EncephalopathyNCT06958341
Neuroimmunology Registry and Biobank
An observational study of Encephalopathy and Psychosis, run by Charite University, Berlin, Germany at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Encephalopathy, Psychosis, Impaired Consciousness
- How many people
- 300 participants
- Where
- 2 sitesGermany
- Study dates
- 1 Feb 2021to 1 Jul 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with neurological disease in which a lumbar puncture is indicated for further diagnosis and treatment decision
Who may be able to join
- 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
Who cannot join
- [1] Withdrawal of consent
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany2 sites, 2 recruiting
- Recruiting
Charité - Universitätsmedizin Berlin
Berlin, State of Berlin, 13353
Marc Nikolaus, MD, +49 30 450 566112, marc.nikolaus@charite.de
Markus Schuelke, MD, +49 30 450 566112, markus.schuelke@charite.de
- Recruiting
Universität Ulm
Ulm, 89081
Hayrettin Tumani, MD, +497311775206, hayrettin.tumani@uni-ulm.de
Maximilian Wiesenfarth, MD, +497311775271, maximilian.wiesenfarth@rku.de
About this study
Official title: Registry for Patients With Antibody-mediated Neuroimmunological Diseases
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.
Read the 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.
- Conditions
- Encephalopathy, Psychosis, Impaired Consciousness, Epilepsy, Movement Disorders, Motor Neuropathy
- Keywords
- neuroimmunological diseases, cerebrospinal fluid, cell-based assay, tissue-based assay
- Medical subject headings
- Brain Diseases, Psychotic Disorders, Epilepsy, Movement Disorders, Neuritis, Muscle Spasticity, Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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"
Measured: at recruitment
CSF protein
Measuring the protein content in the patient's CSF. The result will be given as "mg protein per ml CSF".
Measured: at recruitment
CSF albumin
Measuring the albumin content in the patient's CSF. The result will be given as "mg albumin per ml CSF".
Measured: at recruitment
CSF glucose
Measuring the glucose content in the patient's CSF. The result will be given as "mg glucose per liter CSF".
Measured: at recruitment
CSF lactate
Measuring the lactate content in the patient's CSF. The result will be given as "mg lactate per liter CSF".
Measured: 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".
Measured: 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
Measured: at recruitment
Secondary outcomes (6)
Basic clinical data
The investigators will record age, height, weight, and ask about the presence of fever, weight loss, and positive findings on the internal and neurological clinical examination.
Measured: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
Duration from symptom onset to diagnosis
The investigators will record the time delay between the occurrence of the first symptoms and the establishmen of the diagnosis. The results will be recorded as "number of days"
Measured: at recruitment
Assessment of the severity of ataxia
The severity of the ataxia will be quantified using the Scale for the Assessment and Rating of Ataxia (SARA). The SARA score ranges between 0 (no ataxia) and 40 (most severe ataxia).
Measured: 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
The severity of psychiatric symptoms, especially depression, will be quantified with the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is a mulitpurpose instrument for screening, diagnosing, monitoring, and measuring the severity of depression. Interpretation of results: minimal symptoms (5-9), minor depression (10-14), major depression (15-19), severe major depression (20-27)
Measured: 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
The Motor Function Measure (MFM) is a quantitative scale designed to describe the motor abilities of people with neuromuscular disorders. The MFM32 consists of 32 items that are scored between 0 (unable to initiate the task) and 3 (fully able to perform the task). Items fall into one of three different dimensions: Standing and transfers (D1), axial and proximal mobility (D2) and distal motor ability (D3).The raw sum score of the 32 items (maximum 96) is converted to a 0-100 scale. 100 represents full motor function.
Measured: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
Start and end and kind of immunotherapy
The investigators will record the date of initiation and end of the immune therapy and the kind of therapy administered.
Measured: Follow-up of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2025
- Study start1 Feb 2021
- Primary completion1 Jan 2031 (estimated)
- Study completion1 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for EncephalopathyStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ulm
- Responsible party
- Principal investigator, Markus Schuelke, M.D., Charite University, Berlin, Germany
- Investigators
- Marc Nikolaus, MD, Principal investigator, Charite - Universitaetsmedizin BerlinTumani Hayrettin, MD, Principal investigator, University of UlmMaximilian Wiesenfarth, MD, Principal investigator, University of Ulm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06958341
- Sponsor's protocol ID
- EA2_121_17
- Status last verified
- May 2025
- First submitted
- 14 Apr 2025
- Last updated
- 6 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The investigators do not have written consent for the sharing of individual patient data. Publication is only possible in anonymized and aggregated form.
