1
Q
Myasthenia
A
Muscle weakness
2
Q
Atrophy
A
decrease in size of cell , tissue or organ
3
Q
Paresis
A
slight or incomplete paralysis
4
Q
Lesions of the Motor Unit : Soma
A
ALS , Poliomyelitis
5
Q
Lesions of the Motor Unit : Axon
A
Toxins, drugs and axotomy
6
Q
Lesions of the Motor Unit : Schwann cell
A
Guillian - Barre syndrome, Diptheria
7
Q
Lesions of the Motor Unit : Nerve ending
A
Botulism, Lambert-Eaton disease
8
Q
Lesions of the Motor Unit : Synaptic cleft
A
acetylcholine esterase absent
9
Q
Lesions of the Motor Unit : End plate
A
Myasthenia Gravis, nACh receptor defects
10
Q
Lesions of the Motor Unit : Muscle Fiber
A
Myotonia , muscualr dystrophy
11
Q
Variety of lesions of the nerve Soma or Axon
A
- Diseases
- Toxins
- Drugs
- Trauma
12
Q
Signs/symptoms of lesions of the nerve Soma or Axon
A
- Muscle atrophy and weakness
- Fibrillations and fasciculations
- Eventual loss of muscle fibers (replacement by noncontractile fibrous connective tissue)
13
Q
What is Poliomyeltis
A
Infection with the polio virus can affect the whole body but mainly affects the muscles and nerves, particularly the motor neurons of the spinal ventral horns. Severe cases yield permanent paralysis or death.
14
Q
Transmission of Polio virus occurs by
A
By direct person-to-person contact and through oral, nasal
and anal secretions.
Enters through mouth and nose then proliferates in the throat and intestinal tract and spreads through vascular and lymphatic systems
15
Q
Prevention of Poliomyelitis
A
immunization prevents in 90% of cases
16
Q
Variety of Lesions of Schwann cells
A
- Autoimmune disease
- Toxins
17
Q
Manifestations of lesion of Schwann cells
A
Demyelination-dependent conduction slowing or conduction block
18
Q
Toxins that affect Nerve ending, Synaptic Cleft and End-Plate
A
1) Botulism
2) Alpha-Latrotoxin
3) Beta-Bungarotoxin
4) Curare (delta- Tubocurarine)
19
Q
Cause of Botulism
A
Toxic protease from anaerobic bacteria , Clostridium Botulinum
20
Q
Effect of Botulism
A
reduces ACh release by acting on presynaptic proteins involved in exocytosis
21
Q
Transmission of Botulism
A
- Eating food that contains the botulism toxin
- Infection of a wound with Clostridium botulinum
- Consuming spores of Clostridium botulinum
22
Q
Source of Alpha-Latrotoxin
A
The black widow spider (Latrodectus mactans) synthesizes a neurotoxic venom
23
Q
Effect of Alpha-Latrotoxin
A
- causes massive release of ACh
- venom reaches the blood via the lymphatic system
- The venom acts at the nerve endings, causing tetanus, a continuous, painful contraction of the muscle (occasional patchy flaccid paralysis)
24
Q
Source of Beta-Bungarotoxin
A
venom of snake
25
Effect of Beta-Bungarotoxin
reduces ACh release by acting on proteins in nerve terminals involved in exocytosis
26
Effect of Curare (delta- Tubocurarine)
a non-depolarising muscle relaxant that blocks the acetylcholine receptors at the neuromuscular junction
27
What is Lambert-Eaton?
Autoimmune disease, where circulating antibodies
are directed against voltage-gated Ca2+ channels in
motor neuron terminals.
causes insufficient release of ACh into the synaptic cleft
28
Why is strength increased with repeated contraction in Lambert-Eaton?
allow the synaptic concentration of synaptic ACh to rise sufficiently to increase force of contraction
29
Lambert Eaton Syndrome is associated ______________
oat cell carcinoma (of the lung) as a paraneoplastic syndrome.
30
Characteristics of Lambert-Eaton
– Muscle weakness and 'facilitating neuromuscular block'
– Often found in patients with small cell cancers of the lung
– Culture of these cells express voltage-gated calcium
channels
– Immune system makes antibodies to these proteins
– Antibodies cross-link voltage-gated calcium channels in motor nerve terminals
– Reduced ACh release
– Reflexes are decreased
31
Physiological Changes at End Plate in Lambert-Eaton syndrome
– Reduced amplitude of EPP
– Many EPPS do not attain threshold in muscle fibers
– Amplitude of MinEPP is unchanged
32
Tests to confirm Lambert-Eaton syndrome
EMG and nerve conduction velocity
33
Results seen in EMG for Lambert-Eaton syndrome
Waxing is evident in the EMG inresponse to repeated nerve
| stimulation.
