Neurodegenerative Diseases part 2

Question 1

Huntington Disease

1. Hallmarks
2. Morphology
3. Microscopic Exam

Answer 1

Huntington Disease

1. Hallmarks: protein aggregation and intranuclear inclusions containing huntingtin
2. Morphology: small brain with striking atrophy of caudate nucleus and putamen, some dilation of lateral and third ventricles, frontal lobe atrophy
3. Microscopic Exam: profound loss of striatal neurons in caudate nucleus, protein aggregates containing huntingtin found in neurons

Question 2

What is this?

Answer 2

Huntington Disease showing dilation of the ventricles

Question 3

HD

1. Clinical Features

Answer 3

HD

1. Clinical Features:
   
   1. increased motor output- manifested as choreoathetosis
   2. cognitive changes associated with neuronal loss
   3. intercurrent disease is most common cause of natural death (pneumonia)

Question 4

Spinocerebellar degenerations

1. definition:
2. clinical symptoms:
3. what are the three diseases included in this group?

Answer 4

Spinocerebellar degenerations

1. definition: highly heterogeneous groups of illnesses at the clinical, genetic, and pathologic level that involve cerebellum and sometimes other components of the nervous system
2. clinical symptoms: cerebellar and sensory ataxia, spasticity, and sensorimotor peripheral neuropathy
3. the three diseases in this group include:
   
   1. spinocerebellar ataxias (group of diseases)
   2. Friedreich Ataxia
   3. Ataxia-Telangiectasia

Question 5

Spinocerebellar ataxias

1. definition:
2. symptoms:
3. characterized by:

Answer 5

Spinocerebellar ataxias

1. definition: term applied to a series of AD inherited disorders
2. symptoms: progressive ataxia as well as symptoms referable to brainstem, peripheral nerves, and spinal cord
3. characterized by: neuronal loss and secondary degeneration of white matter tracts

Question 6

Friedreich Ataxia

1. inheritence:
2. age of onset:
3. symptoms:
4. Life expectancy

Answer 6

Friedreich Ataxia

1. inheritence: AR
2. age of onset: first decade of life
3. symptoms:
   
   1. gait ataxia clumsiness and dysarthria.
   2. depressed DTR
   3. high arches, scoliosis
   4. accompanying cardiomyopathy (arrythmias and cognitive heart failure)
   5. wheelchair bound within 5 yrs
4. Life expectancy: 40-50 yrs

Question 7

Fridreich Ataxia

1. what nucleotide is expanded?
2. what protein is encoded

Answer 7

Fridreich Ataxia

1. what nucleotide is expanded? GAA
2. what protein is encoded: Frataxin
   
   1. ​affected individuals have very low levels of frataxin which leads to decreased mitochondrial Ox-Phos and increased free iron

Question 8

Ataxia-Telangiectasia

1. age of onset:
2. characterization:
3. clinical features:

Answer 8

Ataxia-Telangiectasia

1. age of onset: early childhood
2. characterization:
   
   1. autosomal recessive disorder
   2. ataxic-dyskinetic syndrome
   3. mutated ATM gene
   4. telangiectasias in the conjunctiva and skin
3. clinical features:
   
   1. death in early second decade
   2. early symptoms include: recurrent sinopulmonary infections and unsteadiness in walking
   3. later symptoms: inhibited speech and eye movement disorders
   4. my develop T-cell leukemias

Question 9

Ataxia-Telangiectasia

1. abnormalities in the _________
   
   1. including loss of _______
   2. cells show bizarre nuclar enlargement. they are referred to as ______
   3. _______ of lymphnodes, thymus, and gonads secondary to the mutation of the ATM gene

Answer 9

Ataxia-Telangiectasia

1. abnormalities in the cerebellum
   
   1. including loss of purkinje and granule cells
   2. cells show bizarre nuclar enlargement. they are referred to as amphicytes
   3. hypoplasia of lymphnodes, thymus, and gonads secondary to the mutation of the ATM gene

Question 10

Amyotrophic Lateral Sclerosis (ALS)

1. what neurons are affected?
2. what mutation is common?
3. morphology:

Answer 10

Amyotrophic Lateral Sclerosis (ALS)

1. what neurons are affected? upper motor neurons in the cerebral cortex and lower motor neurons in the spinal cord
2. what mutation is common? SOD1 mutation
3. morphology: spinal cord anterior roots are thinned secondary to loss of motor neuron fibers. the skeletal muscles which are innervated by these fibers show atrophy
   
   1. ​Loss of upper motor neurons leads to degeneration of corticospinal tracts

Question 11

Amyotrophic Lateral Sclerosis (ALS)

1. clinical features

Answer 11

Amyotrophic Lateral Sclerosis (ALS)

1. clinical features:
   
   1. asymmeetric weakness of hands
   2. cramping/spasticity of arms and legs
   3. diminished muscle strength and bulk
   4. eventually involves respiratory muscles leading to infections

**primary ALS= predominantly upper motor neuron involvement

progressive muscular atrophy: predominance of lower motor neuron involvement

Question 12

Spinal and Bulbar Muscular Atrophy

(Kennedy Disease)

1. inheritance pattern
2. characterization:
3. end result:

Answer 12

Spinal and Bulbar Muscular Atrophy

(Kennedy Disease)

1. inheritance pattern: X-linked polyglutamine repeat-expansion disease
2. characterization: distal limb amylotrophy and bulbar signs
   
   1. atrophy of the tongue and dysphagia
   2. associated with the degeneration of lower motor neurons in the spinal cord and brainstem
3. end result: the expanded repeat blocks the androgen receptor= androgen insensitivity, gynecomastia, testicular atrophy, and oligospermia