Nsp Week 2: Nmj And Muscle Disease (Desousa)

Front 1

List 3 neuromuscular junction disorders

Back 1

1. Myasthenia gravis
2. Lambert-Eaton myasthenic syndrome
3. Congenital myasthenia

Front 2

Is Myasthenia gravis caused by a presynaptic or postsynaptic neuromuscular junction disorder?

Back 2

Postsynaptic

Front 3

Is Lambert-Eaton myasthenic syndrome caused by a presynaptic or post-synaptic neuromuscular junction disorder?

Back 3

Presynaptic

Front 4

Describe the muscle weaknesses associated with Myasthenia Gravis.

Back 4

1. Ocular (binocular diplopia, ptosis)
2. Bulbar (chewing, swallowing, speaking)
3. Limbs (proximal > distal)

Front 5

Which disease is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability?

Back 5

Myasthenia gravis

Front 6

In Myasthenia gravis, what do antibodies attacks, and what is the result?

Back 6

1. ACh-receptors at the NMJ are attacked.
*Results in simplification of postsynaptic folds, inhibiting the stimulatory effect of ACh

2. MuSK Ab (muscle specific kinase)

Front 7

Ocular Myasthenia gravis is only associated with which symptoms?

Back 7

1. Ptsosis
2. Diplopia

Front 8

How is Myasthenia Gravis diagnosed?

Back 8

1. Painless fatiguable weakness
2. Ice pack test
3. Edrophonium (Tensilon) test
4. Ab against AChR or MuSK
5. Electrophysiologic studies (NCS)

Front 9

When performing electrophysiologic studies to diagnosis MG, what are you looking for?

Back 9

Repetitive nerve stimulation --> DECREMENTAL response

Single fiber EMG --> increased jitter

Front 10

List 2 tumors that are associated with myasthenia gravis

Back 10

1. Thymoma
2. Thymic hyperplasia

(Rarely other tumors: Small cell lung carcinoma)

Front 11

List some autoimmune diseases that are associated with myasthenia gravis

Back 11

1. Aplastic anemia
2. Thyrotoxicosis
3. SLE
4. RA
5. Sjogren syndrome
6. Mixed connective tissue disease
7. Multiple sclerosis

Front 12

What is the appropriate symptomatic treatment for myasthenia gravis? What treatments are used for long term therapy?

Back 12

Symptomatic treatment:
AChE inhibitors
(increase availability of ACh at the NMJ)

Immunomodulatory therapy:
1. IVIg
2. Plasma exchange
3. Corticosteroids
4. Immunosuppresants (azathioprine, mycophenolate mofetil)

Front 13

How long does neonatal myasthenia gravis normally last?

Back 13

< 12 weeks
(usually 3 weeks long)

Front 14

What causes neonatal myesthenia gravis?

Back 14

Passive transfer of maternal AChR antibodies
(transient disease)

Front 15

Are most congenital myasthenic disorders autosomal recessive or dominant? Which disease is an exception?

Back 15

Mostly autosomal RECESSIVE
(except Slow channel syndrome, which is AD)

Front 16

Which NMJ disease is frequently paraneoplastic?

Back 16

Lambert-Eaton Myasthenic syndrome

Front 17

What do antibodies attack in Lambert-Eaton myasthenic syndrome?

Back 17

Pre-synaptic VGCC (voltage-gated calcium channels)

Front 18

List 2 diseases associated with Lambert-Eaton Myesthenic syndrome

Back 18

1. Cancers (small cell lung carcinoma)
2. Lymphoma

Front 19

What is the difference in response to fast repetitive nerve stimulation seen in MG and LEMS?

Back 19

MG --> decremental response

LEMS --> incremental response

Front 20

Compare the effects of MG and LEMS on postsynaptic folds of the neuromuscular junction

Back 20

MG --> simplification of postsynaptic folds (autoimmune attack)

LEMS --> Upregulation of postsynaptic folds

Front 21

Does botulism cause problems at the presynaptic or postsynaptic side of the neuromscular junction?

Back 21

Pre-synaptic

Front 22

What is the result of Botulism on the neuromuscular junction?

Back 22

Impaired ACh vesicle docking, fusion, and release from the presynaptic side

Front 23

List some signs/symptoms associated with Botulism.

