Myotonia Flashcards
Define myotonia
tonic spasm after forceful voluntary contraction
T or F. Like cramps myotonic spasm is painful.
F. Painless. But sometimes with post myotonia nocturnal myalgia
Describe myotonia congenita in terms of
- Reaction to cold
- Affecting cardiac and smooth muscles
- Affecting EOMs
- Gestalt
- Facies
- State after rest
- Exaggerates. BUT not as bad with paramyotonia congenita
- NONE
- May cause strabismus
- Hypertrophied muscles. COMPARE with Myotonic dystrophy
- None. COMAPRE WITH Myotonic dystrophy
- Worse. Needs warm-up movements
READ MEGA TABLE!!
What chloride ion channel is affected in myotonia congenita?
CLCN1
What are the recommended drugs for myotonia?
Quinine
Procainamide
Phenytoin
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
SCN4A
In hyperkalemic PP what is the level of:
- Na during attack
- K during attack
- K in between attack
- Low
- 5-6 mmol/L
- Normal
Which diseases? HyperK PP, MC, PMC
- Occurs after a period of rest after exercise
- Increases with Exercise
- Occurs After cold exposure
- No warm-up phenomenon
- With warm up phenomenon
- Hyperkalemic PP and myotonia congenita
- Paramyotonia congenita
- ALL. But PMC is the WORST
- PMC
- MC, HyperK PP
What is the tx for HyperK PP
Acute attack: Glucose, Calcium
Low potassium diet
Acetazolamide 125-250 BID for prevention
What are the triggers for Hypokalemic Periodic Paralysis?
Exercise
Carbo loading
T or F: EMG evidence of myotonia EXCLUDES hyPOk PP
T
What is the pathologic change seen in hypokalemic periodic paralysis?
Vacuolization of the sarcoplasmic reticulum
Tx for HyPOK PP?
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
How does Acetazolamide work for HyPO vs HyPER K PP?
PO: induces acidosis
What drugs commonly trigger malignant hyperthermia?
Halothane and succinylcholine
How does dantrolene work for malignant hyperthermia?
prevents the release of Calcium from the SR
What are the components of the Andersen syndrome?
Defect in the KCNJ2 gene results in:
Potassium sensitive weakness
Ventricular dysrhythmias with long QT syndrome
Facies
Re: Thomsen disease
- Aka?
- Relationship to exercise
- Treatment?
- Inheritance pattern
- Relationship to rest
- Mutation in what ion channel?
- Aka? Myotonia congenita
- Relationship to exercise: Appears after
- Treatment? Mexiletine, quinine, procainamide, phenytoin
- Inheritance pattern: Dominant
- Relationship to rest: Noticeable after a period of inactivity
- Mutation in what ion channel? Chloride (CLCN1 gene CLC1 channel protein)
REMEMBER THAT UNLIKE CRAMPS THIS IS NOT PAINFUL
How to differentiate myotonia congenita from myotonic dystrophy?
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.
Although seen in virtually all forms of myotonia, stiffness exaggerated by cold is most characteristic of?
Paramyotonia congenita
What is aka as a milder myotonia congenita with a later onset?
Myotnoia levior
What are the 3 differentiating features of MC (thomsen disease) and Generalized myotonia (becker disease)?
Becker is autosomal recessive, manifests later in childhood, increased CK during attack
What are the 2 diseases that are models for channelopathies involving the SCN4A gene and the alpha subunit of the muscle membrane Na channel?
Hyperkalemic periodic paralysis
Paramyotonic congenita (Eulenburg)
Re: Hyperkalemic periodic paralysis
- What differentiates it from all the channelopathies in terms of onset of paralysis?
- Loading of what ion induces and episode?
- Serum Ck during attack
- Treatment?
- 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
- Loading of what ion induces and episode? K
- Serum Ck during attack: increased
- Treatment? During an attack give glucose and calcium, acetazolamide, low K diet
What can be done (non pharma) to resolve an attack of hyperKPP?
Attack lasts 15-60 minutes after resting post exercise: Mild exercise can hasten attack
What is the Na level during an attack of HyperKPP?
