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

Swiss Pediatric Inflammatory Bain Disease Cohort Study

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 opened for recruitment after that: Aarau, Basel, Bellinzona, Chur, Geneva, Lausanne, Lucerne, St. Gallen, Winterthur and Zurich. The center in Fribourg is expected open for recruitment in 2025. 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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Optic Neuritis; Neuromyelitis Optica Spectrum Disorder; CNS Sarcoidosis; Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD); CNS Vasculitis; Transverse Myelitis; Rasmussen Encephalitis; Acute Disseminated Encephalomyelitis; 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 Lupus

Detailed Description

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:

1. Gathering representative, population-based epidemiological data on pediatric IBrainD in Switzerland.
2. Monitoring treatment, clinical course, education, social aspects, and outcomes of pediatric IBrainD patients.
3. 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 diagnosed from 2005 onward and with a disease onset before the age of 18.

• Optic neuritis
• Transverse myelitis
• Acute disseminated encephalomyelitis
• Multiple sclerosis
• Neuromyelitis optica spectrum disorders
• Myelin oligodendrocyte glycoprotein antibody-associated disease
• 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:

1. Neurological symptoms due to infectious diseases of the CNS
2. Genetic/metabolic causes of central demyelinating diseases
3. 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, their 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:

Since 2020, the investigators have included 128 people diagnosed with an IBrainD.

Funding:

• Schweizerische Multiple Sklerose Gesellschaft
• PedNet Bern
• SwissPedRegistry, University of Bern
• Roche Pharma (Switzerland) Ltd
• Novartis Pharma Schweiz AG
• Biogen
• Sanofi
• Anna Mueller Grocholski-Stiftung
• Gottfried und Julia Bangerter-Rhyner Stiftung
• Fondation Johanna Dürmüller-Bol

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Lorena F Hulliger, MSc; Phone Number: +41316845678; Email: lorena.hulliger@unibe.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Children's hospital Basel, UKBB
    • Contact: Patricia Dill, Dr. med.
  • Bern, Switzerland, 3010
    • Recruiting
    • University Children's Hospital, Inselspital Bern
    • Contact: Gabriela Oesch Nemeth, Dr. med.
  • Bern, Switzerland, 3012
    • Recruiting
    • Institute of Social and Preventive Medicine, University of Bern
    • Contact: Lorena F Hulliger; Phone Number: +41316845678; Email: lorena.hulliger@unibe.ch
  • Fribourg, Switzerland, 1752
    • Not yet recruiting
    • Hôpital Fribourgeois - Freiburger Spital
    • Contact: Mary Kurian, Dr. med.
  • Geneva, Switzerland, 1211
    • Recruiting
    • University Hospitals of Geneva (HUG)
    • Contact: Stéphanie Garcia-Tarodo, Dr. med.
  • Luzern, Switzerland, 6000
    • Recruiting
    • Kinderspital zentralschweiz
    • Contact: Sandra Bigi
  • Zurich, Switzerland, 8032
    • Recruiting
    • University Children's Hospital Zurich
    • Contact: Annette Hackenberg, Dr. med.
  • Aargau
    • Aarau, Aargau, Switzerland, 5001
      • Recruiting
      • Kantonsspital Aarau
      • Contact: Esmeralda Nava, Dr. med.
  • Graubünden
    • Chur, Graubünden, Switzerland, 7000
      • Recruiting
      • Kantonsspital Graubunden
      • Contact: Susi Strozzi, Dr. med.
  • Saint Gallen
    • St.Gallen, Saint Gallen, Switzerland, 9000
      • Recruiting
      • Children's Hospital of Eastern Switzerland
      • Contact: Ingrid Beck
      • Contact: Oliver Maier, Dr. med.
  • Ticino
    • Bellinzona, Ticino, Switzerland, 6500
      • Recruiting
      • Pediatric Institute of Southern Switzerland, Ospedale San Giovanni
      • Contact: Barbara Goeggel Simonetti, PD Dr. med.
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Recruiting
      • University Children's Hospital Lausanne (CHUV)
      • Contact: Stéphane Darteyre
  • Zurich
    • Winterthur, Zurich, Switzerland, 8400
      • Recruiting
      • Kantonsspital Winterthur
      • Contact: Florian Bauder, Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All patients living and/or treated in Switzerland with a listed IBrainD diagnosed from 2005 onward and a disease onset before the age of 18.

Description

Inclusion Criteria:

All patients living and/or treated in Switzerland with an IBrainD specified in the following list diagnosed from 2005 onward and 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
• Myelin oligodendrocyte glycoprotein antibody-associated disease
• 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patient population; Children, adolescents and adults diagnosed with an IBrainD from 2005 onward and with disease onset before age 18, who are born, treated or living in Switzerland

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: Sanofi; Novartis; University Hospital, Geneva; Biogen; Centre Hospitalier Universitaire Vaudois; Kantonsspital Aarau; University Children's Hospital, Zurich; Luzerner Kantonsspital; Hôpital Fribourgeois; Ente Ospedaliero Cantonale, Bellinzona; Schweizerische Multiple Sklerose Gesellschaft; Kantonsspital Winterthur KSW; University Children's Hospital Basel; Ostschweizer Kinderspital; Kantonsspital Graubünden; Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel; Roche Pharma (Switzerland) Ltd; Insel Gruppe AG, University Hospital Bern; Anna Mueller Grocholski-Stiftung; Fondation Johanna Dürmüller-Bol
• Investigators: Principal Investigator: Sandra Bigi, PD MD, ISPM, University of Bern, Bern; Kinderspital Zentralschweiz, Luzern; Study Director: Sandra Bigi, PD MD, ISPM, University of Bern, Bern Kinderspital Zentralschweiz, Luzern

Publications and helpful links

Helpful Links

• Website of the registry

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2020
• Primary Completion (Estimated): January 1, 2071
• Study Completion (Estimated): January 1, 2071

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Post-Infectious Disorders; Endocrine System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Infections; Peripheral Nervous System Diseases; Eye Diseases; Hypersensitivity; Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases; Neurodegenerative Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Optic Nerve Diseases; Cranial Nerve Diseases; Spinal Cord Diseases; Leukoencephalopathies; Thyroid Diseases; Central Nervous System Infections; Hypersensitivity, Delayed; Thyroiditis, Autoimmune; Thyroiditis; Multiple Sclerosis; Neuromyelitis Optica; Encephalitis; Sarcoidosis; Vasculitis; Autoimmune Diseases of the Nervous System; Hashimoto Disease; Encephalomyelitis; Neuritis; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Encephalomyelitis, Acute Disseminated; Optic Neuritis; Myelitis; Myelitis, Transverse; Vasculitis, Central Nervous System
• Other Study ID Numbers: 2019-00377

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers who wish to develop a nested study need to submit a proposal to the Swiss-Ped-IBrainD committee and request permission. A concept sheet describing the planned analyses must be approved by the Swiss-Ped-IBrainD committee. Nested studies might need separate ethics permission.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No