Disease relevance of Isaacs Syndrome

• Neurophysiological studies indicated that this was due to neuromyotonia mainly involving flexor digitorum superficialis muscles without evidence of underlying peripheral neuropathy, proximal conduction block, or generalised neuromyotonia [1].
• We conclude that mutations in the potassium channel gene (KCNA1) can cause severe neuromyotonia resulting in marked skeletal deformities even if episodic ataxia is not prominent [2].
• Idiopathic generalized myokymia (Isaacs' syndrome) with hand posturing resembling dystonia [3].
• A case of SLE is presented in which muscle twitching and muscle cramps were associated with an autoantibody directed against the voltage-gated potassium channel of peripheral nerves (Isaacs' syndrome) [4].
• Thymoma-associated neuromyotonia with antibodies against voltage-gated potassium channels presenting as chronic intestinal pseudo-obstruction [5].

High impact information on Isaacs Syndrome

• CONCLUSION: The acute neurotoxicity seen with oxaliplatin is characterized by peripheral-nerve hyperexcitability, and the findings are similar to the clinical manifestations of neuromyotonia [6].
• The quantal release of acetylcholine (quantal content) at end-plates in diaphragms from mice treated with neuromyotonia IgG preparations was increased by 21% relative to control values (p = 0.0053) [7].
• We conclude that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine- or alpha-dendrotoxin-sensitive K+ channels in motor and sensory neurons, and they are likely to be implicated in the disease process [7].
• Hereditary neuromyotonia: a mouse model associated with deficiency or increased gene dosage of the PMP22 gene [8].
• By comparison, analysis of the large glycolytic triceps muscle, a forelimb muscle which does not receive pseudomyotonia, indicated that this muscle did not increase in SDH activity in dystrophic animals, which showed the abnormal increase in the activity of the hind limb gastrocnemius [9].

Chemical compound and disease context of Isaacs Syndrome

• Phenytoin is known to reduce neural overactivity (pseudomyotonia) affecting the hind limb musculature in C57B1/6J dystrophic (dy2J/dy2J) mice [10].
• Valproic acid in Isaacs-Mertens syndrome [11].
• Electrophoresis of serum from a patient with Isaacs' syndrome revealed an atypical creatine kinase (CK) isoenzyme pattern which contained an extra band migrating between CK2(MB) and CK3(MM) [12].
• Decreased conduction velocity and pseudomyotonia in hexachlorobenzene-fed rats [13].
• Penicillamine-induced neuromyotonia [14].

Biological context of Isaacs Syndrome

• In these conditions, a proportion of the patients have an underlying tumour, thymoma in both MG and neuromyotonia and small cell lung carcinoma in LEMS, emphasising the putative role of autoimmunity to tumour antigens as a cause of neurological disease [15].

Anatomical context of Isaacs Syndrome

• Myasthenia gravis, the Lambert-Eaton myasthenic syndrome, and acquired neuromyotonia are three disorders of the neuromuscular junction or motor nerve that are caused by autoantibodies to ion channel proteins: acetylcholine receptors, voltage-gated calcium channels and voltage-gated potassium channels, respectively [16].

Gene context of Isaacs Syndrome

• Neuromyotonia, systemic lupus erythematosus and acetylcholine-receptor antibodies [17].
• This indicates that spontaneous motor unit activity may underlie neuromyotonia, which is occasionally observed in Charcot-Marie-Tooth disease [18].
• Systemic juvenile rheumatoid arthritis and associated Isaacs' syndrome [19].
• Sequential antibodies to potassium channels and glutamic acid decarboxylase in neuromyotonia [20].
• Intermittent diplopia and strabismus caused by ocular neuromyotonia [21].

Analytical, diagnostic and therapeutic context of Isaacs Syndrome

• A patient with thymoma-associated neuromyotonia and voltage-gated potassium channel (Kv1.2 and Kv1.6) antibodies by immunoprecipitation and rat brain immunolabeling was treated successfully with immunoadsorption and cyclophosphamide [20].

References