CH46: Neuromuscular Junction, Myotonias and Persistent Muscle Fiber Activity

Question 1

Peak of age of first symptoms of Myasthenia Gravis (p. 1470)

Answer 1

20-30 for women, 50-60 for men

Of patients with thymoma, 50-60 years and males predominate

Question 2

Describe the eye weakness of Myasthenia (p. 1470)

Answer 2

ocular palsies and ptosis are usually accompanied by weakness of eye closure
sustained upward gaze will induce or exaggerate ptosis and may uncover myasthenic ocular motor weakness

Question 3

Twitching of the upper eyelid that appears a moment after the patient moves the eyes from a downward to primary position (p. 1470)

Answer 3

Cogan sign

Question 4

Of the trunk muscles this muscle is most affected by Myasthenia (p. 1470)

Answer 4

Erector spinae

Question 5

MGFA grading (p. 1471)

Answer 5

Class
I eye symptoms only
II mild
III moderate
IV severe
V intubated except during surgery

A- predominantly limb, axial muscles or both
B- predominantly oropharyngeal, respiratory muscles

Question 6

Mortality rate of MG (p. 1472)

Answer 6

before 30% but now less than 5%

Question 7

How many percent of MG had generalization more than 2 years after isolated ocular manifestations (p. 1472)

Answer 7

15%

Question 8

Some of the muscles in MG remain permanently weak such as (p. 1472)

Answer 8

anterior tibialis
triceps
portions of face

Question 9

Pathologic finding of the thymus of MG patients (p. 1472)

Answer 9

lymphoid follicles with active germinal centers

In terms of tumors: 1. histiocytic cells 2. lymphocytic cells

Question 10

Ultrastructural alterations in patients with MG (p. 1473)

Answer 10

reduction and simplification in the surface area of the post synaptic membrane [sparse, shallow, abnormally wide, or absent secondary synaptic clefts]

Question 11

Neuromuscular transmission is impaired in several ways (p. 1474)

Answer 11

1. antibodies block the binding of Ach to the AChR
2. serum IgG from MG patients induce a degradation rate of AchR
3. Antibodies cause a complement- mediated destruction of postsynaptic folds

Question 12

Decrementing response in MG (p. 1474)

Answer 12

rapid reduction in the amplitude of compound muscle action potentials during a series of repetitive stimulations of a peripheral nerve at a rate of 3 per second

Question 13

Findings in singe fiber EMG in MG (p. 1475)

Answer 13

inconstancy of the normally invariant interval between the firing of muscle fibers connected to the same motor unit

Question 14

MOA of neostigmine (p. 1475)

Answer 14

prolong and exaggerate the effects of ACh in the synapse and thereby produce an increment in muscle power in the patient with myasthenia

Question 15

Clinical effect of edrophonium and neostigmine (p. 1475)

Answer 15

5 min with edrophonium

60 min with neostigmine

Question 16

Antibody findings in MG (p. 1475)

Answer 16

found 80-90% of patients with generalized myasthenia

60% of those with ocular myasthenia

Question 17

enzyme that plays a role in supporting the normal structure of the post synaptic membrane and in the arrangement of AChR but its main function may be in developmental synaptic differentiation (p. 1475)

Answer 17

muscle specific kinase

Question 18

MG vs botulism (p. 1476)

Answer 18

In botulism, pupils are usually large and unreactive, and the eye signs are followed in rapid succession by involvement of bulbar, trunk and limb muscles

Question 19

Adverse effect of Mycophenolate (p. 1478)

Answer 19

Diarrhea

Question 20

Remission rate of thymectomy (p. 1478)

Answer 20

35% provided that the procedure is done in the first year or 2 after onset of the disease
Maximal effect after 3 years

Question 21

An impending cholinergic effect is betrayed by this finding (p. 1480)

Answer 21

constriction of pupils

Question 22

Clinical presentation difference of Lambert- Eaton syndrome

Answer 22

muscles of the trunk, shoulder girdle, pelvic girdle and lower extremities are those that become weak and fatigable

symmetrical muscle weakness with fatigability of proximal muscles, dry mouth, sphincter disturbances, aching muscles and diminished reflexes

Question 23

Cancer associated with Lambert- Eaton Myasthenic Syndrome (p. 1481)

Answer 23

60% small cell lung cancer but also with breast cancer, prostate, stomach, rectum and lymphomas

Question 24

Pathology of LEMS (p. 1482)

Answer 24

defect in the release of ACh quanta from the presynaptic nerve terminals

Question 25

Treatment for LEMS (p. 1482)

