Hypokalaemic periodic paralysis

Neurology

Clinicals - History

Fact Explanation
Weakness Hypokalemic periodic paralysis is the commonest cause of periodic paralysis, which is caused as a result of a channelopathy. Periodic paralysis is classified as hypokalemic when it occurs in association with low serum potassium levels. The disease has 2 varieties. Type 1, which is the commonest, is caused by the calcium channel mutation. This occurs early in the life. Type 2 variant is caused by a rare mutation of Potassium channels which occur in late life. Defect in a voltage-gated calcium channel is the commonest cause. As a result, the depolarization of the muscle is failed. This inexcitability of the muscle membrane ultimately leads to the flaccidity of certain muscles. The severity ranges from mild to severe. The distribution of the affected muscles are limited. It involves only a group of muscles unilaterally or partially. The commonest sites are legs. The less common severe forms of disease present with generalized weakness/ complete paralysis. They are acute or insidious in onset. The weakness is usually bilateral, and may spread to the proximal parts of the upper limbs, trunk and neck later. Patients waking up with the weakness in the morning is very common. An attack usually last for several hours and resolves spontaneously. There is no associated pain. Other possible but rare outcomes are complete, paralysis and very rarely, death. Weakness
Hypokalemic periodic paralysis is the commonest cause of periodic paralysis, which is caused as a result of a channelopathy. Periodic paralysis is classified as hypokalemic when it occurs in association with low serum potassium levels. The disease has 2 varieties. Type 1, which is the commonest, is caused by the calcium channel mutation. This occurs early in the life. Type 2 variant is caused by a rare mutation of Potassium channels which occur in late life. Defect in a voltage-gated calcium channel is the commonest cause. As a result, the depolarization of the muscle is failed. This inexcitability of the muscle membrane ultimately leads to the flaccidity of certain muscles. The severity ranges from mild to severe. The distribution of the affected muscles are limited. It involves only a group of muscles unilaterally or partially. The commonest sites are legs. The less common severe forms of disease present with generalized weakness/ complete paralysis. They are acute or insidious in onset. The weakness is usually bilateral, and may spread to the proximal parts of the upper limbs, trunk and neck later. Patients waking up with the weakness in the morning is very common. An attack usually last for several hours and resolves spontaneously. There is no associated pain. Other possible but rare outcomes are complete, paralysis and very rarely, death.
Heaviness of the limbs Flaccid limbs are often heavy. Patients may complain of an unusual heaviness of the lower limbs and this may be the sole complains in the mild disease. Heaviness of the limbs
Flaccid limbs are often heavy. Patients may complain of an unusual heaviness of the lower limbs and this may be the sole complains in the mild disease.
Difficulty on walking Patients initially present with difficulty in extending/flexing the proximal parts of the lower limbs such as hips and knees and the weakness of the thigh or calves. Thus the initial paralysis usually affects the lower limbs making the walking difficult during the attack. Difficulty on walking
Patients initially present with difficulty in extending/flexing the proximal parts of the lower limbs such as hips and knees and the weakness of the thigh or calves. Thus the initial paralysis usually affects the lower limbs making the walking difficult during the attack.
Reduced urine output Accumulation of the water in the muscle cells results in the reduction of the urinary output during the attacks. Reduced urine output
Accumulation of the water in the muscle cells results in the reduction of the urinary output during the attacks.
Difficulty in breathing Difficulty breathing, speaking, or swallowing during attacks are rare presentation and are secondary to the bulbar muscle involvement. Difficulty in breathing
Difficulty breathing, speaking, or swallowing during attacks are rare presentation and are secondary to the bulbar muscle involvement.
Chest pain This is due to arrythmias owing to the hyperkalaemia. It is an infrequent presentation as that much of decline of serum potassium level does not occur. Chest pain
This is due to arrythmias owing to the hyperkalaemia. It is an infrequent presentation as that much of decline of serum potassium level does not occur.
Triggers Attacks/ episodes are characteristically provoked during/ minutes to hours after a stressful event, high carbohydrate meals, infection, menstruation, sleep deprivation and certain drugs such as beta-agonists, insulin and corticosteroids. Triggers
Attacks/ episodes are characteristically provoked during/ minutes to hours after a stressful event, high carbohydrate meals, infection, menstruation, sleep deprivation and certain drugs such as beta-agonists, insulin and corticosteroids.
Past history of similar events Hypokalaemic periodic paralysis is a recurring disease. patients often have past events with similar characteristics. Patients are usually normal and asymptomatic in between these episodes. Rarely after sometimes, there may be a residual mild weakness following an acute attack. Past history of similar events
Hypokalaemic periodic paralysis is a recurring disease. patients often have past events with similar characteristics. Patients are usually normal and asymptomatic in between these episodes. Rarely after sometimes, there may be a residual mild weakness following an acute attack.
At risk population Age of onset is variable. It could be either during the childhood or in the third decade of life. Acquired cases of Hypokalaemic periodic paralysis accounts for one third of cases. Hyperthyroidism is the commonest secondary/ acquired cause of Hypokalaemic periodic paralysis. Patients may give details of a disease history or follow up regarding thyroid disorder. Most of the cases are hereditary usually with an autosomal dominant inheritance pattern. Therefore, patients with a family history are also predisposed. The disorder is three to four times more commonly clinically shown in men. At risk population
Age of onset is variable. It could be either during the childhood or in the third decade of life. Acquired cases of Hypokalaemic periodic paralysis accounts for one third of cases. Hyperthyroidism is the commonest secondary/ acquired cause of Hypokalaemic periodic paralysis. Patients may give details of a disease history or follow up regarding thyroid disorder. Most of the cases are hereditary usually with an autosomal dominant inheritance pattern. Therefore, patients with a family history are also predisposed. The disorder is three to four times more commonly clinically shown in men.
Complications Eye myotonia is a common complication in which the patient is unable to open his/ her eyes for a short period of time. Cardiac arrythmias/ irregular heart beats, difficulty in breathing, speaking, or swallowing and residual muscle weakness that worsens over time are the complications of the disease. Kidney stones can occur as a side effect of acetazolamide, that is used in the treatment. Complications
Eye myotonia is a common complication in which the patient is unable to open his/ her eyes for a short period of time. Cardiac arrythmias/ irregular heart beats, difficulty in breathing, speaking, or swallowing and residual muscle weakness that worsens over time are the complications of the disease. Kidney stones can occur as a side effect of acetazolamide, that is used in the treatment.

