Hyperkalaemic Periodic paralysis

Neurology

Clinicals - History

Fact Explanation
Weakness Hyperkalemic periodic paralysis is a rare form of autosomal dominant mutation of the gene SCN4A which codes protein Nav1.4. This results in a channelopathy in the of the sodium channels that encourage the uncontrolled influx of sodium ions. The muscle sustains the depolarization for a while and become unable to accept further action potentials which ultimately leads to weakness/ paralysis. The degree of severity varies. Patients usually experience weakness in the proximal parts of the limbs such as hips and shoulder areas. At early stage, however the weakness is limited to the lower limbs. Later on it may spread to the upper limbs and neck. The less common severe forms of disease present with generalized weakness/ complete paralysis. The attack is usually painless and lasts for hours before regress spontaneously in many cases. Weakness
Hyperkalemic periodic paralysis is a rare form of autosomal dominant mutation of the gene SCN4A which codes protein Nav1.4. This results in a channelopathy in the of the sodium channels that encourage the uncontrolled influx of sodium ions. The muscle sustains the depolarization for a while and become unable to accept further action potentials which ultimately leads to weakness/ paralysis. The degree of severity varies. Patients usually experience weakness in the proximal parts of the limbs such as hips and shoulder areas. At early stage, however the weakness is limited to the lower limbs. Later on it may spread to the upper limbs and neck. The less common severe forms of disease present with generalized weakness/ complete paralysis. The attack is usually painless and lasts for hours before regress spontaneously in many cases.
Heaviness of the limbs Heaviness of the affected legs is the initial symptom in many cases. This may be the only complain in the mild form of disease. Patients find themselves unable to move during rest following a strenuous activity. Heaviness of the limbs
Heaviness of the affected legs is the initial symptom in many cases. This may be the only complain in the mild form of disease. Patients find themselves unable to move during rest following a strenuous activity.
Lid lagging Lagging of upper eyelid can be the initial symptom, specially in children. Mothers may complain of upper eye lid being unable to follow the eye movements, specially on downward gaze. Lid lagging
Lagging of upper eyelid can be the initial symptom, specially in children. Mothers may complain of upper eye lid being unable to follow the eye movements, specially on downward gaze.
Difficulty of walking As the hip and knee of lower limbs are more prone to the weakness, patients find difficult to walk during the attack. Difficulty of walking
As the hip and knee of lower limbs are more prone to the weakness, patients find difficult to walk during the attack.
Muscle pain Rarely, some patients may complain of a muscle pain associated with the weakness. This occurs in patients that have residual weakness following many frequent episodes. Muscle pain
Rarely, some patients may complain of a muscle pain associated with the weakness. This occurs in patients that have residual weakness following many frequent episodes.
"pins and needles" feeling This is also a rare complain. Some patients may get sense of paraesthesia in the affected muscles. "pins and needles" feeling
This is also a rare complain. Some patients may get sense of paraesthesia in the affected muscles.
Difficulty in breathing Hyperkalemic periodic paralysis usually does not affect respiratory muscles. So, it is very rare, that a patients comes up with a complain of labored breathing. Difficulty in breathing
Hyperkalemic periodic paralysis usually does not affect respiratory muscles. So, it is very rare, that a patients comes up with a complain of labored breathing.
Chest pain As the sodium ions are accumulated with in the muscle cells during the attack, potassium ions tend to remain extracellularly. Sodium influx facilitates water influx as well, worsening the serum potassium concentration. If this exceed the above limit of normal reference range, it may rarely triggers arrhythmias that can manifest as chest pain. Chest pain
As the sodium ions are accumulated with in the muscle cells during the attack, potassium ions tend to remain extracellularly. Sodium influx facilitates water influx as well, worsening the serum potassium concentration. If this exceed the above limit of normal reference range, it may rarely triggers arrhythmias that can manifest as chest pain.
Triggers Fasting, rigorous exercises, exposure to cold, consuming potassium-rich foods or taking medicines that contain potassium, certain pollutants such as cigarette smoke can induce an paralytic attack. Triggers
Fasting, rigorous exercises, exposure to cold, consuming potassium-rich foods or taking medicines that contain potassium, certain pollutants such as cigarette smoke can induce an paralytic attack.
Past history of similar events Hyperkalaemic 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
Hyperkalaemic 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 Hyperkalaemic periodic paralysis is an autosomal dominantly inherited disease. So, positive family history can be present. Disease is more common among male sex. Patients present in their infancy. The severity and frequency can increase or stabilize until the fourth or fifth decade where attacks may cease, decline or continue on into old age. At risk population
Hyperkalaemic periodic paralysis is an autosomal dominantly inherited disease. So, positive family history can be present. Disease is more common among male sex. Patients present in their infancy. The severity and frequency can increase or stabilize until the fourth or fifth decade where attacks may cease, decline or continue on into old age.