Back 23

1. Constipation
2. Generalized and extraocular muscle weakness
3. Difficulty swallowing
4. Difficulty breathing
5. May require mechanical ventilation

Front 24

Raw honey fed to babies less than six months can cause what kind of NMJ disorder?

Back 24

Botulism
"floppy infant" syndrome

Front 25

Which enzymes may be elevated in myopathies?

Back 25

1. Creatine phosphokinase (CK or CPK)
2. Aldolase
3. Lactase
4. ALT, AST

Front 26

What are some general signs of myopathies.

Back 26

1. Muscle cramps or exercise-induced pain
2. Myoglobulinuria

Front 27

List some inherited forms of myopathy

Back 27

1. Muscular dystrophies
2. Metabolic myopathies
3. Congenital myopathies
4. Mitochondrial myopathies

Front 28

List some acquired forms of myopathy

Back 28

1. Inflammatory myopathies (Polymyositis, dermatomyositis, inclusion body myositis)
2. Infectious myopathies
3. Toxic myopatheis

Front 29

What kind of EMG and NCS tests results are indicative of myopathy?

Back 29

EMG --> myopathic motor unit potentials, early recruitment

NCS --> normal

Front 30

List some various causes of elevated CK.

Back 30

1. Myopathy
2. Muscle trauma
3. Exercise
4. Increased muscle mass

Front 31

List 4 characteristics of muscular dystrophies

Back 31

1. Hereditary
2. Progressive
3. Degenerative
4. Variable onset and intensity

Front 32

Compare the effects of muscle use in patients with MG and LEMS.

Back 32

MG--> muscle use results in fatigue (gets worse with exercise and by the end of the day)
LEMS --> muscles are apparently fatiguable, but somehow muscle strength improves with muscle use

Front 33

Lambert-Eaton Myasthenic syndrome causes autonomic dysfunction, resulting in what kind of symptoms?

Back 33

1. Dry mouth
2. Impotence
3. Constipation
4. Urinary incontinence

Front 34

List 7 muscular dystrophies

Back 34

1. Duchenne (DMD)
2. Becker (BMD)
3. Limb-girdle (LGMD)
4. Emery-Dreifuss (EDMD)
5. Facioscapulohumeral (FSHMD)
6. Oculopharyngeal (OPMD)
7. Myotonic dystrophy (DM1, DM2)

Front 35

What is the inheritance pattern of Duchenne muscular dystrophy, and which protein is mutated?

Back 35

X-linked
Dystrophyn

Front 36

What is the inheritance pattern of Becker muscular dystrophy, and which protein is mutated?

Back 36

X-linked
Dystrophyn
(milder form that DMD)

Front 37

What is the inheritance pattern of limb-girdle muscular dystrophy?

Back 37

AD, AR, or X-linked

Front 38

List 6 drugs that can cause toxic myopathies

Back 38

1. Lipid lowering agents (statins, fibrates)
2. Antiretrovirals (Zidovudine)
3. Amiodarone
4. Procainamide
5. Choroquine
6. D-penicillamine

Front 39

Exercise-induced cramps, pain, weakness, and stiffness along with myoglobinuria are signs of what kind of disease?

Back 39

Metabolic myopathy

Front 40

What are "ragged red fibers," and what may they be indicative of?

Back 40

Abnormal mitochondria clustered next to the muscle membrane

May be seen in:
1. Mitochondrial myopathies
2. Non-specifically in elderly patients

Front 41

Episodic attacks of sudden, transient weakness is associated with what kind of disease?

Back 41

Muscle channellopathy

Front 42

List some things that can induce periodic paralysis seen with muscle channellopathies.

Back 42

1. Rigorous exercise
2. Large carbohydrate meals
3. Emotional stress
4. Changes in serum K+ levels

Front 43

What are the two types of periodic paralyses associated with muscle channellopathies?

Back 43

1. Hypokalemic periodic paralysis
2. Hyperkalemic periodic paralysis

Front 44

Which attacks last longer-- those associated with hypokalemic or hyperkalemic periodic paralysis?

Back 44

Hypokalemic periodic paralysis lasts longer (hours to days)
(hyperkalemic periodic paralysis lasts minutes to hours)

Front 45

Which channels are defective in hypokalemic and hyperkalemic periodic paralysis?

Back 45

Hypokalemic --> Ca2+ channels
Hyperkalemic --> Na2+ channels