic    cardiomyopathy which    commonly causes death </li></ul></ul><ul><ul><ul><li>-  diabetes me...
<ul><li>DEGENERATIVE DISEASES (AD) </li></ul><ul><li>(Alzheimer Disease) </li></ul><ul><li>principle cause of “so-called” ...
<ul><li>e)  2 associations </li></ul><ul><li>i)  amyloid   -protein (A  ) </li></ul><ul><ul><li>-     deposition in    ...
Alzheimer Disease 1.-  amyloid  β -protein (A β ) a)  evidence points to    in    neuritic plaques of A β i)  located in ...
2.-  Neurofibrillary tangles (NFT) a)  microtubule-associated    protein i)  abnormal helical form    which is termed “tau...
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<ul><li>d)  most cases of AD are associated    with lots of LEWY bodies </li></ul><ul><li>e)  genetic association </li></u...
<ul><li>b)  microscopic findings </li></ul><ul><li>i)  senile plaques </li></ul><ul><li>ii)  NFT </li></ul><ul><li>iii)  n...
<ul><li>b)  AD is progressive </li></ul><ul><li>i)  previously intelligent and    productive persons </li></ul><ul><li>-  ...
c)  difficult to distinguish from AD d)  most cases are sporadic e)  occurs in mid adult life i)  progress to death in 3-1...
<ul><li>h)  inclusions contain tau and      argentophilic and are referred to    as “Pick bodies” </li></ul><ul><li>i)  de...
<ul><li>rarely metastatic outside of CNS </li></ul><ul><li>classes: </li></ul><ul><li>a)  gliomas </li></ul><ul><li>b)  ne...
a)  Astrocytoma i)  fibrillary astrocytoma ii)  glioblastoma iii)  pilocytic astrocytoma iv)  pleomorphic    xanthoastrocy...
<ul><li>Fibrillary astrocytoma </li></ul><ul><li>i)  ~ 80 % of adult primary tumors </li></ul><ul><li>ii)  found in cerebr...
-  low grade astrocytoma show    inactivation of tumor    suppressor gene p53 -  high grade astrocytoma show      inactiv...
1.   -  short, rapidly progressive, arising    without preexisting low grade      tumor   -  typically in older patients (...
C) Pilocytic astrocytoma i)  young adults ii)  relatively benign iii)  mainly cerebellum -  may occur in floor of 3 rd    ...
<ul><li>Oligodendroglioma  </li></ul><ul><li>a)  5-10 % of gliomas </li></ul><ul><li>b)  most common in 4 th  and 5 th    ...
<ul><li>d)  most common genetic defect </li></ul><ul><li>i)  involves chromosome 1   and    19q </li></ul><ul><li>e)  cli...
ii)  first 2 decades of life -  near 4 th  ventricle -  5-10 % of primary tumors    in this age group iii)  in adults spin...
-  CSF dissemination is    common -  average survival ~ 4 years iii)  several other tumors occur -  lining of ventricles -...
<ul><li>Subependymomas </li></ul><ul><li>a)  solid </li></ul><ul><li>i)  sometimes calcified </li></ul><ul><li>b)  slow gr...
<ul><li>Choroid plexus papillomas  </li></ul><ul><li>a)  occur anywhere along choroid      plexus </li></ul><ul><li>b)  mo...
<ul><li>i)  causes noncommunicating </li></ul><ul><li>  hydrocephalus </li></ul><ul><li>-  may be rapidly fatal </li></ul>...
b)  more commonly exist as admixture  i)  with glioma neoplasm -  lesion termed    “ganglioglioma”  -  usually presents wi...
<ul><li>ii)  childhood </li></ul><ul><li>-  presents with seizures </li></ul><ul><li>iii)  slow growth </li></ul><ul><li>-...
<ul><li>iv)  rapid and aggressive growth </li></ul><ul><li>b)  central neurocytoma </li></ul><ul><li>i)  low grade </li></...
<ul><li>d)  clinical </li></ul><ul><li>i)  highly malignant </li></ul><ul><li>ii)  very radiosensitive </li></ul><ul><li>i...
<ul><li>e)  clinical </li></ul><ul><li>i)  occur prior to 5 years of age </li></ul><ul><li>ii)  death within a year follow...
c)  in nonimmunosuppressed  i)  occurs after age 60 d)  often presents at multiple sites e)  extra CNS involvement is rare...
<ul><li>g)  very aggressive </li></ul><ul><li>i)  poor response to treatment </li></ul><ul><li>  compared to peripheral </...
c)  teratomas i)  most common tumor that -  presents as congenital    tumor d)  in pineal region i)  male predominance ii)...
<ul><li>ii)  similar classification to    seminoma in testis </li></ul><ul><li>-  termed “germinoma” </li></ul><ul><li>pin...
<ul><li>c)  Gliomas also found in pineal region </li></ul><ul><li>meningioma </li></ul><ul><li>a)  benign </li></ul><ul><l...
