How do we treat autoimmune encephalitis?

At present, there are no prospective clinical trials, but only good retrospective therapeutic data on anti-NMDAR encephalitis. Therefore, the therapy of the autoimmune types of encephalitides is oriented on the therapy established for anti-NMDAR encephalitis (Figure). When rapid-onset immunotherapy is given, the prognosis is not only principally good for anti-NMDAR encephalitis, but also for other encephalitides with antibodies against neuronal surface proteins. That is why any delays in treatment initiation should be minimized.

The following principles apply: The therapy of paraneoplastic and non-paraneoplastic autoimmune encephalitides in which antibodies against intracellular and membrane-based neuronal antigens are demonstrated should consist of a combination of

  1. Adequate cancer therapy (surgery, radiation chemotherapy), provided a tumor can be detected
  2. Immunotherapy and
  3. Symptomatic therapy.

According to experts’ opinion, the following immunosuppressant dosage and interval regimens are mostly used:

First-line therapy:

  • Plasmapheresis/immunoadsorption (5-10 cycles)
  • Intravenous immunoglobulins (2 g/kg body weight for 5 days)
  • Intravenous methylprednisolone pulse therapy (1 g/day for 5 days)

Second-line therapy:

  • Rituximab (1000 mg i.v. twice at 14-day intervals, repeat after 6 months as needed) → innumerable experts meanwhile give rituximab as first-line therapy, underpinned by its comparatively favorable side effect profile and its relatively selective action on the depletion of B cells
  • Cyclophosphamide for 6-12 months at a dose of 750-1000 mg/m² body surface area i.v. every 4 weeks with dose escalation as a function of leukocyte nadir
  • Azathioprine (100-250 mg/day)
  • MTX (7.5-25 mg/week), folic acid rescue

Some specialists recommend a second-line therapy (including a combination of enhancement therapy drugs, e.g. rituximab together with cyclophosphamide) after as early as 10-14 days of no response (Dalmau 2011). In therapy-refractory patients, more recent observations suggest a positive effect of bortezomib, the proteasome inhibitor used to deplete mainly mature plasma cells (Scheibe et al.).

References

  1. Dalmau J, Lancaster E, Martinez-Hernandez E, et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10(1):63–74.
  2. Scheibe F, Prüss H, Mengel AM, Kohler S, Nümann A, Köhnlein M, Ruprecht K, Alexander T, Hiepe F, Meisel A. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology. 2017 Jan 24;88(4):366-370.

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References

Peer M, Prüss H, Ben-Dayan I, Paul F, Arzy S, Finke C.
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Heine J, Prüss H, Kopp UA, Wegner F, Then Bergh F, Münte T, Wandinger KP, Paul F, Bartsch T, Finke C.
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Autoantibody-mediated encephalitis - differential diagnosis in patients with impaired consciousness of unclear origin

Wandinger, Klaus-Peter; Leypoldt, Frank; Junker, Ralf
Dtsch Arztebl Int 2018; 115(40): 666-73; DOI: 10.3238/arztebl.2018.0666
Link: https://www.aerzteblatt.de/archiv/201062/Autoantikoerper-vermittelte-Enzephalitiden

Dalmau J, Graus F.
N Engl J Med. 2018 Mar 1;378(9):840-851. doi: 10.1056/NEJMra1708712. Review. No abstract available.
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Link: https://www.nejm.org/doi/full/10.1056/NEJMra1708712

Mueller SH, Färber A, Prüss H, Melzer N, Golombeck KS, Kümpfel T, Thaler F, Elisak M, Lewerenz J, Kaufmann M, Sühs KW, Ringelstein M, Kellinghaus C, Bien CG, Kraft A, Zettl UK, Ehrlich S, Handreka R, Rostásy K, Then Bergh F, Faiss JH, Lieb W, Franke A, Kuhlenbäumer G, Wandinger KP, LeypoldtF; German Network for Research on Autoimmune Encephalitis (GENERATE).
Ann Neurol. 2018 Apr;83(4):863-869. doi: 10.1002/ana.25216.
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Malviya M, Barman S, Golombeck KS, Planagumà J, Mannara F, Strutz-Seebohm N, Wrzos C, Demir F, Baksmeier C, Steckel J, Falk KK, Gross CC, Kovac S, Bönte K, Johnen A, Wandinger KP, Martín-García E, Becker AJ, Elger CE, Klöcker N, Wiendl H, Meuth SG, Hartung HP, Seebohm G, Leypoldt F, Maldonado R, Stadelmann C, Dalmau J, Melzer N, Goebels N.
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