VGKC autoantibodies mimicking CJD

Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2008; 70: 1883-1890.


VGKC antibodies have been described in a variety of patient types, and may present with a symptom c0mplex including cognitive impairment and myoclonus, mimicking Creutzfeld-Jacob disease, which is untreatable. Some cases of VGKC may be treatable with IVIG or other anti-immune strategies.

Paraneoplastic VGKC have been identified as paraneoplastic antibodies in neuroendocrine tumors (including small cell lung cancer), retinoblastoma, oligodendroglioma, melanoma, leiomyosarcoma, and hematologic malignancies. They are also seen as markers of neuromyotonia, Morvan's, epilepsy, limbic encephalits, and dysautonomia with hyperhidrosis and GI dysmotility. Animal passive transfer experiments suggest pathogenicitiy. IVIG and plasma exchange are beneficial.

Among 80 patients in this Mayo Clinic series, was usually an inflammatory or neurodegenerative disease. 11 were correctly thought to have autoimmune encephalopathy, 10 with CJD, 5 with viral encephalitis, 3 with recurrent TGA, 4 with psychiatric (anxiety disorder/panic attacks/ conversion disorder). Examination showed frontosubcortical involvement, pesonality change, executive dysfunction, disinhibition, visual hallucinations (10%), agitation or depression. Short term memory impairment, with 58 % having some form of seizure disorder (all types seen) . Cranial nerve involvement was seen in 19 % including diplopia (not MG associated), dysarthria, dysphagia, vision loss, hemifacial spasm, hyperphagia, hyponatremia, EPS, cerebellar ataxia, recurrent ON without NMO antibodies, myoclonus, hypersomnia, autonomic dysfunction. MRI's showed abnormalities in bilateral hippocampi, CN head, splenium , frontal lobe, or multifocal suspicious for CJD. MRI improved partly or wholly. SPECT, EEG, CSF generally or often abnormal. 47% had documented neoplasia, of whom 76 % were smokers, and VGKC preceded diagnosis by five or more months.

Coexisting antibodies included ANNA-1, PCA2, amphiphysin IgG, CRMP 5 IgG with ultimate diagnosis of 5 small cell lung CA, three thymic CA, four prostate adenoCA, Becelllymphoma, CLL, mycosis fungoides, 3 head and neck CA, one colonic adenoca. There also were benign neoplasia including 5 pituitary adenoca, one adrenal, one colonic, one parathyroid, one renal oncocytoma, one gastric leiomyoma. Other AI disorders were Hashimoto titers in 15, endocrine pancreas in 8, and pernicious anemia. 89 % improved with treatment, half dramatically so, including 8 of 10 with initial misdiagnosis of CJD. These included six patients with increased 14,3,3 or NSE, 5 of whom improved remarkably.