Current Journal of Neurology

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Publication Ethics

Indexing and Abstracting

Peer Review Process

Journal Metrics

News

Publication Ethics and Malpractice Statement

Isaacs’ syndrome: Clinical and paraclinical perspectives in a series of cases

Articles in Press

Document Type : Original Article

Authors

1 Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Neuromuscular Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

2 Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Neuromuscular Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Isaacs’ syndrome is a form of generalized peripheral nerve hyperexcitability (PNH) causing increased and continuous muscle activity characterized by muscle twitching, stiffness, cramps, myokymia, and pseudomyotonia. Herein, we aimed to review the clinical and paraclinical aspects of Isaacs’ syndrome in a number of cases.
Methods: We reported a series of 12 patients with Isaacs’ syndrome, including their clinical features, electrophysiological findings, laboratory parameters, malignancy work-up, and therapeutic management.
Results: In all cases, clinical and electrodiagnostic assessment was suggestive of Isaacs’ syndrome. Of the 12 studied cases, 5 patients were positive for both leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies, 5 patients were CASPR2 positive and LGI1 negative, and 1 had borderline positive titers for CASPR2 with negative LGI1 antibody. The search for underlying malignancies was inconclusive in all subjects. After symptomatic treatment, mostly with carbamazepine or gabapentin, immunotherapies with double filtration plasmapheresis or Intravenous immunoglobulin (IVIG) provided favorable outcomes. Ultimately, all subjects fully recovered after 3-6 months of follow-up and all signs and symptoms resolved.
Conclusion: Despite the rarity of the disease, our results provide valuable information for understanding the epidemiological, clinical, and paraclinical features of Isaacs’ syndrome.