Clinicals - Examination

Fact Explanation
Lid lag This is due to extensive disease that is complicated with eye myotonia. Patients may show a difficulty in opening or closing the eye. Sometimes this may be the only clinical signs in hyperkalemic periodic paralysis. Lid lag
This is due to extensive disease that is complicated with eye myotonia. Patients may show a difficulty in opening or closing the eye. Sometimes this may be the only clinical signs in hyperkalemic periodic paralysis.
muscle atrophy Progressive muscle atrophy has been described in some patients with hyperkalemic periodic paralysis. Proxiamal muscles of the lower limbs are commonly wasted. This is specially marked when hyperkalemic periodic paralysis is associated with motor neuron degeneration. This is in contrary with the hyperkalaemic paralysis where the affected muscles are tend to be hypertrophied. muscle atrophy
Progressive muscle atrophy has been described in some patients with hyperkalemic periodic paralysis. Proxiamal muscles of the lower limbs are commonly wasted. This is specially marked when hyperkalemic periodic paralysis is associated with motor neuron degeneration. This is in contrary with the hyperkalaemic paralysis where the affected muscles are tend to be hypertrophied.
Muscle fasciculation Muscle fasciculation is a rare finding in the hypokalaemic periodic paralysis. Small, local, involuntary muscle contraction and relaxation which may be visible under the skin can be demonstrated in the affected areas such as in calves, and thighs. Muscle fasciculation
Muscle fasciculation is a rare finding in the hypokalaemic periodic paralysis. Small, local, involuntary muscle contraction and relaxation which may be visible under the skin can be demonstrated in the affected areas such as in calves, and thighs.
Muscle weakness Patient usually present with heaviness, weakness of a group of muscles localized to proximal lower limbs around the hips and knees. In more generalized severe form, a generalized weakness can be demonstrated involving the upper, lower limbs, and trunk. The proximal weakness is far more common than the involvement of the distal parts. Muscle weakness
Patient usually present with heaviness, weakness of a group of muscles localized to proximal lower limbs around the hips and knees. In more generalized severe form, a generalized weakness can be demonstrated involving the upper, lower limbs, and trunk. The proximal weakness is far more common than the involvement of the distal parts.
Hypotonia The causative calcium channel defect results in the inexcitability of the muscle membrane. This result in the failed depolarization and flaccidity. This is commonly manifest in the proximal parts of the lower limb during the initially and more generalized in severe cases. The limbs are unusually heavy and flabby. Hypotonia
The causative calcium channel defect results in the inexcitability of the muscle membrane. This result in the failed depolarization and flaccidity. This is commonly manifest in the proximal parts of the lower limb during the initially and more generalized in severe cases. The limbs are unusually heavy and flabby.
Dyspnea This is very rare and is due to the bulbar muscle involvement in severe cases. Dyspnea
This is very rare and is due to the bulbar muscle involvement in severe cases.
Absent stretch reflexes Stretch reflexes such as knee reflex is diminished due to the failed transmission of the action potential in to the muscle contraction. Absent stretch reflexes
Stretch reflexes such as knee reflex is diminished due to the failed transmission of the action potential in to the muscle contraction.
Important negative findings The sensation of any sort is not affected in the periodical paralysis. Important negative findings
The sensation of any sort is not affected in the periodical paralysis.

