Background: The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. Objective: The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). Methods: We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. Results: The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Conclusion: Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression.

Keywords:
Motor neuron diseases, Amyotrophic lateral sclerosis, Biomarker, Immunotherapy, Neuroinflammation
1.
Vincent A, Bien CG, Irani SR, Waters P: Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol 2011;10:759-772.
2.
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 J Neurol 2010;133:2734-2748.
3.
Klein CJ, Lennon VA, Aston PA, McKeon A, O'Toole O, Quek A, et al: Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol 2013;70:229-234.
4.
Fujita K, Yuasa T, Watanabe O, Takahashi Y, Hashiguchi S, Adachi K, et al: Voltage-gated potassium channel complex antibodies in Creutzfeldt-Jakob disease. J Neurol 2012;259:2249-2250.
5.
Rossi M, Mead S, Collinge J, Rudge P, Vincent A: Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 2015;86:692-694.
6.
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;85:625-630.
7.
Calvo AC, Manzano R, Mendonca DMF, Munoz MJ, Zaragoza P, Osta R: Amyotrophic lateral sclerosis: a focus on disease progression. Biomed Res Int 2014;2014:925101.
8.
Simon NG, Turner MR, Vucic S, Al-Chalabi A, Shefner J, Lomen-Hoerth C, et al: Quantifying disease progression in amyotrophic lateral sclerosis. Ann Neurol 2014;76:643-657.
9.
Nardo G, Trolese MC, Tortarolo M, Vallarola A, Freschi M, Pasetto L, et al: New insights on the mechanism of disease course variability in ALS from mutant SOD1 mouse models. Brain Pathol 2016;26:237-247.
10.
Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases: El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:293-299.
11.
De Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, et al: Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 2008;119:497-503.
12.
The Amyotrophic Lateral Sclerosis Functional Rating Scale. Assessment of activities of daily living in patients with amyotrophic lateral sclerosis. The ALS CNTF treatment study (ACTS) phase I-II Study Group. Arch Neurol 1996;53:141-147.
13.
Turner MR, Parton MJ, Shaw CE, Leigh PN, Al-Chalabi A: Prolonged survival in motor neuron disease: a descriptive study of the King's database 1990-2002. J Neurol Neurosurg Psychiatry 2003;74:995-997.
14.
McCombe PA, Henderson RD: The role of immune and inflammatory mechanism in ALS. Curr Mol Med 2011;11:246-254.
15.
Fialová L, Svarcová J, Bartos A, Ridzon P, Malbohan I, Keller O, et al: Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis. Eur J Neurol 2010;17:562-566.
16.
Puentes F, Topping J, Kuhle J, Van der Star BJ, Douiri A, Giovannoni G, et al: Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2014;85:274-278.
17.
Nwosu VK, Royer JA, Stickler DE: Voltage gated potassium channel antibodies in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2010;11:392-394.
18.
Chhetri SK, Majeed T, Lekwuwa G, Boothman B: Very high titers of voltage-gated potassium channel antibodies in a patient with amyotrophic lateral sclerosis. Muscle Nerve 2015;1:147.
19.
Irani SR, Gelfand JM, Al-Diwani A, Vincent A: Cell-surface central nervous system autoantibodies: clinical relevance and emerging paradigms. Ann Neurol 2014;76:168-184.
20.
Bedlack RS, Vaughan T, Wicks P, Heywood J, Sinani E, Selsov R, et al: How common are ALS plateaus and reversals? Neurology 2016;86:808-812.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.