Neuroimmunology Registry and Biobank

NCT ID: NCT06958341

Last Updated: 2025-05-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-02-01

Study Completion Date

2031-07-01

Brief Summary

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A variety of antineuronal antibodies have been detected in the cerebrospinal fluid (CSF) of patients with neurological diseases. This raises the question of whether these antibodies are disease-specific or merely an epiphenomenon of inflammatory processes in the brain.

The registry was established with the following objectives: \[1\] Are antineuronal antibodies much more common than previously thought in various neurological disorders for which the etiology has not yet been elucidated? \[2\] Can further correlations, such as those between HSV infection and NMDA receptor autoimmunity, be identified? \[3\] Are these antibodies mainly non-specific epiphenomena or are they crucial for the pathogenesis? \[4\] What is the clinical course of patients with antineuronal antibodies and their response to therapy? These questions will be addressed in a broad immunohistological screening of a large number of CSF samples and a clinical database of patients with neurological disorders.

Detailed Description

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The hypothesis that autoimmunity is a driving force behind many neurological diseases has become an established view in adult and pediatric neurology. This is particularly true for diseases of the central nervous system that are mediated by or at least associated with autoantibodies against neuronal surface antigens, the group of "autoimmune encephalitis".

This group of diseases has become increasingly important in adult neurology over the past 15 years and is now gaining importance in pediatric neurology. Since the first description of a fulminant encephalitis with autoantibodies against the N-methyl-D-aspartate (NMDA) receptor in 2007, researchers and physicians are beginning to understand that many patients worldwide with encephalopathy or epileptic and psychiatric symptoms may be suffering from previously unrecognized but treatable autoimmune diseases. As a result, the new field of "autoimmune encephalitis" has been established and new diagnostic tools are being developed. Despite a rapidly growing list of disease entities - now ranging from relatively common diagnoses such as anti-NMDA receptor, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, or anti-leucine-rich glioma-inactivated 1 (LGI1) receptor encephalitis to rare entities caused by antibodies against the metabotropic glutamate receptor 5 (mGuR5) - the field of autoimmune encephalitis is still in its infancy. The field of autoimmune encephalitis continues to evolve.

A better understanding of autoimmune encephalitis could improve the chances of treatment and even cure for many patients with previously unexplained diagnoses. This is especially true for antibody-negative autoimmune encephalitis and rare syndromes with only suspected autoantibody associations, such as corea minor and other autoimmune movement disorders, as well as ataxias, opsoclonus-myoclonus syndrome, antibody-associated motor neuronopathies, and juvenile amyotrophic lateral sclerosis (ALS). The goal of this registry is to gain new insights into the etiology of autoimmune encephalitis and non-encephalitic overlap syndromes and to investigate the role of neuronal autoantibodies in these and other neurological diseases.

The investigators will enroll patients with suspected neurologic autoimmune diseases into the database. The database will record their medical history, cardinal symptoms of the current disease, diagnostic results with emphasis on CSF analysis and imaging, as well as final diagnosis, therapy, and disease course. Residual CSF samples from lumbar punctures performed as part of the routine diagnostic workup are collected, cataloged, and stored in a CSF biobank.

The following methods are used to detect and characterize anti-neuronal antibodies: \[1\] highly sensitive immunofluorescence staining of fresh mouse brain (tissue-based assay, TBA), \[2\] immunoprecipitation from mouse brain homogenates and analysis of bound proteins by mass spectrometry, \[3\] flow cytometric methods (FACS, fluorescence-activated cell sorting and cell sorting), isolation and cloning of specific monoclonal autoantibodies from B-cells and plasma cells, and functional characterization studies.

Conditions

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Encephalopathy Psychosis Impaired Consciousness Epilepsy Movement Disorders Motor Neuropathy Spasticity Ataxia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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patients with suspected neuroimmunological disease

patients with suspected neuroimmunological disease in whom a lumbar puncture is indicated for routine clinical work-up and for treatment decisions

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Differential diagnosis: suspected neuroimmunological disease in which a lumbar puncture is indicated for further diagnosis and treatment decision
2. Individuals with unclear clinical diagnosis where additional CSF is to be collected for isolation of B cells and production of monoclonal antibodies. The clinical condition of the patients and his/her compliance have to allow an extra 2-3 ml of CSF to be collected.
3. Age: all age groups
4. Gender: patients of both sexes will be included

Exclusion Criteria

\[1\] Withdrawal of consent
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Ulm

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role lead

Responsible Party

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Markus Schuelke, M.D.

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marc Nikolaus, MD

Role: PRINCIPAL_INVESTIGATOR

Charite - Universitaetsmedizin Berlin

Tumani Hayrettin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Ulm

Maximilian Wiesenfarth, MD

Role: PRINCIPAL_INVESTIGATOR

University of Ulm

Locations

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Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, Germany

Site Status RECRUITING

Universität Ulm

Ulm, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Markus Schuelke, MD

Role: CONTACT

+49 30 450 566112

Marc Nikolaus, MD

Role: CONTACT

+49 30 450 566112

Facility Contacts

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Marc Nikolaus, MD

Role: primary

+49 30 450 566112

Markus Schuelke, MD

Role: backup

+49 30 450 566112

Hayrettin Tumani, MD

Role: primary

+497311775206

Maximilian Wiesenfarth, MD

Role: backup

+497311775271

References

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Kreye J, Wright SK, van Casteren A, Stoffler L, Machule ML, Reincke SM, Nikolaus M, van Hoof S, Sanchez-Sendin E, Homeyer MA, Cordero Gomez C, Kornau HC, Schmitz D, Kaindl AM, Boehm-Sturm P, Mueller S, Wilson MA, Upadhya MA, Dhangar DR, Greenhill S, Woodhall G, Turko P, Vida I, Garner CC, Wickel J, Geis C, Fukata Y, Fukata M, Pruss H. Encephalitis patient-derived monoclonal GABAA receptor antibodies cause epileptic seizures. J Exp Med. 2021 Nov 1;218(11):e20210012. doi: 10.1084/jem.20210012. Epub 2021 Sep 21.

