Periodic paralysis

Classification according to ICD-10
G72.3	Periodic paralysis
ICD-10 online (WHO version 2019)

Periodic paralysis is a recurring muscle paralysis that is typically associated with abnormalities in blood potassium levels. They belong to the so-called canal diseases . This includes muscle diseases that have in common the mutation of genes that code for certain channel-like membrane proteins on and in the muscle cells. These proteins are responsible for the passage of ions through the cell compartments and thus influence the electrical excitability of the muscles.

General

The flaccid paralysis occurs within minutes to hours, mainly affects the extremities near the trunk, and may last for several days. In the interval, i.e. in the period between two paralysis attacks, those affected remain largely symptom-free. Otherwise there is hardly any evidence that would indicate the presence of this disorder. One distinguishes between

• hypo- kalemic paralysis
• hyperkalemic paralysis (Adynamia episodica hereditaria, Gamstorp syndrome)

Ironically, the pathological gene products are not potassium channels. The specific role of potassium in the pathogenesis (development of the disease) seems complex and is still unexplained. Other canal diseases with similar symptoms are paramyotonia congenita (Eulenburg), Andersen syndrome and congenital myotonia (Becker and Thomson).

Even if the patients appear symptom-free in the interval, a chronically progressive muscle disease (chronic progressive myopathy) develops. However, this only becomes symptomatic after many years of illness. The weighting of the associated muscle weakness lies in the proximal parts of the extremity muscles. The main weakness is the shoulder and pelvic girdle. In the long term, in severe cases, this can lead to an inability to walk. No correlation can be established between the severity or frequency of the sudden (paroxysmal) paralysis and the severity of the chronic myopathy.

Important differentiating criteria

paralysis	Hypokalemic	Hyperkalemic
Initial manifestation	1 and 2 decade of life at night or early in the morning	2 decade of life during the day after activity or food leave
Symptoms	Gait disorder, ascending paralysis	Gait disorder, paralysis of the facial and throat muscles
Duration	Hours to days	Minutes to hours
Serum potassium	<2 mmol / l	> 6 mmol / l
therapy	Potassium chloride	Calcium gluconate

Periodic hypokalemic paralysis

Epidemiology and genetics

The prevalence of hypokalemic paralysis is estimated at 1/100 000 inhabitants. This paralysis usually manifests itself in adolescence, sometimes also in childhood. It is an autosomal - dominant inherited and mainly affects men. Men are also more sick than women. The associated gene defect (CACNA1S) was detected on chromosome 1 . The affected gene product is an incorrectly configured subunit of a voltage-dependent calcium channel in the tubular system of the muscle cells. Occasionally there are also sporadic cases in which no genetic disorder has yet been proven.

Pathogenesis

In a way that has not yet been clarified, sodium and water are stored in the cells during the attack. At the same time, there is an extracellular potassium deficiency. The increased conductivity of sodium across the muscle cell membranes leads to a disruption of the membrane potential or to disruption of muscle excitation and a subsequent (consecutive) paralysis of the muscles.

Symptoms

Usually before the age of 20, often in childhood, the first symptoms set in. Typically, the paralysis attacks first occur at intervals of several months. Over the years, the frequency and severity of the seizures increase continuously. After reaching a frequency peak, around mid-life, the frequency of the seizures steadily decreases again to fade out completely around the age of 50.

The paralysis typically occurs at night or early in the morning. Emotional excitement, exposure to cold, meals rich in carbohydrates and previous strong physical exertion also provoke these attacks. The seizures can occur unexpectedly during the day. This can lead to very noticeable symptoms. For example, a hiker who takes a short breather after completely unproblematic physical activity may develop a sudden inability to walk.

