Clinical trial NCT06958341: Neuroimmunology Registry and Biobank
Official title: Registry for Patients With Antibody-mediated Neuroimmunological Diseases
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Encephalopathy
Psychosis
Impaired Consciousness
Epilepsy
Movement Disorders
Motor Neuropathy
Spasticity
Ataxia
Keywords: neuroimmunological diseases
cerebrospinal fluid
cell-based assay
tissue-based assay
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: University of Ulm
First posted: 2025-05-06
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with neurological disease in which a lumbar puncture is indicated for further diagnosis and treatment decision

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Screening for a panel of anti-neuronal antibodies via commercial assays
timeFrame: at recruitment
measure: Screening for unknown anti-neuronal antibodies via immunofluorescence staining on fresh mouse brain (tissue-based assay, TBA)
timeFrame: at recruitment
measure: Determination of the molecular weight of the antibody target
timeFrame: at recruitment
measure: CSF cell count
timeFrame: at recruitment
measure: CSF protein
timeFrame: at recruitment
measure: CSF albumin
timeFrame: at recruitment
measure: CSF glucose
timeFrame: at recruitment
measure: CSF lactate
timeFrame: at recruitment
measure: CSF IgG
timeFrame: at recruitment
measure: CSF oligoclonal bands
timeFrame: at recruitment
Secondary outcomes:
measure: Basic clinical data
timeFrame: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
measure: Duration from symptom onset to diagnosis
timeFrame: at recruitment
measure: Assessment of the severity of ataxia
timeFrame: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
measure: Assessment for the severity of psychiatric symptoms
timeFrame: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
measure: Assessment of the severity of motor symptoms
timeFrame: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
measure: Start and end and kind of immunotherapy
timeFrame: Follow-up of 5 years
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Ulm
country: Germany
facility: Universität Ulm
Study officials:
affiliation: Charite - Universitaetsmedizin Berlin
name: Marc Nikolaus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ulm
name: Tumani Hayrettin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ulm
name: Maximilian Wiesenfarth, MD
role: PRINCIPAL_INVESTIGATOR
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