What Is Myotonia?

Definition of myotonia

Myotonia describes symptoms experienced by individuals experiencing impaired muscle relaxation (prolonged contraction). Neuromuscular disorders could cause myotonia and are best observed when there is a slowed relaxation or muscle unable to relax following a normal muscle contraction. Generally, myotonia could affect any muscle group, and organs such as the heart, lungs, digestive tract, brain and eyes could be affected. The affected individuals often describe the symptoms as muscle stiffness (if it affects skeletal muscle only), and affected individuals often require repeated muscle movement and effort to relax the muscle.

Classifications of myotonia 

There are two types of myotonia - dystrophic and non-dystrophic myotonia.

Dystrophic myotonia includes Muscular Dystrophy or DM, "Dystrophia Myotonica" in Latin. It is further divided into:

• DM 1
• DM 2

Non-dystrophic myotonia is mainly caused by channelopathies (diseases of ion channel transport). These include:¹

• Congenital Muscular Dystrophy (CMD), also called 'Myotonia Congenita'
• Paramyotonia Congenita
• Myotonic Dystrophy
• Hyperkalemic periodic paralysis
• Hypokalemic periodic paralysis
• Sodium channel myotonia

Causes and mechanism of myotonia

Causes of dystrophic myotonia (muscular dystrophy/DM)

In DM, the genes that were responsible for healthy muscle structure and function become mutated. Mutated genes can run in families or can be spontaneously acquired by the individual. These gene mutations can lead to muscle weakness and can eventually result in disability.

Depending on the type of Muscular Dystrophy, the condition could be a:

• Recessive inherited disorder
• Dominant inherited disorder - The types of MD that are inherited in this way include :
  • myotonic dystrophy
  • facioscapulohumeral MD
  • oculopharyngeal MD
  • Some types of limb-girdle MD
• Sex-linked (X-linked) disease - Types of MD inherited like this include:
  • Duchenne MD
  • Becker MD
• Spontaneous gene mutations

Causes of non-dystrophic myotonia/NDM

Ion channel dysregulations / Channelopathies²

Non-dystrophic myotonia is caused by channelopathies resulting from the dysfunction of ion channels in the membranes of all cells and many cellular organelles. It can be subdivided into :

• Genetic type - occurs when there are gene mutations that cause defects in channel function. It is the most common cause of channelopathies.
• Acquired type - caused by acquired disorders, drug use, toxins, etc.

Neuromuscular junction dysfunction

When there is dysfunction at the location where nerves and muscles connect, it is called neuromuscular junction dysfunction, which can cause myotonia. 

This type of myotonia can be seen in diseases such as:

• Lambert - Eaton Syndrome, which is often seen in cancer patients, causes muscle weakness.
• Myasthenia Gravis is a muscle weakness and fatigue caused by a communication problem between nerves and muscles. 

Risk or trigger factors of myotonia

• Cold temperature
• Fasting / irregular meals
• High or low-potassium food ingestion
• Rest following exercise/warm-up
• Stress
• Disturb sleep cycle - working overnight.

Types of myotonia

1. Congenital myotonia^3,4
   • Becker disease (most common form)
   • Thomsen disease (rare and milder form)

Thomsen's disease is also known as Myotonia Congenita, a muscular disorder with autosomal dominant inheritance. This disorder could be observed at birth or early childhood and progress throughout life. A common sign of Thomsen's disease is muscle hypertrophy after a series of muscle stiffness. 

On the other hand, Becker's disease is another type of Myotonia Congenita caused by autosomal recessive inheritance. Becker's disease resembles Thomsen's disease in many aspects; however, Becker's disease is found mostly later in life and presents transient muscle weakness during muscle exertion after rest.

• Paramyotonia congenita

Unlike myotonia, where symptoms of muscle stiffness wear off when the muscle is exercised, paramyotonia congenita is when muscle stiffness is brought on upon exercising - the stiffness worsens as exercising is carried on.

Myotonia is called the 'warm-up' effect; the opposite is 'paradoxical' or 'paramyotonia'. Genetic mutations cause Paramyotonia in a specific gene, the SCN4A gene, which is involved in making a protein that controls the movement of sodium into the muscle cells. Hence, paramyotonia is congenital; another name is 'sodium channel myotonia'.

• Myotonic dystrophy (DM)⁵

• Type 1 DM
• Type 2 DM

Myotonic Dystrophy Type 1, also known as Steinert Disease and Type 2, a milder form of DM1, are multisystem disorders caused by autosomal dominant inheritance. It is characterized by skeletal muscle weakness, myotonia, and other systemic issues such as cardiac conduction abnormalities, cataracts, endocrine disturbances, gastrointestinal disorders, and respiratory abnormalities. (See 'Clinical Presentations' below)

Clinical presentation

Most common clinical presentations of Myotonia present with few prominent symptoms. These are :

• Muscle weakness

Skeletal muscle weakness is one of the clinical presentations of DM1 and DM2. There are some differences in the muscle group involved in DM1 and DM2. Weakness in DM1 occurs mainly in facial muscles and usually occurs at the early stages of the disease. Facial weakness may occur in DM2, mostly at later stages of the disease; however, it is not as prominent as DM1. It is universal mainly to have neck flexor muscle involvement in DM1 and DM2. (See this Table for more info).

• Muscle stiffness and delayed relaxation

Upon examining a patient with myotonia, the patient is instructed to grip the examiner's fingers firmly and let them go rapidly. One will observe a delay in finger relaxation in a patient with grip myotonia. Hence, individuals with myotonia may have trouble releasing their grip on objects.