34
Therapy for Lambert-Eaton syndrome
– Remove underlying tumor and give immunosuppressive drugs
– Do plasma exchange
– Calcium gluconate to enhance calcium influx into nerve terminal
– Give 4-aminopyridine to prolong presynaptic action potential and improve transmitter release
35
Congenital Forms of Myasthenia (Muscle Weakness)
1)Deficiency of ACh-esterase in synaptic cleft
2)Slow Channel Syndrome
3)Other forms
a)One form where the binding of ACh to nAChR is
abnormal
b) One form where the ACh-gated channels have very
brief opening times
36
Effect of congenital myasthenia due to deficiency of ACh-esterase in synaptic cleft
- EPP amplitude is larger and longer than normal
- Single motor nerve stimuli delivered at low frequency cause single muscle twitches
- High-frequency motor nerve stimuli produce temporal summation of EPPs and cause depolarization block of muscle
37
Effect of congenital myasthenia due to Slow Channel Syndrome
- Inherited rare condition presents at birth or early childhood
- Muscle weakness
- Rapid fatigue
- Progressive atrophy
- ACh binding to nAChRs causes prolonged opening of ACh receptor channels and, consequently, depolarization block
38
Age of onset of congenital myasthenias
appear before the age of 2
39
What is Myasthenia Gravis?
a chronic disease due to an autoimmune process. Antibodies to nAChRs develop and reduce transmission at the skeletal NMJ and other peripheral synapses with nAChRs. There is a genetic susceptibility to Myasthenia Gravis.
40
Main sign indicative of Myasthenia Gravis
weakness of voluntary muscles, which improves after rest and worsens with muscular activity
41
Symptoms of Myasthenia Gravis
– Weakness in muscles innervated by cranial nerves (eg,
ptosis)
*Ocular changes: Diplopia (double vision)Ptosis
(drooping eyelids)
*Patients with generalized disease may experience:
Difficult swallowing and frequent choking
– Weakness in limb muscles
*usually later in the day and recovery with rest
– Weakness not associated with denervation
– Serum from patients causes disease symptoms in animals
42
Tests for myasthenia Gravis
```
EMG
Tensilon Test (acetylcholinesterase inhibitor)
```
43
Results seen in EMG for Myasthenia Gravis
In repetitive stimulation, ‘waning pattern’
44
Results seen in Tensilon test for
Positive test
45
Describe the effect of antibodies at the nAChR in Myasthenia Gravis
– Antibodies bind to alpha subunits of nAChR
– Antibodies do not compete with ACh for binding sites on
subunits
– Antibodies cross link neighboring nAChRs hastening
resorption.
46
Normal turn over time for ACh receptors
5-7 days
47
Turnover time for ACh receptors in Myasthenia Gravis
2-5 days
48
Who does myasthenia Gravis mostly affect?
Young Women and Older men
49
Describe the resorption of ACh receptors
– Endocytosis of nAChRs in end plate membranes
– Lysosomal destruction
– Enhanced removal rate of nAChRs but no enhanced rate of insertion of nAChRs into end plate membrane
50
Treatment of Myasthenia Gravis
1) AChesterase Inhibitors- Neostigmine or pyridostigmine
2) Prednisone (Cortisone) or immune suppressors such as azathioprine or cyclosporine can be applied after dissatisfying responses to other drugs.
3) Remission sometimes follows thymectomy.
51
Myasthenia gravis is associated with ________
Tumors of thymus gland
52
Structural changes at the Motor Endplate in Myasthenia Gravis
– Fewer nAChRs
– Wider synaptic cleft
– Smaller junctional folds
53
What is a Myasthenic Crisis
Breathing difficulty may be life threatening.
54
Myotonia Congenita aka
Chloride channel Syndrome
55
What is Myotonia Congenita?
Autosomal dominant disease, influencing the gene
encoding chloride channels in the muscle membrane
Fewer chloride channels are expressed and inserted in the cell membrane
56
Function of Chloride channels in normal muscle
the numerous chloride channels help to keep the
membrane potential close to ECl during recovery from an
action potential when potassium ions are accumulating in
the transverse tubular system (TTS)
57
Effect of Myotonia Congenita
– Increased excitability: smaller depolarization is required to evoke an action potential and may even cause a train of
action potentials
– Potassium accumulation in TTS causes some depolarization leading to spontaneous firing of the muscle after the end of nerve stimulation
58
relaxation?
repetitive firing?
59
What is Duchenne's Muscular dystrophy?
– X-linked–recessive disorder of muscles in males
– Onset of disease in early childhood (3-5 yrs)
– Muscle weakness develops progressively
– Patients die from cardiovascular and respiratory insuffiency
– Cause: absence of muscle protein - dystrophin
60
Causes of Lower Motor Neuron Syndrome
- Viral infections (e.g. poliomyelitis)
- Trauma
- Degenerative disease
61
Signs of LMN syndrome
```
Muscle weakness (paresis)
Flaccid paralysis
Loss of reflexes
Fasciculations
Fibrillations
Muscular atrophy progressing to complete myocytic death
```
62
Expression of nAChR in embryo vs adult
In embryonic muscle fiber the nAChRs are distributed across the entire surface of muscle cells
In adult muscle fibers, normal nerve stimulation leads to aggregation of nAChRs under nerve endings
63
What happens to expression of nAChR after denervation of muscle?
nAChRs return to a supersensitive embryonic state, with an
| adult state re-emerging with reinnervation
Neuroscience
flashcards
Decks in class (32)
# Cards
-
Module B-0182
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Module B-0232
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Module B-0334
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Module B-0442
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Module B-0530
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Module B-0680
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Module B-0754
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Module B-0847
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Module C111
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Module D-0132
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Module D-0263
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Module D-0327
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Module D-0433
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Module D-0541
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Module D-0656
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Module D-0741
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Module D-0846
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Module D-0946
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Module D-1026
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Module D-1165
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Module D-1225
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Module D-1353
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Module E-0138
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Module E-0262
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Module E-0343
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Module E-0457
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Module E-0563
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Module E-0654
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Module E-0774
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Module E-0846
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Module E-0945
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Module E-100
