Periodic paralysis Flashcards
What is familial periodic paralysis?
rare inherited condition with considerable variation in penetrance characterised by episodes of flaccid paralysis with loss of deep tendon reflexes and failure of muscle to respond to electrical stimulation
What is the inheritance pattern of familial periodic paralysis?
autosomal dominant
What type of paralysis is seen with familial periodic paralysis?
Episodes of flaccid paralysis
What are 3 clinical features typically seen in all types of familial periodic paralysis?
- Episodes of flaccid paralysis
- Loss of deep tendon reflexes
- Failure of muscle to respond to electrical stimulation
What are the 4 forms of familial periodic paralysis?
- Hypokalaemic
- Hyperkalaemic
- Thyrotoxic
- Andersen-Tawil syndrome
How is a diagnosis of familial periodic paralysis made?
indicated by history, confirmed by provoking an episode e.g. giving dextrose and insulin to cause hypokalaemia or potassium chloride to cause hyperkalaemia
What differentiates the pathophysiology of each form of familial periodic paralysis?
each form involves a different gene and electrolyte channel
What is the pathophysiology of the hypokalaemic form of familial periodic paralysis? 2 types
- 70% of affected people have mutation in alpha-subunit of the voltage-sensitive muscle calcium channel gene on chromosome 1q (HypoPP type I)
- in some families, the mutation is the alpha-subunit of the sodium channel gene on chromosome 7 (HypoPP type II)
What is the most common form of familial periodic paralysis?
Hypokalaemic form (although still rare - prevalence 1/ 100 000)
What is the pathophysiology of the hyperkalaemic form of familial periodic paralysis?
mutations in the gene that encodes the alpha-subunit of the skeletal muscle sodium channel (SCN4A)
What is the pathophysiology of the thyrotoxic form of familail periodic paralysis?
mutations and affected electrolyte channels are unknown but this form usually involves hypokalaemia and is associated with symptoms of thyrotoxicosis
In which patient group is the incidence of the thyrotoxic form of FPP most common?
Asian men
What is the pathophysiology of Andersen-Tawil syndrome?
due to an autosomal dominant defect of the inward-rectifying potassium chanel; patients can have a high, low or normal serum potassium level
At what age do episodes of hypokalaemic periodic paralysis typically begin?
usually before age 16
How does hypokalaemic periodic paralysis often present?
the day after vigorous exercise, patient often awakens with weakness, which may be mild and limited to certain muscle groups or may affect all 4 limbs
What are 6 things which can precipitate hypokalaemic periodic paralysis episodes?
- Vigorous exercise on preceding day
- Carbohydrate-rich meals
- Emotional stress
- Physical stress
- Alcohol ingestion
- Cold exposure
What are 3 groups of muscles which are spared in hypokalaemic periodic paralysis?
- Ocular
- Bulbar
- Respiratory muscles
Is consciousness altered in hypokalaemic periodic paralysis?
no
What are the findings on blood and urine tests in hypokalaemic periodic paralysis?
serum and urine potassium are decreased
How long may weakness last in hypokalaemic periodic paralysis?
up to 24 h
How does the presentation of hyperkalaemic periodic paralysis compare with hypokalaemic PP?
episodes often begin at an earlier age and usually are shorter, more frequent, and less severe
What are 3 things that precipitate episodes of hyperkalaemic periodic paralysis?
- Rest after exercise
- Exercise after meals
- Fasting
What feature, alongside paralysis, is a common feature of hyperkalaemic periodic paralysis and how may this present?
myotonia - delayed relaxation after muscle contraction
eyelid myotonia may be the only symptom
How long do episodes of thyrotoxic periodic paralysis last?
episodes last hours to days
What are 3 things that can precipitate thyrotoxic periodic paralysis?
- Exercise
- Stress
- Carbohydrate load
What are 8 features that may be present with thyrotoxic periodic paralysis?
