Information on the following diseases can be found in the Related Disorders section of this report:

• Episodic Ataxia I
• Neurodegeneration with Brain Iron Accumulation Type 1
• Paraplegia, Hereditary Spastic
• Schwartz Jampel Syndrome
• Stiff Man Syndrome

Neuromyotonia is characterized by involuntary continuous muscle fiber activity (fasciculations) that cause stiffness and delayed relaxation in the affected muscles. Continuous vibration of fine muscle movements (myokymia) may occur along with these symptoms. Affected individuals may, at times, be unable to coordinate voluntary muscle movement and find difficulty in walking (ataxia). Other symptoms may include staggering and reeling (titubation), stiffness, and lack of balance in response to being startled. There may be diminished spontaneous gross motors activity.

The disorder is characterized by progressive stiffness, cramping, and weakness. Muscle activity is constant, and patients describe the feeling of continuous writhing or rippling of muscles (myokymia) under the skin. These movements continue during sleep, and offer one way of distinguishing neuromyotonia from stiff man syndrome. In stiff man syndrome, such movements stop during sleep. Diminished reflexes are also frequently a sign of this disorder. Involvement of the autoimmune system is suggested by excessive sweating (hyperhidrosis) and rapid heart beats (tachycardia).

In some instances, muscle relaxation following voluntary muscle movement is delayed (grip myotonia) in the affected muscle(s). For example, affected individuals may be not be able to open their fists or eyes immediately, after closing them tightly for a few seconds.

In slightly fewer than 20% of the cases, a set of symptoms, including arrhythmias, excessive salivation, memory loss, confusion, hallucinations, constipation, personality change and/or sleep disorders, are found. In such cases the disorder may be referred to as Morvan syndrome.

There are both hereditary and acquired forms of this disorder. Acquired neuromyotonia is an autoimmune disease, or a disease in which the immune system malfunctions so that it damages parts of one’s own body.

Some cases are the result of a tumor of the thymus gland located in the chest. The thymus glands are the source of a number of specialized cells associated with autoimmune functions. The disorder also co-exists, in some cases, with myasthenia gravis.

It is believed that most cases of neuromyotonia are caused by auto-antibodies that affect the points at which the signals from the nerve fiber meet the muscle cell (neuromuscular junction).

A relatively small proportion of cases of neuromyotonia are genetic in origin and tend to occur in families. Neuromyotonia of this type is inherited as an autosomal dominant genetic trait. The gene responsible has been traced to the following chromosomal location: 12p13.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 12p13" refers to band 13 on the short arm of chromosome 12. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Neuromyotonia is a rare disorder affecting males and females of almost any age but it is most frequent among adults and is slightly more common among men.

Symptoms of the following disorders can be similar to those of neuromyotonia. Comparisons may be useful for a differential diagnosis:

Hallervorden-Spatz disease is a rare neurological disorder characterized by symptoms that resemble dystonia (a slow, steady muscle contraction distorting limbs, neck, face, mouth or trunk into certain positions), muscular rigidity (uncontrolled tightening of the muscles), and choreoathetosis (spontaneous, non-repetitive, slow writhing movements, usually of the extremities). Muscle spasms are present in one third of affected individuals. Less common symptoms are dysarthria (difficulty in speaking), mental retardation, facial grimacing, dysphasia (impaired speech), muscle atrophy (shrinking muscles) and seizures. Symptoms vary in different individuals. (For more information on these disorders, choose "Hallervorden-Spatz" or "Dystonia" as your search terms in the Rare Disease Database.)

Initial symptoms of hereditary spastic paraplegia usually include weakness, muscle spasms, and stiffness of the legs. Leg muscles may contract or a heel deformity may occur making walking difficult. Speech disturbances can also appear. Difficulty in swallowing, exaggeration of tendon reflexes and general muscle weakening may develop as this disorder progresses. Symptoms can range from mild to severe depending upon the mode of inheritance (dominant or recessive genes), and the degree to which the nerves are compressed or damaged. (For more information on this disorder, choose "paraplegia" as your search term in the Rare Disease Database.)

Stiff man syndrome is a very rare neurological disorder. It is characterized by progressive rigidity and spasms of the voluntary muscles of the neck, trunk, shoulders, and proximal extremities. It is caused by abnormal nerve activity most likely in the central, rather than peripheral, nervous system. The electrical activity measured by the EMG may begin in the spinal cord, rather than the peripheral nerves. (For more information on this disorder, choose "stiff-man" as your search term in the Rare Disease Database.)
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Diagnosis
The diagnosis of neuromyotonia depends on the presence of continuous muscle contractions (myokymia), especially in the face and hands, rhythmic tics or twitches (fasciculations), and muscle cramps. The diagnosis is confirmed by studies of the electrical signs of muscle activity (electromyography).