Low becauase it shifts into the muscle
T or F Certain channelopathies such as hypo and hyperK PP, generalized myotonia and anderson disease can induce a permanent myopathy.
T
Which 2 channelopathies induce a vacuolar type of myopathy?
Hyper and hypo K periodic paralysis.
What are the key differences between parayotonia congenita and hyperkalemic periodic paralysis?
No episodic paralysis in PC
PC has onset at birth
PC has a stronger reaction to cold
What can be given to prevent attacks of hyperkalemic periodic paralysis?
Acetazolamide
Consider: Dichlorphenamide
What is mexiletine?
Antiarrhythmic and anesthetic similar to lidocaine– used for myotonia channelopathies
`What is the EMG pattern of myotonic muscle?
Characteristic discharges that persist following the cessation of voluntary contraction. (Dive bomber sound!)
T or F even with curare myotonia persists.
T
How do defects in the Chloride and Sodium channels produce myotonia?
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.
Re: HypoK PP
- What is the inheritance pattern?
- What gene and protein are involved?
- Conductance of what ion is affected?
- What is serum K during attack?
- Treatment?
- What is the inheritance pattern? AD
- What gene and protein are involved? DHP receptor and Dihydropyridine receptor
- Conductance of what ion is affected? Calcium
- What is serum K during attack? Decreased
- Treatment? Kcl during attack; acetazolamide 250mg TID to prevent; low sodium diet elss than 160mEq/ day
Which channelopathy causing myotonia/ periodic paralysis has abnormal K in between attacks?
NONE
What are the unusual triggers for HypoK PP?
Exercise and carbohydrate load
T or F: The presence of myotonia, clinically or on EMG ESSENTIALLY EXCLUDES THE DIAGNOSIS OF HYPOKALEMIC PERIODIC PARALYSIS.
T
What are the EMG NCV findings in hyper and hypokalemic periodic paralysis?
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.
How to do provocative testing for hypoK PP?
Load naCl 2g hourly for 7 doses or glucose 50-100g followed by vigorous exercise
For an acute attack, what dose should be given to hypoK PP?
0.25mEg KCl/kg– may be given orally
What is the most common cause secondary kalemic periodic paralyses?
The use of laxatives and excessive use of diuretics
What is also known as the Conn Syndrome?
What two types of attacks does it lead to?
Hypokalemic weakness with primary aldosteronism
Attacks of tetany and hypokalemic weakness
Re: Malignant Hyperthermia
- What gene and protein is involved?
- Conductance of what ion is deranged?
- Myopathology?
- Tx
- What gene and protein is involved? RYR1, Ryanodine recepor
- Conductance of what ion is deranged? Calcium
- Myopathology? Rhabdomyolysis, cores
- Tx: IV dantrolene 1mg per kg; DISCONTINUE the ansethetic
What is the only channelopathy that has an autosomal recessive inheritance pattern?
Generalized myotonia (Becker disease)
What are the most notorious anesthetic compounds to cause malignant hyperthermia?
How does halothane cause this?
Halothane and succinylcholine
halothane releases calcium from the SR and prevents its reaccumulation
What disorders predispose to malignant hyperthermia?
Central core myopathy
King-Denbrorough syndrome: dislocated patellae, ptosis, strabismus, ptosis
Evans myopathy
What is the triad of Anderson syndrome?
KCNJ2 encoding a type of K channel
- Periodic potassium-sensitive weakness
- Ventricular dysrhythmias with long QT
- Dysmorphic features
Why are the muscles in Tarui and Mcardle disease electrically silent even if they are in a state of contraction?
It’s a physiologic contracture– they no longer use energy
What endocrinologic disturbance results in Pseudomyotonia?
Hypothyroidism
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?
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
What syndrome is characterised by continuous muscle activity, muscle stiffness and a sense of weakness? AKA Acquired neuromyotonia
Treatment?
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
What is the pathophysiologic basis of Stiff person syndrome?
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.
What protein is mutated in the Schwartz-Jampel syndrome?
Perlecan
