NORD gratefully acknowledges Professor Matthew Kiernan AM, PhD, DSc, FRACP, FAHMS Bushell Chair of Neurology, Brain & Mind Centre, The University of Sydney, for assistance in the preparation of this report.
Acquired neuromyotonia is an inflammatory disorder characterized by abnormal nerve impulses from the peripheral nerves that result in continuous muscle fiber activity. Affected individuals often experience progressive muscle stiffness and cramping especially in the hands and feet, increased sweating (hyperhidrosis), and delayed muscle relaxation. Symptoms may persist even during sleep or under general anesthesia.
Acquired neuromyotonia is characterized by involuntary continuous muscle fiber activity (fasciculations, doublet and triplet discharges on electromyography) that cause stiffness and delayed relaxation in the affected muscles. Muscle twitching with a rippling appearance (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 motor 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 under the skin. These movements continue during sleep. Diminished reflexes are also frequently a sign of this disorder. In some instances, muscle relaxation following voluntary muscle movement is delayed (grip myotonia) in the affected muscles. For example, affected individuals may not be able to open their fists or eyes immediately after closing them tightly for a few seconds.
Affected individuals frequently have excessive sweating (hyperhidrosis), rapid heartbeats (tachycardia) and weight loss. Symptoms of pain are common.
In slightly fewer than 20% of patients, a set of symptoms, including arrhythmias, excessive salivation, memory loss, confusion, hallucinations, constipation, personality change and sleep disorders, are found. In such cases the disorder may be referred to as Morvan syndrome.
Approximately 20% of affected individuals have a tumor of the thymus gland (thymoma). The thymus glands are the source of a number of specialized cells associated with autoimmune functions. The disorder is also associated with peripheral neuropathies and autoimmune diseases including myasthenia gravis in some individuals. It has also been reported following infections and radiation therapy.
Acquired neuromyotonia is an autoimmune disease in which the immune system malfunctions so that it damages parts of one’s own body. Approximately 40% of affected individuals have antibodies to voltage-gated potassium channels (VGKC’s) that affect the points at which the signals from the nerve fiber meet the muscle cell (neuromuscular junction).
Aquired neuromyotonia is a rare disorder affecting males and females but is slightly more common among men. Disease onset is usually between the ages of 15 and 60 years but has also been reported in childhood.
The diagnosis of acquired neuromyotonia is based 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). Serum investigations include auto-immune serology and specifically testing for the presence of anti-VGKC.
Acquired neuromyotonia may be treated with anticonvulsant drugs such as phenytoin or 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.
Testing for acetylcholine receptor antibodies should be done if thymoma is suspected. The thymus gland should be surgically removed if thymoma is present.
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Adams RD, Victor M, Ropper AA, eds. Principles of Neurology. 6th ed. McGraw-Hill Companies. New York, NY; 1997:1490-93.
Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:2170.
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.
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.
Vincent A, Pettingill P, Pettingill R, Lang B, Birch R, Waters P, Kiernan MC. Association of leucine-rich glioma inactivated protein 1, contactin-associated protein 2, and contactin 2 antibodies with clinical features and patient-reported pain in acquired neuromyotonia. JAMA Neurol. 2018 Dec 1;75(12):1519-1527.
Noto Y, Simon NG, Selby A, Garg N, Shibuya K, Shahrizaila N, Kiernan MC. Ectopic impulse generation in peripheral nerve hyperexcitability syndromes and amyotrophic lateral sclerosis. Clinical Neurophysiology. 2018;129(5):974-80.
Kiernan MC, Vucic S, Cheah BC, et al. Amyotrophic lateral sclerosis. The Lancet. 2011;377:942-955.
Vucic S, Cheah BC, Yiannikas C, Vincent A and Kiernan M. Corticomotoneuonal function and hyperexcitability in acquired neuromyotonia. Brain. 2010:133;2727-2733.
Imam I, Edwards, S and Hanemann CO. Acquired neuromyotonia following upper respiratory tract infection: a case report. Cases Journal. 2009:2:7982.
Gonzelez G, Barros G, Russi ME, Nunez A and Scavone C. Acquired neuromyotonia in childhood: case report and review. Ped Neurol. 2008:38;61-63.
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.
NINDS Isaac’s syndrome Information Page. Last Update 2019-03-27. https://www.ninds.nih.gov/Disorders/All-Disorders/Isaacs-Syndrome-Information-PageAccessed. Accessed Feb 13, 2020.
Hasan SM, D’Adamo MC. Episodic Ataxia Type 1. 2010 Feb 9 [Updated 2018 Nov 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK25442/ Accessed Feb 13, 2020.
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