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. 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. 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. 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. 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. 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. 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. 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.
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.
13.
14.
15.
16.
17.
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. 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
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.
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.
25.
26.
27.
28.
29.
30.
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
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. 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
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.
49.
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.
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
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.
56.
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. - 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.
60.
61.
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.
64.
65.
66.
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.
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
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. 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. 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. 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. The most radiosensitive primary intracranial neoplasm is (A) ependymoma (B) glioblastoma (C) medulloblastoma (D) oligodendroglioma www.freelivedoctor.com
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
![[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],www.freelivedoctor.com](https://image.slidesharecdn.com/cnsdegenerationdemyelinationandtumors-100416235807-phpapp01/85/cns-degeneration-demyelination-and-tumors-1-320.jpg)
