Neurodegenerative Disorders

Question 1

Give an example of motor neurodegenerative disorder

Answer 1

Amyotrophic lateral sclerosis

Question 2

Mention reversible causes of dementia

Answer 2

Obstructive hydrocephalus, vitamin deficinecy, hypothyroidism, neurosyphilis & HIV encephalitis

Question 3

…….allele inc risk of Alzheimer 4-fold

Answer 3

ApoE4

Question 4

Describe mechanism of formation of amyloid deposits & tangles

Answer 4

Abeta is formed when amyloid precursor protein is cleaved by b-amyloid converting enzyme and gamma-secretase. When APP is cleaved by alpha & g-secretase a different non-pathogenic peptide is formed. Mytations in APP (ch21), or enzymes that break it down lead to familial AD
Amyloid deposits leads to hyper-phosphorylation of microtubule binding protein tau so it redistributes to dendrites & cell bodies forming tangles
Amyloid deposits inc glutamate leading to inc Ca++2 influx into neurons & cell apoptosis, excitotoxicity.

Question 5

Cross picture of Alzheimer’s disease

Answer 5

1. Brain weight reduction
2. Cortical atrophy of frontal, parietal & temporal lobes, with widening of sulci
3. Compensatory ventricular dilatation in severe cases (hydrocephalus ex vacuo)

Question 6

Describe micro features of alzheimer

Answer 6

1. Neuronal loss & gliosis
2. Neuritic plaques, central amyloid core with surrounding dystrophic neurities +reactive astrocytes & microglia
3. Intracellular Neurofibrillary tangles containing tau protein in cell bodies in H&E stained sections. Better seen with IHC or silver
4. Amyloid angiopathy

Question 7

C/P & cause of fronto-temporal dementia

Answer 7

Temporal (language) frontal (behaviour) lobes degeneration & atrophy, these symptoms precede memory loss differenctiating it from Alzheimer
AD in 40% of cases, different genes including mutations in genes encoding for microtubule-associated protein tau.

Question 8

Describe G&M picturecof frontotemporal dementia

Answer 8

G, atrophy of frontal & temporal lobes
M, defining inclusions sometimes contain tau protein but has different configuration than that of Alzheimer. One recognized type is Pick’s disease with smooth round inclusions known as Pick bodies

Question 9

Compare demyelinating(1) & dysmyelinating disease(2)

Answer 9

1. MS & other related disorders where normal healthy myelin is destoyed by toxin, chemical or autoimmune, Viral infection of oligodendrocytes as in PML.
2. Myelin is abnormal (not formed properly or has abnormal turnover kinetics, associated with mutations that disrupt function of proteins required for normal myelin formation), thus degenerates (Krabbe disease)

Question 10

Mode of inheritance of Krabbe disease is……, due to deficiency of……

Answer 10

Autosomal recessive
Galactosylceramidase

Question 11

Describe etiology of MS

Answer 11

Autoimmune disease caused by a combination of environmental & geentic factors that result in loss of tolerance to myelin antigens
The initiating agent is suggested to be infectious but remains uncertain
Genetic factors related to HLA-DR & genes encoding IL-2 & IL-7 receptors which are known to control T-cell mediated immune responses

Question 12

Describe gross picture of MS

Answer 12

White matter disease, multiple well-circumscribes slightly depressed, glassy-appearning, gray-tan, irregularly shaped lesions termed plaques. Common in optic nerve, chaism, brain stem, ascending & descending tracts cerebellum, spinal cord.

Question 13

Describe micro. picture of MS

Answer 13

Sharply defined borders
In active plaque there is ongoing myelin breakdown with myelin debris in macrophages. Lymphocytes & macrophages form a perivascular cuff.
Small lesion centered on veins
Axons preserved but may be reduced in number.

Question 14

CSF exam of MS patient shows chch Igs called…..

Answer 14

Oligoclonal bands