• Muscle pain
• Stiff Gait - difficulty rising from a seated position
• Systemic presentations⁶
  • Speech and swallowing difficulties (in DM1)
  • Cardiac and respiratory involvement (in DM)
  • Endocrinopathies
  • Cataracts

Diagnosing myotonia⁷

• Clinical evaluation

One of the methods of diagnosing myotonia is through clinical presentation and history taking by the healthcare provider. A clinician will be able to understand what happened to the individuals by asking about the symptoms and family health history before ordering tests for further investigations, ruling out conditions such as thyroid disease, and suggesting other kinds of tests such as those below.

• Blood test
• Creatinine Kinase (CK) is a type of protein (muscle enzyme) in blood. Individuals with myotonia will have elevated CK levels.
• Potassium level: The potassium level is useful to rule out channelopathies caused by myotonia. This test looks for hyperkalemic periodic paralysis (high potassium) or hypokalemic periodic paralysis (low potassium).

If there is high clinical suspicion pointing to the cause of myotonia, healthcare providers might recommend other diagnostic testing, such as: 

• Electromyography (EMG) and nerve conduction studies (NCS)

To confirm the presence of myotonia, EMG and NCS could be utilised. EMG involves a small needle being inserted into the muscle, and the electrical activity of the muscle and characteristic patterns of muscle electrical discharge are studied. A negative EMG could be followed by confirmatory genetic testing.

• Genetic testing

Healthcare providers might also take blood samples to test for genetic testing. Tests that demonstrate the presence of genetic mutations will prompt the type of mutated genes and help with optimal diagnosing the cause of myotonia.

• Short exercise test

A healthcare provider will monitor nerve or muscle response during short exercise tests - contracted muscles at intervals are measured.

Treatment and management of myotonia

Treatment of myotonia requires proper diagnosis before starting any medications or targeted therapy for specific causes of myotonia. Generally, we cannot change or treat gene mutations that occur at birth; hence, treatment focuses on symptoms.

Managing myotonia might require interaction with a multidisciplinary team, depending on the cause of the disease.

Symptomatic relief

• Physical therapy

Managing myotonia with physical therapy could depend on the distribution and severity of muscle involvement - either stiffness, weakness or pain. It also involves multidisciplinary teams such as occupational and physical therapists, neurologists and pain management teams.

The use of a walker, wheelchair, or moulded ankle-foot orthoses might be helpful with gait stability, reducing pain and weakness symptoms, as well as preventing foot drop. Low to moderate-intensity strength training for patients with myotonia in DM Type 1 and Type 2 are suggested to the extent of the patient's capability. However, there is currently no clear evidence of the benefit or harm of physical exercise.⁸

• Warm-up exercises

It is also suggested gentle stretching actions or exercise at the joints involved. Stretching at dorsiflexion at the ankle, extension at the knees, and hip abduction may be helpful with muscle stiffness, improving the symptoms and helping prevent joint contractures.⁹

• Medications - Drugs that have been used to treat myotonia include:¹⁰
  • Sodium channel blockers: procainamide, phenytoin and mexiletine
  • Tricyclic antidepressant drugs: clomipramine or imipramine 
  • Benzodiazepines
  • Calcium antagonists
  • Taurine 
  • Prednisone
  • Nonsteroidal anti-inflammatory drugs: ibuprofen, naproxen
  • Gabapentin - up to 300 mg three times per day

Genetic counselling

The following individuals are at risk and should be referred for genetic counselling, even if they are asymptomatic:

• Parents of an affected individual
• Couples with one affected spouse or a spouse at risk who plan to have children.
• Other family members of an affected individual
• Siblings of an affected individual who is approaching childbearing age
• Offspring of an affected individual, even if asymptomatic

Disease-specific management (DM1 and DM2)

Respiratory support: such as follow-up on clinical assessment, vaccination against pneumonia and influenza, and assessing sleep quality to rule out Obstructive Sleep Apnea (OSA).

Cardiac monitoring: including exercise testing with ECG monitoring as routine evaluations as well as referral to a cardiologist.

Summary

Myotonia is a condition with impaired muscle relaxation resulting in prolonged contraction. Myotonia is characterised as a neuromuscular disorder caused by multifactorial problems such as gene mutations and channelopathies, and myotonia could also affect various muscle groups and manifest systemically acting on organs like the heart, lungs and digestive tract. 

Myotonia could also be categorised as dystrophic and non-dystrophic myotonia. Dystrophic myotonia (DM) includes subtypes DM1 and DM2, both caused by gene mutation but with slight differences in presentation. Non-dystrophic myotonia is caused mainly by channelopathies, further divided by genetic or acquired type. Either way, it affects muscle and neuromuscular junctions, leading to muscle stiffness and weakness. 

Risk and trigger factors for myotonia include colds, irregular meals, stress and disturbed sleep. Myotonia can be presented with muscle weakness, stiffness, pain, delayed relaxation and systemic issues. Diagnosing myotonia could involve clinical evaluation, blood tests, electromyography (EMG), nerve conduction studies (NCS) and genetic testing. 

Treatment and management focus on symptomatic relief, physical therapy, warm-up exercises, and medications, such as sodium channel blockers, tricyclic antidepressants, benzodiazepines, and other drugs, which may be used to alleviate symptoms. Genetic counselling is recommended for those at risk of inheriting myotonia. Disease-specific management for DM1 and DM2 involves respiratory support, cardiac monitoring, and multidisciplinary approaches.