Path - Degenerative

Question 1

Parkinsonian Symptoms

Answer 1

TRAP
resting Tremor
Rigidity
Akinesia/Bradykinesia
Postural Instability

Question 2

Who gets Parkinson disease?

Answer 2

Elderly men typically

2% of the population

Question 3

Viral induce Parkinson

Answer 3

Von Economo

Question 4

MPTP

Answer 4

1-Methyl-4- phenyl tetrahydropyridine
MAOs break down in dopamine cells to MPP+ which kills mitochondria and kills cells
The Frozen Addicts

Question 5

Late Stage Parkinson’s

Answer 5

Dementia

Question 6

Parkinson disease neuronal pathway

Answer 6

Decrease in dopamine made by the substantia nigra for the nigrastriatal pathway

Question 7

Lewy bodies are associated with what degenerative disease?

Answer 7

Parkinson Disease

Pick’s disease (a-synuclein)

Question 8

Explain the Dopamine synthesis Pathway

Answer 8

Phenylalanine –> Tyrosine –> L-Dopa -> Dopamine

Question 9

What neurotransmitter is made at Locus Ceruleus

Answer 9

Dopamine –> NE

Question 10

What neurotransmitter is made at Adrenal Medulla?

Answer 10

NE –> Epinephrine

Question 11

What are some other clinical signs of Parkinson besides those in TRAP?

Answer 11

Facial is expressionless (mask)

Decrease swallowing causes drooling

Question 12

What are some treatments for Parkinson symptoms?

Answer 12

L-Dopa (Levodopa)

Neural transplantation into striatum
Deep brain stimulation for motor symptoms

Question 13

What are some complications of Levodopa use?

Answer 13

Drug can become ineffective

Can cause Levodopa induce dykinesia (chorea, dystonia or athetosis movements)

Question 14

Who gets Amyotrophic Lateral Sclerosis?

Answer 14

Most cases are sporadic; Middle ages men (50 y/o)

Question 15

Familial ALS arises from what enzyme defect?

Answer 15

Zinc-Copper superoxide dismutase (SOD1) mutation leading to free radical injury in neurons. Mutation on gene 21q

Question 16

Where are the defects in ALS?

Answer 16

Motor nuclei in brainstem (e.g. hypoglossal nuclei (LMN)

Degeneration of the Lateral Cortical Spinal tracts in (UMN); and the anterior horn (LMN)

Question 17

What are some symptoms of ALS?

Answer 17

Patients will have muscle weakness, paralysis, increased tone, hyporeflexive and hyperreflexive and have a Babinski sign

Fassiculations, atrophy, areflexia in LMN; and
Increased tone, positive Babinski sign, hyperreflexia in UMN

Question 18

What test can be performed to confirm ALS?

Answer 18

Muscle biopsy for grouped atrophy

Question 19

Patient presents with weakness in hands and arms but has no sensory impairment. What could be a cause?

Answer 19

ALS; hand paralysis without sensation loss is an early sign of ALS

Question 20

How does ALS progress?

Answer 20

Increase loss of muscles will lead to inability to speak, and loss of respiratory muscles. Intellectual capacity is preserved. The feeling of being trapped inside your body.

Question 21

Prognosis for patients with ALS?

Answer 21

Clinical course usually does not extend beyond 10 years

Question 22

What kind of inheritance is Huntington disease?

Answer 22

Autosomal Dominant that also exhibits anticipation. Future generations tend to exhibit symptoms earlier in life than the previous generation

Question 23

What are the symptoms of Huntington disease?

Answer 23

Chorea (jerky, hyperkinetic movements, sometimes dystonic movements)

Leads to dimentia and depression

Question 24

What are the genetics for Huntington disease?

Answer 24

Chromosome 4p16.3 encodes for protein huntingtin. Mutation is a trinucleotide repeat within the coding sequence that expands

Question 25

Where is the degeneration located at in Huntington disease?

Answer 25

GABAergic neurons in the caudate nucleus of the basal nuclei

Question 26

Describe Chorea movements.

Answer 26

Brief, semi-directed, irregular movements that are not repetitive or rhythmic, but appear to flow from one muscle to the next. Jerky, involuntary movement of all parts of the body that is a group of neurological disorders called dyskinesias. Hyperkinesia

Question 27

What are patients of Huntington disease more at risk for when hearing about being diagnosed?

Answer 27

Suicide

Question 28

Describe athetosis

Answer 28

Slow, involuntary twisting or writhing movements of the fingers, hands, toes and feet and in some cases the arms, legs , neck and tongue.

Question 29

An intention tremor is also known as a _____.

Answer 29

Cerebellar tremor. A dyskinetic disorder characterized as a broad, coarse, and low frequency (below 5 Hz) tremor.

Question 30

Describe Dystonia.

Answer 30

Sustained muscle contraction causing twisting or abnormal postures

Question 31

Describe Dystonic Tremors

Answer 31

occur when involuntary muscle contraction causes twisting and repetitive motions and/or abnormal posture or positions.

Question 32

What are spinocerebellar ataxias?

Answer 32

Loss of neurons and neural tracts in the cerebellum, brainstem, and spinal cord Friedreich's ataxia is a spinocerebellar ataxia

Question 33

What are the important genetics of Friedreich Ataxia?

