Myotonia

Question 1

Define myotonia

Answer 1

tonic spasm after forceful voluntary contraction

Question 2

T or F. Like cramps myotonic spasm is painful.

Answer 2

F. Painless. But sometimes with post myotonia nocturnal myalgia

Question 3

Describe myotonia congenita in terms of

1. Reaction to cold
2. Affecting cardiac and smooth muscles
3. Affecting EOMs
4. Gestalt
5. Facies
6. State after rest

Answer 3

1. Exaggerates. BUT not as bad with paramyotonia congenita
2. NONE
3. May cause strabismus
4. Hypertrophied muscles. COMPARE with Myotonic dystrophy
5. None. COMAPRE WITH Myotonic dystrophy
6. Worse. Needs warm-up movements

READ MEGA TABLE!!

Question 4

What chloride ion channel is affected in myotonia congenita?

Answer 4

CLCN1

Question 5

What are the recommended drugs for myotonia?

Answer 5

Quinine
Procainamide
Phenytoin

Question 6

Hyperkalemic periodic paralysis, Myotonia fluctuans and paramyotonia congenita are due to mutation in the gene encoding the alpha subunit of the membrane bound voltage gated sodium channel in the skeletal muscle

Answer 6

SCN4A

Question 7

In hyperkalemic PP what is the level of:

1. Na during attack
2. K during attack
3. K in between attack

Answer 7

1. Low
2. 5-6 mmol/L
3. Normal

Question 8

Which diseases? HyperK PP, MC, PMC

1. Occurs after a period of rest after exercise
2. Increases with Exercise
3. Occurs After cold exposure
4. No warm-up phenomenon
5. With warm up phenomenon

Answer 8

1. Hyperkalemic PP and myotonia congenita
2. Paramyotonia congenita
3. ALL. But PMC is the WORST
4. PMC
5. MC, HyperK PP

Question 9

What is the tx for HyperK PP

Answer 9

Acute attack: Glucose, Calcium
Low potassium diet
Acetazolamide 125-250 BID for prevention

Question 10

What are the triggers for Hypokalemic Periodic Paralysis?

Answer 10

Exercise

Carbo loading

Question 11

T or F: EMG evidence of myotonia EXCLUDES hyPOk PP

Answer 11

T

Question 12

What is the pathologic change seen in hypokalemic periodic paralysis?

Answer 12

Vacuolization of the sarcoplasmic reticulum

Question 13

Tx for HyPOK PP?

Answer 13

Acetazolamide
Spironolactone
Daily 5-10g of KCl UNsweetened solution

Acute: 0.25mEq KCl/kg or 0.1meq per kg bolus in mannitol 5% AVOID NSS and glucose

Question 14

How does Acetazolamide work for HyPO vs HyPER K PP?

Answer 14

PO: induces acidosis

Question 15

What drugs commonly trigger malignant hyperthermia?

Answer 15

Halothane and succinylcholine

Question 16

How does dantrolene work for malignant hyperthermia?

Answer 16

prevents the release of Calcium from the SR

Question 17

What are the components of the Andersen syndrome?

Answer 17

Defect in the KCNJ2 gene results in:
Potassium sensitive weakness
Ventricular dysrhythmias with long QT syndrome
Facies

Question 18

Re: Thomsen disease

1. Aka?
2. Relationship to exercise
3. Treatment?
4. Inheritance pattern
5. Relationship to rest
6. Mutation in what ion channel?

Answer 18

1. Aka? Myotonia congenita
2. Relationship to exercise: Appears after
3. Treatment? Mexiletine, quinine, procainamide, phenytoin
4. Inheritance pattern: Dominant
5. Relationship to rest: Noticeable after a period of inactivity
6. Mutation in what ion channel? Chloride (CLCN1 gene CLC1 channel protein)

REMEMBER THAT UNLIKE CRAMPS THIS IS NOT PAINFUL

Question 19

How to differentiate myotonia congenita from myotonic dystrophy?

