Course and outcome of a voltage-gated potassium channel antibody negative Morvan’s syndrome

Abstract

Morvan's syndrome is a rare disease characterized by peripheral nerve hyperexcitability, associated with CNS and autonomic systems involvement. High serum voltage-gated potassium channel (VGKC) antibody titers have been reported, and, till now, Morvan's syndrome has been considered as a VGKC antibody associated disease. We describe a patient with Morvan's syndrome associated with myasthenia gravis and a thymoma in his previous history, with surprisingly undetectable levels of VGKC antibodies. The clinical course is similar to those cases of Morvan's syndrome with VGKC-Ab, except for the lack of response to plasma exchange, previously considered as the first choice treatment. Nevertheless, the good response to corticosteroids therapy and the association with myasthenia confirm an autoimmune origin of the disease.

Morvan's syndrome associated with antibodies to multiple components of the voltage-gated potassium channel complex

“…It is now clear that the patient's antibodies bind mostly to VGKC-associated proteins rather to the VGKC channels themselves [7]. This could explain the previously reported antibody-negative cases of MoS [5,6]. There is an emerging correlation between antigenic targets and clinical manifestations within the clinical spectrum of autoimmunity to VGKCcomplex proteins: antibodies against Lgi1 are almost exclusively associated with LE and epilepsy.…”

“…Mild tachypnea and breathing difficulty were present on admission. The occurrence of respiratory symptoms as well as the development of pneumonia in patients with Mos is noted quite frequently in the literature, even as a presenting symptom [3,5,6]. In some cases this presentation has been attributed to laryngeal spasm due to NMT [6].…”

“…The diagnosis was supported by the presence of VGKCcomplex antibodies in serum which were detected at high titres (1416 pM/L) as well as by immunohistochemistry and by cell binding assay. There are very few MoS cases described in the English literature [4,3,5,6,[10][11][12][13][14], although 29 additional cases have been collected (Irani SR, Vincent A in preparation). In a recent study by Irani et al (2010) [7], of 96 patients positive for VGKC antibodies, only 5 were identified as having MoS, illustrating the rarity of the syndrome.…”

“…Plasma exchange was proposed initially as the mainstay of treatment for Mos [12]. Steroids have also proved beneficial [5,10] while IVIG did not show efficacy in two other cases. Spontaneous recovery has also been reported [3].…”

“…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, autonomic symptoms (hyperidrosis, tachycardia, constipation) and central 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 encephalitis (LE) and in a few cases of adult-onset epilepsy.…”