Symptoms of thyrotoxicosis:
- Anxiety
- Emotional lability
- Weakness
- Tremor
- Palpitations
- Heat intolerance
- Increased perspiration
- Weight loss
Within what time in relation to each other may symptoms of thyrotoxicosis and periodic paralysis occur in thyrotoxic periodic paralysis?
clinical features of hyperthyroidism often precede onset of periodic paralysis by months or years; however, features have been noted to occur at same time as periodic paralysis or after development of it
At what age do episodes of Andersen-Tawil syndrome usually begin?
before age 20
What is the clinical triad present in Andersen-Tawil syndrome?
- Periodic paralysis
- Prolonged QT interval and ventricular arrhythmias
- Dysmorphic physical features
all or some may be present
What are 9 of the dysmorphic physical features which may be present in Andersen-Tawil syndrome?
- Short stature
- High-arched palate
- Low-set ears
- Broad nose
- Micrognathia
- Hypertelorism (increased distance between eyes)
- Clinodactyly of fingers
- Short index fingers
- Syndactyly of toes
What precipitates episode of paralysis in Andersen-Tawil syndrome?
rest after exercise
How long do episodes of periodic paralysis last in Andersen-Tawil syndrome and how frequently may these occur?
may last for days, occur monthly
What are the 3 key things which a diagnosis of periodic paralysis is based upon?
- Clinical evaluation
- Serum potassium level during symptoms
- Sometimes provocative testing
What is the best diagnostic indicator of periodic paralysis?
history of typical episodes
When might serum potassium be abnormal in periodic paralysis?
if measured during an episode
How can episodes of hypokalaemic periodic paralysis be triggered?
by giving dextrose and insulin
How can episodes of hyperkalaemic periodic paralysis be triggered to help diagnosis?
giving potassium chloride
Who are the only people who should attempt provocative testing in periodic paralysis and why?
only experienced physicians - respiratory paralysis or cardiac conduction abnormalities may occur
What can be used to aid the diagnosis of the hyperkalaemic form of periodic paralysis?
clinical findings and/or identification of a heterozygous pathogenic variant in the alpha-subunit of the skeletal muscle sodium channel
What is the acute management of hypokalaemic periodic paralysis?
potassium chloride 2 to 10 g in an unsweetened oral solution or giving potassium chloride IV
What 5 aspects of prevention of hypokalaemic periodic paralysis episodes?
- Low-carbohydrate diet
- Low-sodium diet
- Avoiding strenuous activity
- Avoiding alcohol after periods of rest
- Acetazolamide 250mg PO twice a day
What are 2 aspects of the management mild paralysis caused by hyerpkalaemic periodic paralysis?
light exercise and 2g/kg oral carbohyrate load
What are 3 drugs which may be required to treat established episodes of hyperkalaemic periodic paralysis?
- Thiazides
- Acetazolamide
- Inhaled beta-agonists (e.g. salbutamol)
What are 2 drugs that can be used to treat severe episodes of hyperkalaemic periodic paralysis?
- Calcium gluconate
- Insulin and dextrose IV
What are 4 forms of preventions of hyperkalaemic periodic paralysis episodes?
- Regularly ingesting carbohydrate-rich, low-potassium meals
- Avoiding fasting
- Avoiding strenuous activity after meals
- Avoiding cold exposure
What is the management of acute episodes of thyrotoxic periodic paralysis?
give potassium chloride, and serum potassium levels closely monitored
What are 2 ways to prevent episodes of thyrotoxic periodic paralysis?
- Maintaining a euthyroid state and
- Giving beta blockers e.g. propranolol
What are 2 ways to prevent episodes of paralysis due to Andersen-Tawil syndrome?
- Tightly controlled levels of exercise of activity
- Carbonic anhydrase inhibitor e.g. acetazolamide
What is the major complication of Andersen-Tawil syndrome?
sudden death resulting from cardiac arrhythmias
What intervention may be required in Andersen-Tawil syndrome due to the risk of sudden death from cardiac arrhythmias?
cardiac pacemaker or implantable cardioverter-defibrillator may be required to control cardiac smypomts