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<ul><li>metastatic tumors </li></ul><ul><li>a)  mostly carcinomas </li></ul><ul><li>i)  25-50 % of hospitalized    patient...
<ul><li>c)  meninges frequent site of        metastatic tumors </li></ul><ul><li>d)  present as mass lesion </li></ul><ul>...
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BOARD QUESTIONS www.freelivedoctor.com
Which of the following disorders affecting myelin is most likely to be found in a 30-year-old woman?  (A) multiple scleros...
A disease characterized by widespread patches of demyelination with less prominent axis cylinder destruction and glial ove...
Reactive astrocytes surrounding eosinophilic fibers radiating from a central core which stains for amyloid is characterist...
Lewy bodies are most commonly encountered in  (A) idiopathic Parkinsonism  (B) post-encephalitic Parkinsonism  (C) rabies ...
The most radiosensitive primary intracranial neoplasm is  (A) ependymoma (B) glioblastoma (C) medulloblastoma  (D) oligode...
A child presents with nausea and vomiting, a recent onset of ataxia, and a posterior fossa tumor. The most likely diagnosi...
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Cns degeneration, demyelination and tumors

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Cns degeneration, demyelination and tumors

  1. 1. <ul><li>Demyelinating Diseases </li></ul><ul><li>Selective loss of myelin </li></ul><ul><li>a) MS is demyelinating, whereas </li></ul><ul><li>b) necrosis, etc. is not demyelinating </li></ul><ul><li>Leukodystrophies reflect inherited </li></ul><ul><li>disturbances in formation and </li></ul><ul><li>preservation of myelin </li></ul><ul><li>a) metachromatic leukodystrophy </li></ul><ul><li>i) most common leukodystrophy </li></ul><ul><li>ii) autosomal recessive disorder of myelin metabolism </li></ul>www.freelivedoctor.com
  2. 2. - characterized by  of a cerebroside (galactosyl sulfatide) in white matter of brain and PNS iii) predominates in infancy iv) lethal within several years b) Krabbe disease i) fatal, early months of life ii) deficiency of galactocerbroside ß- galactosidase iii) autosomal recessive www.freelivedoctor.com
  3. 3. iv) almost complete loss of oligodendroglia and myelin v) presence of gobloid cells found around blood vessels c) adrenoleukodystrophy (ALD) i) x-linked inherited disorder of adrenal cortex and demyelination of nervous system ii) children 3-10 yrs iii)  levels of very long chain FA in tissues and body fluids www.freelivedoctor.com
  4. 4. iv) enzyme mutation - impairs capacity to degrade VLCFA’s v) more severe demyelination in cortical white matter - parieto-occipital regions d) Alexander disease i) rare neurological disease ii) infants and children iii) loss of myelin in brain iv)  accumulation of irregular, extracellular fibers (Rosenthal fibers) www.freelivedoctor.com
  5. 5. v) psychomotor retardation, progressive dementia, paralysis  death vi) mutation of gene encoding GFAP  Rosenthal fibers  vii) deposited around blood vessels Multiple Sclerosis (MS) a) chronic demyelinating disease b) most common chronic CNS disease of young adults in USA www.freelivedoctor.com
  6. 6. c) affects sensory and motor functions d) acquired disease, mean age ~ 30yrs i) women 2:1 e) etiology remains obscure i) genetic predisposition f) colder climates  risk g) immune factors i) chronic MS  perivascular lymphocytes, macrophages and CD4+ and CD8+ T cells www.freelivedoctor.com
  7. 7. h) infectious agents i) wide variety of viruses - mumps, rubella, herpes simplex and measels (via vaccination) I) demyelinated plaque is hallmark of MS i) usually in white matter ii) preference for optic nerves, chiasm www.freelivedoctor.com
  8. 8. iii) neurons are spared, while axons degenerate when next to plaque! iv) MS has “focal” areas of injury v) demyelination is complete when in presence of plaque vi) old MS plaque exhibit gliosis (“scar”) impairs structural integrity of axons www.freelivedoctor.com
  9. 9. J) clinical i) onset 30-40 yrs ii) PNS are uniformly spared iii) usually begins with symptoms in optic nerves, brainstem or spinal cord (loss of vision in one eye usually presenting complaint) iv) lesions in spinal cord  leg weakness or numbness www.freelivedoctor.com