The paralysis set in step by step. Sometimes other symptoms can precede the paralysis. Preceding symptoms (prodromal symptoms) are bloating, paresthesia , sweating or a general feeling of weakness. Thereafter, a symmetrically pronounced muscle weakness develops increasingly. It starts close to the torso on the shoulder and pelvic girdle and progresses towards the torso and neck within a few hours. The severity of muscle weakness can vary. It can range from mild paresis to quadriplegia . The muscles that are supplied by the cranial nerves are usually not involved. The respiratory muscles are usually not affected either. If it is, it is a very dangerous circumstance, as is the cardiac arrhythmia that increases during an attack. The symptoms of paralysis can last for hours or even several days. The vigilance (awareness) of those affected remains completely undisturbed.

diagnosis

• Status: During the seizure, the muscle reflexes are weakened or extinguished. The muscle tone is severely reduced. The disorder mainly affects the motor skills of the arms and legs (paresis to paralysis). Rarely affects Atonie the muscles of internal organs (bowel or bladder atonia ). The sensitivity seems to be preserved. Pain is also not a symptom of this disease.
• EMG: The electromyogram (EMG) is used for diagnostic purposes. The individual potentials are low and short. Furthermore, there is a clearing of the activity pattern.
• Laboratory: The serum potassium values ​​are <2 mmol / l. The interval values, however, are largely normal. During the seizure, there is also a decrease in serum creatinine and an increase in sodium and lactic acid levels in the blood.
• ECG: as a further possibility, hypokalaemia can be diagnosed by means of an electrocardiogram (extended QT time , ST depression, U waves).
• In the case of hypokalemic periodic paralysis during the attack, muscle biopsy reveals central vacuoles in the muscle fibers , which correspond to enlarged transverse tubules . These vacuoles contain glycogen and are strongly colored in the PAS stain .

Seizures can be provoked by influencing the glycogen balance (administration of carbohydrates , insulin , ACTH ). These provocation tests are not advisable, mainly because of the complications they cause. The combination of the above findings and the response to the correct therapy largely secure the diagnosis anyway.

Differential diagnosis

Much more often, hypokalemia is an expression of a basic internal medical condition. Secondary reductions in potassium levels (based on an underlying disease) can also cause very similar muscle weaknesses and may lead to mix-ups. However, the intermittent nature of the paralysis does not exist in this form. These symptomatic hypokalemia are ruled out based on anamnestic and laboratory tests.

Disorders that lead to decreased potassium levels are, for example, chronic vomiting ( vomiting ), chronic diarrhea ( diarrhea ), liver cirrhosis , kidney failure , adrenal insufficiency , or hyperaldosteronism . Extremely low potassium levels and muscle paralysis have also been described after excessive consumption of beverages containing sugar and caffeine, such as cola .

Above all, it is important to distinguish it from thyrotoxicosis . Mostly one finds a noticeable increase in body temperature and tachycardia . A check of the thyroid hormones is absolutely necessary.

Therapy with diuretics can also produce this clinical picture. A potassium deficiency syndrome can also occur in the context of anorexia nervosa . Delineate further the psychogenic paralysis and myasthenia gravis .

therapy

• Attack: The administration (application) of high doses of potassium chloride is suitable for interrupting (stopping) the attack. Oral administration is preferable to intravenous administration whenever possible. The latter always carries the risk of severe impairment of the heart. However, if it is essential to administer potassium parenterally (emergency, dysphagia , ...), a parallel infusion of glucose or NaCl must be avoided, as both substances would further reduce the potassium level. The ECG should be checked continuously during treatment. The symptoms usually resolve within an hour after treatment.
• Interval: The focus is on trying to largely avoid attacks. This should also prevent the muscle weakness that develops over time. It is important to educate the patient. The person concerned should limit the consumption of carbohydrate-rich food and table salt. High-carbohydrate foods should be avoided if possible, especially in the evening. Physical activity is certainly not advisable, but excessive muscle strain should be avoided. Administration of potassium is not suitable for seizure prophylaxis. Acetazolamide can be administered prophylactically . This leads to a decrease in the frequency of seizures. Paradoxically, this action lowers the potassium level. The therapy is therefore not entirely risk-free. The reason why acetazolamide has a protective effect is not entirely clear. It is believed that the protective effect is due to the lowering of the blood pH level. This effect seems to outweigh the lowering of blood potassium levels. Other drug methods include the administration of triamterene , spironolactone, or lithium . Drug interval therapy should only be prescribed by proven experts.

Periodic hyperkalemic paralysis

Epidemiology and genetics

The expression “hyperkalemic paralysis” is certainly not a very fortunate choice. Often those affected do not have a blood potassium level above the norm during an attack of paralysis. However, it can be observed that an intake of potassium and the subsequent, sometimes only slight increase in the blood potassium level causes the said paralysis. The potassium level does not necessarily have to be too high during an attack of paralysis.

