Motor Disorders 2

Question 1

What is the difference in prevalance of Huntington’s (hs) in the West vs. Taiwan, Hongkong and Japan?

Answer 1

1 in 7300 for the West, 1-7 in a million in the other. Aka much higher prevalance in populations of European descent

Question 2

How is HD inherited?

Answer 2

The HTT gene is found on chromosome 4 (two copies, obv), HD is an autosomal dominant disorder, meaning that a mutation in only one of the copies is enough to cause the disease (also person with mutation has 50% chance of passing it down)

Question 3

Explain the genetics of HD?

Answer 3

A defect in the HTT gene, CAG trinucleotide repeat expansion, caused HD. This means that the CAG codon has more repeats than a normal copy does (>36). With >40 almost always develop HD

Question 4

What is de novo HD?

Answer 4

The mutation causing the disease can occur on its own, not being passed down by a parent (maybe between 27 and 35 repeats of the CAG codons). This is incredibly rare

Question 5

What does the HTT gene do?

Answer 5

Encodes the protein Huntingtin

Question 6

What does the protein Huntingtin play a role in?

Answer 6

It’s role is not fully understood, but plays a role in nervous system development, BDNF production and cell adhesion

Question 7

What is meant by toxic gain-of-function disease?

Answer 7

The mutation in the gene (HTT in this case) results in abnormal functioning of some type that interrupts the functioning of the protein leading to cell toxicity (it seems to lead to aggregation of huntingtin protein?)

Question 8

What are neurodegenerative patterns seen in HD?

Answer 8

There is a higher expression of HTT in neurons than in glia, Most severe neural loss in the striatum (specifically the caudate and the putamen). In general a progressive thinning and loss of neurons in the cerebral cortex and an enlarged lateral ventricle, lastly, an overall decrease in brain volume.

Note: Some of this seems already prevelant in prodromal stages

Question 9

What do striatal degeneration and impaired motor neurons lead to in HD?

Answer 9

involuntary movements, tremors, and poor coordination

Question 10

What do cortical atrophy and selective vulnerability of specific
neurons contribute to in HD?

Answer 10

impaired memory, reasoning, and
executive function

Question 11

What do disruptions in dopaminergic and other neurotransmitter
systems contribute to in HD?

Answer 11

depression, anxiety, and irritability, and
other psychiatric symptoms

Question 12

In general, what are symtpoms of HD?

Answer 12

involuntary movements, tremors, and poor coordination.

Impaired memory, reasoning and executive function

Depression, anxiety and irritability

Question 13

Explain in more specifics the motor symptoms of HD

Answer 13

Involuntary movements which are not repetitive or rhythmic, makes walking/coordination difficult and severe motor impairments (ov voluntary movement) in later stages

Question 14

Explain in more specifics the cognitive symptoms of HD

Answer 14

These can manifest years before motor symptoms, cognitive decline is gradual and include attention, mental flexibility, planning and emotion recognition. Later stages resemble AD

Question 15

What were the TRACK-HD study findings?

Answer 15

Tests such as the symbol digit modalities test, circle tracing test, and
Stroop word-reading test showed differences with control. All of these had some significant motor or psychomotor component, which highligts the link between motor and cognition in HD

Question 16

What is chorea?

Answer 16

involuntary, irregular or unpredictable muscle movements

Question 17

Which drugs are approved to treat HD?

Answer 17

Tetrabenazine for chorea (only approved)

Antipsychotics often used to treat involuntary movements

Antidepressants/Anxiolytics

Question 18

Common interventions for HD?

Answer 18

Physical therapy to maintain mobility and reduce rigidity, occupational therapy to improve daily living, speech and language therapy and palliative care in late stages (to relieve pain, etc.)

Question 19

What are some emerging treatments for HD?

Answer 19

Gene Silencing Strategies: Antisense oligonucleotides (ASOs) to reduce mutant huntingtin protein (it blocks the messenger, preventing damaged protein)

Question 20

Epidemiology of multiple sclerosis (MS)?

Answer 20

Most prevalent neurological disorder in ya, 2x more common in women and more common in Western countries

Question 21

Aetiology of MS?

Answer 21

Multiple factors, about 20-30% heritability, 10-15 times higher risk if parent has it,
increased risk with viral infection (Epstein-Barr virus - herpes virus), increased risk with vitamin-D deficiency, smoking and obesity

Question 22

Neuropatholgy of MS?

Answer 22

Demyelination, this triggers autoimmune response (inflammation) and neurodegeneration (grey and white)

Question 23

There are four types of disease course in MS, which are these and explain them

Answer 23

Relapsing-remitting (85%): loss of function, followed by recovery

Secondary progressive (10-30%): R-R followed by period without relapse, but gradual decline

Primary progressive (12%): No relapses, but gradual decline

Progressive relapsing (less common): Relapse and gradual decline

Question 24

There are many symptoms in MS, but what are some generally affected domains/impairments.

Answer 24

Visual impairment (double vision, involuntary eye movements), Sensory impairment (tingling sensations), Motor impairment (bladder/bowel, sexual dysfunction) and mild cognitive impairment (fatigue)

Question 25

The McDonald criteria are used to diagnose MS, what does this mean?

Answer 25

Incorporates clinical, imaging and laboratory finds. Dissemation in both space and time

Question 26

Dissemination in Space and Time meaning?

Answer 26

Space: evidence of lesions in 2+ regions
Time: Evidence of new lesion at a later time (second assessment)

Question 27

Common cognitive consequences in MS?

Answer 27

Slowed information processing, deficits in attention and executive function. Relatively stable in first phase

Secondary progressive MS most cognitive impairments

More severe in men

Question 28

Pharmacological Treatment MS?

Answer 28

No cure,
Anti-inflammatory drugs reduce relapses in relapsing forms of MS, two other drugs are currently available for non-relapsing MS to slow down neurodegeneration
and additional pharmacological treatments for managing other symptoms like fatigue, sleep problems, sensorimotor complaints

Question 29

What is a common complaint in MS?

Answer 29

Fatigue