Mer Scott
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PHCY320 (Neurology) Quiz on NE10 Other neurological disorders, created by Mer Scott on 11/10/2019.

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NE10 Other neurological disorders

Question 1 of 16

1

By the end of this lecture you will be able to:
1. Describe the pathophysiology of motor neurone disease and multiple sclerosis
2. Describe available treatments for these disorders
• Mechanisms of action
• Main unwanted effects

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    OK

Explanation

Question 2 of 16

1

Motor neurone disease is of motor neurons. The most affected group is .
Motor neurons - Upper ones originate in brain, lower ones originate in spinal cord. MND affects upper and lower. Also know as:
Disease
• Charcot's Disease (in Europe).
• Amyotrophic Lateral (in US)

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    progressive degeneration
    middle aged males
    both
    Sclerosis
    Lou Gehrig's

Explanation

Question 3 of 16

1

Which of these is NOT a presentation of MND?

Select one of the following:

  • Stumbling

  • Dropping, difficulty holding things

  • Hoarse voice/slurred speech

  • Muscle cramps

  • Dysphagia

  • Fatigue

  • Behavioural/emotional changes

  • Severe cognitive difficulties

Explanation

Question 4 of 16

1

What causes MND?
Most cases ...
infection
mediated damage
• Premature motor neuron
• Loss of
% hereditary ( mutation).

Pathophysiology?
• TDP-43 dysfunction
• Excessive activation
• Intracellular
• Mitochondrial damage
cell death
• Oxidative stress ()

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    sporadic
    Viral
    Immune
    aging
    growth factors
    5-10
    SOD
    glutamate R
    Ca2+ overload
    Excitotoxic
    free radicals
    RNA splicing

Explanation

Question 5 of 16

1

Tx for motor neurone disease:
1. Riluzole
Slows progression, prolongs median survival time by
Multiple effects on neurotransmission.
Presynapic: inhibits - inhibits channels
Postsynaptic: prevents - non competitive Rreceptors
Contraindicated: hepatic impairment
Caution: (fever, sore-throat, malaise)

2. Endaravone (not available in NZ). First FDA approved MND therapy in years. Free scavenger.

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    2-3 months
    glutamate
    voltage gated Na+
    release
    action
    blockade of NMDA
    neutropenia
    22
    radical

Explanation

Question 6 of 16

1

Which of these is not a common unwanted effect of riluzole?

Select one of the following:

  • Nausea and vomiting

  • Lethargy

  • Dizziness

  • Diarrhoea

Explanation

Question 7 of 16

1

Multiple Sclerosis is an disorder that affects nerve . There are multiple areas of in the brain, and spinal cord. Inflammation causes relapse. cause:
Optic neuritis, weakness, spasticity, ataxia, dysfunction.

Epidemiology:
- Affects 1 in 1000
- adults (average age 37 years old)
- three times more than men

• People in climates

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    autoimmune
    conduction
    scarring
    Demyelination and axon damage
    bladder and bowel
    Young
    Women
    Caucasians
    cooler

Explanation

Question 8 of 16

1

Pathology of MS:
Trigger = immune response. Primed lymphocytes cross . Upregulation of causes ,

Inflammation -
autoimmune response involving INF-g, IL-17, TNF-b.

cell mediated - myelin destruction

-
Destroy myelin , damage dendrocytes. Demyelination leads to damage

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    peripheral
    T and B
    BBB
    integrins
    adhesion
    Th1 lymphocytic
    B
    antibodies
    Initiate
    Macrophages
    sheath
    oligo
    axon

Explanation

Question 9 of 16

1

Drug treatment for MS:
Reduction of symptoms.
15% of patients have progressive MS, 85% MS ( progressive MS).
• Modulating immune response early reduces

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    primary
    relapsing- remitting
    secondary
    disability

Explanation

Question 10 of 16

1

Fingolimob
• Oral (reversible )
• Agonist of R
• Then internalisation prevents egress, reduced to lesions
Immunomodulator - risk
UEs: Headache, migraine,
Caution: patients with risk – transient bradycardia, heart block.

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    prodrug
    phosphorylation
    sphingosine-1-phosphate
    lymphocyte
    migration
    infections
    dizziness, paraesthesia, depression
    CV

Explanation

Question 11 of 16

1

Teriflunomide
• Immunomodulator, anti-inflammatory
• Selective, inhibition of dihydro-orotate dehydrogenase
• Key in de novo synthesis
• Reduced of activated T and B cells (without cell death)
Contraindicated: disorders, severe
Caution: >65 years, significant consumption

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    irreversible
    enzyme
    pyrimidine
    proliferation
    blood
    immunodeficiency
    alcohol

Explanation

Question 12 of 16

1

Dimethyl fumarate
• Immunomodulatory
• Anti-
• Anti-
• MMF upregulates nuclear factor (erythroidlike)2 (Nrf2) pathways
• Activated by oxidative-stress
Unwanted effects: , GI -

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    oxidative
    inflammatory
    flushing, abdominal pain, rash, itching
    diarrhoea, N&V

Explanation

Question 13 of 16

1

- humanized monoclonal antibody
• Selective for
• Prevents with R
• Cant cross
Unwanted effects ( related): flushing, rigors, fatigue, fever, arthralgia, sore throat… reactions (1%)

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    Natalizumab
    a4 integrin
    interaction
    BBB
    infusion
    hypersensitivity

Explanation

Question 14 of 16

1

Interferons
Reduce immune response (directed @ ) to reduce of relapses
Unwanted effects:
symptoms common
@ injection site

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    myelin
    frequency
    Flu-like
    Ulceration

Explanation

Question 15 of 16

1

Glatiramer acetate - Used when interferon effectiveness reduced.
• Synthetic
Unwanted effects:

• Post injection reaction: shortness of , tightness, flushing (15-30 mins)

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    breath
    chest
    Lipoatrophy
    tetra peptide immunomodulator

Explanation

Question 16 of 16

1

Ocrelizumab - Not funded, under consultation
monoclonal that targets
Unwanted effects:
- related reactions
-
- Oral herpes reactivation, neoplasms

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    Humanised
    CD20+ B cells
    Infusion
    URTIs

Explanation