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

Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis

Brändle SM, Cerina M, Weber S et al. PNAS March 2, 2021 118 (9) e1916337118.

Dieses Paper wurde vom Research4Rare Verbund zum Paper of the Month gewählt und erscheint im April dieses Jahres im BMBF Newsletter!

A Therapeutic Non-self-reactive
SARS-CoV-2 Antibody
Protects from Lung Pathology
in a COVID-19 Hamster Model

Kreye J, Momsen Reincke S, Kornau HC et al.
Cell. 2020 Nov 12;183(4):1058-1069.e19.

CD8+ T-Lymphocyte–Driven Limbic
Encephalitis Results in Temporal Lobe
Epilepsy

Pitsch J, van Loo KMJ, Gallus M et al.
Ann Neurol. 2021; 00:1-20.

Low CSF CD4/CD8+ T-cell proportions are associated with blood-CSF barrier dysfunction in limbic encephalitis.

Hansen N, Schwing K, Önder D, et al. Epilepsy Behav. 2020;102:106682.

An expanded parenchymal CD8+ T cell clone in GABAA receptor encephalitis.

Bracher A, Alcalá C, Ferrer J, et al. Ann Clin Transl Neurol. 2020;7(2):239‐244.

Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome

Bien CG, Bien CI, Dogan Onugoren M, et al. [published online ahead of print, 2020 Apr 3] [published correction appears in J Neurol. 2020 May 12;:]. J Neurol. 2020;10.1007/s00415-020-09814-3.