isaacs syndrome

Summary

Summary: A rare neuromuscular disorder with onset usually in late childhood or early adulthood, characterized by intermittent or continuous widespread involuntary muscle contractions; FASCICULATION; hyporeflexia; MUSCLE CRAMP; MUSCLE WEAKNESS; HYPERHIDROSIS; TACHYCARDIA; and MYOKYMIA. Involvement of pharyngeal or laryngeal muscles may interfere with speech and breathing. The continuous motor activity persists during sleep and general anesthesia (distinguishing this condition from STIFF-PERSON SYNDROME). Familial and acquired (primarily autoimmune) forms have been reported. (From Ann NY Acad Sci 1998 May 13;841:482-496; Adams et al., Principles of Neurology, 6th ed, p1491)

Top Publications

  1. Oh S, Alapati A, Claussen G, Vernino S. Myokymia, neuromyotonia, dermatomyositis, and voltage-gated K+ channel antibodies. Muscle Nerve. 2003;27:757-60 pubmed
    ..The presence of antibodies to voltage-gated potassium channels and the association with dermatomyositis indicated an autoimmune cause for myokymia, which may have been due to reversible peripheral nerve hyperexcitability...
  2. Sukajintanakarn D, Mitrabhakdi E, Phanthumchinda K. Acquired neuromyotonia (Isaacs' syndrome): a case report with autonomic physiologic studies. J Med Assoc Thai. 2006;89:1308-12 pubmed
    ..The investigations for conditions associated with Isaacs' syndrome were unrevealing. VGKCs antibody were not performed. Treatment with carbamazepine resulted in substantial improvement of the symptoms within 7 days...
  3. Dhand U. Isaacs' syndrome: clinical and electrophysiological response to gabapentin. Muscle Nerve. 2006;34:646-50 pubmed
    ..Subsequent nerve conduction studies showed decreased amplitude and later an absence of M-wave afterdischarges. Gabapentin thus appears to be an effective treatment for Isaacs' syndrome...
  4. Fukushima K, Sato T, Mitsuhashi S, Kaneko K, Yazaki M, Matsuda M, et al. Isaacs' syndrome associated with myasthenia gravis, showing remission after cytoreductive surgery of pleural recurrence of thymoma. Neuromuscul Disord. 2006;16:763-5 pubmed
    ..Cytoreductive treatment for recurrent thymoma should be actively considered as a potent therapeutic option in refractory patients with disabling neuromyotonia symptoms...
  5. Testoni S, Boni P, Gentile A. Congenital pseudomyotonia in Chianina cattle. Vet Rec. 2008;163:252 pubmed
  6. Drogemuller C, Drogemuller M, Leeb T, Mascarello F, Testoni S, Rossi M, et al. Identification of a missense mutation in the bovine ATP2A1 gene in congenital pseudomyotonia of Chianina cattle: an animal model of human Brody disease. Genomics. 2008;92:474-7 pubmed publisher
    ..491G>A) leading to a p.Arg164His substitution. Arg164 represents a functionally important and strongly conserved residue of SERCA1. This study provides a suitable large animal model for human Brody disease...
  7. Liguori R, Vincent A, Clover L, Avoni P, Plazzi G, Cortelli P, et al. Morvan's syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain. 2001;124:2417-26 pubmed
    ..The relationship between VGKC antibodies, neurohormonal levels, autonomic, limbic and sleep disorders requires further study...
  8. Sacchetto R, Testoni S, Gentile A, Damiani E, Rossi M, Liguori R, et al. A defective SERCA1 protein is responsible for congenital pseudomyotonia in Chianina cattle. Am J Pathol. 2009;174:565-73 pubmed publisher
    ..We believe that Chianina cattle pseudomyotonia might, therefore, be the true counterpart of human Brody's disease, and that bovine species might be used as a suitable animal model...
  9. Tomlinson S, Tan S, Kullmann D, Griggs R, Burke D, Hanna M, et al. Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1. Brain. 2010;133:3530-40 pubmed publisher
    ..1 dysfunction in patients with episodic ataxia type 1. The simple 15 min test may be useful in diagnosis, since it can differentiate patients with episodic ataxia type 1 from normal controls with high sensitivity and specificity. ..

