Autoimmune Encephalitis

What is autoimmune encephalitis?

Autoimmune encephalitis is the term used to describe a broadening group of autoimmune inflammatory diseases that primarily affect the grey matter of the central nervous system. This includes the limbic system, neocortex, basal ganglia, cerebellum and brain stem.

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How does this pathological process appear to unfold?

The majority of patients with autoimmune encephalitis test positive for autoantibodies against nerve cell components. These antibodies are typically found in the cerebrospinal fluid (CSF) and blood serum and can be detected using modern assay methods (Diagnostics).

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How do we diagnose autoimmune encephalitides?

The clinical suspicion of autoimmune encephalitis is usually founded on the acute or subacute onset and rapid progression (<3 months) of short-term and working memory deficits, on a qualitative and quantitative impairment of consciousness or on the subacute onset of psychiatric symptoms reflected as personality changes, behavioral anomalies and affective disorders (Graus 2016).

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How are neuronal antibodies detected?

In recent years, the testing options for antineuronal antibodies have grown in both quantity and complexity. Like every test system, the assays employed can produce both false-positive and false-negative findings. A number of measures, however, can minimize these drawbacks. Performed correctly, the detection of antineuronal antibodies facilitates differential diagnostics, enables a more accurate prognosis, defines the recommended therapy and informs the search for tumors.

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When and how is it appropriate to search for an underlying tumor?

In seropositive autoimmune encephalitides, the probability and most common localization of an underlying tumor can be predicted regardless of the detected neuronal antibody. Of course, risk factors (e.g. smoking history), age and gender should also be taken into account in these considerations. Tumor diagnostics should be graded.

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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.

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References

Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis.

Gallus M, Roll W, Dik A, Barca C, Zinnhardt B, Hicking G, Mueller C, Naik VN, Anstötz M, Krämer J, Rolfes L, Wachsmuth L, Pitsch J, van Loo KMJ, Räuber S, Okada H, Wimberley C, Strippel C, Golombeck KS, Johnen A, Kovac S, Groß CC, Backhaus P, Seifert R, Lewerenz J, Surges R, Elger CE, Wiendl H, Ruck T, Becker AJ, Faber C, Jacobs AH, Bauer J, Meuth SG, Schäfers M, Melzer N. Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis. Sci Adv. 2023 Jun 9;9(23):eabq7595. doi: 10.1126/sciadv. abq7595. Epub 2023 Jun 9. PMID: 37294768; PMCID: PMC10256169.

Crebrospinal fluid proteomics indicates immune dysregulation and neuronal dysfunction in antibody associated autoimmune encephalitis.

Räuber S, Schroeter CB, Strippel C, Nelke C, Ruland T, Dik A, Golombeck KS, Regner-Nelke L, Paunovic M, Esser D, Münch C, Rosenow F, van Duijn M, Henes A, Ruck T, Amit I, Leypoldt F, Titulaer MJ, Wiendl H, Meuth SG, Meyer Zu Hörste G, Melzer N. Cerebrospinal fluid proteomics indicates immune dysregulation and neuronal dysfunction in antibody associated autoimmune encephalitis. J Autoimmun. 2023 Feb;135:102985. doi: 10.1016/j.jaut.2022.102985. Epub 2023 Jan 6. PMID: 36621173.

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.



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