Reference Type BACKGROUND
PMID: 34546336 (View on PubMed)

Nikolaus M, Kuhne F, Tietze A, Thumfart J, Kempf C, Gratopp A, Knierim E, Bittigau P, Kaindl AM. Modified Zipper Method, a Promising Treatment Option in Severe Pediatric Immune-Mediated Neurologic Disorders. J Child Neurol. 2022 May;37(6):505-516. doi: 10.1177/08830738221089476. Epub 2022 Apr 18.

Reference Type BACKGROUND
PMID: 35435761 (View on PubMed)

Nikolaus M, Koch A, Stenzel W, Elezkurtaj S, Sahm F, Tietze A, Stoffler L, Kreye J, Hernaiz Driever P, Thomale UW, Kaindl AM, Schuelke M, Knierim E. Atypical NMDA receptor expression in a diffuse astrocytoma, MYB- or MYBL1-altered as a trigger for autoimmune encephalitis. Acta Neuropathol. 2022 Aug;144(2):385-389. doi: 10.1007/s00401-022-02447-y. Epub 2022 Jun 21. No abstract available.

Reference Type BACKGROUND
PMID: 35727368 (View on PubMed)

Schnell S, Knierim E, Bittigau P, Kreye J, Hauptmann K, Hundsdoerfer P, Morales-Gonzalez S, Schuelke M, Nikolaus M. Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease. Cells. 2023 Feb 13;12(4):606. doi: 10.3390/cells12040606.

Reference Type BACKGROUND
PMID: 36831273 (View on PubMed)

Wilpert NM, de Almeida Marcelino AL, Knierim E, Incoronato P, Sanchez-Sendin E, Staudacher O, Drenckhahn A, Bittigau P, Kreye J, Pruss H, Schuelke M, Kuhn AA, Kaindl AM, Nikolaus M. Pediatric de novo movement disorders and ataxia in the context of SARS-CoV-2. J Neurol. 2023 Oct;270(10):4593-4607. doi: 10.1007/s00415-023-11853-5. Epub 2023 Jul 29.

Reference Type BACKGROUND
PMID: 37515734 (View on PubMed)

Viezens I, Knierim E, Deubzer HE, Hauptmann K, Fassbender J, Morales-Gonzalez S, Kaindl AM, Schuelke M, Nikolaus M. Expression of mGluR5 in Pediatric Hodgkin and Non-Hodgkin lymphoma-A Comparative Analysis of Immunohistochemical and Clinical Findings Regarding the Association between Tumor and Paraneoplastic Neurological Disease. Cancers (Basel). 2024 Jul 4;16(13):2452. doi: 10.3390/cancers16132452.

Reference Type BACKGROUND
PMID: 39001514 (View on PubMed)

Wendel EM, Tibussek D, Barisic N, Bertolini A, Panzer A, Chang P, Geis T, Knierim E, Nikolaus M, Nosadini M, Sartori S, Schoene-Bake JC, Yilmaz D, Reindl M, Pakeerathan T, Ayzenberg I, Rostasy K. Children with MOG-IgG positive bilateral optic neuritis misdiagnosed as fulminant idiopathic intracranial hypertension. Mult Scler Relat Disord. 2025 Jan;93:106205. doi: 10.1016/j.msard.2024.106205. Epub 2024 Dec 15.

Reference Type BACKGROUND
PMID: 39675122 (View on PubMed)

Cramer P, Nikolaus M, Loos S, Denecke J, Knierim E, Muller D, Weber LT, Taylan C, Thumfart J. Immunoadsorption is equally effective as plasma exchange in paediatric neuroimmunological disorders - A retrospective multicentre study. Eur J Paediatr Neurol. 2025 Jan;54:58-63. doi: 10.1016/j.ejpn.2024.12.005. Epub 2024 Dec 21.

Reference Type BACKGROUND
PMID: 39752845 (View on PubMed)

Kauth F, Bertolini A, Wendel EM, Koukou G, Naggar IE, Chung J, Baumann M, Schodl C, Lechner C, Bigi S, Blaschek A, Hengstler JG, Schimmel M, Nosadini M, Sartori S, Puthenparampil M, Van's Gravesande KS, Drenckhahn A, Nikolaus M, Kauffmann B, Thiels C, Hausler MG, Eckenweiler M, Karenfort M, Marina AD, Selek A, Oncel I, Kornek B, Reindl M, Rostasy K. Characterization of children with early onset pediatric multiple sclerosis. Eur J Paediatr Neurol. 2025 Jan;54:113-120. doi: 10.1016/j.ejpn.2025.01.006. Epub 2025 Jan 23.

Reference Type BACKGROUND
PMID: 39879856 (View on PubMed)

Other Identifiers

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EA2_121_17

Identifier Type: -

Identifier Source: org_study_id

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