More Information

Publications62

  1. Tomimitsu H, Arimura K, Nagado T, Watanabe O, Otsuka R, Kurono A, et al. Mechanism of action of voltage-gated K+ channel antibodies in acquired neuromyotonia. Ann Neurol. 2004;56:440-4 pubmed
    ..Thus, cross-linking of the channels by divalent antibodies is likely to be an important mechanism in reducing K+ currents...
  2. Kleopa K, Elman L, Lang B, Vincent A, Scherer S. Neuromyotonia and limbic encephalitis sera target mature Shaker-type K+ channels: subunit specificity correlates with clinical manifestations. Brain. 2006;129:1570-84 pubmed
    ..Although more than one type of antibody is often detectable in individual sera, higher affinity for certain subunits or subunit combinations may determine the range of clinical manifestations...
  3. Antozzi C, Frassoni C, Vincent A, Regondi M, Andreetta F, Bernasconi P, et al. Sequential antibodies to potassium channels and glutamic acid decarboxylase in neuromyotonia. Neurology. 2005;64:1290-3 pubmed
    ..The range of antibodies produced in thymoma-associated neuromyotonia is richer, and the timing of antibody appearance more complex, than previously suspected...
  4. Grünberg W, Sacchetto R, Wijnberg I, Neijenhuis K, Mascarello F, Damiani E, et al. Pseudomyotonia, a muscle function disorder associated with an inherited ATP2A1 (SERCA1) defect in a Dutch Improved Red and White cross-breed calf. Neuromuscul Disord. 2010;20:467-70 pubmed publisher
    ..Arg559Cys). The present case presents similarities to human Brody's disease, but also to pseudomyotonia and congenital muscular dystonia previously described in different cattle breeds...
  5. Paterson R, Zandi M, Armstrong R, Vincent A, Schott J. Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre. J Neurol Neurosurg Psychiatry. 2014;85:625-30 pubmed publisher
    ..However, there are patients with positive levels in whom the significance is uncertain...
  6. Asensio Sánchez V, Morales Gómez I, Rodríguez Vaca I. [Ocular neuromyotonia]. Arch Soc Esp Oftalmol. 2008;83:673-4 pubmed
    ..He developed a large angle exotropia of the left eye that gradually returned to normal after 50 seconds. Between episodes he was asymptomatic. Partial resolution of his symptoms was obtained after treatment with carbamazepine...
  7. Maddison P. Neuromyotonia. Clin Neurophysiol. 2006;117:2118-27 pubmed
    ..Clinical, electrophysiological and immunological measurements are important in defining the phenotype of neuromyotonia, and other, milder forms of peripheral nerve hyperexcitability...
  8. Fontaine B. Muscle channelopathies and related diseases. Handb Clin Neurol. 2013;113:1433-6 pubmed publisher
    ..The creation of specialized reference centers in the Western world has greatly benefited the proper recognition of these neuromuscular diseases...
  9. Vincent A. Antibody-mediated disorders of neuromuscular transmission. Suppl Clin Neurophysiol. 2004;57:147-58 pubmed
  10. Irani S, Alexander S, Waters P, Kleopa K, Pettingill P, Zuliani L, et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain. 2010;133:2734-48 pubmed publisher
  11. Gantenbein A, Wiederkehr M, Meuli Simmen C, Schwegler G. Focal neuromyotonia: do I love you?. J Neurol. 2010;257:1727-9 pubmed publisher
    ..This clinical picture shows a rare but rather salient differential diagnosis of Dupuytren's contracture. EMG of the affected muscles may yield a diagnosis and prevent the patient from a long and ineffective treatment "odyssey"...
  12. Vanhaesebrouck A, Van Soens I, Poncelet L, Duchateau L, Bhatti S, Polis I, et al. Clinical and electrophysiological characterization of myokymia and neuromyotonia in Jack Russell Terriers. J Vet Intern Med. 2010;24:882-9 pubmed publisher
    ..Generalized myokymia and neuromyotonia (M/NM) in Jack Russell Terriers (JRTs) is related to peripheral nerve hyperexcitability syndrome in humans, a symptom complex resulting from diverse etiologies...