  10. 10. <ul><li>v) disease usually follows chronic relapsing and remitting course  develop permanent lesions </li></ul><ul><li>vi) death usually from respiratory paralysis or UTI while in terminal coma </li></ul><ul><li>vii) survival 20-30 yrs following initial symptoms </li></ul><ul><li>MS variants </li></ul><ul><li>a) neuromyelitis optica (Devic disease) </li></ul><ul><li>i) Asians </li></ul>www.freelivedoctor.com
  11. 11. ii) present as bilateral optic neuritis and spinal cord involvement iii) lesions similar to MS but more destructive - grey matter involvement b) Acute MS (Marburg form) i) young individuals ii) fulminant course over several months www.freelivedoctor.com
  12. 12. <ul><li>Acute disseminated encephalomyelitis </li></ul><ul><li>a) follow either </li></ul><ul><li>i) viral infection or </li></ul><ul><li>ii) viral immunization </li></ul><ul><li>b) symptoms develop 1-2 weeks following (i or ii above) </li></ul><ul><li>c) clinical </li></ul><ul><li>i) headache </li></ul><ul><li>ii) lethargy or </li></ul><ul><li>iii) coma </li></ul><ul><li>iv) these occur rather than focal findings </li></ul>www.freelivedoctor.com
  13. 13. <ul><li>v) symptoms progress rapidly  fatal in 20% and remaining cases  complete recovery </li></ul><ul><li>Acute necrotizing hemorrhagic </li></ul><ul><li>encephalomyelitis </li></ul><ul><li>a) fulminant syndrome of CNS demyelination </li></ul><ul><li>b) usually preceded by upper respiratory infection </li></ul><ul><li>i) mycoplasma pneumoniae </li></ul><ul><li>ii) most times of indeterminate cause </li></ul>www.freelivedoctor.com
  14. 14. <ul><li>iii) highly fatal </li></ul><ul><li>Central pontine myelinolysis </li></ul><ul><li>a) loss of myelin </li></ul><ul><li>b) preservation of neurons and axons </li></ul><ul><li>c) believed to be caused by rapid correction of hyponatremia </li></ul><ul><li>i) also to extreme hyperosmolarity or </li></ul><ul><li>ii) other metabolic imbalances </li></ul><ul><li>d) clinical </li></ul><ul><li>i) rapidly developing quadriplegia </li></ul><ul><li>ii) lesion in basis pontis </li></ul>www.freelivedoctor.com
  15. 15. <ul><li>iii) can occur during setting of: </li></ul><ul><li>- alcoholism </li></ul><ul><li>- severe electrolyte/osmolar imbalances </li></ul><ul><li>- orthopic liver transplantation </li></ul><ul><li>Marchiafava – Bignami disease </li></ul><ul><li>a) rare disorder of myelin </li></ul><ul><li>i) corpus callosum and </li></ul><ul><li>ii) anterior commissure </li></ul>www.freelivedoctor.com
  16. 16. <ul><li>Degenerative Diseases </li></ul><ul><li>Parkinson Disease </li></ul><ul><li>a) Common movement disorder </li></ul><ul><li>b) Characterized by loss of neurons (substantia nigra) </li></ul><ul><li>i) accumulation of Lewy bodies </li></ul><ul><li>c) Tremors at rest </li></ul><ul><li>d) Muscle rigidity </li></ul><ul><li>e) Expressionless </li></ul>www.freelivedoctor.com
  17. 17. <ul><li>Epidemiology </li></ul><ul><li>a) 6-8 decades </li></ul><ul><li>b) more than 2% in North America develop disease </li></ul><ul><li>c) men more than women </li></ul><ul><li>d) most cases are sporadic </li></ul><ul><li>i) missense mutations cause rare autosomal dominant e) most are idiopathic, exceptions </li></ul><ul><li>i) induced following viral encephalitis </li></ul><ul><li>- Von Economo encephalitis </li></ul>www.freelivedoctor.com
  18. 18. ii) toxin intake - MPTP (1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine) f) substantia nigra relays information to basal ganglia through Dopaminergic synapses i) aging  dopamine ii) exaggerated in PD iii) Lewy bodies are filamentous aggregates seen in substantia nigra - also other areas www.freelivedoctor.com
  19. 19. iv) oxidative stress (of catecholamines) during melanin formation injures neurons in substantia nigra g) loss of pigmentation in substantia nigra and locus ceruleus and formation of inclusion bodies (Lewy bodies) h) clinical: i) slowness of all voluntary movement and muscle rigidity - disappears with use www.freelivedoctor.com
  20. 20. www.freelivedoctor.com