Answer 25

3,4- diaminopyridine | At times, prednisone and Azathioprine

Question 26

Localization of congenital myasthenic syndrome (p. 1483)

Answer 26

3/4 of the case, presynaptic

Question 27

Clinical presentation of congenital myasthenic syndrome (p. 1483)

Answer 27

Increase in ptosis, and in bulbar and respiratory weakness when crying

Question 28

congenital myasthenia caused by a recessive mutation in this gene that causes simplified structure of the synapse but no alteration in acetylcholine receptor (p. 1484)

Answer 28

DOK 7

Question 29

Anthrogryposis, pterygia and respiratory distress (p. 1484)

Answer 29

Escobar syndrome

Question 30

Myotonia, muscle hypertrophy, nonprogressive course, dominant inheritance (p. 1485)

Answer 30

Thomsen Disease

Question 31

Channel affected by Thomsen Disease (p. 1485)

Answer 31

Voltage-gated Chloride channel gene (CLCN1)

Question 32

Thomsen vs cramp (p. 1485)

Answer 32

The myotonic spasm is painless but after prolonged activity

Question 33

Congenital myotonia presentation in children (p. 1487)

Answer 33

infant's eyes are noted to open slowly after it has been crying or sneezing and its legs are consciously stiff as the child tries to take its. first steps

Question 34

patient unable to release a handshake, must slowly open the fingers one at a time (p. 1487)

Answer 34

grip myotonia

Question 35

myoedema vs myotonia (p. 1487)

Answer 35

unlike the lump or ridge produced in hypothyroid or cachectic muscle, the myotonic contraction involves an entire fasciculus or an entire muscle

Question 36

idiomuscular irritability vs myotonia (p. 1487)

Answer 36

unlike idiomuscular irritability, it persists for several seconds

Question 37

biopsy finding in Thomsen disease (p. 1487)

Answer 37

enlargement of muscle fibers, this change occurs only in hypertrophied muscles

Question 38

Mild form of Thomsen diseae (p. 1487)

Answer 38

Myotonia levior

Question 39

Treatment for Thomsen disease (p. 1487)

Answer 39

Procainamide and mexiletine | Phenytoin in soem cases

Question 40

Autosomal recessive congenital myotonia Chloride ion channel of the muscle fiber membrane will manifest at 10-14 years old Transient weakness follows an initial muscle contraction In contrast to Thomsen, CK may be elevated (p. 1488)

Answer 40

Becker Disease

Question 41

sodium channel diseases (p. 1488)

Answer 41

Hyperkalemic periodic paralysis | paramyotonia congenita

Question 42

Unit defective in sodium channel gene of sodium channel disease (p. 1488)

Answer 42

Alpha

Question 43

Weakness appearing after a period of rest that follows exercise (p. 1488)

Answer 43

Hyperkalemic Periodic Paralysis

Question 44

Weakness developing during exercise and worsening as the exercise continues (p. 1489)

Answer 44

Paramyotoniua congenita (Eulenburg disease)

Question 45

EMG findings in paramyotonia congenita (p. 1489)

Answer 45

myotonic discharges in all muscles even at normal temperatures

Question 46

Treatment for Sodium channel diseases (p. 1489)

Answer 46

``` Acetazolamide Dichlorphenamide Hydrochlorothiazide Mexilitine Albuterol, salbutamol Procainamide ```

Question 47

In sodium channel diseases, the normal action potential in all neural and muscular tissue, membrane depolarization is terminated by 2 events (p. 1490)

Answer 47

1. depolarization induced inactivation of the sodium channel | 2. subsequent action of the outward potassium current

Question 48

Calcium channel diseases (p. 1491)

Answer 48

Hypokalemic periodic paralysis

Question 49

Distribution of paralysis in hypokalemic periodic paralysis (p. 1491)

Answer 49

limbs than trunk muscles; | proximal than distal

Question 50

EMG findings of hypokalemic periodic paralysis (p. 1491)

Answer 50

associated with a decrease in the amplitude, eventual loss of muscle action potentials and failure of excitation by supramaximal stimulation of peripheral nerve or by strong voluntary effort

Question 51

Pathologic finding of hypokalemic periodic paralysis (p. 1492)

Answer 51

vacuolization of the sarcoplasm

Question 52

Treatment for hypokalemic periodic paralysis (p. 1492)

Answer 52

Low sodium diet Avoidance of large meals Acetazolamide Dichlorphenamide

Question 53

Clinical manifestation of malignant hyperthermia (p. 1493)

Answer 53

jaw muscles unexpectedly become tense rather than relaxed and soon rigidity extends to all of the muscles

Question 54

Only valid diagnostic testing in malignant hyperthermia (p. 1493)

Answer 54

in vitro exposure of a muscle biopsy specimen to halothane and to caffeine and detection of muscle contracture with both agents

Question 55

Treatment for malignant hyperthermia (p. 1493)

Answer 55

dantrolene

Question 56

Potassium channel diseases (p. 1493)

Answer 56

Andersen- Tawil Disease | Morvan Syndrome

Question 57

Triad of Andersen-Tawil Disease (p. 1493)

Answer 57

