CH46: Neuromuscular Junction, Myotonias and Persistent Muscle Fiber Activity Flashcards
Peak of age of first symptoms of Myasthenia Gravis (p. 1470)
20-30 for women, 50-60 for men
Of patients with thymoma, 50-60 years and males predominate
Describe the eye weakness of Myasthenia (p. 1470)
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
Twitching of the upper eyelid that appears a moment after the patient moves the eyes from a downward to primary position (p. 1470)
Cogan sign
Of the trunk muscles this muscle is most affected by Myasthenia (p. 1470)
Erector spinae
MGFA grading (p. 1471)
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
Mortality rate of MG (p. 1472)
before 30% but now less than 5%
How many percent of MG had generalization more than 2 years after isolated ocular manifestations (p. 1472)
15%
Some of the muscles in MG remain permanently weak such as (p. 1472)
anterior tibialis
triceps
portions of face
Pathologic finding of the thymus of MG patients (p. 1472)
lymphoid follicles with active germinal centers
In terms of tumors: 1. histiocytic cells 2. lymphocytic cells
Ultrastructural alterations in patients with MG (p. 1473)
reduction and simplification in the surface area of the post synaptic membrane [sparse, shallow, abnormally wide, or absent secondary synaptic clefts]
Neuromuscular transmission is impaired in several ways (p. 1474)
- antibodies block the binding of Ach to the AChR
- serum IgG from MG patients induce a degradation rate of AchR
- Antibodies cause a complement- mediated destruction of postsynaptic folds
Decrementing response in MG (p. 1474)
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
Findings in singe fiber EMG in MG (p. 1475)
inconstancy of the normally invariant interval between the firing of muscle fibers connected to the same motor unit
MOA of neostigmine (p. 1475)
prolong and exaggerate the effects of ACh in the synapse and thereby produce an increment in muscle power in the patient with myasthenia
Clinical effect of edrophonium and neostigmine (p. 1475)
5 min with edrophonium
60 min with neostigmine
Antibody findings in MG (p. 1475)
found 80-90% of patients with generalized myasthenia
60% of those with ocular myasthenia
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)
muscle specific kinase
MG vs botulism (p. 1476)
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
Adverse effect of Mycophenolate (p. 1478)
Diarrhea
Remission rate of thymectomy (p. 1478)
35% provided that the procedure is done in the first year or 2 after onset of the disease
Maximal effect after 3 years
An impending cholinergic effect is betrayed by this finding (p. 1480)
constriction of pupils
Clinical presentation difference of Lambert- Eaton syndrome
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
Cancer associated with Lambert- Eaton Myasthenic Syndrome (p. 1481)
60% small cell lung cancer but also with breast cancer, prostate, stomach, rectum and lymphomas
Pathology of LEMS (p. 1482)
defect in the release of ACh quanta from the presynaptic nerve terminals
Treatment for LEMS (p. 1482)
3,4- diaminopyridine
At times, prednisone and Azathioprine
Localization of congenital myasthenic syndrome (p. 1483)
3/4 of the case, presynaptic
Clinical presentation of congenital myasthenic syndrome (p. 1483)
Increase in ptosis, and in bulbar and respiratory weakness when crying
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)
DOK 7
Anthrogryposis, pterygia and respiratory distress (p. 1484)
Escobar syndrome
Myotonia, muscle hypertrophy, nonprogressive course, dominant inheritance (p. 1485)
Thomsen Disease
Channel affected by Thomsen Disease (p. 1485)
Voltage-gated Chloride channel gene (CLCN1)
Thomsen vs cramp (p. 1485)
The myotonic spasm is painless but after prolonged activity
Congenital myotonia presentation in children (p. 1487)
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
patient unable to release a handshake, must slowly open the fingers one at a time (p. 1487)
grip myotonia
myoedema vs myotonia (p. 1487)
unlike the lump or ridge produced in hypothyroid or cachectic muscle, the myotonic contraction involves an entire fasciculus or an entire muscle
idiomuscular irritability vs myotonia (p. 1487)
unlike idiomuscular irritability, it persists for several seconds
biopsy finding in Thomsen disease (p. 1487)
enlargement of muscle fibers, this change occurs only in hypertrophied muscles