  21. 21. ii) coarse tremor of distal extremities - at rest iii) face is expressionless (mask-like) - reduced rate of swallowing (leading to drooling) iv)  incidence of depression/dementia (~10- 15%) www.freelivedoctor.com
  22. 22. <ul><li>v) early PD tx with L-dopa </li></ul><ul><li>- after several years becomes ineffective </li></ul><ul><li>vi) neural transplantation (dopaminergic) into striatum </li></ul><ul><li>vii) deep brain stimulation can provide relief of motor symptoms of PD </li></ul><ul><li>Multiple system atrophy </li></ul><ul><li>a) rare disorder </li></ul><ul><li>b) mimics PD </li></ul>www.freelivedoctor.com
  23. 23. c) less severe changes in substantia nigra and locus ceruleus d) associated with Shy-Drager disease and olivopontocerebellar atrophy (i.e., these are known as multiple system atrophy) i) patients usually have symptoms of both diseases e) 2 principle symptoms i) PD www.freelivedoctor.com
  24. 24. <ul><li>ii) Autonomic dysfunction </li></ul><ul><ul><li> orthostatic hypotension </li></ul></ul><ul><li>f) when present as isolated lesion  </li></ul><ul><li> i) Shy-Drager </li></ul><ul><li> ii) Striatal degeneration </li></ul><ul><li>iii) Presentation of isolated ataxic disorder with cerebellar dysfunction  olivopontocerebellar atrophy </li></ul>www.freelivedoctor.com
  25. 25. <ul><li>Amyotrophic lateral sclerosis (ALS) </li></ul><ul><li>a) leads to profound weakness and death </li></ul><ul><li>b) affects motor neurons of brain and spinal cord </li></ul><ul><li>c) worldwide disease </li></ul><ul><li>i) 1:100,000 </li></ul><ul><li>d) peaks in incidence in 5th decade </li></ul><ul><li>e) ~ 2:1 incidence in men </li></ul><ul><li>f) Guam, Papua new guinea and parts of Japan </li></ul>www.freelivedoctor.com
  26. 26. <ul><li>i) Chomoro people in Guam </li></ul><ul><ul><li> disease is rich in tau NFT </li></ul></ul><ul><li> now classified as “neurodegerative taupathies </li></ul><ul><li>g) familial cases </li></ul><ul><li> i) autosomal dominant (gene 21q) </li></ul><ul><ul><li>ii) ~ 5 % of all cases </li></ul></ul><ul><ul><li>iii) missense mutation that codes for SOD1 </li></ul></ul><ul><li>iv) disease not due to SOD activity </li></ul>www.freelivedoctor.com
  27. 27. <ul><li>h) affects motor neurons (3 locations) </li></ul><ul><li>i) anterior horn cells of cord </li></ul><ul><li>ii) motor nuclei of brainstem </li></ul><ul><ul><li>- hypoglossal nuclei </li></ul></ul><ul><li>iii) upper motor neurons of cerebral cortex </li></ul><ul><li>iv) loss of large motor neurons accompanied by mild gliosis </li></ul><ul><li>- may cause inclusions  sphenoids </li></ul>www.freelivedoctor.com
  28. 28. <ul><li>v) loss of pyramidal “Betz” cells in motor cortex </li></ul><ul><li>vi) loss of myelinated fibers in lateral corticospinal tracts </li></ul><ul><li>vii) anterior nerve roots are atrophic and affected muscles are pale and shrunken </li></ul><ul><li>I) clinical </li></ul><ul><ul><li>i) begins as weakness and wasting of muscles </li></ul></ul><ul><ul><li>- hand (often with painful cramps) </li></ul></ul>www.freelivedoctor.com
  29. 29. <ul><ul><li>- irregular rapid contractions of muscles that do not move limbs (fasciculations) </li></ul></ul><ul><ul><li>- progressive disease </li></ul></ul><ul><ul><li>- speech unintelligent </li></ul></ul><ul><ul><li>- respiratory weakness </li></ul></ul><ul><ul><li>- intellectual capacity is preserved </li></ul></ul><ul><li>- clinical course usually does not extend beyond 10 years </li></ul>www.freelivedoctor.com
  30. 30. <ul><li>Huntinton disease </li></ul><ul><li>a) inherited autosomal dominant disease </li></ul><ul><li>b) progressive movement disorders and dementia </li></ul><ul><li>c) degeneration of striatal neurons </li></ul><ul><li>d) movement disorder chorea </li></ul><ul><li> i) jerky </li></ul><ul><li>ii) hyperkinetic </li></ul><ul><li>iii) sometimes dystonic movements </li></ul><ul><li>iv) affecting all parts of body </li></ul>www.freelivedoctor.com
  31. 31. e) progressive i) course ~ 15 years f) HD gene  4p16.3 encodes a protein i) huntingtin ii) repeat mutation (“trinucleotide” repeat disorder) iii) greater the # of repeats  earlier onset of disease www.freelivedoctor.com
