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Isaacs syndrome

This is part of Rare diseases.

Diagnosis: Isaacs syndrome

Synonyms: --

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Publication date: 2011-12-29
Version: 3.0

ICD 10 code

G71.1

The Disease

Isaacs syndrome is the most well-known syndrome associated with neuromyotonia (neuro = nerve, myotonia = muscle stiffness). Neuromytonia is a condition caused by rapid bursts of nerve impulses, resulting in muscle twitching and cramping

Isaacs syndrome was first described by South African physician Hyam Isaacs in 1961, and is also known as acquired neuromytonia.

Occurrence

The occurrence of Isaacs syndrome is unknown, but it is estimated that a maximum of twenty individuals in Sweden have the disease.

Cause

Evidence suggests that Isaacs syndrome is an autoimmune disease, meaning that the immune system is impaired and attacks the body’s own tissues. The individual may, for example, produce autoreactive antibodies. In Isaacs syndrome autoreactive antibodies target voltage-gated potassium channels (VGKCs). These antibodies block the function of these channels or cause them to degenerate.

VGKCs are located on the cell membranes of nerve fibres and extend all the way from the spinal cord to the muscles. Their function is to restore the voltage difference between the outside and inside of the nerve fibre after a nerve impulse has passed. Impaired VGKC function prolongs the effect of the nerve impulse (depolarisation), resulting in spontaneous serial repetitions. This phenomenon is referred to as neuromyotonia and causes muscular contractions.

The premise that antibodies attacking potassium channels causes Isaacs syndrome, is supported by the effectiveness of plasmapheresis, a procedure that temporarily removes antibodies from the blood. The syndrome often occurs concurrently with other autoimmune conditions including gluten sensitivity (coeliac disease), insulin-dependent diabetes, rheumatic diseases and myasthenia gravis (exercise-induced muscle weakness), providing further evidence that Isaacs syndrome is an autoimmune disease. Sometimes thymoma (a benign tumour of the thymus), also manifests in people with Isaacs syndrome.

Heredity

Isaacs syndrome is not a hereditary condition.

Symptoms

Muscle stiffness usually presents during adolescence, although many individuals remain asymptomatic until adulthood. The condition can manifest in two ways. One form is characterised by prolonged, involuntary, muscle activity (myokymia, from myo = muscle and kyma = wave). The other form is characterised by muscles failing to relax after intense activity (myotonia, neuromyotonia). High levels of muscle activity cause the muscles of the trunk, arms, and legs to become stiff, rigid and tense for long periods. Elevated levels of muscular activity persist, even during sleep and under general anaesthesia. The condition is visible as muscle contractions ripple along the muscle, under the skin. Stiffness is more pronounced in the hands and feet than in the upper arms and thighs. The gait becomes stiff and tense. Continuous muscular activity results in increased muscle stiffness and fatigue, and in temporary muscle weakness. Tongue and pharyngeal muscles are sometimes affected, leading to swallowing difficulties and hoarseness.

Approximately one third of people with Isaacs syndrome experience numbness and tingling in the skin, but they do not experience muscle pain. Weight loss may occur and some individuals perspire excessively owing, it is thought, to the increased energy expenditure required by constant muscular activity.

There is a form of Isaacs syndrome characterised not only by muscle activity and excessive perspiration, but also by its effect on the brain. Symptoms include personality changes, hallucinations, mood swings and sleeping disorders. This variant is known as Morvan syndrome.

Diagnosis

An electromyogram (EMG) is used to diagnose neuromyotonia. An EMG entails inserting a thin needle into a muscle and registering its electrical activity. In Isaacs syndrome an EMG will show evidence of neuromyotonia, presenting as a series of very high frequency discharges (150 to 300 times/second (Hz)) in the muscles. The EMG will also reveal myokymia, manifesting as rhythmic bursts of activity with two, three or more sets of electrical discharges. The frequency of the discharges is between two and ten per second (Hz). Myokymia may also present in a number of other neurological disorders involving muscle paralysis.

When neuromyotonia is confirmed, the concentrations of certain chemicals in the blood (calcium, magnesium, phosphate and potassium) are measured in order to exclude imbalances between these substances as the underlying cause of the disorder. If Isaacs syndrome is suspected, a test to establish the presence of antibodies directed at the potassium channel should be performed. Approximately 40 per cent of all those with Isaacs syndrome have elevated levels of these antibodies (anti-VGKC), although in certain cases this can indicate other diseases. It is therefore important that the results of all investigations are considered before a diagnosis is made.

Spinal fluid analyses may sometimes indicate that the immune system has become active.

A computer tomography (a CT scan) or magnetic resonance imaging (MRI scan) of the chest should be carried out to exclude a tumour in the thymus. Thymoma is present in approximately 20 per cent of people with Isaacs syndrome.

Myasthenia gravis is present in 10 to 20 per cent of people with the syndrome, and is particularly common in thymoma patients.

Treatment/interventions

There is currently no cure for the disorder, and efforts are directed at relieving symptoms. Much can be done to support the individual and compensate as much as possible for functional limitations. All interventions should be adapted to suit the age and lifestyle of the individual.