Answer 19

MC has NO typical facies of MD: narrow face, frontal balding, cataracts

Also MC patients have muscle hypertrophy– a feature NOT prsent in MD pxs

Also MD is usually NOT present in the first few years of life, whereas MC already presents with slow opening of eyes after crying or sneezing and the legs may be conspicuously stiff ast he child tries to take its first steps.

Question 20

Although seen in virtually all forms of myotonia, stiffness exaggerated by cold is most characteristic of?

Answer 20

Paramyotonia congenita

Question 21

What is aka as a milder myotonia congenita with a later onset?

Answer 21

Myotnoia levior

Question 22

What are the 3 differentiating features of MC (thomsen disease) and Generalized myotonia (becker disease)?

Answer 22

Becker is autosomal recessive, manifests later in childhood, increased CK during attack

Question 23

What are the 2 diseases that are models for channelopathies involving the SCN4A gene and the alpha subunit of the muscle membrane Na channel?

Answer 23

Hyperkalemic periodic paralysis

Paramyotonic congenita (Eulenburg)

Question 24

Re: Hyperkalemic periodic paralysis

1. What differentiates it from all the channelopathies in terms of onset of paralysis?
2. Loading of what ion induces and episode?
3. Serum Ck during attack
4. Treatment?

Answer 24

1. What differentiates it from all the channelopathies in terms of onset of paralysis? Similar to hypokalemic periodic paralysis they are the only ones with EPISODIC PARALYSIS
2. Loading of what ion induces and episode? K
3. Serum Ck during attack: increased
4. Treatment? During an attack give glucose and calcium, acetazolamide, low K diet

Question 25

What can be done (non pharma) to resolve an attack of hyperKPP?

Answer 25

Attack lasts 15-60 minutes after resting post exercise: Mild exercise can hasten attack

Question 26

What is the Na level during an attack of HyperKPP?

Answer 26

Low becauase it shifts into the muscle

Question 27

T or F Certain channelopathies such as hypo and hyperK PP, generalized myotonia and anderson disease can induce a permanent myopathy.

Answer 27

T

Question 28

Which 2 channelopathies induce a vacuolar type of myopathy?

Answer 28

Hyper and hypo K periodic paralysis.

Question 29

What are the key differences between parayotonia congenita and hyperkalemic periodic paralysis?

Answer 29

No episodic paralysis in PC PC has onset at birth PC has a stronger reaction to cold

Question 30

What can be given to prevent attacks of hyperkalemic periodic paralysis?

Answer 30

Acetazolamide Consider: Dichlorphenamide

Question 31

What is mexiletine?

Answer 31

Antiarrhythmic and anesthetic similar to lidocaine-- used for myotonia channelopathies

Question 32

`What is the EMG pattern of myotonic muscle?

Answer 32

Characteristic discharges that persist following the cessation of voluntary contraction. (Dive bomber sound!)

Question 33

T or F even with curare myotonia persists.

Answer 33

T

Question 34

How do defects in the Chloride and Sodium channels produce myotonia?

Answer 34

Chloride: During repolarization outward there is outward flow of K+ into the T tubules-- this would cause depolarization if it weren't for the large opposing CHLORIDE conductance that is also present that counteracts the influence of potassium accumulation Sodium: For normal repolarization to occur there needs to be rapid inactivation of the sodium channel-- this process is impaired in those with mutations such as the Hyperk PP.

Question 35

Re: HypoK PP 1. What is the inheritance pattern? 2. What gene and protein are involved? 3. Conductance of what ion is affected? 4. What is serum K during attack? 5. Treatment?

Answer 35

1. What is the inheritance pattern? AD 2. What gene and protein are involved? DHP receptor and Dihydropyridine receptor 3. Conductance of what ion is affected? Calcium 4. What is serum K during attack? Decreased 5. Treatment? Kcl during attack; acetazolamide 250mg TID to prevent; low sodium diet elss than 160mEq/ day

Question 36

Which channelopathy causing myotonia/ periodic paralysis has abnormal K in between attacks?

