Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody

Objectives: To describe the clinical features and coexisting serum autoantibodies in seven patients with encephalitis associated with autoantibodies to α-dendrotoxin-sensitive voltage-gated potassium channels (VGKCs), and to compare this disorder with other autoimmune encephalopathies. Methods: Clinical information was obtained from a retrospective review of medical records and telephone interviews. All autoantibody testing was performed in a single laboratory. Results: The seven patients were examined for subacute cognitive and behavioral changes. Seizures, usually temporal-onset complex partial type, were documented in six patients, and all seven patients had EEG abnormalities. None had symptoms or signs of neuromuscular hyperexcitability. One described hypersalivation. Four patients had additional autoantibody markers of neurologic autoimmunity (muscle acetylcholine receptor, striational, P/Q-type calcium channel, or GAD65), and two had thyroperoxidase antibodies. Two patients had a history of cancer: one had active prostate adenocarcinoma, and the second had a remote history of tongue carcinoma. Cranial MRI demonstrated mesial temporal lobe abnormalities in all patients. One patient improved spontaneously, and six were treated with IV methylprednisolone. Three improved remarkably with treatment. At follow-up evaluation, one had no cognitive deficits, four had mild persistent short-term memory dysfunction, and two had persistent disabling behavioral deficits. Conclusions: Voltage-gated potassium channel antibodies are a valuable serologic marker of a potentially reversible autoimmune encephalopathy. The neurologic manifestations of this disorder are indistinguishable from paraneoplastic limbic encephalitis but are distinct from Morvan syndrome and Hashimoto encephalopathy.

[1]  V. Lennon,et al.  Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. , 2003, Mayo Clinic proceedings.

[2]  A. Vincent,et al.  Voltage‐gated potassium channel antibodies in limbic encephalitis , 2003, Annals of neurology.

[3]  V. Lennon,et al.  Muscle and Neuronal Autoantibody Markers of Thymoma , 2003, Annals of the New York Academy of Sciences.

[4]  M. Rossor,et al.  Amnesia, cerebral atrophy, and autoimmunity , 2003, The Lancet.

[5]  L. Rowland,et al.  Hashimoto encephalopathy: syndrome or myth? , 2003, Archives of neurology.

[6]  V. Lennon,et al.  Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability , 2002, Muscle & nerve.

[7]  K. Mills,et al.  Phenotypic variants of autoimmune peripheral nerve hyperexcitability. , 2002, Brain : a journal of neurology.

[8]  G Plazzi,et al.  Morvan's syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. , 2001, Brain : a journal of neurology.

[9]  J. Oger,et al.  Potassium channel antibodies in two patients with reversible limbic encephalitis , 2001, Annals of neurology.

[10]  E. Benarroch,et al.  CRMP‐5 neuronal autoantibody: Marker of lung cancer and thymoma‐related autoimmunity , 2001, Annals of neurology.

[11]  G. Farrugia,et al.  Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. , 2000, The New England journal of medicine.

[12]  S. Gultekin,et al.  Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. , 2000, Brain : a journal of neurology.

[13]  V. Lennon,et al.  New Purkinje cell antibody (PCA‐2): Marker of lung cancer–related neurological autoimmunity , 2000, Annals of neurology.

[14]  B. Scheithauer,et al.  Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy. , 1999, Neurology.

[15]  S. Gultekin,et al.  A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. , 1999, The New England journal of medicine.

[16]  R. Maselli,et al.  Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma , 1998, Journal of neurology, neurosurgery, and psychiatry.

[17]  J. Walikonis,et al.  Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. , 1998, Mayo Clinic proceedings.

[18]  J. Noseworthy,et al.  Paraneoplastic encephalomyelitis and seminoma , 1998, Neurology.

[19]  C. Harper,et al.  Reversible MRI findings in a patient with Hashimoto's encephalopathy , 1997, Neurology.

[20]  O. Pongs,et al.  Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia , 1997, Annals of neurology.

[21]  V. Lennon The case for a descriptive generic nomenclature , 1994, Neurology.

[22]  M. Burt,et al.  Limbic encephalitis secondary to malignant thymoma. , 1994, The Annals of thoracic surgery.

[23]  T. Walls,et al.  Hashirnoto's encephalopathy , 1991, Neurology.

[24]  K P Offord,et al.  A short test of mental status: description and preliminary results. , 1987, Mayo Clinic proceedings.

[25]  J. Brierley,et al.  SUBACUTE ENCEPHALITIS OF LATER ADULT LIFE. MAINLY AFFECTING THE LIMBIC AREAS , 1960 .

[26]  P. Shaw,et al.  Hashimoto's encephalopathy: a steroid-responsive disorder associated with high anti-thyroid antibody titers--report of 5 cases. , 1991, Neurology.

[27]  K. Millingen,et al.  Limbic Encephalitis Associated with Malignant Thymoma , 1988, Pathology.

[28]  V. Lennon,et al.  Autoimmunity in the Lambert-Eaton myasthenic syndrome. , 1982, Muscle & nerve.