An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis

Department of Neurology, The Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 10/2010; 81(10):1167-9. DOI: 10.1136/jnnp.2009.178293
Source: PubMed


Voltage-gated potassium channel antibody-positive limbic encephalitis (VGKC+LE) frequently improves with immunotherapy, although the optimum regimen is unknown. The effectiveness of a combination immunomodulatory regimen was tested in consecutive VGKC+LE patients.
This was an open-label prospective study of nine VGKC+LE patients. All patients had plasma exchange (50 ml/kg), intravenous immunoglobulin (2 g/kg) and intravenous methylprednisolone (1 g×3), followed by maintenance oral prednisolone (1 mg/kg/day). Mycophenolate (2 g/day) was used in the first three patients. Assessments included serial clinical, cognitive, brain MRI and VGKC antibody testing.
Within 1 week, seizures and hyponatraemia remitted in all affected patients. Cognitive function improved in all patients within 3 months. MRI appearances improved substantially within 9 months, with remission of inflammation in the majority of patients. All achieved immunological remission with normal VGKC antibody titres within 1-4 months. Major adverse events of therapy included one septicaemia and one thrombosis on plasma exchange and one death from sepsis after incidental bowel surgery. One patient remains in remission after 40 months of follow up, 26 months after being off all treatment.
Our immunotherapy regimen was effective for the treatment of the clinical, cognitive and immunological features of VGKC+LE. Radiological improvement was seen in the majority. Pending randomised controlled trials, this regimen is proposed for the treatment of VGKC+LE.

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    • "However, pathological investigation of brain tissue from patients with VGKC-complex antibodies have shown neuronal degeneration in the hippocampus with infiltrating T cells (Bien et al. 2012), and the presence of human IgG and components of the complement cascade (Bien et al. 2012). Steroids, intravenous immunoglobulins and plasmapheresis, and, occasionally, cyclophosphamide have been found to improve the neurological deficits, suggesting that the autoantibodies are pathogenic (Vincent et al. 2004;Wong et al. 2010).Antibodies to the intracellular enzyme GAD are found at low to moderate levels in patients with diabetes. However, high levels of GAD antibodies have been recorded in a number of neurological syndromes, including stiff-person syndrome , cerebellar ataxia, and epilepsy. "
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    ABSTRACT: This review reports the available evidence on the activation of the innate and adaptive branches of the immune system and the related inflammatory processes in epileptic disorders and the putative pathogenic role of inflammatory processes developing in the brain, as indicated by evidence from experimental and clinical research. Indeed, there is increasing knowledge supporting a role of specific inflammatory mediators and immune cells in the generation and recurrence of epileptic seizures, as well as in the associated neuropathology and comorbidities. Major challenges in this field remain: a better understanding of the key inflammatory pathogenic pathways activated in chronic epilepsy and during epileptogenesis, and how to counteract them efficiently without altering the homeostatic tissue repair function of inflammation. The relevance of this information for developing novel therapies will be highlighted.
    Full-text · Article · Dec 2015 · Cold Spring Harbor Perspectives in Medicine
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    • "The patients typically present after an insidious onset with rapidly progressive cognitive decline, frequently with a fluctuating course and inflammatory cerebrospinal fluid findings [4,5,6]. These patients often have autoantibody markers, including anti-cation channel complex antibodies, and respond to immunosuppression [5,7,8]. However, autoimmune phenomena are common in the normal adult population, particularly if defined as the presence of antibodies against cellular components. "
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    ABSTRACT: Background Autoimmunity is considered an uncommon but under-recognised cause of cognitive decline. Methods Serum samples from 3,253 randomly selected subjects enrolled in the Hunter Community Study, aged 55-85 years, were assayed for thyrotropin stimulatory hormone, anti-thyroid peroxidase antibodies (TPO-Ab), anti-nuclear antibodies (ANA) and extractable nuclear antigens (ENA). Cognitive function was assessed using the Audio Recorded Cognitive Screen (ARCS) tool. Results TPO-Ab were found in 8.4% and ANA in 27.9% of the study population, of whom 3% had positive ENA findings. No relationship was found between the ARCS score and either TPO-Ab (coefficient = 0.133; 95% CI −0.20, 0.82, p = 0.616), ANA at a low (coefficient = 1.01; 95% CI −2.58, 0.55, p = 0.203) or a high titre (coefficient = −0.65; 95% CI −2.59, 1.28, p = 0.508), or ENA antibodies (coefficient = 5.12; 95% CI −0.53, 10.77; p = 0.076). Conclusions Autoantibody findings are common in an aging population and are not associated with cognitive decline.
    Full-text · Article · May 2014
    • "Optimum treatment of VGKC-Abs associated LE has not been studied in prospective randomized studies. Wong et al.[13] in an open-label prospective study of 9 patients described a combination of immuno-modulatory treatment in patients with VGKC-Abs associated LE. All patients had plasma exchange, immunoglobulin and methyprednisolone in the acute phase, followed by oral prednisolone. "
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    ABSTRACT: Autoimmune limbic encephalitis (LE) associated with voltage gated potassium channel antibodies (VGKC-Abs) in children is more common than previously thought and is not always paraneoplastic. Non-neoplastic, autoimmune LE associated with VGKC-Abs has been described recently. However, only few case reports in children as the disease is predominantly described in the adult population. It is likely that this type of autoimmune encephalitis is currently under-diagnosed and hence, under-treated, especially in children. We present a 13-year-old previously fit and healthy African girl diagnosed with LE and we reviewed the literature for its current management.
    No preview · Article · Oct 2013 · Annals of Indian Academy of Neurology
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