The first manifestation takes place around the age of 10. It also This is an autosomal - dominant inherited disease. There is no gender preference. Men and women seem to be affected equally often. The defective gene SCN4a is located on chromosome 17 and codes for a sodium channel .

Pathogenesis

The disease is based on a defect in a sodium channel in the membrane of muscle cells. If the potassium level is too high, it seems to induce an electrolyte shift in the membrane of the muscle cells via mechanisms that have not yet been precisely explained . There is an outflow of potassium from the muscle cells, and via the defective sodium channel there is an increased influx of sodium into the muscles. The consequence is a disruption of the membrane potential in the form of a depolarization . This is associated with a reduced excitability of the muscles, and consequently symptoms of paralysis.

Symptoms

The intake of large amounts of potassium, the state of rest after strenuous exercise, diets and exposure to the cold can cause these paralyzes. Moderate physical activity, on the other hand, seems to have a protective effect. The paralysis attacks are less severe and shorter, but more frequent than in hypokalemic paralysis. They usually last a few minutes to hours. Sometimes they occur every day. Interestingly, many sufferers complain of a strong feeling of thirst . The paresis typically affects the legs and tends to spread towards the trunk. Mimic muscles and pharyngeal muscles can also be affected. Involvement of the respiratory muscles is rare. The paralysis usually occurs during the day. However, there is no evidence of an accumulation at certain times of the day. Sometimes a seizure can be delayed or even prevented by eating after the symptoms first appear.

diagnosis

• EKG: The electrocardiogram (EKG) is noticeable. One finds the tent-shaped T-waves typical of hyperkalemia, a widened QRS complex , a flattened P-wave and an extension of the PQ-time.

• Status: The muscle reflexes are extinguished in the attack.
• EMG: The electromyogram (EMG) also shows abnormalities. Potentials are reduced and amplitudes lowered.
• Laboratory: Elevated Serum Potassium.

The ECG changes, together with an increased serum potassium level and the acutely occurring flaccid paralysis symptoms, confirm the diagnosis.

Cold can trigger a myotonic reaction . This is expressed e.g. B. through impaired articulation ability after eating cold food, or in a fine motor clumsiness of the hands after bathing in cold water.

Provocation tests, such as the application of potassium, are not necessary to diagnose the disease and are even dangerous.

Differential diagnosis

Psychogenic paralysis : Confusion arises from the fact that the psychogenic paralysis has a similar symptom and occasionally a similar anamnesis (occurrence after physical exertion). However, the patient's lack of self-reflexes, which is typical of hyperkalemic paralysis, cannot be imitated by the patient, which is why careful neurological assessment or the use of an electromyogaram (EMG) should protect against this confusion.

Narcolepsy : Strong exogenous stimuli can interrupt a narcoleptic waking attack . The loss of muscle tone occurs much more suddenly than the hyperkalemic paralysis. The respiratory muscles are also not involved. The loss of muscle tension in narcolepsy is usually short-lived.

therapy

• Seizure: An intravenous infusion of calcium gluconate (1–2 g) is required during an attack . Alternatively, the hyperkalemia can also be eliminated with the parallel infusion of glucose and insulin . This method is used to treat hyperkalemia of various causes.
• Interval: The consumption of foods rich in potassium (bananas) should be restricted. A high-carbohydrate diet and a sufficiently high salt intake are recommended. Prophylactic administration of the carbonic anhydase inhibitor acetazolamide can be attempted. Also, hydrochlorothiazide can reduce the severity and frequency of seizures. Drug interval therapy should only be prescribed by a specialist neurologist, if at all.

literature

• Klaus Poeck, Werner Hacke: Neurology. 11th edition. Springer, Berlin 2001, ISBN 3-540-41345-6 .

Individual evidence

1. ↑ V. Tsimihodimos, V. Kakaidi, M. Elisaf: Cola-induced hypokalaemia: pathophysiological mechanisms and clinical implications. In: The International Journal of Clinical Practice. Vol. 63, Issue 6, pp. 900-902. (German-language summary) Spiegel Online

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