Systematic review of the clinical spectrum of CASPR2 antibody syndrome

Anti‐LGI1, anti‐GABABR, and Anti‐CASPR2 encephalitides in Asia: A systematic review

“…variant is associated with a wide range of signs and symptoms which go beyond the central nervous system. In our study, despite the low sample size, symptoms like cognitive defects, epilepsy, peripheral nerve hyperexcitability/neuromyotonia, neuropathic pain, cerebellar symptoms, and dysautonomia presenting either as limbic encephalitis or Morvan's syndrome were noted, reflecting the variability in presentation reported in previous works (Becker et al, 2012;Bien et al, 2017;Boyko et al, 2020;Klein et al, 2013;van Sonderen, Ariño, et al, 2016).…”

Isaacs syndrome: the frontier of neurology, psychiatry, immunology and cancer

“…9 Similarly, CASPR2 antibodies are associated with both CNS and peripheral-predominant clinical presentations, 9 and associated with neuromyotonia in <40% of cases. 10 Further clinical and molecular phenotyping of large-scale cohorts will be necessary to determine specific associations with neuromyotonia across syndromes.…”

“…In particular, CASPR2 antibodies are associated with thymoma in 20% of cases. 10 The association with cancer suggests that Isaacs syndrome can develop through paraneoplastic mechanisms, with tumourassociated antigens triggering an autoimmune response via cross-reacting antibodies with nerve related epitopes. 7 In terms of understanding the clinical hallmark of Isaacs syndrome, namely continuous muscle activity, the site of origin for this spontaneous activity remains to be determined.…”

Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report

“… 1 , 13 As part of VGKC complex, Caspr2 is located in the juxtaparanodal region of myelinated fibers in both CNS and peripheral nervous system (PNS), and participates in synapse synthesis and construction of central neural network. 2 , 3 , 14 , 15 Non-complement-activating IgG4 antibodies dominate in anti-Caspr2 antibody-associated autoimmune encephalitis. 10 , 12 Although mechanisms responsible for coexisting double or more autoantibodies are still undetermined, the phenomenon may be partially explained by the concept of epitope spreading, that is, persistent recognition and activation to self-antigens lead to chronic immune responses accompanying with the development of antibodies against diverse dominant epitopes within the same antigen (intramolecular) or to different antigens (intermolecular).…”

“… 1 Similarly, antibody against contactin associated protein-like 2 (Caspr2) – a component of the voltage-gated potassium channel (VGKC) complex at the juxtaparanodal region of myelinated axons – refers to a recently recognized autoimmune encephalitis (AE) with a low incidence, and is also detected in several peripheral neurological syndromes including neuromyotonia and Morvan syndrome. 2 , 3 Meanwhile, overlapping or coexisting syndromes have been noticeable with double or multi-antibodies targeting distinct CNS antigens such as MOG, aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), N -methyl- d -aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and Caspr2. 4 – 6 However, double positivity for MOG-IgG and Caspr2-IgG in the same patient has not yet been reported.…”