Periodic paralysis

Question 1

What is familial periodic paralysis?

Answer 1

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

Question 2

What is the inheritance pattern of familial periodic paralysis?

Answer 2

autosomal dominant

Question 3

What type of paralysis is seen with familial periodic paralysis?

Answer 3

Episodes of flaccid paralysis

Question 4

What are 3 clinical features typically seen in all types of familial periodic paralysis?

Answer 4

1. Episodes of flaccid paralysis
2. Loss of deep tendon reflexes
3. Failure of muscle to respond to electrical stimulation

Question 5

What are the 4 forms of familial periodic paralysis?

Answer 5

1. Hypokalaemic
2. Hyperkalaemic
3. Thyrotoxic
4. Andersen-Tawil syndrome

Question 6

How is a diagnosis of familial periodic paralysis made?

Answer 6

indicated by history, confirmed by provoking an episode e.g. giving dextrose and insulin to cause hypokalaemia or potassium chloride to cause hyperkalaemia

Question 7

What differentiates the pathophysiology of each form of familial periodic paralysis?

Answer 7

each form involves a different gene and electrolyte channel

Question 8

What is the pathophysiology of the hypokalaemic form of familial periodic paralysis? 2 types

Answer 8

1. 70% of affected people have mutation in alpha-subunit of the voltage-sensitive muscle calcium channel gene on chromosome 1q (HypoPP type I)
2. in some families, the mutation is the alpha-subunit of the sodium channel gene on chromosome 7 (HypoPP type II)

Question 9

What is the most common form of familial periodic paralysis?

Answer 9

Hypokalaemic form (although still rare - prevalence 1/ 100 000)

Question 10

What is the pathophysiology of the hyperkalaemic form of familial periodic paralysis?

Answer 10

mutations in the gene that encodes the alpha-subunit of the skeletal muscle sodium channel (SCN4A)

Question 11

What is the pathophysiology of the thyrotoxic form of familail periodic paralysis?

Answer 11

mutations and affected electrolyte channels are unknown but this form usually involves hypokalaemia and is associated with symptoms of thyrotoxicosis

Question 12

In which patient group is the incidence of the thyrotoxic form of FPP most common?

Answer 12

Asian men

Question 13

What is the pathophysiology of Andersen-Tawil syndrome?

Answer 13

due to an autosomal dominant defect of the inward-rectifying potassium chanel; patients can have a high, low or normal serum potassium level

Question 14

At what age do episodes of hypokalaemic periodic paralysis typically begin?

Answer 14

usually before age 16

Question 15

How does hypokalaemic periodic paralysis often present?

Answer 15

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

Question 16

What are 6 things which can precipitate hypokalaemic periodic paralysis episodes?

Answer 16

1. Vigorous exercise on preceding day
2. Carbohydrate-rich meals
3. Emotional stress
4. Physical stress
5. Alcohol ingestion
6. Cold exposure

Question 17

What are 3 groups of muscles which are spared in hypokalaemic periodic paralysis?

Answer 17

1. Ocular
2. Bulbar
3. Respiratory muscles

Question 18

Is consciousness altered in hypokalaemic periodic paralysis?

Answer 18

no

Question 19

What are the findings on blood and urine tests in hypokalaemic periodic paralysis?

Answer 19

serum and urine potassium are decreased

Question 20

How long may weakness last in hypokalaemic periodic paralysis?

Answer 20

up to 24 h

Question 21

How does the presentation of hyperkalaemic periodic paralysis compare with hypokalaemic PP?

Answer 21

episodes often begin at an earlier age and usually are shorter, more frequent, and less severe

Question 22

What are 3 things that precipitate episodes of hyperkalaemic periodic paralysis?

Answer 22

1. Rest after exercise
2. Exercise after meals
3. Fasting

Question 23

What feature, alongside paralysis, is a common feature of hyperkalaemic periodic paralysis and how may this present?

Answer 23

myotonia - delayed relaxation after muscle contraction

eyelid myotonia may be the only symptom

Question 24

How long do episodes of thyrotoxic periodic paralysis last?

Answer 24

episodes last hours to days

Question 25

What are 3 things that can precipitate thyrotoxic periodic paralysis?

Answer 25

1. Exercise 2. Stress 3. Carbohydrate load

Question 26

What are 8 features that may be present with thyrotoxic periodic paralysis?

Answer 26

Symptoms of thyrotoxicosis: 1. Anxiety 2. Emotional lability 3. Weakness 4. Tremor 5. Palpitations 6. Heat intolerance 7. Increased perspiration 8. Weight loss

Question 27

Within what time in relation to each other may symptoms of thyrotoxicosis and periodic paralysis occur in thyrotoxic periodic paralysis?

