Table 2

Comparisons of autoantibodies against LGI1, CASPR2, and the double-negative VGKC antibodies

LGI1CASPR2Double-negative VGKC
Clinical featuresWell-delineated clinical syndromes?Yes24 25:
Faciobrachial dystonic seizures;
Limbic encephalitis (other frequent focal seizure semiologies, encephalopathy, sleep disorder, amnesia, anxiety, emotionality dysautonomia);
Hyponatraemia in ~65%
More rarely, neuromyotonia and Morvan’s syndrome
Yes8 9 23:
CNS: limbic encephalitis—seizures, confusion, hallucinations, insomnia
PNS: neuromyotonia (neuropathic pain, spasms, cramps)
Morvan’s syndrome: above including insomnia and dysautonomia, often with weight loss
No: 5% rate in healthy controls and detected in heterogeneous, often non-immune, syndromes including varied epilepsies; widespread, non-neuropathic pain; Parkinson’s disease; headache; primary psychiatric conditions26 28 32
Demographics: gender ratio and median age of onsetM (2:1)
60–70 years25
M (8:1)
50–60 years
No known predilection
(M:F 1:1; 18–85 years with no peak onset age26 28 32)
Immunotherapy-responsive (%)Highly:
97%25 29
Limited, and likely accounted for by referral bias and/or placebo effect:
SerologicalEpitopeExtracellular (both receptor docking and non-docking domains of this secreted protein;8 21 28)Extracellular domain8 9 28 Intracellular aspects (including Kv1 channels), and non-mammalian targets28
Rate in healthy controls<1%38 <1%38 ~5%,2 6 28 39
Other associations/markersRarely thymoma <5%Thymoma 20-50%, especially those with Morvan’s syndrome and neuromyotoniaPossibly malignancies33 36
GeneticHLA associationsHLA-DRB1*07:01 (~95%)26 32 40 41 HLA-DRB1*11:01 (~50%)32 Nil32
Evidence of pathogenicityIn vitro and in vivoFunctional blocking of LGI1-ADAM22 interactions21 42
Internalisation21 25
LGI1 IgGs and monoclonal antibodies induce memory deficits in vivo20 21
Internalisation noted in some studies; pain reproduced in experimental animals43 Nil
  • ADAM, a disintegrin and metalloprotease; CASPR2, contactin-associated protein like-2; CNS, central nervous system; F, female; HLA, human leukocyte antigen; LGI1, leucine-rich glioma-inactivated 1; M, male; PNS, peripheral nervous system; VGKC, voltage-gated potassium channel.