Investigations - Diagnosis

Fact Explanation
Serum potassium level Serum potassium level is normal during the attack. The muscle weakness along with this result usually confirm the diagnosis. The serum potassium level does not necessarily below normal in many cases. They are usually borderline. Serum potassium should be meticulously measured during the hospital stay to prevent serious declines that can result in rare, but fatal complications such as arrythmias. Serum potassium level
Serum potassium level is normal during the attack. The muscle weakness along with this result usually confirm the diagnosis. The serum potassium level does not necessarily below normal in many cases. They are usually borderline. Serum potassium should be meticulously measured during the hospital stay to prevent serious declines that can result in rare, but fatal complications such as arrythmias.
Creatine phosphokinase (CPK) level CPK level rises during attacks. The ratio between serum potassium to creatinine distinguished primary hypokalemic paralysis from secondary cases. Values of more than 3.0 mmol/mmol indicated secondary hypokalemic periodic paralysis. Creatine phosphokinase (CPK) level
CPK level rises during attacks. The ratio between serum potassium to creatinine distinguished primary hypokalemic paralysis from secondary cases. Values of more than 3.0 mmol/mmol indicated secondary hypokalemic periodic paralysis.
Nerve conduction studies Reduced amplitude of action potential can be observed during the attacks. Sensory nerve conduction study findings are normal. Nerve conduction studies
Reduced amplitude of action potential can be observed during the attacks. Sensory nerve conduction study findings are normal.
Electromyography Muscles are electrically silent during the attacks due to the inexcitability of the affected areas. Electromyography
Muscles are electrically silent during the attacks due to the inexcitability of the affected areas.
Muscle biopsy Results are abnormal, more typically in patients with hypokalemic type paralysis. Single or multiple centrally placed vacuoles are the commonest finding. Tubular aggregates may be seen in some patients. Muscle biopsy
Results are abnormal, more typically in patients with hypokalemic type paralysis. Single or multiple centrally placed vacuoles are the commonest finding. Tubular aggregates may be seen in some patients.
Genetic studies Mutations like CALCL1A3 and SCN4A are commonly found in these patients. Genetic studies
Mutations like CALCL1A3 and SCN4A are commonly found in these patients.
Oral glucose loading test Oral glucose loading test is a provocative test that is rarely used in the diagnosis. Glucose loading is a triggering factor for appearance of the symptoms. In this test, oral glucose is given in a dosage of 1.5g/kg.
Physical examination to assess the muscle strength and serum electrolytes are performed half an hourly. If a weakness is detected within 2-3 hours, it is diagnostic. Intravenous glucose challenge and Intra-arterial epinephrine test are additional provocative investigations that are rarely used nowadays.
Oral glucose loading test
Oral glucose loading test is a provocative test that is rarely used in the diagnosis. Glucose loading is a triggering factor for appearance of the symptoms. In this test, oral glucose is given in a dosage of 1.5g/kg.
Physical examination to assess the muscle strength and serum electrolytes are performed half an hourly. If a weakness is detected within 2-3 hours, it is diagnostic. Intravenous glucose challenge and Intra-arterial epinephrine test are additional provocative investigations that are rarely used nowadays.
Electrocardiogram Bradycardia, flat T waves, U waves and ST-segment depressions can be detected due to the low serum potassium levels. Electrocardiogram
Bradycardia, flat T waves, U waves and ST-segment depressions can be detected due to the low serum potassium levels.
Serum thyroxine This is done to differentiate the hypokalaemic periodic paralysis from thyrotoxic periodic paralysis when the thyroid enzyme levels are abnormally high. Serum thyroxine
This is done to differentiate the hypokalaemic periodic paralysis from thyrotoxic periodic paralysis when the thyroid enzyme levels are abnormally high.