Answer 33

Autosomal recessive mutation. A triple repeat expansion (GAA) in chromosome 9 of the Fratxin gene. Fritaxin is essential for mitochondrial iron regulation; the iron buildup creates free radical damage. The primary site of pathology is spinal cord and peripheral nerves. Sclerosis and degeneration of dorsal root ganglion, spinocerebellar tracts, Lateral corticospinal tracts, and posterior columns.[8] The motor neurons of the spinal cord are spared. In peripheral nerves there is a loss of large myelinated fibres.

Question 34

Who gets Friedreich ataxia?

Answer 34

Children with kyphoscoliosis | Younger kids 5-20 y/o with peak in teens

Question 35

What are the symptoms of Friedreich ataxia? (bad version)

Answer 35

i. ) Upper and lower extremity ataxia ii. ) Systemic abnormalities of the MSK system causing scoliosis and Pes Cavus iii. ) degeneration of the cerebellum and spinal cord (posterior and lateral funiculi of the spinal cord) iv. ) clumsy hand and gait disturbance v. ) loss of stretch reflexes vi. ) flexor spasms, extensor plantar response due to corticospinal tract involvement

Question 36

What are the signs and symptoms of Friedreich ataxia?

Answer 36

Ataxia of upper and lower limbs and disturbances in gait Loss of vibratory and proprioception. Pinprick is intact. Muscle weakness in lower extremities. Areflexia Nystagmus

Question 37

What is the cause of death of patients with Friedreich ataxia?

Answer 37

Hypertrophic cardiomyopathy

Question 38

Who is effected from Alzheimer disease?

Answer 38

Older women (women:men 2:1) 1-2% of people under 65 years old 10% over 85

Question 39

What are the genetics for Alzheimer disease?

Answer 39

Most cases are sporadic but some familial. Early onset chromosome 1,14,21 Late onset chromosome 19 APP encoded on chromosome 21 Presenilin 1 protein gene chromosome 14 Presenilin 2 protein chromosome 1 ApoE4 chromosome 19

Question 40

What will the brain appear like on an MRI in a patient with Alzheimer's?

Answer 40

The sulci will be larger and the gyri will have atrophied

Question 41

What two accumulations are diagnostic for Alzheimer disease?

Answer 41

Amyloid Beta protein (AB) and Neurofibrillary Tangles

Question 42

What protein has been disrupted in AB for Alzheimer disease?

Answer 42

Amyloid Precursor Protein (APP) is fragmented in Beta Amyloid fragments

Question 43

What other characteristic of amyloid is helpful for definitive diagnosis?

Answer 43

Red Congo stain. Clumps of amyloid will stain with Congo Red dye and visualize under a polarized light will appear "apple green" birefringence.

Question 44

Describe Congophilic angiopathy

Answer 44

Neurons and glial cells will accumulate amyolid plaques around blood vessels and will stain with Conga Red dye

Question 45

Describe Neurofibrillary tangles.

Answer 45

A familial mutation in chromosome 17 wil cause the abnormal configuration of the microtubule associated protein called Tau. These Tau proteins become phosphorylated and form helical aggregations that disrupt the neuron. When the neuron dies the tau tangles are left behind and congregate in the interstitium.

Question 46

What genetic disease is associated with Alzheimer dementia?

Answer 46

Down syndrome patients have an increased risk of developing Alzheimer

Question 47

How does Alzheimer disease progress? What areas of the brain does it start and what cognitive impairments occur?

Answer 47

1. Start in the hippocampus with memory loss 2. Move to around Broca's area and diminishes ability to speak 3. Move to the frontal lobe decreasing congitive ability 4. Moves caudally impairing the ability to regulate emotion 5. eventuall leads to complete dissemination and death

Question 48

Describe the pathology of Alzheimer disease

Answer 48

``` Neurons die Gliosis occurs Gyri Narrow Sulci Expand Cortical atrophy (that is bilateral and symmetrical) ```

Question 49

What is Pick's disease?

Answer 49

Frontal temporal dementias caused by spherical tau protein aggregates Behavioral and language disturbances; parkinsonian aspects

Question 50

Who get's Pick's disease?

Answer 50

Mid adult life

Question 51

How is Frontal temporal dementia pathology different from Alzheimer disease

Answer 51

Usually starts unilaterally and is localized just to the frontal temporal regions. Alzhheimer is symmetrical and bilateral. Also Alzheimer usually occurs in the older population while Pick's occurs in mid-adult life Pick's patients tend to suffer more from behavioral and language problems than memory issues and may precede memory impairments

Question 52

What happens to patients with Pick's disease?

Answer 52

Dementia | Progress to death in 3-10 yrs

Question 53

How will Alzheimer disease progress?

Answer 53

Early stage dementia will progress to loss of intelligence 2. patients will be mute 3. incontinence 4. bed ridden 5. pneumonia will cause death

Question 54

What is a characteristic feature of cortical atrophy in Pick's disease

Answer 54

Knife-blade atrophy that leaves edge of gyri thin

Question 55

What is the inclusion body in Pick's disease?

Answer 55

argentophilic globules or Pick bodies. hyperchromatic with silver stain. Tau protein is a major portion of Pick bodies