``` periodic potassium sensitive weakness ventricular dysrhymti with long QT syndrome dysmorphic features (micrognathia, short stature, scaphocephaly, hypertelorism, broad nose, low-set ears, short index fingers) ```

Question 58

gene affected by Andersen- Tawil Diseases (p. 1493)

Answer 58

dominant- negative mutation in KCNJ2

Question 59

abnormality in the voltage-gated potassium channel result of paraneoplastic reaction tho thymoma continuous muscle fiber activity or neuromyotonnia (p. 1493)

Answer 59

Morvan syndrome (Choree Fibrillaire)

Question 60

Contracted muscle (unlike in cramp, continuous muscular activity syndrome, myotonia and other involuntary spasms) no longer use energy for which reason they are almost silent electrically in EMG (p. 1495)

Answer 60

physiologic contracture

Question 61

muscle contract and relax slowly myoedema basis is slowness in the reaccumulation of calcium ions in the ER and in the disengagement of actin and myosin filaments (p. 1495)

Answer 61

Pseudomyotonia

Question 62

EMG of tetanus (p. 1495)

Answer 62

expected interference pattern of muscle action potentials

Question 63

Clinical manifestation of black widow spider bite (p. 1495)

Answer 63

cramps and spasms and then a painful rigidity of abdominal, trunk and leg muscles followed by weakness

Question 64

localization of black widow spider venom (p. 1495)

Answer 64

presynaptic; rapidly releases quanta of ACh

Question 65

Treatment of Black Widow Spider Bite (p. 1495)

Answer 65

Calcium gluconate Diazepine IV magnesium sulfate

Question 66

State of abnormal rippling muscle activity maybe generalized or limited to one part of the body such as muscles of the shoulder or of the lower extremity (p. 1496)

Answer 66

myokymia

Question 67

EMG findings of myokimia (p. 1496)

Answer 67

repetitive firing of 1 motor unit firing at 5 to 60 Hz and recurring regularly at 0.2 to 10 s intervals

Question 68

Continuous muscle fiber activity hyperexcitability of terminal parts of motor nerve fibers from partial loss of motor innervation and compensatory collateral sprouting of surviving axons armadillo syndrome (p. 1497)

Answer 68

Isaacs syndrome

Question 69

Treatment for Isaacs syndrome (p. 1497)

Answer 69

Phenytoin | Carbamazeine

Question 70

Persistent and intense muscle spasms Proximal lower limbs and lumbar paraspinal muscles robotic appearance to walking and an exaggerated lumbar lordosis rock-like mobility (p. 1497)

Answer 70

Stiffman syndrome

Question 71

EMG of stiffman syndrome (p. 1497)

Answer 71

activated but normally configured motor units | no evidence of distal motor nerve disturbance

Question 72

central origin of Stiffman syndrome is proved by (p. 1497)

Answer 72

absence during sleep, during general anesthesia and with proximal nerve block

Question 73

About 2/3 of Stiffman syndrome, have this antibody (p. 1498)

Answer 73

anti-GAD

Question 74

Treatment for Stiffman syndrome (p. 1498)

Answer 74

Diazepam

Question 75

Rippling muscle disease - unusual sensitivity to stretch manifested by rippling waves of muscle contraction Which protein is problematic? (p. 1498)

Answer 75

caveolin

Question 76

Continuous muscle fiber activity, stiffness and blepharospasm with obvious dysmorphic features (dwardism, pinched face with low- set ears, blepharophimosis, high-arched palate, receding chin, diffuse metaphyseal and epiphyseal bone dysplasia with flattened vertebrae) p. 1499

Answer 76

Schwartz- Jampel syndrome

Question 77

problem in Schartz- Jampel syndrome (p. 1499)

Answer 77

Perlacan

Question 78

Electron microscopy findings in Schartz- Jampel syndrome (p. 1499)

Answer 78

dilated T system Z-band streaming dilatation of mitochondria