Answer 36

NONE

Question 37

What are the unusual triggers for HypoK PP?

Answer 37

Exercise and carbohydrate load

Question 38

T or F: The presence of myotonia, clinically or on EMG ESSENTIALLY EXCLUDES THE DIAGNOSIS OF HYPOKALEMIC PERIODIC PARALYSIS.

Answer 38

T

Question 39

What are the EMG NCV findings in hyper and hypokalemic periodic paralysis?

Answer 39

Decrease in amplitude and eventual loss of muscle action potentials and there is failure of excitation by supramaximal stimulation of peripheral nerve or by strong voluntary effort.

Question 40

How to do provocative testing for hypoK PP?

Answer 40

Load naCl 2g hourly for 7 doses or glucose 50-100g followed by vigorous exercise

Question 41

For an acute attack, what dose should be given to hypoK PP?

Answer 41

0.25mEg KCl/kg-- may be given orally

Question 42

What is the most common cause secondary kalemic periodic paralyses?

Answer 42

The use of laxatives and excessive use of diuretics

Question 43

What is also known as the Conn Syndrome? What two types of attacks does it lead to?

Answer 43

Hypokalemic weakness with primary aldosteronism Attacks of tetany and hypokalemic weakness

Question 44

Re: Malignant Hyperthermia 1. What gene and protein is involved? 2. Conductance of what ion is deranged? 3. Myopathology? 4. Tx

Answer 44

1. What gene and protein is involved? RYR1, Ryanodine recepor 2. Conductance of what ion is deranged? Calcium 3. Myopathology? Rhabdomyolysis, cores 4. Tx: IV dantrolene 1mg per kg; DISCONTINUE the ansethetic

Question 45

What is the only channelopathy that has an autosomal recessive inheritance pattern?

Answer 45

Generalized myotonia (Becker disease)

Question 46

What are the most notorious anesthetic compounds to cause malignant hyperthermia? How does halothane cause this?

Answer 46

Halothane and succinylcholine halothane releases calcium from the SR and prevents its reaccumulation

Question 47

What disorders predispose to malignant hyperthermia?

Answer 47

Central core myopathy King-Denbrorough syndrome: dislocated patellae, ptosis, strabismus, ptosis Evans myopathy

Question 48

What is the triad of Anderson syndrome? KCNJ2 encoding a type of K channel

Answer 48

1. Periodic potassium-sensitive weakness 2. Ventricular dysrhythmias with long QT 3. Dysmorphic features

Question 49

Why are the muscles in Tarui and Mcardle disease electrically silent even if they are in a state of contraction?

Answer 49

It's a physiologic contracture-- they no longer use energy

Question 50

What endocrinologic disturbance results in Pseudomyotonia?

Answer 50

Hypothyroidism

Question 51

What is known as the state of abnormal rippling muscle activity that may be generalized or limited to one part of the body such as the muscles of the shoulders or and the lower extremity?

Answer 51

Myokymia MOST often in demyelinating condition of the peripheral nerve following injury and thus it is neuropathic in nature Happens in GBS affecting facial nerve, MS, radiation damage

Question 52

What syndrome is characterised by continuous muscle activity, muscle stiffness and a sense of weakness? AKA Acquired neuromyotonia Treatment?

Answer 52

Isaac Syndrome Approximately 40% of affected individuals have antibodies to voltage-gated potassium channels (VGKC’s) that affect the points at which the signals from the nerve fiber meet the muscle cell (neuromuscular junction). Phenytoin or CBZ

Question 53

What is the pathophysiologic basis of Stiff person syndrome?

Answer 53

Autoantibodies against glutamic acid decarboxylase GAD the synthesizing enzyme for gamma amino butyric acid antibody for the glycine receptor also present in some There is disinhibition of the interneurons in the gray matter of the spinal cord.

Question 54

What protein is mutated in the Schwartz-Jampel syndrome?

Answer 54

Perlecan