Management - Supportive

Fact Explanation
Patient/ parent education parents/ patients should be educated regarding the disease and its good prognosis. Triggering factors such as heavy carbohydrate diets, sleep deprivation, certain medications and stressful situations should be best avoided. Infections should be treated promptly. Still, hypokalemic periodic paralysis cannot be cured as it can be inherited. However, patients regain full range of function after sometime. Genetic counseling may be advised for couples at risk of the disorder. As the patient encounters some degree of initial weakness/ heaviness of the legs, doing mild exercises is thought to prevent a full-blown attack. Patient/ parent education
parents/ patients should be educated regarding the disease and its good prognosis. Triggering factors such as heavy carbohydrate diets, sleep deprivation, certain medications and stressful situations should be best avoided. Infections should be treated promptly. Still, hypokalemic periodic paralysis cannot be cured as it can be inherited. However, patients regain full range of function after sometime. Genetic counseling may be advised for couples at risk of the disorder. As the patient encounters some degree of initial weakness/ heaviness of the legs, doing mild exercises is thought to prevent a full-blown attack.
Prophylaxis Acetazolamide, a carbonic anhydrase inhibitor, is the preferred drug that is used as a prophylaxis in prevention of an attack. Acetazolamide produced a mild metabolic acidosis but did not have a demonstrable effect on total body sodium, total body potassium, or thyroid function. Still, it is considered as the most effective drug in prevention. Acetazolamide at a dose of 125-1500 mg/d in divided doses is administered as prophylaxis. Spironolactone is an alternative/ second line option. Prophylaxis
Acetazolamide, a carbonic anhydrase inhibitor, is the preferred drug that is used as a prophylaxis in prevention of an attack. Acetazolamide produced a mild metabolic acidosis but did not have a demonstrable effect on total body sodium, total body potassium, or thyroid function. Still, it is considered as the most effective drug in prevention. Acetazolamide at a dose of 125-1500 mg/d in divided doses is administered as prophylaxis. Spironolactone is an alternative/ second line option.
Dietary interventions Low-carbohydrate and low-sodium diet has been proven to reduce the frequency of episodes. Daily oral potassium supplementation are recommended in some patients though the effectiveness is not definite. Dietary interventions
Low-carbohydrate and low-sodium diet has been proven to reduce the frequency of episodes. Daily oral potassium supplementation are recommended in some patients though the effectiveness is not definite.

Management - Specific

Fact Explanation
Oral potassium supplementation Potassium should be given during an acute attack. This may not prevent or suppress further attacks, but may prevent serious complications such as arrythmias. Oral potassium chloride supplementation is preferred over intravenous access in many cases. The initial dose is 60 mEq which increases the serum potassium concentration by 1.0-1.5 mEq/L. According to the response, dose can be raised up to maximum of 200 mEq per day. But close monitoring of serum electrolyte levels is essential. Oral potassium supplementation
Potassium should be given during an acute attack. This may not prevent or suppress further attacks, but may prevent serious complications such as arrythmias. Oral potassium chloride supplementation is preferred over intravenous access in many cases. The initial dose is 60 mEq which increases the serum potassium concentration by 1.0-1.5 mEq/L. According to the response, dose can be raised up to maximum of 200 mEq per day. But close monitoring of serum electrolyte levels is essential.
Intravenous potassium supplementation Intravenous potassium chloride is reserved for refractory cases and severe episodes that are comlicated by arrythmias and respiratory compromization. IV potassium chloride 0.05-0.1 mEq/kg body weight is the recommended dosage. 5% mannitol is used as solvent instead of normal saline or dextrose as both sodium and dextrose have a potential to worsen the attack. It is mandatory to titrate and monitor the treatment with continuous ECG monitoring and frequent serum potassium measurements. Intravenous potassium supplementation
Intravenous potassium chloride is reserved for refractory cases and severe episodes that are comlicated by arrythmias and respiratory compromization. IV potassium chloride 0.05-0.1 mEq/kg body weight is the recommended dosage. 5% mannitol is used as solvent instead of normal saline or dextrose as both sodium and dextrose have a potential to worsen the attack. It is mandatory to titrate and monitor the treatment with continuous ECG monitoring and frequent serum potassium measurements.

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