Insights From LGI1 and CASPR2 Potassium Channel Complex Autoantibody Subtyping

Klein, Christopher J.; Lennon, Vanda A.; Aston, Paula A.; McKeon, Andrew; O’Toole, Orna; Quek, Amy May Lin; Pittock, Sean J.

doi:10.1001/jamaneurol.2013.592

Cited by 174 publications

(188 citation statements)

References 17 publications

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“…Patients were identified by the following 2 mechanisms: 1) A search of the Mayo Clinic Life Sciences System (a clinical data repository containing patient demographics, diagnoses, hospital and clinical notes, laboratory results, and pathology data obtained from multiple clinical and hospital source systems) by using the keywords "voltagegated potassium channel" or "VGKC" and "seizures," "epilepsy," "encephalitis" or "encephalopathy" identified 11 patients presenting between January 1, 2001, and June 1, 2008, seropositive for VGKC Ab with associated seizures; 2) From June 1, 2008, to June 30, 2010, comprehensive serologic evaluation of patients with unexplained neurologic symptoms was performed at our institution, identifying 1992 patients who were seropositive for VGKC Ab. 13 A search of this data base identified 33 additional patients with associated seizures.…”

Section: Methodsmentioning

confidence: 99%

MRI Findings in Autoimmune Voltage-Gated Potassium Channel Complex Encephalitis with Seizures: One Potential Etiology for Mesial Temporal Sclerosis

Kotsenas¹,

Watson²,

Pittock

et al. 2013

AJNR Am J Neuroradiol

114

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BACKGROUND AND PURPOSE:Autoimmune voltage-gated potassium channel complex encephalitis is a common form of autoimmune encephalitis. Patients with seizures due to this form of encephalitis commonly have medically intractable epilepsy and may require immunotherapy to control seizures. It is important that radiologists recognize imaging characteristics of this type of autoimmune encephalitis and suggest it in the differential diagnosis because this seizure etiology is likely under-recognized. Our purpose was to characterize MR imaging findings in this patient population.

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Section: Methodsmentioning

confidence: 99%

MRI Findings in Autoimmune Voltage-Gated Potassium Channel Complex Encephalitis with Seizures: One Potential Etiology for Mesial Temporal Sclerosis

Kotsenas¹,

Watson²,

Pittock

et al. 2013

AJNR Am J Neuroradiol

114

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“…Epidemiology: In the UK, where the incidence of encephalitis is estimated at 5.23 cases/100,000/year based upon admissions to the National Health Service between 2005 and 2009, Granerod and colleagues [120] estimated the incidence of encephalitis as 4.32 cases/100,000 population/year. A capture-recapture model estimated the incidence of encephalitis to be 8.66 cases/100,000/year.…”

Section: Anti-vgkc-complex Encephalitismentioning

confidence: 99%

Autoimmune Encephalitides

Younger¹

2017

WJNS

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Autoimmune encephalitis is a potentially severe disorder of the brain of diverse causes with a complex differential diagnosis. Recent advances in the past decade have led to the elucidation of new syndromes and biological markers transforming the approach to diagnosis and management of autoimmune encephalitis. Limbic encephalitis, the commonest form of autoimmune encephalitis, combines common presentations of cognitive, psychiatric, and epileptic disorders and has until recently been considered paraneoplastic or postinfectious in origin. The autoimmune encephalitides are clinically and histopathologically associated with serum and intrathecal antibodies to intracellular and surface neuronal antigens, and constituents of the limbic system neuropil. This has led to a reconsideration of a number of neuropsychiatric and neurocognitive disorders as having shared mechanisms of origin. This chapter reviews their historical background, clinical presentation, laboratory evaluation, histopathology, diagnosis and management. KeywordsAutoimmune, Encephalitis, Hashimoto, Encephalopathy Historical PerspectiveCorsellis and colleagues [1] coined the term limbic encephalitis (LE) in 1968, noting a relation to bronchial cancer in three patients in the sixth to eighth decade of life, and showing close clinicopathologic similarity to cases described by Brierley and colleagues [2] six years earlier. All three cases had subacute temporal lobe seizures, neuropsychiatric, and memory disturbances for two years before death. Postmortem examination showed inflammatory lesions in limbic grey matter sections of the brain, especially in medial temporal lobe structures of the uncus and amygdala nuclei, and hippocampal, cingulum and dentate gyri. Case 2 had an undifferentiated non-metastatic lung carcinoma removed six months after onset of neurological symptoms, while two others had a clinically unsus- The formulation of the relation of GAD antibodies to SPS has been especially instructive in understanding how far the science of autoimmune neurologic disorder has advanced. In 1988, Solimena and colleagues [28] investigated the existence of non-paraneoplastic CNS autoimmunity in a patient with SPS, epilepsy and type-1 diabetes (T1D), and increased titers of oligoclonal CSF IgG. Both the serum and CSF produced identical intense staining of all gray-matter regions. GAD65 was thence an important autoantigen in T1D, being highly expressed in the cytoplasm of pancreatic β cells. GAD-derived peptides were presentable by main histocompatibility complex (MHC) class I molecules and recognized by CD8+ cells on the surface of β cells [29]. Activation of CD8+ GAD-specific T-cells further differentiated into memory cells suggesting a pathogenic role in T1D [30]. However, only patients with very high titers of GAD were associated with LE [31], and they typically presented with recent-onset temporal lobe epilepsy (TLE) and intrathecal secretion, defining a form of non-paraneoplastic LE. Other patients within the SPS spectrum harbored antibodies agains...

