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PHYSL 372 > Motor disorders - Spasticity > Flashcards

Motor disorders - Spasticity Flashcards

1
Q

What is the pathophysiology of myasthenia gravis? What are 2 theories for this?

A

Immune system attacks the acetylcholine receptor by producing
antibodies to this receptor. One theory suggests that viral or
bacterial infections trigger the inappropriate immuno-response. Others relate to
abnormalities of thymus.

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2
Q

What are the symptoms of myasthenia gravis?

A

External ocular muscles are affected initially in 50% of cases. Followed
by other cranial nerves, proximal muscles, distal muscles.

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3
Q

Describe the typical scenario for myasthenia gravis.

A
  • ptosis (drooping of eyelid)
  • blurred vision
  • mouth starts to hang
    open
  • smile resembles a snarl because facial muscles pulling the corner of lips are
    affected first
  • increased difficulty in swallowing, choking etc.
  • weakness of the
    respiratory muscles causing dyspnea (sensation of shortness of breath) upon mild
    exercise
  • spread to trunk and finally limb muscles
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4
Q

What is the age of onset of myasthenia gravis in females? males?

A
  • female = 28 years
  • male = 42 years
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5
Q

treatment for myasthenia gravis?

A
  • Remove thymus
  • immunosuppressants: anticholinesterase drugs
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6
Q

Describe the viral hypothesis for onset of myasthenia gravis.

A
  • herpes simplex virus has same peptide sequence in one area as the ACh receptor
  • T cells and B cells attack and destroy herpes simplex virus
  • T cells and B cells mistake ACh receptor as herpes simplex virus –> AUTOIMMUNE ATTACK
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7
Q

Which muscles is first affected in myasthenia gravis?

A

muscles controlling eyelids

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8
Q

TRUE or FALSE: in myasthenia gravis, antibody binding to ACh receptors leads to decreased rate of endocytosis.

A

FALSE: INCREASED rate of endocytosis (faster turnover rate of ACh receptors)

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9
Q

How was myasthenia gravis discovered? What did this experiment provide key evidence for?

A
  • in 1970s, tried to label ACh receptor from electric fish by injecting it into mice, and fluorescently labeling the resultant antibodies
  • experiment went wrong: fish and mouse receptor so similar that antibodies start attacking not only fish ACh receptors but also mouse ACh receptors
  • key evidence that MG is an autoimmune disease
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10
Q

What are the events at the NMJ?

A
  1. motor neuron AP
  2. Ca2+ enter voltage-gated channels
  3. ACh release
  4. Na+ entry to post-synaptic cell
  5. local current between depolarized end plate and adjacent muscle plasma membrane
  6. muscle fiber action potential initiation
  7. propagated AP in muscle plasma membrane
  8. ACh degradation
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11
Q

How is neostigmine used to treat MG?

A
  • anti-cholinesterase drug
  • prevent breakdown of ACh
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12
Q

Neostigmine is reversible. What does this imply about daily intake?

A

you need to keep taking it daily

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13
Q

What is the pathophysiology of multiple sclerosis (MS)?

A
  • Immune system attacks myelin and oligodendrocytes in the
    CNS (in stage 1 of disease)
  • Scars near vessels in BBB
    -Local inflammation and then immune attack
  • Later stage of disease occurs about a decade later (stage 2) where axons that lack myelin for many years eventually
    die
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14
Q

what are the symptoms of MS?

A
  • Blurred vision
  • numbness
  • incoordination
  • speech disturbances
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15
Q

What are the 2 basic stages of MS symptoms?

A
  1. gradual decline in myelination and an increase in deficits
  2. cycles of symptoms interspersed with remissions
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16
Q

Within 9 years, ____% need cane to walk, as stage 2 of MS progresses.

A

50

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17
Q

Cognition is
affected in _____% of MS patients

A

50

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18
Q

What is the age of onset of MS?

A

20-40 years

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19
Q

What is the female to male ratio of MS?

A

3:1

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20
Q

Why is it suspected that environmental factors play a role in onset of MS?

A

more prevalent in northern hemisphere

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21
Q

TRUE or FALSE: MS is more prevalent in the northern hemisphere

A

TRUE

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22
Q

What is the treatment for MS?

A

corticosteroids or other drugs to SUPPRESS immune system

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23
Q

Describe the animal model for MS. What is the treatment?

A
  • Inject myelin proteins or CNS tissue together with agents that stimulate the immune system
  • treat with immunosuppressants
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24
Q

What is the pathophysiology for Guilain-Barre syndrome?

A

Immune system attacks myelin and Schwann cells in
the peripheral nervous system PNS. Typically follows
infection (EBV, mononucleosis) and associated
inflammation.

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25
Q

What is the main difference between pathophysiology of GBS and MS?

A
  • GBS = attack PNS
  • MS = attack CNS
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26
Q

TRUE or FALSE: MS often resolves spontaneouslty

A

FALSE: GBS resolves spontaneously

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27
Q

TRUE or FALSE: there is no known hereditary predisposition for MS

A

FALSE: GBS

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28
Q

What are the symptoms of Guillain-Barré Syndrome?

A

Depends on severity; can lead to paralysis

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29
Q

What is the treatment for GBS?

A

Suppress immune system. If needed, support breathing with respirator until disease resolves.

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30
Q

How does loss of myelin cause an axon to die?

A
  1. lose myelin
  2. increase number of Na+ channels
  3. increase Na+ pumps
  4. use more ATP
  5. cells swell and die
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31
Q

TRUE or FALSE: GBS can be linked to gut biome

A

FALSE: MS

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32
Q

TRUE or FALSE: most people who have MS had GBS before

A

TRUE

33
Q

TRUE or FALSE: while eye muscles have a 1:1 muscle nerve ration, biceps have 750:1 ratio

A

TRUE

34
Q

What is the pathophysiology in amyotrophic lateral sclerosis (ALS)?