  13. Doi H, Arimura K, Ohyagi Y, Kira J. Frostbite-like skin lesion as an autonomic symptom of Isaacs' syndrome. Intern Med. 2011;50:1113-5 pubmed
    ..The lesion completely disappeared 2 days later. An incidental episode occurred at the same site 8 months later. Frostbite-like skin lesions may be a rare autonomic manifestation in Isaacs' syndrome...
  14. Basiri K, Fatehi F. Isaacs syndrome associated with chronic hepatitis B infection: a case report. Neurol Neurochir Pol. 2009;43:388-90 pubmed
    b>Isaacs syndrome or acquired neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by regular or irregular myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction, and hyperhidrosis...
  15. Rana S, Ramanathan R, Small G, Adamovich B. Paraneoplastic Isaacs' syndrome: a case series and review of the literature. J Clin Neuromuscul Dis. 2012;13:228-33 pubmed publisher
    ..Our objective was to discuss the relationship of Isaacs' syndrome to paraneoplastic syndromes as reported in the available literature and in 3 patients evaluated at our academic medical center...
  16. Watanabe O. [VGKC-complex antibodies]. Brain Nerve. 2013;65:401-11 pubmed
    ..Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease)...
  17. Iguchi M, Morimatsu A, Kondo T, Shirata A, Yamane K. [Case of Isaacs' syndrome associated with Hashimoto disease]. Rinsho Shinkeigaku. 2007;47:662-4 pubmed
    ..About 23% of Isaacs' syndrome cases are associated with some other autoimmune diseases and myasthenia gravis was most common. This is the first case report of Isaacs' syndrome associated with Hashimoto disease in Japan...
  18. Wermund T, Salchow D. [Ocular neuromyotonia--clinical appearance and thoughts on pathogenesis]. Klin Monbl Augenheilkd. 2009;226:881-5 pubmed publisher
    ..Neuroimaging with attention to the affected cranial nerve should be obtained in order to exclude a compressive cause. Therapy of ONM with carbamazepine is usually effective...
  19. Merchut M. Management of voltage-gated potassium channel antibody disorders. Neurol Clin. 2010;28:941-59 pubmed publisher
    ..Most cases respond favorably to immunosuppression with plasma exchange, intravenous immunoglobulin or pulse intravenous methylprednisolone, usually followed by oral steroids...
  20. Salchow D, Wermund T. Abducens neuromyotonia as the presenting sign of an intracranial tumor. J Neuroophthalmol. 2011;31:34-7 pubmed publisher
    ..Neuroimaging should be performed if patients with ANM lack the typical history of radiation therapy, as ANM may be the presenting sign of an intracranial mass...
  21. Myers K, Baker S. Late-onset seropositive Isaacs' syndrome after Guillain-Barré syndrome. Neuromuscul Disord. 2009;19:288-90 pubmed publisher
    ..When treated with intravenous immunoglobulins (IVIg) he developed an eczematous rash that differed markedly in pattern and duration from the usual presentation for this IVIg reaction...
  22. Mizuno Y, Yamaguchi H, Uehara T, Yamashita K, Yamasaki R, Kira J. A case of stiff-person syndrome due to secondary adrenal insufficiency. Rinsho Shinkeigaku. 2017;57:298-302 pubmed publisher
  23. van Waveren M, Herzau V, Besch D. [Ocular neuromyotonia after radiation therapy]. Ophthalmologe. 2009;106:47-51 pubmed publisher
    ..An adduction deficit on the right side could be triggered by holding the gaze to the right over a longer period of time, leading to exotropia in the primary position and gaze to the left. Symptoms were reduced with carbamazepine...
  24. Georgesco M, Salerno A. [Spontaneous electromyographic activity. Practical importance]. Neurophysiol Clin. 2000;30:289-305 pubmed
    ..The practical consequences are discussed and a new classification of these spontaneous activities is proposed...
  25. Rosich Estrago M. [Paraneoplastic diseases of the motor end-plate and muscle]. Rev Neurol. 2000;31:1225-8 pubmed
    ..Paraneoplastic necrotizing myopathy and some cases of inflammatory myopathy (polymyositis-dermatomyositis) are paraneoplastic myopathies...
  26. Lahrmann H, Albrecht G, Drlicek M, Oberndorfer S, Urbanits S, Wanschitz J, et al. Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin's disease. Muscle Nerve. 2001;24:834-8 pubmed
    ..The patient's complaints, including dysarthria, improved after carbamazepine treatment...