  32. 32. <ul><li>g) clinical </li></ul><ul><li>i) 4-5th decade at onset </li></ul><ul><li>ii) motor symptoms usually precede cognitive disorders (in ~ 50% of patients) </li></ul><ul><li>iii) movement disorders are chorioform </li></ul><ul><ul><li>- jerky, involuntary movement of all parts of body </li></ul></ul><ul><ul><li>-  risk of suicide (genetic screening) </li></ul></ul>www.freelivedoctor.com
  33. 33. www.freelivedoctor.com
  34. 34. <ul><li>Spinocebellar ataxias </li></ul><ul><li>loss of neurons and neural tracts in </li></ul><ul><li>cerebellum, brainstem and spinal cord </li></ul><ul><li>a) ataxia </li></ul><ul><li>b) intention tremor </li></ul><ul><li>c) rigidity </li></ul><ul><li>d) tremor </li></ul><ul><li>e) loss of deep tendon reflexes and </li></ul><ul><li>f) vibration sense and </li></ul><ul><li>g) pain </li></ul>www.freelivedoctor.com
  35. 35. <ul><li>Friedreich ataxia </li></ul><ul><li>a) most common inherited ataxia </li></ul><ul><li>b) autosomal recessive </li></ul><ul><li>c) onset of symptoms less than 25 years </li></ul><ul><li>d) hallmark is </li></ul><ul><li>i) combined ataxia of both upper and lower limbs </li></ul><ul><li>ii) Systemic abnormalities of skeletal system </li></ul><ul><ul><li>- scoliosis </li></ul></ul><ul><ul><li>- pes cavus </li></ul></ul>www.freelivedoctor.com
  36. 36. <ul><ul><li>- hypertrophic cardiomyopathy which commonly causes death </li></ul></ul><ul><ul><ul><li>- diabetes mellitus </li></ul></ul></ul><ul><ul><li>e) genetic defect </li></ul></ul><ul><ul><li>i) chromosome 9 </li></ul></ul><ul><ul><li>ii) lack of “frataxin” production </li></ul></ul><ul><ul><li>iii) triplet expansion (GAA repeat expansion) </li></ul></ul><ul><ul><li>- confirms diagnosis </li></ul></ul>www.freelivedoctor.com
  37. 37. <ul><li>DEGENERATIVE DISEASES (AD) </li></ul><ul><li>(Alzheimer Disease) </li></ul><ul><li>principle cause of “so-called” senility </li></ul><ul><li>worldwide disease </li></ul><ul><li>most common cause of dementia in aged </li></ul><ul><li>a) more than half of all cases </li></ul><ul><li>age prevalence </li></ul><ul><li>a) before age 65 years  1-2 % </li></ul><ul><li>b) after 85 years  ~ 10% </li></ul><ul><li>c) women 2:1 </li></ul><ul><li>d) most cases are sporatic </li></ul><ul><li>i) familial variant is recognized </li></ul>www.freelivedoctor.com
  38. 38. <ul><li>e) 2 associations </li></ul><ul><li>i) amyloid  -protein (A  ) </li></ul><ul><ul><li>-  deposition in neuritic plaques of AD </li></ul></ul><ul><li>- plaques in cerebral cortex </li></ul><ul><li>ii) NFT </li></ul>www.freelivedoctor.com
  39. 39. Alzheimer Disease 1.- amyloid β -protein (A β ) a) evidence points to  in neuritic plaques of A β i) located in cerebral cortex ii) linked to intellectual function iii) constant feature of AD b) neurons and glial cells also accumulate A β in walls of cerebral blood vessels www.freelivedoctor.com
  40. 40. 2.- Neurofibrillary tangles (NFT) a) microtubule-associated protein i) abnormal helical form which is termed “tau” b) in AD phosphorylation of tau in certain areas of brain form NFT c) mutations of tau gene on chromosome 17 causes familial dementia and parkinsonism www.freelivedoctor.com
  41. 41. www.freelivedoctor.com
  42. 42. www.freelivedoctor.com
  43. 43. www.freelivedoctor.com
  44. 44. <ul><li>d) most cases of AD are associated with lots of LEWY bodies </li></ul><ul><li>e) genetic association </li></ul><ul><li>Pathology of AD: </li></ul><ul><li>a) during course of AD </li></ul><ul><li>i) neurons are lost </li></ul><ul><li>ii) gliosis occurs </li></ul><ul><li>iii) gyri narrow </li></ul><ul><li>iv) sulci narrow </li></ul><ul><li>v) cortical atrophy </li></ul><ul><li>- bilateral and symmetrical </li></ul>www.freelivedoctor.com
  45. 45. <ul><li>b) microscopic findings </li></ul><ul><li>i) senile plaques </li></ul><ul><li>ii) NFT </li></ul><ul><li>iii) neuron loss </li></ul><ul><li>iv) Lewy bodies and granulovacuolar degeneration </li></ul><ul><li>Clinical: </li></ul><ul><li>a) patients usually present with: </li></ul><ul><li>i) gradual loss of memory and </li></ul><ul><li>ii) cognitive function </li></ul><ul><li>iii) difficulty with language </li></ul><ul><li>iv) changes in behavior </li></ul>www.freelivedoctor.com