A

motor neuron death in spinal cord (CST); mitochondrial damage

35
Q

What are the symptoms of ALS?

A

muscle weakness, paralysis

36
Q

When does death occur in ALS? What is the main cause of death?

A
  • death occurs 3-5 years from onset
  • respiratory failure
37
Q

What are the 2 forms of ALS? Which one more rare?

A
  • sporadic
  • familial (rare)
38
Q

ALS occurs in __ to __ people per 100, 000.

A

1 to 3

39
Q

Age of onset for ALS?

A

40-70 years

40
Q

TRUE or FALSE: ALS is more common in men than women

A

TRUE

41
Q

What disease did Stephen Hawking have?

A

ALS

42
Q

TRUE or FALSE: ALS is not always genetically linked

A

TRUE

43
Q

Which enzyme/gene is mutated in ALS?

A

superoxidase dismutase (SOD1)

44
Q

What kind of enzyme is SOD1?

A

mitochondrial

45
Q

SOD1 enzyme protects cells from ___________________________.

A

reactive oxidase species (ROS), O2-

46
Q

SOD1 mutation causes SOD1 to be _________________.

A

pro-apoptotic

47
Q

TRUE or FALSE: You need 2 copies of the mutated SOD1 to get ALS

A

FALSE: you only need a single copy

48
Q

Mutation leads to SOD1 aggregates, oxidative stress and _____________________.

A

mitochondria damage

49
Q

What is the animal model for ALS? What is the treatment?

A
  • animal model: mutate SOD1 gene
  • treatment: Na+ channel blocker, RILUZOLE, to stop excessive motorneuron activity, but not effective
50
Q

What is the role of poor Ca2+ buffering in ALS?

A

poor Ca2+ buffering –> mitochondrial damage (excitotoxicity) –> more ROS –> damage neurons and glial cells

51
Q

TRUE or FALSE: increased AMPARs in ALS leads to more Ca2+ load

A

TRUE

52
Q

What is the pathophysiology of spinal muscular atrophy (SMA)?

A

autosomal recessive disease caused by genetic defect in SMN1 gene, which encodes SMN, a protein widely
expressed in all eukaryotic cells

53
Q

SMN1 is apparently selectively necessary for ____________________________, as diminished abundance of the protein results in ________________________ in the ventral horn of the spinal cord and subsequent system-wide _________________________.

A

development of motor neurons; death of neuronal cells; muscle atrophy

54
Q

What is the most common genetic cause of infant death?

A

SMA

55
Q

What are the symptoms of SMA?

A
  • weakened muscles
  • respiratory problems
  • scoliosis
  • difficulty walking and sitting
56
Q

What physical symptoms can be used to diagnose SMA?

A
  • poor muscle tone in the limbs and trunk
  • feeble movements of the arms and legs
  • swallowing difficulties
  • a weak sucking reflex
  • impaired breathing
57
Q

What is major problem for infnats with SMA?

A

breathing and swallowing difficulties

58
Q

Severity of the SMA disease is reduced with more _______________________, but ______ often makes ___________________.

A
  • copies of the backup gene SMN2
  • truncated ineffective SMN
59
Q

Improving function of SMN2 gene by ____________________ _____________________ __________________ cures SMA by ______________ _________ ____________ to make more full length copies of SMN protein.

A
  • antisense oligonucleotide Nusinersen
  • altering pre-mRNA splicing
60
Q

What is the pathophysiology of Duschene muscular dystrophy (DMD)?

A
  • muscle wasting disease
  • genetic origin: defect in dystrophin gene, an extremely large gene on X chromosome which encodes the protein dystrophin
61
Q

what does dystrophin do in muscles?

A

stability by creating a link between the contractile machinery and the extracellular matrix

62
Q

Is DMD more common in males or females? Why?

A

males bc the dystrophin gene is on the X chromosome

63
Q

When do symptoms for DMD start showing?

A

age 3

64
Q

Where does weakness occur first in DMD?

A

legs; child does not run

65
Q

What is pseudohypertrophy and what is it a symptom of?

A
  • disease where leg muscles look big, but it is all fibrous tissue
  • symptom of DMD
66
Q

Duchene muscular dystrophy can be detected with about ______% accuracy by genetic studies performed during pregnancy.

A

95

67
Q

WHat is the treatment for DMD?

A

no treatment

68
Q

What tool can be used to clinically detect muscle diseases?

A

EMG

69
Q

What is the 3rd leading cause of death in the US?

A

stroke

70
Q

What is the leading cause of disability in the US?

A

stroke

71
Q

What is the most frequent presenting problem in stroke patients that survive?

A

hemiplegia, associated with muscle paralyses and spasticity

72
Q

Whta does the right hemisphere control?

A
  • movement of LEFT side of body
  • anlaytical and perceptual tasks
73
Q

What does the left hemisphere control?

A
  • movement of RIGHT side of body
  • speech and language skills
74
Q

TRUE or FALSE: if you have a right hemisphere stroke, you will lose control of movement of the right side of the body and speech and language skills

A

FALSE: lose LEFT control and analytical and perceptual tasks

75
Q

TRUE or FALSE: it is easier to survive a brain stem stroke than a cerebellar stroke

A

FALSE: brain stem stroke more difficult to survive

76
Q

What is the time window to use clot-busters in stroke?

A

within 3 hours

77
Q

What is cerebral palsy? What is the main symptom?

A
  • chronic disability of CNS
  • aberrant control of movement of posture
78
Q

TRUE or FALSE: cerebral palsy is the result of a prgressive neurological disesase

A

FALSE: it is chronic

PHYSL 372 (21 decks)

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