Treatment
Neuromyotonia may be treated with anticonvulsant drugs such as phenytoin, or with carbamazepine, which may stop the abnormal impulses and prevent the symptoms from reoccurring. Plasma exchange (plasmapheresis) and intravenous immune globulin have been effective in a few cases but no long-term, controlled, clinical studies have been carried out.

Genetic counseling may be of benefit for patients and their families with inherited forms of neuromyotonia. Other treatment is symptomatic and supportive.

Of interest to patients with neuromyotonia is a clinical trial sponsored by the National Institute for Neurological Disorders and Stroke (NINDS) entitled Screening: Neurological Disorders with Muscle Stiffness.

The purpose of the trial is to evaluate about 60 patients for possible participation in future research studies and clinical trials. In addition to providing a detailed history, persons selected will undergo magnetic resonance imaging studies, blood work-ups and electromyographic (EMG) analysis.

For further information contact:
Patient Recruitment and Liaison Office
National Institute for Neurological Disorders and Stroke
9000 Rockville Pike
Bethesda, MD 20892
Tel: 1-800-411-1222
e-mail: prpl@mail.cc.nih.gov
Study ID Numbers are: 010145; 01-N-0145

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Episodic Ataxia Type 1. Entry Number; 160120: Last Edit Date; 4/7/2003.

TEXTBOOKS
Vincent A. Neuromyotonia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:635.

Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1496.

Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:2170.

Adams RD, Victor M, Ropper AA, eds. Principles of Neurology. 6th ed. McGraw-Hill Companies. New York, NY; 1997:1490-93.

REVIEW ARTICLES
Arimura K, Sonoda Y, Watanabe O, et al. Isaac’s syndrome as a potassium channelopathy of the nerve. Muscle Nerve. 2002;Supple 11:S55-58.

Gutmann L, Libell D, Gutmann L. When is myokymia neuromyotonia? Muscle Nerve. 2001;24:151-53.

Benetar M. Neurological potassium channelopathies. QJM. 2000;93:787-97.

Vincent A. Understanding myotonia. Muscle Nerve. 2000;23:655-57.

Lawson K. Is there a role for potassium channel openers in neuronal ion channel disorders? Expert Opin Invest Drugs.2000;9:2269-80

JOURNAL ARTICLES
Vernino S, Lennon VA. Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve. 2002;26:702-07.

Daube JR. Myokymia and neuromyotonia. Muscle Nerve. 2001;24:1711-12.

Liguori R, Vincent A, Clover L, et al. Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to votage-gated potassium channels. Brain. 2001;124:2417-26.

Hayat GR, Kulkantrakorn K, Campbell WW, et al. Neuromyotonia: autoimmune pathogenesis and response to immune modulating therapy. J Neurol Sci. 2000;181:38-43.

Nakatsuji Y, Kaido M, Sugai F, et al. Isaacs’ syndrome successfully treated by a immunoadsorption plasmapheresis. Acta Neurol Scand. 2000;102:271-73.

Alessi G, De Reuck J, De Bleecker, et al. Successful immunoglobulin treatment in a patient with neuromyotonia. Clin Neurol Neurosurg. 2000;102:173-75.

Van den Berg JS, van Engelen BG, Boerman RH, et al. Acquired neuromyotonia: superiority of plasma exchange over high-dose intravenous immunoglobulin. J Neurol. 1999;57:623-25.

FROM THE INTERNET
NINDS Isaac’s syndrome Information Page. Reviewed: 01-28-2003. 2pp.
www.ninds.nih.gov/health_and_medical/disorders/isaacs_syndrome.htm

Muscle Fiber Activity & Cramps. Isaac’s Syndrome. nd. 4pp.
www.neuro.wustl.edu/neuromuscular/mother/activity.htlm

HONselect. Isaac Syndrome. Last modified: Mar 28, 2003. 2pp.
www.hon.ch/cgi-bin/HONselect?browse+C05.651.392

Verma A. Isaacs’ Syndrome. Baylor College of Medicine. Department of Neurology. nd. 3pp.
www.bcm.tmc.edu/neurol/index.html

Song S. Myokymia. EMedicine. Last Updated: April 26, 2002. 10pp.
www.emedicine.com/neuro/topic235.htm