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“…Only about 4% to 5.5% of unselected cases were seropositive by RIA with confirmatory retesting using 125 I-α-dendrotoxin alone (radioligand for Kv1.1, Kv1.2, and Kv1.6 channels) [3] [18] [19], making the test unreliable as a screen for LE without further subtyping for LGI1 and CASPR2-IgG. So selected, 26% [3] to 28% [19] of seropositive VGKC sera revealed reactivity with LGI1 and/or CASPR2-IgG, with a significant association between LGI1-IgG-positivity and cognitive impairment andseizures (P < 0.05), and CASPR2-IgG-positivity and peripheral motor excitability (P = 0.004) [3], however neither autoantibody was pathognomonic for a specific neurologic presentation. Yet there was concern for screening of unselected sera for VGKC-complex antibodies by RIA.…”

Section: Vgkc-complex Subtypingmentioning

confidence: 99%

“…There is a diversity and overlap of neurological phenotypes that relate to VGKC-Complex-IgG values in the serum and CSF and Ig-subtype specificity. The commonest presentation of VGKCcomplex autoantibodies is LE in the CNS and neuromyotonia or Morvan syndrome in the PNS [3]. We present the clinical and laboratory findings of a patient that manifested PNS, CNS and autonomic nervous system (ANS) involvement.…”

Section: Introductionmentioning

confidence: 98%

Limbic Encephalitis Associated with Voltage-Gated Potassium Channel-Complex Antibodies: Patient Report and Literature Review

Younger¹

2017

WJNS

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Background: The family of disorders associated with antibodies against neuronal surface antigens is a rapidly expanding category of autoimmune neurologic disease. Methods: Clinical and laboratory findings of a patient with voltage-gated Kv1 potassium channel (VGKC)-complex autoantibodies are reported and the literature is reviewed. Results: New-onset faciobrachial dystonic seizures, distal large and painful small fiber peripheral neuropathy, dysautonomia, cognitive and memory disturbances were associated with hypometabolism of the left temporal lobe without evidence of systemic malignancy in whole-body positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography. Brain MRI and cerebrospinal fluid were normal with absent intrathecal VGKC-complex antibodies consistent with extrathecal production. Epidermal nerve fiber studies confirmed small fiber neuropathy in association with abnormal autonomic laboratory testing. Discussion: Neurologic involvement associated with VGKC complex autoimmunity is a precisely delineated disorder involving the central, peripheral, and autonomic nervous system.

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Insights From LGI1 and CASPR2 Potassium Channel Complex Autoantibody Subtyping

Cited by 174 publications

References 17 publications

MRI Findings in Autoimmune Voltage-Gated Potassium Channel Complex Encephalitis with Seizures: One Potential Etiology for Mesial Temporal Sclerosis

MRI Findings in Autoimmune Voltage-Gated Potassium Channel Complex Encephalitis with Seizures: One Potential Etiology for Mesial Temporal Sclerosis

Autoimmune Encephalitides

Limbic Encephalitis Associated with Voltage-Gated Potassium Channel-Complex Antibodies: Patient Report and Literature Review

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