  46. 46. <ul><li>b) AD is progressive </li></ul><ul><li>i) previously intelligent and productive persons </li></ul><ul><li>- become demented </li></ul><ul><li>- mute </li></ul><ul><li>- incontinent </li></ul><ul><li>- bed ridden </li></ul><ul><li>- bronchopneumonia usually cause of death </li></ul><ul><li>Pick disease </li></ul><ul><li>a) loss of function </li></ul><ul><li>b) dementia </li></ul>www.freelivedoctor.com
  47. 47. c) difficult to distinguish from AD d) most cases are sporadic e) occurs in mid adult life i) progress to death in 3-10 yrs f) cortical atrophy i) initially unilateral - bilateral with progression ii) localized to frontotemporal g) severe atrophy i) gyri reduced to thin edge - “knife-blade” atrophy www.freelivedoctor.com
  48. 48. <ul><li>h) inclusions contain tau and argentophilic and are referred to as “Pick bodies” </li></ul><ul><li>i) densely aggregated straight filaments </li></ul><ul><li>TUMORS </li></ul><ul><li>annual incidence 10-17 per 100,000 </li></ul><ul><li>a) 1-2 per 100,000 for intraspinal </li></ul><ul><li>50-75% are primary tumors </li></ul><ul><li>a) remainder are metastatic </li></ul>www.freelivedoctor.com
  49. 49. <ul><li>rarely metastatic outside of CNS </li></ul><ul><li>classes: </li></ul><ul><li>a) gliomas </li></ul><ul><li>b) neuronal tumors </li></ul><ul><li>c) poorly differentiated </li></ul><ul><li>d) meningiomas </li></ul><ul><li>1.- GLIOMAS (astrocytomas, oligodendrogliomas, ependymomas) </li></ul>www.freelivedoctor.com
  50. 50. a) Astrocytoma i) fibrillary astrocytoma ii) glioblastoma iii) pilocytic astrocytoma iv) pleomorphic xanthoastrocytoma v) all these have histological characteristics, distribution, age and clinical course vi) mean survival time is ~ 5 yrs www.freelivedoctor.com
  51. 51. <ul><li>Fibrillary astrocytoma </li></ul><ul><li>i) ~ 80 % of adult primary tumors </li></ul><ul><li>ii) found in cerebral hemispheres </li></ul><ul><li>iii) 4-6 th decade may occur in cerebellum, brainstem, spinal cord </li></ul><ul><li>iv) most common presenting sign is </li></ul><ul><li>- seizures </li></ul><ul><li>- headache </li></ul><ul><li>- focal neurological deficits </li></ul><ul><li>v) grading predicts prognosis </li></ul><ul><li>- WHO classification </li></ul><ul><li>- grades 1-4 </li></ul>www.freelivedoctor.com
  52. 52. - low grade astrocytoma show inactivation of tumor suppressor gene p53 - high grade astrocytoma show  inactivation of p53 as well as RB gene, p16/CDKNZA gene and tumor suppressor gene on chromosome 19q B) Glioblastoma i) prognosis very poor - 8 to 10 months following Dx ii) 2 distinct clinical histories www.freelivedoctor.com
  53. 53. 1. - short, rapidly progressive, arising without preexisting low grade tumor - typically in older patients (primary glioblastoma 2. - younger patients - previously diagnosed low grade astrocytoma (secondary astrocytoma) - p53 mutations www.freelivedoctor.com
  54. 54. C) Pilocytic astrocytoma i) young adults ii) relatively benign iii) mainly cerebellum - may occur in floor of 3 rd ventricle, optic nerves, and occasionally in cerebral hemispheres iv) often cystic looking v) grow slowly vi) WHO grade 1 vii) rare p53 mutations www.freelivedoctor.com
  55. 55. <ul><li>Oligodendroglioma </li></ul><ul><li>a) 5-10 % of gliomas </li></ul><ul><li>b) most common in 4 th and 5 th decades </li></ul><ul><li>i) may have had many years of complaints </li></ul><ul><li>- seizures </li></ul><ul><li>c) lesions found most often in cerebral hemispheres </li></ul><ul><li>i) mainly white matter </li></ul>www.freelivedoctor.com
  56. 56. <ul><li>d) most common genetic defect </li></ul><ul><li>i) involves chromosome 1  and 19q </li></ul><ul><li>e) clinical: </li></ul><ul><li>i) better prognosis re: astrocytomas </li></ul><ul><li>ii) average survival 5 to 10 years </li></ul><ul><li>Ependymomas </li></ul><ul><li>a) arise next to ependyma-lined ventricular system </li></ul><ul><li>i) also central canal of cord </li></ul>www.freelivedoctor.com
  57. 57. ii) first 2 decades of life - near 4 th ventricle - 5-10 % of primary tumors in this age group iii) in adults spinal cord most common location b) clinical i) posterior fossa ependymoma - often with hydrocephalus, secondary to obstruction, rather than invasion ii) poor prognosis www.freelivedoctor.com
