Normokalaemic periodic paralysis - Clinicals, Diagnosis, and Management

Neurology

Clinicals - History

Fact Explanation
Weakness Normokalaemic periodic paralysis (NormoKPP) is thought to be a variant of hyperkalaemic periodic paralysis (HyperKPP) though at time, it is treated as a separate disease entity. NormKPP is an autosomal dominant mutation of the gene SCN4A that codes for the protein Nav1.4 which is an important part of the sodium channel. This channelopathy results in uncontrolled influx of the sodium ions in to the muscle during excitation. As sodium ions enter, muscle sustains the depolarization for a while and become unable to accept further action potentials which ultimately leads to weakness/ paralysis. Over influx of sodium ions is not well opposed by the efflux of potassium ions in some patients as does in most of the cases of HyperKPP. This causes normal serum potassium levels during the attack. Episodic/ periodic paralysis along with normokalaemia make a distinct form of periodic paralysis called NormoKPP.
The clinical presentation of the disease is more or less similar to HyperKPP. Initially, patients complain of a heaviness in the affected limbs. This is followed by a paralysis.Weakness is mild to severe and the proximal muscle groups of the upper limbs and lower limbs are frequently affected. The neck area may be affected as well. Rarely, patients may present with generalized muscle weakness. A typical mild episode is painless and usually lasts for few hours before patient recovers spontaneously. The severe attacks began in the
morning and lasted from 2 hours to 7 days.
Weakness
Normokalaemic periodic paralysis (NormoKPP) is thought to be a variant of hyperkalaemic periodic paralysis (HyperKPP) though at time, it is treated as a separate disease entity. NormKPP is an autosomal dominant mutation of the gene SCN4A that codes for the protein Nav1.4 which is an important part of the sodium channel. This channelopathy results in uncontrolled influx of the sodium ions in to the muscle during excitation. As sodium ions enter, muscle sustains the depolarization for a while and become unable to accept further action potentials which ultimately leads to weakness/ paralysis. Over influx of sodium ions is not well opposed by the efflux of potassium ions in some patients as does in most of the cases of HyperKPP. This causes normal serum potassium levels during the attack. Episodic/ periodic paralysis along with normokalaemia make a distinct form of periodic paralysis called NormoKPP.
The clinical presentation of the disease is more or less similar to HyperKPP. Initially, patients complain of a heaviness in the affected limbs. This is followed by a paralysis.Weakness is mild to severe and the proximal muscle groups of the upper limbs and lower limbs are frequently affected. The neck area may be affected as well. Rarely, patients may present with generalized muscle weakness. A typical mild episode is painless and usually lasts for few hours before patient recovers spontaneously. The severe attacks began in the
morning and lasted from 2 hours to 7 days.
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 Most patients with moderate to severe disease present as the are unable to walk as the lower limbs are affected with the weakness. Difficulty of walking
Most patients with moderate to severe disease present as the are unable to walk as the lower limbs are affected with the weakness.
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 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
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 Normokalaemic periodic paralysis is an autosomal dominantly inherited disease. So, positive family history can be present. Disease is more common among male sex. And individuals at any age can be affected. At risk population
Normokalaemic periodic paralysis is an autosomal dominantly inherited disease. So, positive family history can be present. Disease is more common among male sex. And individuals at any age can be affected.

Clinicals - Examination

Fact Explanation
Lid lag Infants may have a lid lag during the downward gazing. Lid lag
Infants may have a lid lag during the downward gazing.
Muscle weakness Muscle weakness can be demonstrated specially in the limbs. Hips and shoulders are commonly affected. 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. 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.
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 usually normal during the attack. Serum potassium level
Serum potassium level is usually normal during the attack.
Creatine phosphokinase (CPK) level CPK levels are elevated in most of the cases. Creatine phosphokinase (CPK) level
CPK levels are elevated in most of the cases.
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.
Genetic studies SCN4A mutation is commonly found in these patients. Genetic studies
SCN4A mutation is commonly found in these patients.

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 Carbonic acid anhydrase inhibitors such as dichlorphenamide or acetazolamide are thought to be effective. Prophylaxis
Carbonic acid anhydrase inhibitors such as dichlorphenamide or acetazolamide are thought to be effective.
Dietary modifications Patients should be encouraged to have meals with a high content of carbohydrate components and less potassium. Dietary modifications
Patients should be encouraged to have meals with a high content of carbohydrate components and less potassium.

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