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Isaacs Syndrome



Michael Rubin

, MDCM, New York Presbyterian Hospital-Cornell Medical Center

Last full review/revision Dec 2020| Content last modified Dec 2020
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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. It may also accompany other disorders (eg, myasthenia gravis, thymoma, Hashimoto thyroiditis, vitamin B12 deficiency, celiac disease, connective tissue disorders) or can be inherited.

Cause of Isaacs syndrome is unknown. Abnormalities are thought to originate in peripheral nerves because abnormalities are abolished by curare but usually persist after general anesthesia.

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.

Plasma exchange and, to a lesser degree, IVIG are usually beneficial and are often used with prednisone and azathioprine.

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.

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