  58. 58. - CSF dissemination is common - average survival ~ 4 years iii) several other tumors occur - lining of ventricles - other cells that form wall of ventricles  choroid plexus (rare) iv) benign low grade tumor - except the rare choroid plexus carcinoma www.freelivedoctor.com
  59. 59. <ul><li>Subependymomas </li></ul><ul><li>a) solid </li></ul><ul><li>i) sometimes calcified </li></ul><ul><li>b) slow growing nodules </li></ul><ul><li>i) attached to ventricular lining </li></ul><ul><li>ii) protrude into ventricles </li></ul><ul><li>c) usually asymptomatic </li></ul><ul><li>i) may cause hydrocephalus </li></ul><ul><li>d) most often found in lateral and 4 th ventricles </li></ul><ul><li>i) difficult to remove </li></ul><ul><li>ii) have distinct histology </li></ul>www.freelivedoctor.com
  60. 60. <ul><li>Choroid plexus papillomas </li></ul><ul><li>a) occur anywhere along choroid plexus </li></ul><ul><li>b) most common in children </li></ul><ul><li>i) lateral ventricles </li></ul><ul><li>ii) 4 th ventricle in adults </li></ul><ul><li>c) usually present with hydrocephalus </li></ul><ul><li>Colloid cyst of 3 rd ventricle </li></ul><ul><li>a) non-neoplastic lesion </li></ul><ul><li>b) young adults </li></ul><ul><li>c) attached to roof of 3 rd ventricle </li></ul>www.freelivedoctor.com
  61. 61. <ul><li>i) causes noncommunicating </li></ul><ul><li> hydrocephalus </li></ul><ul><li>- may be rapidly fatal </li></ul><ul><li>d) headache (sometimes positional) </li></ul><ul><li> important symptom </li></ul><ul><li>NEURONAL TUMORS </li></ul><ul><li>Several types contain mature appearing </li></ul><ul><li>neurons (ganglion cells) </li></ul><ul><li>a) gangliocytoma </li></ul><ul><li>i) comprised only of ganglion cells </li></ul>www.freelivedoctor.com
  62. 62. b) more commonly exist as admixture i) with glioma neoplasm - lesion termed “ganglioglioma” - usually presents with seizures c) most slow growing i) glioma part may progress rapidly d) dysembryoplastic neuroepithelial tumor i) low grade, distinct tumor www.freelivedoctor.com
  63. 63. <ul><li>ii) childhood </li></ul><ul><li>- presents with seizures </li></ul><ul><li>iii) slow growth </li></ul><ul><li>- good prognosis after Tx </li></ul><ul><li>iv) located </li></ul><ul><li>- superficial temporal lobe </li></ul><ul><li>Tumors with only neuronal elements </li></ul><ul><li>a) cerebral neuroblastoma </li></ul><ul><li>i) rare </li></ul><ul><li>ii) children </li></ul><ul><li>iii) hemispheres </li></ul>www.freelivedoctor.com
  64. 64. <ul><li>iv) rapid and aggressive growth </li></ul><ul><li>b) central neurocytoma </li></ul><ul><li>i) low grade </li></ul><ul><li>ii) lateral and 3 rd ventricle </li></ul><ul><li>POORLY DIFFERENTIATED NEOPLASMS </li></ul><ul><li>most common is medullablastoma </li></ul><ul><li>a) ~ 20% of brain tumors in children </li></ul><ul><li>b) exclusive to the cerebellum </li></ul><ul><li>c) largely undifferentiated </li></ul><ul><li>i) glial and neuronal markers </li></ul><ul><li> occasionally </li></ul>www.freelivedoctor.com
  65. 65. <ul><li>d) clinical </li></ul><ul><li>i) highly malignant </li></ul><ul><li>ii) very radiosensitive </li></ul><ul><li>iii) prognosis also depends on </li></ul><ul><li> amount of tumor resected </li></ul><ul><li>iv) total resection plus radiation </li></ul><ul><li>- 5 year survival ~ 75 % </li></ul><ul><li>Atypical teratoid/rhabdoid tumors </li></ul><ul><li>a) highly malignant </li></ul><ul><li>b) young children </li></ul><ul><li>c) posterior fossa </li></ul><ul><li>d) presence of rhabdoid cells is Dx </li></ul>www.freelivedoctor.com
  66. 66. <ul><li>e) clinical </li></ul><ul><li>i) occur prior to 5 years of age </li></ul><ul><li>ii) death within a year following </li></ul><ul><li> diagnosis </li></ul><ul><li>OTHER PARENCHYMAL TUMORS </li></ul><ul><li>primary CNS lymphomas </li></ul><ul><li>a) ~ 2 % of extra nodal lymphomas </li></ul><ul><li>i) ~ 1 % of intracranial tumors </li></ul><ul><li>b) most common CNS neoplasm in </li></ul><ul><li> immunosuppressed patients </li></ul>www.freelivedoctor.com
