Morvan's syndrome associated with antibodies to multiple components of the voltage-gated potassium channel complex Panayiotis Loukaides a , Natasa Schiza b , Philippa Pettingill c , Lakis Palazis a , Emmelia Vounou a , Angela Vincent c , Kleopas A. Kleopa b, ⁎ a Limassol General Hospital, Limassol, Cyprus b Neurology Clinics and Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus c Nuffield Department of Clinical Neurosciences, University of Oxford, UK abstract article info Article history: Received 30 May 2011 Received in revised form 11 August 2011 Accepted 16 August 2011 Available online 8 September 2011 Keywords: Morvan's syndrome VGKC Lgi1 Caspr2 Contactin-2/Tag-1 Neuromyotonia We describe a patient presenting with a combination of muscle fasciculations, paresthesias, hyperhidrosis, as well as insomnia, agitation and confusion. He went on to develop psychosis and respiratory failure requiring intensive care. Electromyography confirmed the presence of neuromyotonia and CSF showed mild pleocyto- sis. Routine testing for voltage-gated potassium channel complex (VGKC-complex) antibodies was highly positive, confirming the clinical diagnosis of Morvan's syndrome. The patient improved after treatment with intravenous immunoglobulin and methylprednisolone. Further investigation of the antigenic targets using immunohistochemistry and cell-based assays revealed that he had autoantibodies targeting Lgi1, Caspr2 and Contactin-2/Tag-1, all proteins known to be complexed with VGKC in peripheral nerves and CNS. This is the first case of Morvan's syndrome from Cyprus and illustrates the clinical features as well as the emerging complexity of antigenic targets involved in the pathogenesis. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Neuromyotonia (NMT) or Isaac's syndrome is a neurological disor- der of continuous motor unit activity attributed to peripheral nerve hyperexcitability. It is characterized by widespread myokymia, cramping, muscle stiffness, pseudomyotonia and often excessive sweating. Acquired NMT can be associated with autoimmune disor- ders, thymoma or lung cancer [1,2]. Morvan's syndrome (MoS) or Morvan's “Fibrillary chorea” initially described by Morvan in 1890, is a very rare disorder characterized by the combination of NMT, au- tonomic symptoms (hyperidrosis, tachycardia, constipation) and cen- tral nervous system (CNS) involvement, including confusion, agitation, anxiety, insomnia, and hallucinations. Antibodies to voltage gated potassium channels (VGKC) have been detected in MoS [3,4], although antibody negative cases have been reported [5,6]. The same antibodies are implicated in NMT, in autoimmune limbic en- cephalitis (LE) and in a few cases of adult-onset epilepsy. It is now clear that antibodies associated with the clinical spectrum of VGKC- related autoimmunity are directed mainly against other proteins that are tightly complexed with VGKCs in neuronal tissue, explaining some of the clinical correlations [7–9]. In this report we describe the first reported patient with Morvan's syndrome in Cyprus, presenting with typical manifestations of pe- ripheral nerve and CNS hyperexcitability, and unusually high cell count in the cerebrospinal fluid (CSF). Autoimmunity to multiple VGKC-associated proteins was confirmed by serological assay, immu- nohistochemistry and cell based assay. 2. Case report A 67-year-old man with a medical history of hypertension and heavy alcohol consumption presented with a 15-day history of pain and burning dysesthesias in both lower limbs. His wife reported that he had difficulty sleeping during the past three months and she also no- ticed that he was sweating a lot and had developed mild memory prob- lems in the last 2 weeks. On admission his examination revealed deficits in short term memory and irritability. Cranial nerves were intact, but he was slightly dysarthric. Hyperhidrosis was noted along with abundant muscle fasciculations that were evident more in the lower limbs and to a lesser extent in the muscles of the shoulder girdle. Muscle bulk and strength were normal in all four limbs but deep tendon reflexes were unobtainable. Plantar responses were flexor. Sensory examination showed no focal deficits for pinprick of vibration. There was no cerebel- lar dysfunction. Journal of the Neurological Sciences 312 (2012) 52–56 ⁎ Corresponding author. The Cyprus Institute of Neurology and Genetics, 6 International Airport Avenue, P.O. Box 23462, 1683 Nicosia, CYPRUS. Tel.: +357 22 358600; fax: +357 22 392786. E-mail address: kleopa@cing.ac.cy (K.A. Kleopa). URL: http://www.cing.ac.cy (K.A. Kleopa). 0022-510X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2011.08.024 Contents lists available at SciVerse ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns