Swiss Pediatric Inflammatory Brain Disease Registry (Swiss-Ped-IBrainD)

Study Overview
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Brief Summary
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The Swiss-Ped-IBrainD is a national patient registry that collects information on diagnosis, symptoms, treatment, and follow-up of pediatric patients with an inflammatory brain disease in Switzerland. It was first implemented in 2020 in the pediatric clinic of the university hospital in Bern. Further centers all over Switzerland were opened for recruitment in 2021; Aarau, Basel, Bellinzona, Chur, Geneva, Lausanne, Lucerne, St. Gallen, and Zurich. The center in Winterthur is expected to be open for recruitment by autumn 2021. The registry provides data for national and international monitoring and research. It supports research on inflammatory brain diseases in Switzerland and the exchange of knowledge between clinicians, researchers, and therapists. The registry aims to improve the treatment of children with inflammatory brain diseases and optimizing their health care and quality of life.

Detailed Description
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Background: Pediatric onset MS and other inflammatory brain diseases (IBrainDs) are severe diseases affecting children and adolescents in a period of essential brain development. This possibly leads to a variety of focal neurological deficits as well as early cognitive impairment. In turn, the cognitive impairment may impact school performance and vocational achievements. Timely diagnosis and treatment initiation as well as individually tailored management are important for a favorable disease course. However, the diagnosis of the different IBrainDs can be challenging, especially in young children, since their first acute inflammation is often accompanied by unspecific symptoms common to all IBrainDs. A systematic assessment of similarities and differences between clinical signs, symptoms, and diagnostic workup of different IBrainDs will enable faster and more reliable diagnosis. Furthermore, neither epidemiological data nor information on health care management and disease outcome of pediatric IBrainD patients exist in Switzerland. Therefore, a national registry is being established, which will allow a deeper understanding of pediatric IBrainD epidemiology, clinical presentation, and management. Ultimately, the registry will improve the care of children suffering from an IBrainD in Switzerland. The Swiss-Ped-IBrainD Registry (title: Swiss Pediatric Inflammatory Brain Disease Cohort Study, project number: 2019-00377) has been approved by the ethics committees of Bern, the Ethikkommission Nordwest- und Zentralschweiz (EKNZ), the Ethikkommission Ostschweiz (EKOS), and the ethics committees of Zürich, Lausanne, Geneva, and Bellinzona. Objectives: The registry pursues the following goals: Gathering representative, population-based epidemiological data on pediatric IBrainD in Switzerland. Monitoring treatment, clinical course, education, social aspects, and outcomes of pediatric IBrainD patients. Providing a platform to facilitate research, national and international collaboration and exchange of knowledge between experts. The registry thus addresses the increasing requests for medical trial participation and promotes the exchange with existing adult registries (e.g., Swiss MS Registry). Inclusion/exclusion criteria: All patients living and/or treated in Switzerland with an IBrainD specified in the following list with a disease onset before the age of 18. Optic neuritis Transverse myelitis Acute disseminated encephalomyelitis Multiple sclerosis Neuromyelitis optica spectrum disorders Anti-NMDA-R associated autoimmune encephalitis Anti-GAD65 associated autoimmune encephalitis Anti-AMPAR-1/2 associated autoimmune encephalitis Anti-Lgi-1 associated autoimmune encephalitis Anti-CASPR-2 associated autoimmune encephalitis Anti-GABAR-1/2 associated autoimmune encephalitis Onconeuronal antibody (Hu, Ri, Yo, Amphiphysin, CRMP-5, Ma-1, Ma-2, SOX-1) associated autoimmune encephalitis Hashimoto encephalopathy CNS vasculitis CNS sarcoidosis CNS Lupus Rasmussen's encephalitis Excluded are patients with: Neurological symptoms due to infectious diseases of the CNS Genetic/metabolic causes of central demyelinating diseases Neurological symptoms due to Guillain-Barré-Syndrome Registration of Patients and Collection of Medical Data: Pediatricians, pediatric neurologists, neurologists, specialists in rehabilitation, and primary care physicians at the participating centers are responsible to identify children with the listed IBrainDs during regular medical consultations. Upon identification, treating physicians inform patients and their parents orally and in writing about the Swiss-Ped-IBrainD. Patients (and their legal representatives if applicable) who want to participate must give their informed consent. Once a patient consents to participate, his/her medical data will be entered in the registry. The diagnostic workup and treatment of patients continue as usual and are independent from participation; no examination will be carried out specifically for the Swiss-Ped-IBrainD. Medical data is collected through the following sources: Medical records and reports Oral/written information from treating physician Oral/written information from patient/family Routine statistics and other medical registries Questionnaires for patients and families The data collection focuses on diagnostic, follow-up, and relapse variables. Routine data and linkages: Communities; Federal Statistical Office (e.g. the birth register, cause of death statistics, hospital statistics) Current status: From 2020-2021, the investigators have included 17 persons diagnosed with an IBrainD. Funding: Schweizerische Multiple Sklerose Gesellschaft PedNet Bern Roche Pharma (Switzerland) Ltd Novartis Pharma Schweiz AG SwissPedRegistry, University of Bern

Official Title
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Swiss Pediatric Inflammatory Bain Disease Cohort Study

Conditions
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Optic Neuritis, Transverse Myelitis, Acute Disseminated Encephalomyelitis, Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, Anti-NMDAR Encephalitis, Anti-GAD65 Associated Autoimmune Encephalitis, Anti-AMPAR-1/2 Associated Autoimmune Encephalitis, Anti-Lgi-1 Associated Autoimmune Encephalitis, Anti-CASPR-2 Associated Autoimmune Encephalitis, Anti-GABAR-1/2 Associated Autoimmune Encephalitis, Onconeuronal Antibody (Hu, Ri, Yo, Amphiphysin, CRMP-5, Ma-1, Ma-2, SOX-1) Associated Autoimmune Encephalitis, Hashimoto Encephalitis, CNS Vasculitis, CNS Sarcoidosis, CNS Lupus, Rasmussen Encephalitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients living and/or treated in Switzerland with an IBrainD specified in the following list with a disease onset before the age of 18. Written informed consent by patients (and/or legal representative(s), if applicable) Optic Neuritis Transverse Myelitis Acute disseminated encephalomyelitis Multiple Sclerosis Neuromyelitis Optica Spectrum Disorders Anti-NMDA-R Encephalitis Anti-GAD65 Associated Autoimmune Encephalitis Anti-AMPAR-1/2 Associated Autoimmune Encephalitis Anti-Lgi-1 Associated Autoimmune Encephalitis Anti-CASPR-2 Associated Autoimmune Encephalitis Anti-GABAR-1/2 Associated Autoimmune Encephalitis Onconeuronal Antibody (Hu, Ri, Yo, Amphiphysin, CRMP-5, Ma-1, Ma-2, SOX-1) Associated Autoimmune Encephalitis Hashimoto Encephalopathy CNS Vasculitis CNS Sarcoidosis CNS Lupus Rasmussen Encephalitis Exclusion Criteria: Neurological symptoms due to infectious diseases of the CNS Genetic/metabolic causes of central demyelinating diseases Neurological symptoms due to Guillain-Barré-Syndrome

Ages Eligible for Study
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Minimum Age: 0 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient population<br>Children, adolescents and adults diagnosed with an IBrainD before age 18, who are born, treated or living in Switzerland | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Personal data | Registering patient's personal data | At registration (Life-long; Up to 80 years) | 
| Diagnosis | Diagnosis of IBrainD | Until reaching of adulthood (0 to 18 years) | 
| Age at diagnosis | Age at diagnosis (months and years) | Until reaching of adulthood (0 to 18 years) | 
| First symptoms | Symptoms before diagnosis | Until reaching of adulthood (0 to 18 years) | 
| Age at first symptoms | Age at first symptoms | Until reaching of adulthood (0 to 18 years) | 
| Diagnostic delay | Time elapsed between symptom-onset and diagnosis (days) | Until reaching of adulthood (0 to 18 years) | 
| Hospitalization | Length of hospitalization at diagnosis or during a relapse (days) | Until reaching of adulthood (0 to 18 years) | 
| Rehabilitation | Length and type of rehabilitation at diagnosis or during a relapse (days) | Until reaching of adulthood (0 to 18 years) | 
| Death date | Date of death | Life-long; Up to 80 years | 
| Death cause | Cause of death | Life-long; Up to 80 years | 
| Change in EDSS | EDSS change over time | Until reaching of adulthood (0 to 18 years) | 
| Change in Neurostatus | Neurostatus change over time | Until reaching of adulthood (0 to 18 years) | 
| Change in medication | Change of IBrainD medication over time | Until reaching of adulthood (0 to 18 years) | 
| Change in Education | Evolution of education over time | Until reaching of adulthood (0 to 18 years) | 
| Change in MRI data | Change in number of CNS lesions | Until reaching of adulthood (0 to 18 years) | 
| Change in MRI data | Change in activity of CNS lesions | Until reaching of adulthood (0 to 18 years) | 
| Change in laboratory test data | Change in diagnostic markers | Until reaching of adulthood (0 to 18 years) | 
| Electrophysiological testing | Assessment if the patient did undergo electrophysiological testing. | Until reaching of adulthood (0 to 18 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Future questionnaires | Data from validated instrument such as the Pediatric Quality of Life Inventory (PedsQL); Scale from 0-100, where 100 is the best possible outcome and 0 the worst possible outcome. | Life-long; Up to 80 years; Will mainly concern childhood (until reaching of adulthood; 0 to 18 years) |