Publications
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.
PubMed 34546336Nikolaus 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.
PubMed 35435761Wilpert 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.
PubMed 37515734Cramer 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.
PubMed 39752845Kauth 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.
PubMed 39879856Nikolaus 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.
PubMed 35727368Schnell 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.
PubMed 36831273Viezens 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.
PubMed 39001514Wendel 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.
PubMed 39675122
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Registry for Patients With Antibody-mediated Neuroimmunological Diseases
- ClinicalTrials.gov ID
- NCT06958341
- Acronym / sponsor ID
- EA2_121_17
- Conditions
- Encephalopathy, Psychosis, Impaired Consciousness, Epilepsy, Movement Disorders, Motor Neuropathy
- Keywords
- neuroimmunological diseases, cerebrospinal fluid, cell-based assay, tissue-based assay
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- University of Ulm
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 1 Jan 2031 (estimated)
- Study completion
- 1 Jul 2031 (estimated)
- First posted
- 6 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with neurological disease in which a lumbar puncture is indicated for further diagnosis and treatment decision
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (1 listed)
- [1] Withdrawal of consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Screening for a panel of anti-neuronal antibodies via commercial assays
Time frame: at recruitment
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.
Screening for unknown anti-neuronal antibodies via immunofluorescence staining on fresh mouse brain (tissue-based assay, TBA)
Time frame: at recruitment
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.
Determination of the molecular weight of the antibody target
Time frame: at recruitment
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
CSF cell count
Time frame: at recruitment
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"
CSF protein
Time frame: at recruitment
Measuring the protein content in the patient's CSF. The result will be given as "mg protein per ml CSF".
CSF albumin
Time frame: at recruitment
Measuring the albumin content in the patient's CSF. The result will be given as "mg albumin per ml CSF".
CSF glucose
Time frame: at recruitment
Measuring the glucose content in the patient's CSF. The result will be given as "mg glucose per liter CSF".
CSF lactate
Time frame: at recruitment
Measuring the lactate content in the patient's CSF. The result will be given as "mg lactate per liter CSF".
CSF IgG
Time frame: at recruitment
Measuring the total IgG content in the patient's CSF. The result will be given as "mg IgG per liter CSF".
CSF oligoclonal bands
Time frame: at recruitment
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
6 secondary outcomes
Basic clinical data
Time frame: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
Duration from symptom onset to diagnosis
Time frame: at recruitment
Assessment of the severity of ataxia
Time frame: 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
Time frame: 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
Time frame: at recruitment, month 1, month 3, month 6, month 12, year 2, year 3, year 4, year 5
Start and end and kind of immunotherapy
Time frame: Follow-up of 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2025.
- Background: PubMed 34546336Kreye 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.
- Background: PubMed 35435761Nikolaus 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.
- Background: PubMed 37515734Wilpert 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.
- Background: PubMed 39752845Cramer 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.
- Background: PubMed 39879856Kauth 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.
- Results publication: PubMed 35727368Nikolaus 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.
- Results publication: PubMed 36831273Schnell 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.
- Results publication: PubMed 39001514Viezens 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.
- Results publication: PubMed 39675122Wendel 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.
- Individual participant dataSharing planned: No. The investigators do not have written consent for the sharing of individual patient data. Publication is only possible in anonymized and aggregated form.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marc Nikolaus, MD principal investigator
Charite - Universitaetsmedizin Berlin
Tumani Hayrettin, MD principal investigator
University of Ulm
Maximilian Wiesenfarth, MD principal investigator
University of Ulm
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Encephalopathy and Psychosis, run by Charite University, Berlin, Germany at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Markus Schuelke, MD (+49 30 450 566112, markus.schuelke@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Screening for a panel of anti-neuronal antibodies via commercial assays (time frame: at recruitment). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06958341, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2025.