Answer 27

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

Question 28

At what age do episodes of Andersen-Tawil syndrome usually begin?

Answer 28

before age 20

Question 29

What is the clinical triad present in Andersen-Tawil syndrome?

Answer 29

1. Periodic paralysis 2. Prolonged QT interval and ventricular arrhythmias 3. Dysmorphic physical features all or some may be present

Question 30

What are 9 of the dysmorphic physical features which may be present in Andersen-Tawil syndrome?

Answer 30

1. Short stature 2. High-arched palate 3. Low-set ears 4. Broad nose 5. Micrognathia 6. Hypertelorism (increased distance between eyes) 7. Clinodactyly of fingers 8. Short index fingers 9. Syndactyly of toes

Question 31

What precipitates episode of paralysis in Andersen-Tawil syndrome?

Answer 31

rest after exercise

Question 32

How long do episodes of periodic paralysis last in Andersen-Tawil syndrome and how frequently may these occur?

Answer 32

may last for days, occur monthly

Question 33

What are the 3 key things which a diagnosis of periodic paralysis is based upon?

Answer 33

1. Clinical evaluation 2. Serum potassium level during symptoms 3. Sometimes provocative testing

Question 34

What is the best diagnostic indicator of periodic paralysis?

Answer 34

history of typical episodes

Question 35

When might serum potassium be abnormal in periodic paralysis?

Answer 35

if measured during an episode

Question 36

How can episodes of hypokalaemic periodic paralysis be triggered?

Answer 36

by giving dextrose and insulin

Question 37

How can episodes of hyperkalaemic periodic paralysis be triggered to help diagnosis?

Answer 37

giving potassium chloride

Question 38

Who are the only people who should attempt provocative testing in periodic paralysis and why?

Answer 38

only experienced physicians - respiratory paralysis or cardiac conduction abnormalities may occur

Question 39

What can be used to aid the diagnosis of the hyperkalaemic form of periodic paralysis?

Answer 39

clinical findings and/or identification of a heterozygous pathogenic variant in the alpha-subunit of the skeletal muscle sodium channel

Question 40

What is the acute management of hypokalaemic periodic paralysis?

Answer 40

**potassium chloride 2 to 10 g in an unsweetened oral solutio**n or giving **potassium chloride IV**

Question 41

What 5 aspects of prevention of hypokalaemic periodic paralysis episodes?

Answer 41

1. Low-carbohydrate diet 2. Low-sodium diet 3. Avoiding strenuous activity 4. Avoiding alcohol after periods of rest 5. Acetazolamide 250mg PO twice a day

Question 42

What are 2 aspects of the management mild paralysis caused by hyerpkalaemic periodic paralysis?

Answer 42

light exercise and 2g/kg oral carbohyrate load

Question 43

What are 3 drugs which may be required to treat established episodes of hyperkalaemic periodic paralysis?

Answer 43

1. Thiazides 2. Acetazolamide 3. Inhaled beta-agonists (e.g. salbutamol)

Question 44

What are 2 drugs that can be used to treat **severe** episodes of hyperkalaemic periodic paralysis?

Answer 44

1. Calcium gluconate 2. Insulin and dextrose IV

Question 45

What are 4 forms of preventions of hyperkalaemic periodic paralysis episodes?

Answer 45

1. Regularly ingesting carbohydrate-rich, low-potassium meals 2. Avoiding fasting 3. Avoiding strenuous activity after meals 4. Avoiding cold exposure

Question 46

What is the management of acute episodes of thyrotoxic periodic paralysis?

Answer 46

give **potassium** **chloride**, and serum potassium levels closely monitored

Question 47

What are 2 ways to prevent episodes of thyrotoxic periodic paralysis?

Answer 47

1. Maintaining a euthyroid state **and** 2. Giving beta blockers e.g. propranolol

Question 48

What are 2 ways to prevent episodes of paralysis due to Andersen-Tawil syndrome?

Answer 48

1. Tightly controlled levels of exercise of activity 2. Carbonic anhydrase inhibitor e.g. acetazolamide

Question 49

What is the major complication of Andersen-Tawil syndrome?

Answer 49

sudden death resulting from cardiac arrhythmias

Question 50

What intervention may be required in Andersen-Tawil syndrome due to the risk of sudden death from cardiac arrhythmias?

Answer 50

cardiac **pacemaker** or **implantable** **cardioverter-defibrillator** may be required to control cardiac smypomts