Acquired Neuromyotonia Heralding Recurrent Thymoma in Myasthenia Gravis

Isaacs’ syndrome in pregnancy

“…Patients with the triad of neuromyotonia, encephalopathy and hyperhidrosis are considered to have Morvan syndrome 2. Some reports identify Isaacs’ syndrome synonymously with neuromyotonia,1 while others report Isaacs’ syndrome more specifically as an acquired neuromyotonia 4 7 11. Other terms referring to this disorder include continuous muscle fibre activity syndrome,12 Quantal Squander syndrome, Armadillo syndrome, Mertens’ syndrome, Mertens-Isaacs’ syndrome, neurotonia, myotonia with impaired muscular relaxation and generalised myokymia 1…”

“…Isaacs’ syndrome is most commonly acquired and associated with autoimmune disorders such as myasthenia gravis,1 Lambert-Eaton myasthenia syndrome,13 Hashimoto thyroiditis, Addison disease, vitiligo, vitamin B 12 deficiency, coeliac disease, rheumatoid arthritis2 4 10 and Guillaine-Barre syndrome 1 9. It has also been associated with infection,1 drugs such as penicillamine,2 exposure to toxins1 and pregnancy 6.…”

“…These antibodies are directed against proteins that form a complex with VGKCs such as LGI1 and Caspr2 as well as other unknown proteins 4. LGI1 is localised to CNS synapses and Caspr2 organises VGKC's on both central and peripheral nervous system axons 4 11. The antibodies do not directly affect VGKC kinetics but rather act to decrease channel density on nerve terminals 7.…”

“…Treatment of this disorder commonly includes anticonvulsants such as phenytoin, carbamazapine, gabapentin, sodium valproate, lamotrigine and acetazolamide 1 4 8 17. Botulinum toxin type A has also been successful in symptom management 17 18.…”

“…The inherited form is associated with episodic ataxia type 1, an autosomal dominant disorder that involves a point mutation in the KCNA1 gene, which encodes a voltage-gated potassium channel (VGKC) subunit 2 3. More commonly Isaacs’ syndrome is acquired and many patients have antibodies directed against VGKC associated proteins 4. The acquired form is usually seen in association with autoimmune disorders, infections, medications, toxin exposure1 and cancer 2 5.…”