Isaacs syndrome is an autoimmune peripheral nerve disorder that causes neuromuscular manifestations, including continuous muscle twitching (myokymia).
(See also Overview of Peripheral Nervous System Disorders.)
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 muscle cramps, stiffness, 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 (1), and many have other solid tumors, which may be diagnosed by chest CT or MRI.
Diagnosis reference
1. van Sonderen A, Ariño H, Petit-Pedrol M, et al: The clinical spectrum of Caspr2 antibody–associated disease. Neurology 87 (5):521–528, 2016. doi: 10.1212/WNL.0000000000002917 Epub 2016 Jul 1.
Treatment of Isaacs Syndrome
Medications to relieve symptoms
Plasma exchange or IV immune globulin (IVIG)
Plasma exchange and, to a lesser degree, IVIG are usually beneficial (3
Treatment references
1. Ahmed A, Simmons Z: Isaacs syndrome: A review. Muscle Nerve 52 (1):5–12, 2015. doi: 10.1002/mus.24632 Epub 2015 Mar.
2. Muacevic A, Adler JR, Horiuchi K, et al: Cureus 14 (10): e30100, 2022. doi: 10.7759/cureus.30100 Epub 2022 Oct 9.
3. Newsom-Davis J, Mills KR: Immunological associations of acquired neuromyotonia (Isaacs' syndrome): Report of five cases and literature review. Brain 116 ( Pt 2):453–469, 1993. doi: 10.1093/brain/116.2.453
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.
