Immunotherapeutics for Autoimmune Encephalopathies and Dementias.
ABSTRACT OPINION STATEMENT: The timely implementation of immunotherapy is key to successful treatment of autoimmune encephalopathies or dementias (from here on will be referred to as autoimmune encephalopathies). There are different levels of diagnostic certainty which should guide the immunological treatment of autoimmune encephalopathies. There is a high level of diagnostic certainty for patients who have classic limbic encephalitis and have a neural antibody detected in serum or CSF (such as potassium channel complex antibody). For these patients, initiating high-dose corticosteroids or IVIg is indicated, with plasma exchange, rituximab or cyclophosphamide used as second-line therapy if first-line therapy proves only partially beneficial. There is a lower level of diagnostic certainty in patients with non-limbic atypical phenotypes (though rapidly progressive) when no neural antibody is detected in serum and CSF. A trial of corticosteroids or IVIg (or both sequentially) may be undertaken in these patients, but if no objective improvements occur, further immunotherapy is unlikely to be beneficial. Antiepileptic treatment also plays a critical role in those who have seizures as well as cognitive symptoms. Evaluation for and treatment of any underlying cancer is another component for those patients with a paraneoplastic cause of encephalitis. An individualized maintenance regimen needs to be designed for patients who do improve with immunotherapy. Individual factors that need to be considered when formulating a program of maintenance treatment include disease severity, antibody specificity and proclivity for disease relapse. Azathioprine and mycophenolate mofetil are frequently used for the purpose of remission maintenance, and should permit gradual withdrawal of steroids, IVIg or more toxic immunosuppressants. The duration of maintenance therapy is uncertain, but this author typically recommends 3-5 years of relapse-free maintenance treatment before discontinuing immunotherapy altogether.
- The Lancet Neurology 12/2013; · 21.82 Impact Factor
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ABSTRACT: Background and purposeThe detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of ‘autoimmune epilepsy’. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy.Methods Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency.ResultsNeural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency.ConclusionsA significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.European Journal of Neurology 08/2014; · 3.85 Impact Factor
- Psychosomatics 11/2014; · 1.67 Impact Factor