Serological results | Clinical features | Disease aetiology | Outcome and treatments | Summary of clinical–serological correlations | |||
---|---|---|---|---|---|---|---|
Age/Sex | VGKC complex antibody (pM) | Kv1-HEK RIA | Kv1-fixed CBA | ||||
59/M | 1346 | + | 1.2 only | Cryptogenic TLE with amnesia/depression | Unknown | No sustained response to three AEDs and CS | Poor. Persistent VGKC-c Abs despite markedly varied SZ frequencies. Online supplementary figure S3C |
49/F | 767 | + | 1.2 only | NMT with EMG confirmation | Autoimmune | Limited response to AEDs and CS | Poor. Highest VGKC-c Abs during clinical remission |
55/M | 533 | + | 1.2 only | NMT with EMG confirmation | Autoimmune | Symptoms over 8 years despite AEDs/AZA/CS | Good. Patient symptomatic with persistent VGKC-c Abs |
77/M | 470 | + | 1.2 only | Chronic myelopathy/encephalopathy | Unknown | Transient response to CS and PLEX | Poor. High VGKC-c Abs despite symptom fluctuations over 3 years |
21/M | 461 | + | 1.2 only | Cryptogenic probable frontal lobe epilepsy | Unknown | Ongoing SZs despite two AEDs | Poor. Online supplementary figure S3E |
50/M | 448 | + | 1.2 only | Isolated amnesia | Unknown | Spontaneous resolution over a few days | Poor. Abs reduced over 12 months. Symptoms resolved at 7 days |
28/F | 278 | + | 1.2 only | Cryptogenic TLE | Unknown | SZ freedom after first AED | Poor. Persistent VGKC-c Abs during SZ freedom |
62/M | 236 | + | 1.2 only | Cryptogenic TLE with amnesia | Unknown | SZs and amnesia at 5 years with 3 AEDs | Poor. VGKC-c Abs disappeared while SZs were ongoing |
18/M | 141 | + | 1.2 only | Limbic encephalitis | Autoimmune | Good response to CS and PLEX | Good. VGKC-c Abs reduced and clinical improvement at 12 months |
25/F | 529 | + | 1.6 only | Diffuse neuropathic pain and depression | Unknown | No response to opioids, CS or IVIG | Poor. High VGKC-c Abs despite marked fluctuations in symptoms |
30/F | 117 | + | 1.6 only | Idiopathic generalised epilepsy | Genetic | Good response to AEDs | NA |
68/M | 240 | + | 1.6 only | Alzheimer's disease; one SZ | Degenerative | Ongoing fall in memory despite CS/IVIG | Poor. Slight fall in VGKC-c Abs but marked reduction in memory over 4 years |
34/M | 577 | + | 1.2 and 1.6 | Widespread neuropathic pain | Unknown | No response to CS, IVIG and PLEX | Poor. Constant pain despite highly varied VGKC-c Abs. Online supplementary figure S3D |
71/F | 2489 | + | 1.1, 1.2 and 1.6 | NMT plus SCLC | Paraneoplastic | Palliative care only | NA. |
67/F | 2120 | + | 1.1, 1.2 and 1.6 | LEMS plus Hu antibody neuropathy and SCLC | Paraneoplastic | Good response to CS | Poor. Persistently high VGKC-c Abs over 5 years despite clinical improvements |
84/F | 282 | + | 1.1 only | Parkinson's disease dementia | Degenerative | No response to CS | Poor. VGKC-c Abs reduced over 12 months despite clinical worsening |
58/M | 304 | + | Negative | Dysautonomia | Unknown | NA | NA |
37/M | 253 | + | Negative | TLE related to left HS | Structural | NA | NA |
59/M | 236 | + | Negative | Healthy smoker | Healthy | Not relevant | Not relevant |
48/F | 223 | + | Negative | TLE related to left HS | Structural | NA | NA |
85/F | 205 | + | Negative | Cryptogenic focal motor SZs | Unknown | SZ free on 1 AED. Amnesia and anxiety benefited from CS/IVIG | Poor. VGKC-c Abs disappeared over 1 year; SZ freedom at 2 years. VGKC-c Abs returned at 4 years without SZs |
33/F | 182 | + | Negative | Cryptogenic TLE | Unknown | SZ freedom after second AED | Moderate. VGKC-c Abs reduced over 6 months and SZ freedom at 1 year |
76/M | 181 | + | Negative | Cryptogenic epilepsy | Unknown | SZ freedom with 1 AED | Poor. SZ freedom at 6 months; VGKC-c Abs sampled after 15 years |
54/F | 139 | + | Negative | Epilepsy after childhood meningitis | Structural | NA | NA |
22/M | 137 | + | Negative | Cryptogenic epilepsy | Unknown | SZ freedom after 1 AED | NA |
54/M | 131 | + | Negative | Cryptogenic epilepsy | Unknown | SZ free at 1 year with 1 AED | Moderate. SZ free at 1 year; VGKC-c Abs absent at 3 months |
77/M | 123 | + | Negative | TLE secondary to CVA | Structural | Ongoing SZs at 4 years | NA |
Patients grouped by the VGKC-c antibody levels, precipitation from Kv1.1/Kv1.2/Kv1.6-cotransfected HEK cell and Kv1.2-transfected HEK cell radioimmunoassays (Kv1-HEK RIA; denoted as positive (+) or negative (−)) and the Kv1 subunit expressed fixed CBAs (Kv1-fixed CBA). All these patients had negative results in live CBAs for antibodies against Kv1s, LGI1, CASPR2, contactin-2 and for binding to live hippocampal neurons. Two patients had SCLC and tumours were not found in the remaining patients.
Ab, antibody; AEDs, antiepileptic drugs; AZA, azathioprine; CASPR2, contactin-associated protein-2; CS, corticosteroids; CBA, cell-based assay; CVA, cerebrovascular accident; EMG, electromyography; F, female; HEK, human embryonic kidney 293T; HS, hippocampal sclerosis; IVIG, intravenous immunoglobulins; LEMS, Lambert-Eaton myasthenic syndrome; LGI1, leucine-rich glioma-inactivated 1; M, male; NA, not available (only single serum sample obtained); PLEX, plasma exchange; SCLC, small cell lung carcinomas; SZ, seizure; TLE, temporal lobe epilepsy; VGKC, voltage-gated potassium channel; VGKC-c, VGKC complex.