Immunotherapeutics for Autoimmune Encephalopathies and Dementias

College of Medicine, Mayo Clinic, 200 1st ST SW, Rochester, MN, 55905, USA, .
Current Treatment Options in Neurology (Impact Factor: 1.94). 06/2013; 15(6). DOI: 10.1007/s11940-013-0251-8
Source: PubMed


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.

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    • "Despite increased recent research interest, no clear guidelines exist for the diagnosis or management of autoimmune epilepsy. Various immunomodulatory therapies, including steroids, intravenous immunoglobulin (IVIG), cyclophosphamide, and rituximab have been utilized to achieve seizure control in ASM-resistant patients [4]. Epilepsy is a recognized manifestation of autoimmune encephalitis [5]. "
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    ABSTRACT: Purpose: Analyze clinical and electrographic characteristics of patients with autoimmune epilepsy, and evaluate the effect of early diagnosis and treatment on reduction of seizure frequency. Methods: Observational retrospective case series, conducted using electronic medical data from two teaching hospitals. Clinical data was collected from 2008 to 2013. Cases of new onset seizures were selected based on the presence of laboratory evidence of autoimmunity. Results: 34 hospitalized patients who presented predominantly due to seizures with concern for autoimmune etiology were identified. Mean age of patients was 44.94 years and 64.7% were males. Autoimmune antibodies were detected in 76.5% (26) of patients as follows: VGKc (8); NMDA-R (7); anti-thyroid (5); GAD (4); GABAB (2). 22 patients had unilateral temporal lobe onset and 4 had bilateral temporal lobe onset, while 8 had extra-temporal onset/multiple ictal foci. Median number of seizures during initial prolonged vEEG monitoring was 8 (range 0–48); median number of anti-seizure medications used was 2 (range 1–5). 9 patients had an underlying malignancy. 94.1% (32) patients received immunomodulation, as follows: high dose corticosteroids (96.8%), plasmapheresis (62.5%), IVIG (34.4%), rituximab (21.8%), mycophenolate (15.6%), cyclophosphamide (12.5%). 63.3% (19) participants achieved ≥50% seizure reduction (Responder Rate) at first clinic visit. Patients without malignancy had better seizure control (p < 0.05). Time from symptom onset to diagnosis (p < 0.005) and symptom onset to immunomodulation (p < 0.005) was significantly lower among patients who achieved responder rate (RR). Conclusion: This study highlights certain important clinical and electrographic aspects of autoimmune epilepsy, and the significance of early diagnosis and initiation of immunomodulatory therapy.
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  • The Lancet Neurology 12/2013; 13(2). DOI:10.1016/S1474-4422(13)70277-1 · 21.90 Impact Factor
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    ABSTRACT: Glucocorticoids represent a cornerstone in the therapy for many neurological disorders. Even though their mechanism of action is still not completely understood, synthetic glucocorticoids are given as first line drugs in a number of immunological and non-immunological disorders of the central or peripheral nervous system. For most of these disorders, however, the level of evidence that glucocorticoids are truly effective is still not sufficient. This is why treatment with glucocorticoids cannot be recommended on an evidenced-based level for many of these disorders. Due to the huge number of acute or chronic side effects, it is essential that the effects are documented by more randomised placebo-controlled cross-over trials. Generally, glucocorticoids can no longer be omitted in the treatment of neurological disorders, the indication to apply glucocorticoids, however, needs to be thoroughly balanced in the light of their many side effects.
    Fortschritte der Neurologie · Psychiatrie 06/2014; 82(6):311-322. DOI:10.1055/s-0034-1366379 · 0.63 Impact Factor
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