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Isaacs Syndrome



Michael Rubin

, MDCM, New York Presbyterian Hospital-Cornell Medical Center

Reviewed/Revised Apr 2022 | Modified Sep 2022

Isaacs syndrome is an autoimmune peripheral nerve disorder that causes neuromuscular manifestations, including continuous muscle twitching (myokymia).

Isaacs syndrome (neuromyotonia) is an autoimmune peripheral nerve hyperexcitability syndrome, generally thought to be a voltage-gated potassium channelopathy; it sometimes occurs as a paraneoplastic syndrome Paraneoplastic Syndromes Paraneoplastic syndromes are symptoms that occur at sites distant from a tumor or its metastasis. Although the pathogenesis remains unclear, these symptoms may be secondary to substances secreted... read more Paraneoplastic Syndromes . It may also accompany other disorders (eg, myasthenia gravis Myasthenia Gravis Myasthenia gravis is characterized by episodic muscle weakness and easy fatigability caused by autoantibody- and cell-mediated destruction of acetylcholine receptors. It is more common among... read more , thymoma, Hashimoto thyroiditis Hashimoto Thyroiditis Hashimoto thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Findings include painless thyroid enlargement and symptoms of hypothyroidism. Diagnosis... read more , vitamin B12 deficiency Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage... read more , celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more Celiac Disease , connective tissue disorders Introduction to Connective Tissue Disorders in Children There are over 200 disorders that involve connective tissue. Certain disorders are characterized by overactivity of the immune system with resulting inflammation and systemic damage to the tissues... read more ) or can be inherited.

Symptoms and Signs of Isaacs Syndrome

In Isaacs syndrome, the limbs are most affected. The sine qua non is myokymia—continuous muscle twitching described as bag-of-worms movements. Other symptoms include fasciculations, carpopedal spasms, intermittent cramps, increased sweating, and pseudomyotonia (impaired relaxation after a strong muscle contraction but without the typical waxing-and-waning electromyography [EMG] abnormality of true myotonia).

Diagnosis of Isaacs Syndrome

  • Clinical evaluation

  • Results of nerve conduction and EMG studies

The diagnosis of Isaacs syndrome is based on the above clinical findings and results of nerve conduction and EMG studies, which show characteristic abnormalities; these abnormalities include after-discharges on nerve conduction studies and, on needle EMG studies, fasciculation potentials, myokymic discharges, neuromyotonic discharges, fibrillation potentials, and cramp discharges, most prominent in distal limb muscles.

Laboratory testing should include tests for antibodies to contactin-associated protein-like 2 (Caspr2), the striational voltage-gated calcium channel, gliadin, glutamic acid decarboxylase (GAD), muscle acetylcholine receptor (AChR), and the voltage-gated potassium channel. About 20% of patients with Caspr2 antibodies have thymoma or other solid tumors, which may be diagnosed by chest CT or MRI.

Treatment of Isaacs Syndrome

  • Drugs to relieve symptoms

  • Plasma exchange or IV immune globulin (IVIG)

Drugs that may relieve symptoms of Isaac syndrome include carbamazepine, phenytoin, gabapentin, mexiletine (experience is limited), valproate, lamotrigine, and clonazepam.

Key Points

  • The sine qua non of Isaac syndrome is myokymia—continuous muscle twitching described as bag-of-worms movements, typically in the limbs.

  • Diagnose based on clinical findings, results of nerve conduction and EMG studies, and laboratory testing for specific antibody markers.

  • Treat with drugs to relieve symptoms (eg, carbamazepine, phenytoin, gabapentin), plasma exchange, and sometimes IVIG.

Drugs Mentioned In This Article

Drug Name Select Trade
Carbatrol, Epitol , Equetro, Tegretol, Tegretol -XR
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek
Active-PAC with Gabapentin, Gabarone , Gralise, Horizant, Neurontin
Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR, Subvenite
Ceberclon , Klonopin
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
Azasan, Imuran
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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