  27. Miwa H, Kajimoto Y, Takagi R, Hironishi M, Kondo T. [Isolated finger flexion caused by continuous muscle fiber activity]. No To Shinkei. 2002;54:503-6 pubmed
    ..The present findings are likely to be similar to those of a novel form of focal neuromytonia reported recently as 'isolated finger flexion'...
  28. Lang B, Vincent A. Autoantibodies to ion channels at the neuromuscular junction. Autoimmun Rev. 2003;2:94-100 pubmed
  29. Ge L, Liu Z, Xiao B, Huang Q. [A case of Isaacs syndrome]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004;29:363 pubmed
  30. Coulter D, Gold S. Thymoma in the offspring of a patient with Isaacs syndrome. J Pediatr Hematol Oncol. 2007;29:797-8 pubmed
    ..We present the first description of a child of a parent with Isaacs syndrome (congenital or acquired neuromyotonia) presenting with a thymoma...
  31. Roper Hall G, Cruz O, Espinoza G, Chung S. Cyclic (alternate day) vertical deviation--possible forme fruste of ocular neuromyotonia. J AAPOS. 2013;17:248-52 pubmed publisher
    ..Cyclic ocular deviations are relatively uncommon and are seldom seen in adults. We report 3 adult patients with cyclic hypotropia that has clinical characteristics similar to neuromyotonia, suggesting a possible common etiology...
  32. Tomlinson S, Rajakulendran S, Tan S, Graves T, Bamiou D, Labrum R, et al. Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1. J Neurol Neurosurg Psychiatry. 2013;84:1107-12 pubmed publisher
    ..1 channel function. The finding of deafness in four individuals raises the possibility of a link between K(v)1.1 dysfunction and hearing impairment. Our findings broaden the phenotypic range associated with mutations in KCNA1. ..
  33. Banks M, Caruso P, Lessell S. Midbrain-thalamic ocular neuromyotonia. Arch Ophthalmol. 2005;123:118-9 pubmed
  34. Arimura K, Arimura Y, Ng A, Uehara A, Nakae M, Osame M, et al. The origin of spontaneous discharges in acquired neuromyotonia. A Macro EMG study. Clin Neurophysiol. 2005;116:1835-9 pubmed
    ..To study the generator sites of spontaneous discharges in patients with immune-mediated neuromyotonia...
  35. Herskovitz S, Song H, Cozien D, Scelsa S. Sensory symptoms in acquired neuromyotonia. Neurology. 2005;65:1330-1 pubmed
  36. Briani C, Cagnin A, Blandamura S, Altavilla G. Multiple paraneoplastic diseases occurring in the same patient after thymomectomy. J Neurooncol. 2010;99:287-8 pubmed publisher
    ..We report on a patient who developed MG after thymomectomy for a malignant thymoma. After MG remission, NMT and Morvan's syndrome occurred, which heralded a mediastinic recurrence, as demonstrated only by autopsy findings...
  37. Canovas D, Martinez J, Viguera M, Ribera G. [Association of renal carcinoma with neuromyotonia and involvement of inferior motor neuron]. Neurologia. 2007;22:399-400 pubmed
    ..We report a rare case, given the presence of two uncommon paraneoplastic manifestations such as neuromyotonia and reversible paraneoplastic lower motor neuronopathy secondary to clear cell renal carcinoma...
  38. Plant G. Putting ocular neuromyotonia in context. J Neuroophthalmol. 2006;26:241-3 pubmed
  39. Toothaker T, Rubin M. Paraneoplastic neurological syndromes: a review. Neurologist. 2009;15:21-33 pubmed publisher
    ..PNS are believed to result from an autoimmune attack of normal neuronal tissue, spurred by similar neuronal antigens ectopically expressed by tumor cells...
  40. Fricke J, Neugebauer A, Kirsch A, Rüssmann W. Ocular neuromyotonia: a case report. Strabismus. 2002;10:119-24 pubmed
    ..The case of a 32-year-old woman suffering from intermittent diplopia six months after radiation therapy of a recurrent pituary gland adenoma is presented...
