(See also Overview of Peripheral Nervous System Disorders Overview of Peripheral Nervous System Disorders The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves and spinal nerves from their origin to their end. The anterior... read more .)
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 
. 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 
, 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.
Cause of Isaacs syndrome is unknown. Abnormalities are thought to originate in peripheral nerves Overview of Peripheral Nervous System Disorders The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves and spinal nerves from their origin to their end. The anterior... read more 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 Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more 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.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
carbamazepine |
Carbatrol, Epitol , Equetro, Tegretol, Tegretol -XR |
phenytoin |
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek |
gabapentin |
Active-PAC with Gabapentin, Gabarone , Gralise, Horizant, Neurontin |
mexiletine |
Mexitil |
lamotrigine |
Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR, Subvenite |
clonazepam |
Ceberclon , Klonopin |
prednisone |
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS |
azathioprine |
Azasan, Imuran |
