Myotonia is a hereditary disease related to channelopathy (diseases associated with the pathology of ion channels). It is manifested by delayed muscle relaxation. Characteristic signs are myotonic discharges detected by needle EMG, and myotonic phenomena that are detected during clinical examination. Congenital form is accompanied by muscular hypertrophy, dystrophic form, on the contrary, is accompanied by muscular atrophy. Diagnosis is carried out with the help of EMG, ENG and the study of evoked potentials. To date, radical drug therapy for myotonia has not been developed. Patients receive symptomatic and metabolic treatment, massage, physical therapy, electrical stimulation.
Etiology and pathogenesis
Among the two types of dystrophic myotonia, type 1, whose gene is mapped at the 19q13 locus, is most common (98%). Like all types of dystrophic myotonia, it is inherited in an autosomal dominant type. The main etiological factor of dystrophic form type 1 is an increase in the number of trinucleotide CTG repeats (up to several thousand). Myotonin, a protein kinase encoded by the DMPK gene, is present not only in skeletal, but also in the myocardium, as well as the central nervous system. This explains the main clinical manifestations of dystrophic form.
Eilenburg’s congenital paramyotonia, associated with the pathology of sodium channels, is transmitted by an autosomal dominant type. The SCN4A gene is mapped at the 17q23.1-q25 locus.3. Paramyotonic manifestations develop due to increased excitability of the muscle fiber membrane and impaired functioning of the contractile elements of the muscle.
Unlike most neuromyotonia, which are acquired diseases, idiopathic neuromyotonia (Isaacs syndrome) is inherited and occurs most often. The effectiveness of the administration of curare for the relief of muscle spasms indicates the neurogenic nature of neuromyotonia, but the final pathogenesis of the disease is still unclear today. With the detection of an increased titer of antibodies to potential-dependent potassium channels, neuromyotonia began to be considered an autoimmune disease. The autoimmune nature of the disease is also indicated by the effectiveness of plasmapheresis observed in some cases.
Classification
The most common forms are:
- dystrophic (two types)
- chondrodystrophic
- congenital autosomal dominant
- congenital autosomal recessive
- Eulenburg paramyotonia
- neuromyotonia
Symptoms
The symptom of a “fist” is the main clinical test for the detection: the patient cannot quickly unclench his fist, for this he needs time and some effort. With repeated attempts, such a myotonic phenomenon fades away with the exception of Eulenburg’s myotonia, when stiffness, on the contrary, increases with each repeated attempt. Stiffness is also observed when unclenching the clenched jaws, quickly open the closed eyes, quickly get up from the chair. Needle electromyography reveals one of the most characteristic phenomena for myotonia — myotonic discharges accompanied by the sound of a “dive bomber”, which occur when the needle electrode is inserted and moved.
A distinctive clinical feature of congenital myotonia is hypertrophy of individual muscle groups, which creates the impression of an athletic physique of the patient. In most cases, muscle strength is preserved, but sometimes it is reduced in the distal muscles of the arms. Dystrophic myotonia is a multisystem disease. In most cases, neurological symptoms are combined with cardiac pathology (left ventricular hypertrophy, arrhythmia), cerebral symptoms (hypersomnia, decreased intelligence), endocrine disorders (menstrual cycle disorders in women; hypogonadism and impotence in men). For paramyotonia, the so—called “cold myotonia” is typical – the occurrence of muscle spasm and paresis in the cold; such attacks can last from several minutes to several hours. Clinical manifestations of neuromyotonia are muscle stiffness, spasms (painless) and constant muscle activity on EMG.
Diagnostics
The onset of dystrophic myotonia usually occurs in adolescence or adulthood, the degree of progression of the disease depends on the genetic defect, therefore, a thorough collection of family history is of great importance in the diagnosis of dystrophic myotonia. Becker’s myotonia debuts at 5-12 years of age and is characterized by a slow course, and Thomsen’s myotonia can debut both in childhood and in adulthood and proceeds, as a rule, heavily and with complications. Physical examination in dystrophic myotonia reveals muscle atrophy and a decrease in their strength. Dystrophic myotonia type 1 is characterized by muscle weakness in the distal extremities, for dystrophic myotonia type 2 — in the proximal.
With the help of laboratory tests, antibodies to potential-dependent potassium channels are detected in neuromyotonia, and dystrophic myotonia is characterized by a slight increase in the activity of CPK in the blood.
The main instrumental method of diagnosing myotonia is needle electromyography (EMG), which determines myotonic discharges — a pathognomonic sign of myotonia. The study is conducted using evoked potentials and electroneurography. With paramyotonia, normal PDE and rare myotonic discharges are recorded on EMG. For congenital myotonia, it is typical to maintain the parameters of DE within the normal range, for dystrophic myotonia — a combination of neuropathic and myopathic traits. To diagnose paramyotonia, a cold test is carried out: slight cooling causes myotonic discharges, with further cooling, “bioelectric silence” occurs (both myotonic phenomena and PDE disappear). DNA diagnostics of dystrophic myotonia is based on the detection of an increased number of CTG repeats in the DMPK gene.
Differential diagnosis
As a rule, the neurologist is able to differentiate congenital myotonia from dystrophic myotonia by clinical signs. However, in some cases of congenital myotonia, mild weakness of the distal muscles of the hands and weak activity in EMG are determined — signs typical of dystrophic myotonia. Constant muscle activity — a clinical sign of neuromyotonia — is part of the stiff-man syndrome, however, unlike neuromyotonia, muscle activity in the “rigid man” syndrome decreases after administration of diazepam, as well as during sleep.
Treatment
The goal of neuromyotonia treatment is to eliminate constant muscle activity and achieve possible remission, the goal of myotonia treatment is to reduce the severity of myotonic manifestations. Non-drug treatment of myotonia consists of a diet with a restriction of potassium salts, exercise therapy, massage, electromyostimulation, as well as prevention of hypothermia, since all myotonic reactions increase when cold. There is no radical medical treatment of myotonia, therefore, in order to reduce the severity of myotonic manifestations, phenytoin is used, and diuretics are used to reduce potassium levels. In some cases, it is possible to achieve remission with the help of immunosuppressive therapy: intravenous administration of human immunoglobulin, prednisone, cyclophosphamide.
Forecast
The prognosis for life with myotonia is generally favorable, with the exception of rare cases of dystrophic myotonia type 1, when sudden cardiac death due to cardiac pathology is possible. The prognosis for the ability to work of patients with congenital myopathies is also favorable (with rational employment).
