Paramyotonia congenita is a separate clinical variant of myotonia inherited in an autosomal dominant way and characterized by the occurrence of myotonic episodes under the influence of cold. In the clinic of the disease, there are also paroxysms of transient muscle weakness. The diagnostic algorithm includes assessment of neurological status, biochemical blood examination, electroneuromyography, genealogical analysis, and, if necessary, the search for a mutation in the SCN4A gene. Treatment is symptomatic. It is possible to use local anesthetics and diuretics. The prognosis for life is favorable.
G71.1 Myotonic disorders
Paramyotonia congenita is a variant of myotonia, in which the main provoking trigger of myotonic phenomena is cold. Described by A. Eulenburg in 1886, in connection with which it is called Eulenburg’s paramyotonia. M. Levandovsky in 1916 gave a description of paramyotonia congenita called “cold paralysis”. In the literature on neurology, the terms “cold myotonia” and “paradoxical myotonia” can also be found. The latter name is associated with an increase in myotonic manifestations typical of paramyotonia against the background of motor activity, in contrast to the classical Thomsen myotonia, in which repeated movements lead to a decrease in rigidity and normalization of muscle work.
Paramyotonia congenita occurs with a frequency of 1 case per 100 thousand people. It is a genetically determined channelopathy, inherited autosomal dominant. Debuts in the first decade of life, in most cases in the first year from the birth of a child. Morbidity does not have gender preferences.
The etiopathogenetic substrate of paramyotonia is a defect in the SCN4A gene (chromosome 17, locus 17q23.1-q25.3) responsible for encoding α-subunits of sodium channels of skeletal muscles. Genetic aberrations at this locus also cause the occurrence of paroxysmal myoplegia. In the case of paramyotonia, a defect in the gene causes an increase in the level and duration of depolarization of the plasma membrane of the muscle fiber (myofibrils). The consequence of this is the difficulty of muscle relaxation (muscle rigidity) due to the long-term non-decreasing tension of its constituent myofibrils. If the depolarization level is too high, the muscle loses its ability to excitability, which is clinically manifested in the form of paresis — muscle weakness. The provoking triggers of myotonic paroxysm are general and local cooling, as well as excessive intake of potassium into the body.
The disease can manifest itself starting from the newborn period. So, experienced mothers note that the child’s eyes are closed for too long when washing it with cold water. The myotonic phenomenon consists in an elongated phase of tonic contraction of the muscle, its delayed relaxation. With paramyotonia congenita, it is provoked by cool weather, lowering the ambient temperature to 10-12 degrees, local cooling (washing hands with cold water, applying ice, eating ice cream, etc.), the presence of potassium-rich foods in the diet.
Myotonic spasms are observed in individual muscle groups. The facial musculature suffers most often — the eyelid muscle, the circular muscle of the mouth, the chewing muscles. Myotonia can be localized in the muscles of the neck, arms, legs, tongue, pharynx. The duration of myotonic muscle contraction varies from 15 minutes to several hours. The pathognomonic sign is an increase in the myotonic phenomenon against the background of repeated movements involving the affected muscles and a decrease in myotonia during warming. In some cases, cold, along with myotonia, provokes the development of muscle weakness (transient paresis), which can last up to several days.
Paramyotonia congenita has several clinical variants, except for the classical form of Eulenburg described above. Fluctuating myotonia is characterized by the occurrence of paramyotonic syndrome 30 minutes after exercise and the variability of its intensity on different days. Acetazole-dependent myotonia is similar to Eulenburg’s paramyotonia, but proceeds without episodes of muscle weakness, accompanied by hypertrophy and muscle stiffness, myalgia. This form got its name due to the effectiveness of treatment with acetazolamide (diacarb). Permanent myotonia is characterized by longer pronounced paramyotonic spasms with damage to the respiratory muscles; accompanied by muscular hypertrophy. Paramyotonia without cold-induced paralysis is characterized by the absence of a connection between the appearance of myotonic phenomena with cooling and progressive course.
The beginning in early childhood and a typical clinic allow the pediatrician to suspect a congenital neuromuscular pathology and refer the child to a neurologist. When making a diagnosis, the latter relies on clinical data, the results of neurological examination, EPI of the neuromuscular system, biochemical blood analysis, genetic studies.
Electroneuromyography or stimulation electromyography allows to determine the safety of nerve impulses along nerve trunks and to establish the primary muscular type of neuromuscular lesion. The blood test determines the normal level of creatine phosphokinase (CPK), which makes it possible to differentiate paramyotonia from progressive muscular dystrophy. A genealogical tree study conducted by a geneticist helps to trace the autosomal dominant path of inheritance. With the help of DNA analysis, it is possible to detect mutations in the SCN4A gene, but this is a rather expensive study.
Treatment and prognosis
Effective therapy has not yet been found. The treatment is symptomatic. According to a number of authors, the use of local anesthetics with the ability to inhibit the transmembrane current of sodium is effective. The drug of choice is mexiletin in capsules, which, unlike lidocaine, is well absorbed when ingested. Studies have shown its effectiveness against rigidity and muscle weakness. To reduce the frequency and severity of myotonic paroxysms, diuretic pharmaceuticals (acetazolamide, hydrochlorothiazide) can be used, the use of which leads to a decrease in the concentration of potassium in the blood.
Paramyotonia congenita, as a rule, is characterized by a benign stable course without progression. The prognosis for recovery is unfavorable. However, despite the persistent paramyotonic symptoms throughout life, the life expectancy of patients does not suffer. Patients do not lose the ability to work and self-service, do not have problems with social adaptation.