Keywords

References
  1. Sawlani K, Katirji B. Peripheral nerve hyperexcitability syndromes. Continuum (Minneap Minn) 2017; 23(5, Peripheral Nerve and Motor Neuron Disorders): 1437-50.
  2. Ahmed A, Simmons Z. Isaacs’s syndrome: A review. Muscle Nerve 2015; 52(1): 5-12.
  3. Barber PA, Anderson NE, Vincent A. Morvan's syndrome associated with voltage-gated K+ channel antibodies. Neurology 2000; 54(3): 771-2.
  4. Arimura K, Sonoda Y, Watanabe O, Nagado T, Kurono A, Tomimitsu H, et al. Isaacs' syndrome as a potassium channelopathy of the nerve. Muscle Nerve Suppl 2002; 11: S55-S58.
  5. Vincent A, Pettingill P, Pettingill R, Lang B, Birch R, Waters P, et al. Association of leucine-rich glioma inactivated protein 1, contactin-associated protein 2, and contactin 2 antibodies with clinical features and patient-reported pain in acquired neuromyotonia. JAMA Neurol 2018; 75(12): 1519-27.
  6. Park SB, Thurbon R, Kiernan MC. Isaacs’s syndrome: The frontier of neurology, psychiatry, immunology and cancer. J Neurol Neurosurg Psychiatry 2020; 91(12): 1243-4.
  7. Falace A, Striano P, Manganelli F, Coppola A, Striano S, Minetti C, et al. Inherited neuromyotonia: A clinical and genetic study of a family. Neuromuscul Disord 2007; 17(1): 23-7.
  8. Rana SS, Ramanathan RS, Small G, Adamovich B. Paraneoplastic Isaacs' syndrome: A case series and review of the literature. J Clin Neuromuscul Dis 2012; 13(4): 228-33.
  9. Isaacs H, Frere G. Syndrome of continuous muscle fibre activity. Histochemical, nerve terminal and end-plate study of two cases. S Afr Med J 1974; 48(38): 1601-7.
  10. Walsh JC. Neuromyotonia: An unusual presentation of intrathoracic malignancy. J Neurol Neurosurg Psychiatry 1976; 39(11): 1086-91.
  11. Zifko U, Drlicek M, Machacek E, Jellinger K, Grisold W. Syndrome of continuous muscle fiber activity and plasmacytoma with IgM paraproteinemia. Neurology 1994; 44(3 Pt 1): 560-1.
  12. Caress JB, Abend WK, Preston DC, Logigian EL. A case of Hodgkin's lymphoma producing neuromyotonia. Neurology 1997; 49(1): 258-9.
  13. Toepfer M, Schroeder M, Unger JW, Lochmuller H, Pongratz D, Muller-Felber W. Neuromyotonia, myocloni, sensory neuropathy and cerebellar symptoms in a patient with antibodies to neuronal nucleoproteins (anti-Hu-antibodies). Clin Neurol Neurosurg 1999; 101(3): 207-9.
  14. Hayat GR, Kulkantrakorn K, Campbell WW, Giuliani MJ. Neuromyotonia: Autoimmune pathogenesis and response to immune modulating therapy. J Neurol Sci 2000; 181(1-2): 38-43.
  15. Forte F, Pretegiani E, Battisti C, Sicurelli F, Federico A. Neuromyotonia as paraneoplastic manifestation of bladder carcinoma. J Neurol Sci 2009; 280(1-2): 111-2.
  16. Issa SS, Herskovitz S, Lipton RB. Acquired neuromyotonia as a paraneoplastic manifestation of ovarian cancer. Neurology 2011; 76(1): 100-1.
  17. Taylor PW. Isaacs' syndrome (autoimmune neuromyotonia) in a patient with systemic lupus erythematosus. J Rheumatol 2005; 32(4): 757-8.
  18. Cerami C, Corbo M, Piccolo G, Iannaccone S. Autoimmune neuromyotonia following human papilloma virus vaccination. Muscle Nerve 2013; 47(3): 466-7.
  19. Odabasi Z, Joy JL, Claussen GC, Herrera GA, Oh SJ. Case of the month: Isaacs' syndrome associated with chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 1996; 19(2): 210-5.
  20. Liu YC, Wu ZA, Wang SJ, Shan DE, Lin KP. Transient syndrome of continuous muscle fiber activity associated with staphylococcal infection. Mov Disord 1998; 13(3): 609-11.
  21. Chaurasia R, Shukla R. Toxin induced continuous muscle fiber activity syndrome. Ann Neurosci 2008; 15(4): 118-9.
  22. Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR. Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 2002; 125(Pt 8): 1887-95.
  23. Gallin WJ, Boutet PA. VKCDB: Voltage-gated K+ channel database updated and upgraded. Nucleic Acids Res 2011; 39(Database issue): D362-6.
  24. Irani SR, Alexander S, Waters P, Kleopa KA, 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(9): 2734-48.
  25. Hart IK, Waters C, Vincent A, Newland C, Beeson D, Pongs O, et al. Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia. Ann Neurol 1997; 41(2): 238-46.
  26. Maddison P. Neuromyotonia. Clin Neurophysiol 2006; 117(10): 2118-27.
  27. Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2008; 70(20): 1883-90.
  28. Vernino S, Lennon VA. Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve 2002; 26(5): 702-7.
  29. Paterson RW, Zandi MS, Armstrong R, Vincent A, Schott JM. Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: Experience from a tertiary referral centre. J Neurol Neurosurg Psychiatry 2014; 85(6): 625-30.
  30. Boyko M, Au KLK, Casault C, de Robles P, Pfeffer G. Systematic review of the clinical spectrum of CASPR2 antibody syndrome. J Neurol 2020; 267(4): 1137-46.
  31. Samogalskyi V, Alcalay Y, Gadoth A, Eilam A, Gilad R. Case report: Isolated muscle neuromyotonia, as presenting feature of Isaacs' syndrome. J Neuroimmunol 2021; 353: 577491.
  32. Zimon M, Baets J, Almeida-Souza L, De Vriendt E, Nikodinovic J, Parman Y, et al. Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia. Nat Genet 2012; 44(10): 1080-3.
  33. Vincent A, Buckley C, Schott JM, Baker I, Dewar BK, Detert N, et al. Potassium channel antibody-associated encephalopathy: A potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004; 127(Pt 3): 701-12.
  34. Harrison TB, Benatar M. Accuracy of repetitive nerve stimulation for diagnosis of the cramp-fasciculation syndrome. Muscle Nerve 2007; 35(6): 776-80.
  35. Levy LM, Dalakas MC, Floeter MK. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med 1999; 131(7): 522-30.
  36. Rubio-Agusti I, Perez-Miralles F, Sevilla T, Muelas N, Chumillas MJ, Mayordomo F, et al. Peripheral nerve hyperexcitability: A clinical and immunologic study of 38 patients. Neurology 2011; 76(2): 172-8.
  37. Benatar M, Chapman KM, Rutkove SB. Repetitive nerve stimulation for the evaluation of peripheral nerve hyperexcitability. J Neurol Sci 2004; 221(1-2): 47-52.
  38. Maddison P, Mills KR, Newsom-Davis J. Clinical electrophysiological characterization of the acquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitability. Muscle Nerve 2006; 33(6): 801-8.
  39. Merchut MP. Management of voltage-gated potassium channel antibody disorders. Neurol Clin 2010; 28(4): 941-59.
  40. Kanmaz S, Ozcan M, Simsek E, Serin HM, Aydogdu I, Gokben S, et al. A rare case of peripheral nerve hyperexcitability in childhood: Isaacs’s syndrome. J Pediatr Neurosci 2020; 15(2): 153-6.
Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 30 December 2023
Files
Share
How to cite
Statistics