  67. 67. c) in nonimmunosuppressed i) occurs after age 60 d) often presents at multiple sites e) extra CNS involvement is rare i) denotes late stage ii) NHL arising outside CNS rarely invades brain parenchyma f) majority are B-cell origin i) in immunosuppressed patients all neoplasms appear to contain EBV genome www.freelivedoctor.com
  68. 68. <ul><li>g) very aggressive </li></ul><ul><li>i) poor response to treatment </li></ul><ul><li> compared to peripheral </li></ul><ul><li> lymphomas </li></ul><ul><li>Germ cell tumors </li></ul><ul><li>a) primary brain germ cell tumor </li></ul><ul><li>i) most commonly occur along midline </li></ul><ul><li>- pineal </li></ul><ul><li>- suprasellar </li></ul><ul><li>b) young (90% in first 2 decades) </li></ul>www.freelivedoctor.com
  69. 69. c) teratomas i) most common tumor that - presents as congenital tumor d) in pineal region i) male predominance ii) not seen in suprasellar region as male predominance e) unlike lymphomas i) CNS germ cell tumors not uncommon www.freelivedoctor.com
  70. 70. <ul><li>ii) similar classification to seminoma in testis </li></ul><ul><li>- termed “germinoma” </li></ul><ul><li>pineal parenchymal tumors </li></ul><ul><li>a) arise from pineocytes </li></ul><ul><li>b) differentiation </li></ul><ul><li>i) well – pinocytoma </li></ul><ul><li>ii) undifferentiated (high grade) </li></ul><ul><li>- pineoblastoma </li></ul><ul><li>- highly aggressive </li></ul><ul><li>- more common in children </li></ul><ul><li>- in pts. with retiniblastoma </li></ul>www.freelivedoctor.com
  71. 71. <ul><li>c) Gliomas also found in pineal region </li></ul><ul><li>meningioma </li></ul><ul><li>a) benign </li></ul><ul><li>b) occur in adults </li></ul><ul><li>c) usually attached to dura </li></ul><ul><li>d) clinical </li></ul><ul><li>i) slow growing </li></ul><ul><li>ii) uncommon in children </li></ul><ul><li>iii) small female preponderance </li></ul><ul><li>- 3:2 </li></ul><ul><li>- 10:1 with spinal meningioma </li></ul>www.freelivedoctor.com
  72. 72. www.freelivedoctor.com
  73. 73. <ul><li>metastatic tumors </li></ul><ul><li>a) mostly carcinomas </li></ul><ul><li>i) 25-50 % of hospitalized patients </li></ul><ul><li>b) sites (accounts for 80% of all metastatic tumors) </li></ul><ul><li>i) lung </li></ul><ul><li>ii) breast </li></ul><ul><li>iii) skin (i.e., melanoma) </li></ul><ul><li>iv) kidney </li></ul><ul><li>v) GI </li></ul>www.freelivedoctor.com
  74. 74. <ul><li>c) meninges frequent site of metastatic tumors </li></ul><ul><li>d) present as mass lesion </li></ul><ul><li>paraneoplastic syndromes </li></ul><ul><li>a) major underlying mechanisms </li></ul><ul><li>i) systemic development of immune response against tumor antigen </li></ul><ul><li>b) may be T-cell mediated neuronal injury in some settings </li></ul>www.freelivedoctor.com
  75. 75. www.freelivedoctor.com
  76. 76. BOARD QUESTIONS www.freelivedoctor.com
  77. 77. Which of the following disorders affecting myelin is most likely to be found in a 30-year-old woman? (A) multiple sclerosis (B) Krabbe disease (C) Alexander disease (D) metachromatic leukodystrophy www.freelivedoctor.com
  78. 78. A disease characterized by widespread patches of demyelination with less prominent axis cylinder destruction and glial overgrowth is (A) syphilis (B) poliomyelitis (C) multiple sclerosis (D) pernicious anemia (E) amyotrophic lateral sclerosis www.freelivedoctor.com
  79. 79. Reactive astrocytes surrounding eosinophilic fibers radiating from a central core which stains for amyloid is characteristic of (A) Alzheimer disease (B) amyotrophic lateral sclerosis (C) olivopontocerebellar atrophy (D) Parkinson disease (E) Wilson disease www.freelivedoctor.com
  80. 80. Lewy bodies are most commonly encountered in (A) idiopathic Parkinsonism (B) post-encephalitic Parkinsonism (C) rabies (D) Tay-Sachs disease (E) herpes simplex encephalitis www.freelivedoctor.com
  81. 81. The most radiosensitive primary intracranial neoplasm is (A) ependymoma (B) glioblastoma (C) medulloblastoma (D) oligodendroglioma www.freelivedoctor.com
  82. 82. A child presents with nausea and vomiting, a recent onset of ataxia, and a posterior fossa tumor. The most likely diagnosis is (A) craniopharyngioma (B) medulloblastoma (C) meningioma (D) neuroblastoma (E) pinealoma www.freelivedoctor.com

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