  41. Hayat G, Kulkantrakorn K, Campbell W, Giuliani M. Neuromyotonia: autoimmune pathogenesis and response to immune modulating therapy. J Neurol Sci. 2000;181:38-43 pubmed
    ..Neuromyotonia (NMT) has been postulated to be an autoimmune channelopathy, probably by affecting voltage gated potassium channels (VGKC) leading to excitation and abnormal discharges [Sinha et al., Lancet 338 (1991) 75]...
  42. Park H, Hwang J, Kim J. Abducens neuromyotonia due to internal carotid artery aneurysm. J Neurol Sci. 2008;270:205-8 pubmed publisher
    ..The episodes resolved with carbamazepine. Aneurysm of the internal carotid artery is a rare cause of abducens neuromyotonia. A compressive lesion may give rise to ocular neuromyotonia even in the absence of prior irradiation...
  43. Kleine B, Stegeman D, Drost G, Zwarts M. Interspike interval analysis in a patient with peripheral nerve hyperexcitability and potassium channel antibodies. Muscle Nerve. 2008;37:269-74 pubmed
    ..We conclude that ISI analysis is a useful tool to understand the membrane dynamics underlying abnormal motor unit activity...
  44. Murgiano L, Sacchetto R, Testoni S, Dorotea T, Mascarello F, Liguori R, et al. Pseudomyotonia in Romagnola cattle caused by novel ATP2A1 mutations. BMC Vet Res. 2012;8:186 pubmed publisher
    ..We observed symptoms of congenital PMT in four related Romagnola beef cattle from Italy and evaluated SERCA1 activity and scanned ATP2A1 for possible causative mutations...
  45. Torres L, Cosentino C, Velez M, Anicama A. [A case of Isaacs' syndrome associated with dextrocardia]. Rev Neurol. 2001;33:1151-4 pubmed
    b>Isaacs syndrome is a disorder of unknown etiology characterized by muscular rigidity, cramps and myokymias. Described by Isaacs in 1961 and called by him as continuous muscular activity syndrome...
  46. Jurkat Rott K, Lerche H, Weber Y, Lehmann Horn F. Hereditary channelopathies in neurology. Adv Exp Med Biol. 2010;686:305-34 pubmed publisher
    ..As more than 35% of marketed drugs target ion channels, there is a high chance to identify compounds that counteract the effects of the mutations...
  47. Maddison P, Mills K, Newsom Davis J. Clinical electrophysiological characterization of the acquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitability. Muscle Nerve. 2006;33:801-8 pubmed
    ..The pathogenic region of abnormality in peripheral nerve hyperexcitability disorders therefore seems to lie within the terminal branches of peripheral motor nerves...
  48. Gómez Choco M, Valls Sole J, Grau J, Graus F. Episodic hyperhidrosis as the only clinical manifestation of neuromyotonia. Neurology. 2005;65:1331-2 pubmed
  49. Skeie G, Apostolski S, Evoli A, Gilhus N, Illa I, Harms L, et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2010;17:893-902 pubmed publisher
    ..Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (Isaacs' syndrome)...
  50. Paliwal V. Neuromyotonia masquerading as tetanus. J Clin Neurosci. 2010;17:814-5 pubmed publisher
    ..We discuss differentiation of neuromyotonia from tetanus and other disorders with similar features on clinical and electrophysiological examination...
  51. Forte F, Pretegiani E, Battisti C, Sicurelli F, Federico A. Neuromyotonia as paraneoplastic manifestation of bladder carcinoma. J Neurol Sci. 2009;280:111-2 pubmed publisher
    Neuromyotonia(NMT) or Isaacs syndrome is a rare syndrome characterized by continuous spontaneous muscle fiber contraction resulting from hyperexcitability of peripheral nerves often associated with autoimmune disorders and tumours...
  52. Bhatti S, Vanhaesebrouck A, Van Soens I, Martlé V, Polis I, Rusbridge C, et al. Myokymia and neuromyotonia in 37 Jack Russell terriers. Vet J. 2011;189:284-8 pubmed publisher
    ..5 years after the start of clinical signs. In conclusion, young Jack Russell terriers with myokymia and neuromyotonia should undergo a complete blood and electrophysiological examination. Long-term prognosis is not favourable...
  53. Watanabe O, Arimura K. [Recent topics on paraneoplastic neurological syndromes: anti-VGKC antibodies]. Nihon Naika Gakkai Zasshi. 2008;97:1838-43 pubmed