Neuroimmunology Registry and Biobank

NCT06958341 | Recruiting

• 1 other identifier: EA2_121_17
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Encephalopathy; Psychosis; Impaired Consciousness; Epilepsy; Movement Disorders; Motor Neuropathy; Spasticity; Ataxia

Keywords

neuroimmunological diseases; cerebrospinal fluid; cell-based assay; tissue-based assay

Outcome Measures

Primary Outcomes (10)

• Screening for a panel of anti-neuronal antibodies via commercial assays

  The investigators use this commercial test battery to identify whether the CSF of the patients contains known anti-neuronal antibodies. The tests will be perfromed by Euroimmune (Lübeck, Germany). If positive, the result will be the kind of the antibody and its titer.

  at recruitment

• Screening for unknown anti-neuronal antibodies via immunofluorescence staining on fresh mouse brain (tissue-based assay, TBA)

  The tissue-based assay is a non-specific screening method for anti-neuronal antibodies. The investigators stain freshly cryosectioned mouse brain with patient cerebrospinal fluid at various dilutions and counterstain the sample with fluorescently labelled anti-human IgG antibodies. The sample is then imaged using fluorescence microscopy. The recorded measure will be the presence and quality of a characteristic staining pattern (cell population stained by the patient CSF) or its absence.

  at recruitment

• Determination of the molecular weight of the antibody target

  If the tissue based assay (TBA) is positive for a cell surface signal, the investigators will use Western blot to determine the molecular weight after staining mouse brain homogenates with patient CSF and secondary anti human anti-IgG antibodies

  at recruitment

• CSF cell count

  Counting and differentiating the cells found in the patient's CSF. Cell number given as "cell number per microliter". The cell type will ge given as "mononuclear cells" or "polymorph-nuclear cells"

  at recruitment

• CSF protein

  Measuring the protein content in the patient's CSF. The result will be given as "mg protein per ml CSF".

  at recruitment

• CSF albumin

  Measuring the albumin content in the patient's CSF. The result will be given as "mg albumin per ml CSF".

  at recruitment

• CSF glucose

  Measuring the glucose content in the patient's CSF. The result will be given as "mg glucose per liter CSF".

  at recruitment

• CSF lactate

  Measuring the lactate content in the patient's CSF. The result will be given as "mg lactate per liter CSF".

  at recruitment

• CSF IgG

  Measuring the total IgG content in the patient's CSF. The result will be given as "mg IgG per liter CSF".

  at recruitment

• CSF oligoclonal bands

  An electrophoresis of the patient CSF and subsequent Coomassie staining will reveal oligoclonal bande in the patient's CSF. As a result the investigators record the "presence" or "absence" of oligoclonal bands

  at recruitment

Secondary Outcomes (6)

• Basic clinical data

  at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5

• Duration from symptom onset to diagnosis

  at recruitment

• Assessment of the severity of ataxia

  at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5

• Assessment for the severity of psychiatric symptoms

  at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5

• Assessment of the severity of motor symptoms

  at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5

Study Arms (1)

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with neurological disease in which a lumbar puncture is indicated for further diagnosis and treatment decision

You may qualify if:

• Differential diagnosis: suspected neuroimmunological disease in which a lumbar puncture is indicated for further diagnosis and treatment decision
• 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.
• Age: all age groups
• Gender: patients of both sexes will be included

You may not qualify if:

• \[1\] Withdrawal of consent

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• University of Ulm: collaborator

Study Sites (2)

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 13353, Germany

RECRUITING

Universität Ulm

Ulm, 89081, Germany

RECRUITING

Related Publications (9)

• 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.

  PMID: 34546336 BACKGROUND

• 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.

  PMID: 35435761 BACKGROUND

• 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.

  PMID: 35727368 BACKGROUND

• 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.

  PMID: 36831273 BACKGROUND

• 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.

  PMID: 37515734 BACKGROUND

• 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.

  PMID: 39001514 BACKGROUND

• 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.

  PMID: 39675122 BACKGROUND

• 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.

  PMID: 39752845 BACKGROUND

• 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.

  PMID: 39879856 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

cerebrospinal fluid (CSF) samples stored at -80°C

MeSH Terms

Conditions

Brain Diseases; Psychotic Disorders; Epilepsy; Movement Disorders; Neuritis; Muscle Spasticity; Ataxia

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Peripheral Nervous System Diseases; Neuromuscular Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dyskinesias

Study Officials

• Marc Nikolaus, MD

  Charite - Universitaetsmedizin Berlin

  PRINCIPAL INVESTIGATOR

• Tumani Hayrettin, MD

  University of Ulm

  PRINCIPAL INVESTIGATOR

• Maximilian Wiesenfarth, MD

  University of Ulm

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Markus Schuelke, MD

CONTACT

+49 30 450 566112; markus.schuelke@charite.de

Marc Nikolaus, MD

CONTACT

+49 30 450 566112; marc.nikolaus@charite.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: May 6, 2025
• Study Start: February 1, 2021
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): July 1, 2031
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)