Complications 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
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 sign is very common in the infancy due to the muscle weakness. The lid lag is more pronounced during downward gaze. Lid lag
This sign is very common in the infancy due to the muscle weakness. The lid lag is more pronounced during downward gaze.
Muscle weakness Muscle weakness can be demonstrated specially in the limbs. Hips and shoulders are commonly affected. Patient may be asked to perform several ranges of movements for this purpose. The proximal weakness is far more common than the involvement of the distal parts. Muscle weakness
Muscle weakness can be demonstrated specially in the limbs. Hips and shoulders are commonly affected. Patient may be asked to perform several ranges of movements for this purpose. The proximal weakness is far more common than the involvement of the distal parts.
Hypotonia As the incoming action potentials cannot be effectively converted in to the contractions, normal resting muscle tone cannot be maintained. So the muscles appear to be heavy and less in tonicity. Hypotonia
As the incoming action potentials cannot be effectively converted in to the contractions, normal resting muscle tone cannot be maintained. So the muscles appear to be heavy and less in tonicity.
Pseudo-hypertrophy of muscles During the attacks both sodium and water enter the affected muscles resulting a visible bulking. Pseudo-hypertrophy of muscles
During the attacks both sodium and water enter the affected muscles resulting a visible bulking.
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 As sodium ion and water continuously enter the muscle fibers, potassium retains extracellularly making the serum concentration high. Serum potassium level may increase to as high as to the upper normal limit (5.5 mEq/L) or exceed up to the cardiotoxic level. Conversely, serum sodium level is reduced. Hyperregulation which occurs at the end of the attack may lead to the reversal of the serum potassium values mimicking hypokalaemic episode. Serum potassium level
As sodium ion and water continuously enter the muscle fibers, potassium retains extracellularly making the serum concentration high. Serum potassium level may increase to as high as to the upper normal limit (5.5 mEq/L) or exceed up to the cardiotoxic level. Conversely, serum sodium level is reduced. Hyperregulation which occurs at the end of the attack may lead to the reversal of the serum potassium values mimicking hypokalaemic episode.
Creatine phosphokinase (CPK) level Mildly elevated CPK levels are seen during attacks. It may further rise by the end of the episode. Creatine phosphokinase (CPK) level
Mildly elevated CPK levels are seen during attacks. It may further rise by the end of the episode.
Nerve conduction studies Reduced amplitude of action potential is seen during the attack. Sensory nerve conduction study findings are normal. Nerve conduction studies
Reduced amplitude of action potential is seen during the attack. Sensory nerve conduction study findings are normal.
Electromyography Muscles are electrically silent during the attacks due to the inexcitability of the affected areas. Myotonic discharge are also evident between attacks. Electromyography
Muscles are electrically silent during the attacks due to the inexcitability of the affected areas. Myotonic discharge are also evident between attacks.
Muscle biopsy Smaller, less numerous peripherally placed vacuoles are seen in biopsy samples. Muscle biopsy
Smaller, less numerous peripherally placed vacuoles are seen in biopsy samples.
Genetic studies SCN4A mutation is commonly found in these patients. Genetic studies
SCN4A mutation is commonly found in these patients.
Electrocardiogram Tall T waves can be detected due to the high serum potassium levels. Electrocardiogram
Tall T waves can be detected due to the high serum potassium levels.
Serum thyroxine This is done to differentiate the hyperkalaemic periodic paralysis from thyrotoxic periodic paralysis when the thyroid enzyme levels are abnormally high. Serum thyroxine
This is done to differentiate the hyperkalaemic 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 fasting, sleep deprivation, certain medications, strenuous exercises and stressful situations should be best avoided. Infections should be treated promptly. Though the disease can not be cured fully, patients regain full range of function after few hours. 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 fasting, sleep deprivation, certain medications, strenuous exercises and stressful situations should be best avoided. Infections should be treated promptly. Though the disease can not be cured fully, patients regain full range of function after few hours. 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 Thiazide diuretics and carbonic anhydrase inhibitors can be used as prophylaxis. Thiazide diuretics are the first line as it has low side effect profile. Hydrochlorothiazide (25 to 75 mg/day) Acetazolamide (125 to 1,000 mg/d) and Dichlorphenamide (50 to 150 mg/day) are the standard regimens. Prophylaxis
Thiazide diuretics and carbonic anhydrase inhibitors can be used as prophylaxis. Thiazide diuretics are the first line as it has low side effect profile. Hydrochlorothiazide (25 to 75 mg/day) Acetazolamide (125 to 1,000 mg/d) and Dichlorphenamide (50 to 150 mg/day) are the standard regimens.
Dietary modifications Glucose-containing food such as candy or carbohydrate diet is helpful in prevention and in reducing the severity of the disease episode. Consuming less fruits and other low potassium containing food may improve the weakness. Dietary modifications
Glucose-containing food such as candy or carbohydrate diet is helpful in prevention and in reducing the severity of the disease episode. Consuming less fruits and other low potassium containing food may improve the weakness.