Mild form of Thomsen diseae (p. 1487)
Myotonia levior
Treatment for Thomsen disease (p. 1487)
Procainamide and mexiletine
Phenytoin in soem cases
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)
Becker Disease
sodium channel diseases (p. 1488)
Hyperkalemic periodic paralysis
paramyotonia congenita
Unit defective in sodium channel gene of sodium channel disease (p. 1488)
Alpha
Weakness appearing after a period of rest that follows exercise (p. 1488)
Hyperkalemic Periodic Paralysis
Weakness developing during exercise and worsening as the exercise continues (p. 1489)
Paramyotoniua congenita (Eulenburg disease)
EMG findings in paramyotonia congenita (p. 1489)
myotonic discharges in all muscles even at normal temperatures
Treatment for Sodium channel diseases (p. 1489)
Acetazolamide Dichlorphenamide Hydrochlorothiazide Mexilitine Albuterol, salbutamol Procainamide
In sodium channel diseases, the normal action potential in all neural and muscular tissue, membrane depolarization is terminated by 2 events (p. 1490)
- depolarization induced inactivation of the sodium channel
2. subsequent action of the outward potassium current
Calcium channel diseases (p. 1491)
Hypokalemic periodic paralysis
Distribution of paralysis in hypokalemic periodic paralysis (p. 1491)
limbs than trunk muscles;
proximal than distal
EMG findings of hypokalemic periodic paralysis (p. 1491)
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
Pathologic finding of hypokalemic periodic paralysis (p. 1492)
vacuolization of the sarcoplasm
Treatment for hypokalemic periodic paralysis (p. 1492)
Low sodium diet
Avoidance of large meals
Acetazolamide
Dichlorphenamide
Clinical manifestation of malignant hyperthermia (p. 1493)
jaw muscles unexpectedly become tense rather than relaxed and soon rigidity extends to all of the muscles
Only valid diagnostic testing in malignant hyperthermia (p. 1493)
in vitro exposure of a muscle biopsy specimen to halothane and to caffeine and detection of muscle contracture with both agents
Treatment for malignant hyperthermia (p. 1493)
dantrolene
Potassium channel diseases (p. 1493)
Andersen- Tawil Disease
Morvan Syndrome
Triad of Andersen-Tawil Disease (p. 1493)
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)
gene affected by Andersen- Tawil Diseases (p. 1493)
dominant- negative mutation in KCNJ2
abnormality in the voltage-gated potassium channel
result of paraneoplastic reaction tho thymoma
continuous muscle fiber activity or neuromyotonnia (p. 1493)
Morvan syndrome (Choree Fibrillaire)
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)
physiologic contracture
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)
Pseudomyotonia
EMG of tetanus (p. 1495)
expected interference pattern of muscle action potentials
Clinical manifestation of black widow spider bite (p. 1495)
cramps and spasms and then a painful rigidity of abdominal, trunk and leg muscles followed by weakness
localization of black widow spider venom (p. 1495)
presynaptic; rapidly releases quanta of ACh
Treatment of Black Widow Spider Bite (p. 1495)
Calcium gluconate
Diazepine
IV magnesium sulfate
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)
myokymia
EMG findings of myokimia (p. 1496)
repetitive firing of 1 motor unit firing at 5 to 60 Hz and recurring regularly at 0.2 to 10 s intervals
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)
Isaacs syndrome
Treatment for Isaacs syndrome (p. 1497)
Phenytoin
Carbamazeine
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)
Stiffman syndrome
EMG of stiffman syndrome (p. 1497)
activated but normally configured motor units
no evidence of distal motor nerve disturbance
central origin of Stiffman syndrome is proved by (p. 1497)
absence during sleep, during general anesthesia and with proximal nerve block
About 2/3 of Stiffman syndrome, have this antibody (p. 1498)
anti-GAD
Treatment for Stiffman syndrome (p. 1498)
Diazepam
Rippling muscle disease
- unusual sensitivity to stretch manifested by rippling waves of muscle contraction
Which protein is problematic? (p. 1498)
caveolin
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
Schwartz- Jampel syndrome
problem in Schartz- Jampel syndrome (p. 1499)
Perlacan
Electron microscopy findings in Schartz- Jampel syndrome (p. 1499)
dilated T system
Z-band streaming
dilatation of mitochondria
