Disease of periodic muscle spasms is a hereditary form of myopathy characterized by a violation of calcium metabolism in the sarcoplasmic reticulum. The main symptoms of the disease are painful spasms, especially during physical exertion, weakness of the leg muscles, general muscle weakness. Pathology is diagnosed on the basis of data from percussion and palpation of muscles, electromyography, muscle tissue biopsy, genetic studies also play an important role. There is no specific treatment for the disease of periodic muscle spasms, non-narcotic analgesics and antispasmodics are used to relieve symptoms.
General information
Disease of periodic muscle spasms belongs to a group of hereditary diseases that are caused by mutations of the CAV3 gene. It also includes such pathologies as lumbar-limb muscular dystrophy type 1C, long QT syndrome, hypertrophic cardiomyopathy. The incidence of this disease is estimated at the level of 1:100000-1000000, however, it is difficult to obtain accurate data, since a number of patients do not consult doctors for a long time due to the non-specificity and low severity of symptoms. Often, the disease of periodic muscle spasms is detected accidentally during a biochemical blood test or other studies that take into account the level of the MM fraction of creatine phosphokinase. Unlike other pathologies of this type, this disease practically does not affect the activity of the myocardium, only skeletal muscles, mainly the lower extremities, are affected.
Causes
The root cause for the development of the disease of periodic muscle spasms is a mutation of the CAV3 gene, which is located on the 3rd chromosome. It encodes a protein called caveolin 3 – a specific protein of skeletal muscle cell membranes and cardiomyocytes. Methods of modern genetics have revealed more than 20 mutations of this gene, which in general form the phenotypes of five hereditary diseases, including diseases of periodic muscle spasms. This pathology is inherited by an autosomal dominant mechanism. Muscle disorders in this disease are caused by a defect in the structure of caveolin 3, which is involved in many important regulatory processes in myocytes.
Caveolin 3 forms oligomeric structures on the cell membrane, additionally attaching cholesterol and some other lipid compounds to itself. In the end, special complexes are formed – caveoles with a diameter of 70-100 nm, which may look like pores or pinocytic bubbles. Caveols can include a huge number of important elements of the membrane – adrenoreceptors, protein kinase C and a number of others. They are also associated with the activity of the dystrophin-glycoprotein complex, which ensures the interaction of the cytoskeleton of the cell. The participation of caveolin 3 in the formation of the T-tubule system has been proven. In the case of a mutation of the CAV3 gene, the protein obtained as a result of its expression is defective and cannot fully perform its functions, which leads to various disorders, including the disease of periodic muscle spasms. In this case, defective caveolin 3 is not able to regulate calcium homeostasis in the endoplasmic reticulum of myocytes, as a result of which, with increased mechanical stress on muscle fibers, their spastic contraction occurs.
Symptoms
Most patients with the disease of periodic muscle spasms note the development of seizures, most often the muscles of the lower extremities, especially during physical exertion. Quite often, after an attack of spasm, soreness in the muscles persists for a long time, weakness and tremor in the legs are not uncommon. There are signs of muscle weakness, but it is moderate and almost never progresses. The frequency of seizures varies greatly in different patients and can range from 1-2 times a day to several cases a year. In many ways, the number of developing spasms depends not on the nature of the course of the disease, but on the level of physical activity and lifestyle of the patient. With relatively calm and sedentary work, the disease of periodic muscle spasms rarely makes itself felt, whereas with heavy physical labor, seizures can occur very often. This leads to the fact that many patients, faced with rare episodes of the disease, do not always consult a doctor about this.
Diagnostics
Diagnosis of the disease of periodic muscle spasms is made on the basis of data from the patient’s examination, electromyography, genetic studies and the study of hereditary anamnesis. Also of diagnostic importance is the determination of the level of creatine phosphokinase in the blood (muscle fraction) and the study of muscle tissues obtained as a result of biopsy. Upon examination of the patient, accelerated muscle activity is revealed, which is stimulated by percussion, slight muscle weakness. Subjectively, patients complain of muscle pain and spasms, sometimes even with a slight load (for example, when stretching).
During electromyography, muscle contraction is detected in response to mechanical stimulation, but there is no “electrical response”. At the same time, the excitement quickly spreads to neighboring fibers, eventually leading to a spasm of the entire muscle. The level of MM fraction of creatine phosphokinase in blood plasma is increased, the study of muscle tissue biopsy shows a sharp decrease in the level of caveolin 3 and a reduced amount of dysferlin protein. At the same time, there are no changes on the part of the myocardium (an increase in the amount of CM-fraction of kratin phosphokinase, pathological ECG).
With the help of a geneticist, direct automatic sequencing of the sequence of the CAV3 gene can be performed, which will reveal the type of mutation and confirm or refute the diagnosis of the disease of periodic muscle spasms. The presence of such disorders in close relatives, determined during the compilation of a hereditary history, is an additional indirect sign of this disease. Differential diagnosis should be made with muscle spasms of a different nature (caused by a violation of water-salt metabolism and blood circulation in the extremities, neurological diseases, fatigue) and some other hereditary pathologies. It is especially difficult to distinguish the disease of periodic muscle spasms from other diseases caused by a mutation of the CAV3 gene – in some cases this is possible only with the use of genetic methods.
Treatment
There is no specific treatment for the disease today, to reduce the frequency of seizures, doctors recommend reducing physical activity, performing a set of special exercises, maintaining an optimal water-salt regime. You should be careful when using medications that affect the functioning of muscles or the concentration of inorganic ions in the body – diuretics, some antibiotics and hormones. However, in general, the prognosis of the disease of periodic muscle spasms, unlike many other types of myopathies, is favorable – the symptoms are not progressive. With an increase in the frequency of seizures, bed rest for 1-2 days and normalization of water-salt balance are necessary.
