Nondystrophic myotonia
Synonyms
1
Overview
The non-dystrophic myotonias are an important group of skeletal muscle channelopathies electrophysiologically characterized by altered membrane excitability. It is characterized by a muscle disorder where the voluntary muscles are slow to relax after movement. The problem occurs intermittently and can sometimes be painful but no muscle wasting occurs. Many distinct clinical phenotypes are now recognized and range in severity from severe neonatal myotonia with respiratory compromise through to milder late-onset myotonic muscle stiffness. Specific genetic mutations in the major skeletal muscle voltage gated chloride channel gene and in the voltage gated sodium channel gene are causative in most patients.
The non-dystrophic myotonias are now known to be caused by dysfunction of key skeletal muscle ion channels and include myotonia congenita, paramyotonia congenita and the sodium channel myotonias.
Symptoms
- Intermittent muscle stiffness
- Sustained muscle tenseness
- Muscle pain Note that Nondystrophic myo
Diagnosis
The main symptom displayed by the patient described here is one of isolated myotonia—referred to by the patient as "stiffness". Upon presentation of this symptom, a diagnosis of either dystrophic or non-dystrophic myotonia should initially be given consideration. Dystrophic myotonia involves myotonic symptoms that are associated with atrophic or dystrophic muscles. Some of the features described in the current patient's clinical presentation should guide the neurologist towards a diagnosis of recessive myotonia congenita (MC)—a non-dystrophic myotonia. Recessive MC is a clinical entity that was first described by Becker in 1966. The mode of transmission is autosomal recessive, and the parents will therefore be asymptomatic heterozygous carriers. Symptoms often begin in the lower limbs between the ages of 4 and 12 years, and there is often a history of freezing and falls. A feeling of stiffness is always the chief complaint, but there is often also a history of transient weakness that occurs when the muscles are exercised after a period of rest. As with myotonia, the transient weakness virtually disappears with continued exercise ('warm-up' effect). Symptoms can become considerable to the extent that they disturb daily activities, and patients sometimes notice an exacerbation of their myotonia during cold or wet weather when they can also suffer from muscle cramps. As in the present case, pregnancy appears to worsen the myotonia in some women, indicating that there is a hormonal influence on the condition. In cases of recessive MC, grip myotonia, percussion myotonia (limbs and tongue), lid lag, and blepharospasm can all be revealed by a neurological examination. The patient's muscle strength often initially appears normal, but sometimes a rapid decrease in power is seen when they undertake short periods of exercise, which then returns to normal after further muscle contraction. Patients often have muscle hypertrophy, and there have been reports of cases involving mild atrophy of the neck muscles (sternocleidomastoid and trapezius). Typically, electrophysiological studies on patients with recessive MC will show normal motor and sensory nerve conductions, whereas repetitive nerve stimulation at 10 Hz and the short exercise test will usually reveal a CMAP decrement of more than 30% from the baseline value. Investigation with needle EMG will reveal myotonic discharges in proximal and distal muscles. These discharges can present either as sustained runs of positive waves, or runs of small triphasic potentials which wax and wane in frequency and amplitude. The patient's motor units may appear to be mildly myopathic. Recessive MC is caused by mutations in the gene that codes for the muscle chloride channel CLCN1 on chromosome 7q35. This channel is composed of a dimer of two subunits that form an hourglass shape; two pores are gated by a common slow gate, and two individual fast gates. CLCN1 is necessary in order to stabilize the high resting membrane potential of skeletal muscle. Dysfunction of this channel as a result of genetic mutation, causes partial depolarization of the membrane and allows a hyperexcitable state to exist, resulting in myotonia. It is postulated that permanent excitability gives rise to constant mild muscle activity, resulting in muscle hypertrophy.
Treatment
Many patients with myotonia can cope with their symptoms without the use of medications. As described in the present case, however, patients with recessive MC can experience severe myotonia, which hinders their daily activities. Muscle stiffness responds well to drugs that reduce the associated hyperexcitability of the sarcolemma by interfering with sodium channels located on it. These drugs theoretically reduce spontaneous discharges of electrical myotonia by decreasing the number of available sodium channels, but they have no known effects on chloride channels.
One such drug is mexiletine, which is able to reduce myotonia with doses of 200 mg two or three times a day. Possible adverse side effects of mexiletine include epigastric discomfort, nausea, tremor, anxiety and headaches, and in patients with recessive MC, there is a possibility of an increase in muscle weakness. Before prescribing mexiletine, an electrocardiogram must be performed to eliminate contraindications such as cardiac arrhythmias, coronary heart disease or cardiomyopathy.
Phenytoin 200–300 mg per day can also be used to treat myotonia. Care must be taken with the use of depolarizing muscle relaxants such as suxamethonium during anesthesia, because they can cause adverse events such as life-threatening muscle spasms and ventilation difficulties following a preoperative injection. Particular care should also be taken with injections of adrenaline or selective beta-adrenergic agonists, because they aggravate myotonia