Management - Specific

Fact Explanation
High-carbohydrate foods As most of the episodes are mild in severity, most of them resolve spontaneously or respond well to a high carbohydrate diet. High-carbohydrate foods
As most of the episodes are mild in severity, most of them resolve spontaneously or respond well to a high carbohydrate diet.
Intravenous glucose Influx of potassium facilitated by IV glucose and insulin helps to reduce the weakness without a loss of total body potassium. Intravenous glucose
Influx of potassium facilitated by IV glucose and insulin helps to reduce the weakness without a loss of total body potassium.
Calcium gluconate Intravenous calcium decreases activity of sodium channels. It may stop sudden attacks. It is also effective in prevention of arrythmias that may occur in higher serum potassium levels. Calcium gluconate
Intravenous calcium decreases activity of sodium channels. It may stop sudden attacks. It is also effective in prevention of arrythmias that may occur in higher serum potassium levels.
Emergency management of hyperkalaemia This has several components. The patients should be assessed with ECG monitoring. IV assess should be instituted. 10ml of 10% IV calcium gluconate is given over 5 minutes. The effect is temporary. The dose can be repeated after 15 minutes. This act protect the myocardium from damage. Insulin 10 units should be given with 50% of IV glucose over 10-15 minutes. This is followed by regular monitoring of blood glucose and plasma potassium. In the presence of acidosis, it must be corrected with sodium bicarbonate. Later, body potassium should be depleted by oral/ rectal administration of polystyrene sulphonate resins. Haemodialysis or peritoneal dialysis has to be considered it the above fails. Emergency management of hyperkalaemia
This has several components. The patients should be assessed with ECG monitoring. IV assess should be instituted. 10ml of 10% IV calcium gluconate is given over 5 minutes. The effect is temporary. The dose can be repeated after 15 minutes. This act protect the myocardium from damage. Insulin 10 units should be given with 50% of IV glucose over 10-15 minutes. This is followed by regular monitoring of blood glucose and plasma potassium. In the presence of acidosis, it must be corrected with sodium bicarbonate. Later, body potassium should be depleted by oral/ rectal administration of polystyrene sulphonate resins. Haemodialysis or peritoneal dialysis has to be considered it the above fails.

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