Medication can relieve muscle cramps and stiffness (neuromyotonia.) Anticonvulsants used to alleviate muscle cramping include carbamazepine, phenytoin, sodium valproate or gabapentin (all of which are commonly used to treat epileptic seizures). Baclophen, a drug commonly used in the treatment of spasticity, may also be prescribed.

Immunomodulating treatment aims to modify immune reactions. The most effective immune therapy is plasmapheresis, in which harmful antibodies are filtered out of the bloodstream. As the effect is only temporary, plasmapheresis is combined with other treatments such as high doses of immunoglobulin, cortisone or other forms of immunosuppressive medication. A period of treatment often keeps patients symptom-free for several years.

Thymomas are removed surgically.

There should be contact with a physiotherapist, who can design a suitable exercise programme and provide general advice. Depending on the individual’s degree of functional disability, new work routines and individualized adaptations and aids may be necessary to help in daily life. If necessary, the home, car and workplace can be adapted to individual needs. An occupational therapist can analyse the need for assistance.

It is important that the psychological and social needs of the whole family are met. Support may be offered by a social worker and/or psychologist.

It is helpful to be well-informed about the disorder when making choices about education and what games and sports to participate in. When deciding on a suitable career, it is important to avoid jobs requiring a high degree of physical exertion. Career guidance and occupational assessment are provided by the Swedish National Labour Market Administration. They also assist in finding suitable workplaces.

The needs of individuals vary greatly. With the correct diagnosis and appropriate treatment, a person with the disease can lead a near-normal life.

Practical advice

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National and regional resources in Sweden

Assessments of people with muscle diseases are carried out primarily at neurology clinics at Swedish university hospitals. People with Isaacs syndrome should be examined by a neurologist with specialist knowledge of the syndrome.

Resource personnel

Associate Professor Christopher Lindberg, Neuromuscular Centre, Sahlgrenska University Hospital/Sahlgrenska, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 10 00, email: christopher.lindberg@vgregion.se.

Courses, exchanges of experience, recreation

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Organizations for the disabled/patient associations

NHR, The Swedish Association for Persons with Neurological Disabilities, St Eriksgatan 44, Stockholm. Mailing address: Box 49084, SE-100 28 Stockholm, Sweden. Tel: +46 8 677 70 10, fax: +46 8 677 13 15, email: nhr@nhr.se, www.nhr.se.

RBU, The Swedish National Association for Disabled Children and Young People, St Eriksgatan 44, Stockholm. Mailing address: Box 8026, SE-104 20 Stockholm, Sweden. Tel: +46 8 677 73 00, fax: +46 8 677 73 09, email: info@riks.rbu.se, www.rbu.se.

Courses, exchanges of experience for personnel

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Research and development (R&D)

Research into autoimmune mechanisms and the association between autoimmune disorders and thymoma is being carried out by Dr Angela Vincent and Dr John Newsom-Davis at the John Radcliffe Hospital in Oxford, England.

Information material

An information leaflet on Isaacs syndrome that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2004-126-1176.) Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.

Literature

Gutmann L, Gutmann L. Myokymia and neuromyotonia. J Neurol 2004; 251: 138-142.

Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR. Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 2002; 125: 1887-1985.

Isaacs H. A syndrome of continuous muscle-fibre activity. J Neurol Neurosurg Psychiatry 1961; 24: 319-325.

Isaacs H. Continuous muscle fibre activity in an Indian male with additional evidence of terminal motor fibre abnormality. J Neurol Neurosurg Psychiatry 1967; 30: 126-133.

Lee EK, Maselli RA, Ellis WG, Agius MA. Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma. J Neurol Neurosurg Psychiatry 1998; 65: 857-862.

Liguori R, Vincent A, Clover L, Avoni P, Plazzi G, Cortelli P et al. Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 2001; 124: 2417-2426.

Maddison P, Mills KR, Newsom-Davis J. Clinical electrophysiological characterization of the aquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitability. Muscle Nerve 2006; 33: 801-808.

Nakatsuji Y, Kaido M, Sugai F, Nakamori M, Abe K, Watanabe O et al. Isaacs’ syndrome successfully treated with immunoadsorption plasmapheresis. Acta Neurol Scand 2000; 102: 271-273.

Newsom-Davis J, Mills KR. Immunological associations of acquired neuromyotonia (Isaacs’ syndrome). Brain 1993; 116: 453-469.

Shillito P, Molenaar PC, Vincent A, Leys K, Zheng W, van der Berg RJ et al. Acquired Neuromyotonia: Evidence for autoantibodies directed against K channels of peripheral nerves. Ann Neurol 1995; 38: 714-722.

Van den Berg JS, van Engelen BG, Boerman RH, de Baets MH. Acquired neuromyotonia: superiority of plasma exchange over high-dose intravenous human immunoglobulin. J Neurol 1999; 246: 623-625.

Database references

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Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Associate Professor Christopher Lindberg, Sahlgrenska University Hospital in Gothenburg, Sweden.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Publication date: 2011-12-29
Version: 3.0
Publication date of the Swedish version: 2011-10-05

For enquiries contact The Swedish Information Centre for Rare Diseases, -The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.