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Cumulative Incidence of Autoimmune Encephalitides and Paraneoplastic Neurological Syndromes in Sweden

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ClinicalTrials.gov Identifier: NCT04708626
Recruitment Status : Recruiting
First Posted : January 14, 2021
Last Update Posted : February 4, 2021
Sponsor:
Information provided by (Responsible Party):
Uppsala University

Brief Summary:

Autoimmune encephalitis and paraneoplastic neurological syndromes are rare diseases caused by an abnormal immune response toward the nervous system. This can lead to life-threatening symptoms, but is in many cases treatable if a swift and correct diagnosis is made. Antibodies targeting neuronal proteins (i.e. "neuronal antibodies") can be detected in serum or cerebrospinal fluid (CSF) in about half of the patients suffering from these conditions. Although an important part of the diagnostical process of these conditions, diagnosis cannot be made only based on a positive antibody test, but the clinical findings have to be compatible as well. As these conditions are so rare, clinicians might struggle to interpret antibody test results.

In this retrospective study the investigators aim to estimate the cumulative incidence of autoimmune encephalitides and paraneoplastic neurological syndromes in the Uppsala-Örebro health care region in Sweden between the years 2015 and 2019. Medical records from patients belonging to the Uppsala-Örebro health care region (a region in the middle of Sweden with a population of approximately 2.1 million), that tested positive for any neuronal antibody in serum or CSF will be studied to obtain clinical, laboratory and radiological data. This data will be used to ascertain if diagnostic criteria are fulfilled as well as to describe clinical characteristics and identifying possible comorbidities.


Condition or disease Intervention/treatment
Autoimmune Encephalitis Paraneoplastic Neurological Syndrome Other: Description and analysis

Detailed Description:

Methods:

  1. Identification of extended cohort:

    The extended cohort consists of all patients in Sweden tested for any neuronal antibody in serum or CSF between 2015 and 2019. Patients will be identified by the only five laboratories that perform tests for neuronal antibodies in Sweden. The following neuronal antibodies will be included: AMPA 1 (Anti-Glutamate Receptor 1), AMPA 2 (Anti-Glutamate Receptor 2), Amphiphysin, CARP VIII (Carbonic Anhydrase-Related Protein VIII), CASPR2 (Contactin-associated protein-like 2), CV2/CRMP5 (collapsin response mediator protein 5), DPPX (dipeptidyl-peptidase-like protein 6), GABA B (γ-Aminobutyric acid-B receptor), GAD65 (glutamic acid decarboxylase) (>2000 IU/ml by ELISA in serum, or detected in CSF), glycine receptor, Homer 3, Hu (antineuronal nuclear antibody-type 1, ANNA-1), IgLON5 (immunoglobulin-like cell adhesion molecule 5 ), ITPR1 (inositol 1,4,5-trisphophate receptor type 1), LGI-1 (Leucine-rich glioma-inactivated 1), Ma2/Ta, NMDAR (anti-N-methyl-D-aspartate receptor), PCA-2 (Purkinje cell cytoplasmic antibody type 2), Tr (Trotter), Ri, SOX1(SRY-Box Transcription Factor 1), VGCC (Voltage-gated calcium channels), Yo, Zic4 (Zinc finger protein).

  2. Identification of geographical region:

    Patients testing positive for any neuronal antibody in serum or CSF will be stratified according to which Swedish health care region that requested the test. Patients whose tests where requested by health care providers in the Uppsala-Örebro health care region (consisting of 7 smaller health care regions with a total population of approximately 2.1 million) will be selected.

  3. Core cohort:

    Patients with a positive test result that belong to the Uppsala-Örebro health care region will be contacted and asked to participate in the study. Written informed consent must be signed to be included in the core cohort. If the patient is deceased, consent will be presumed.

  4. Case ascertainment:

Medical records from patients included in the core cohort will be reviewed to obtain clinical, laboratory and radiological data. Ascertainment of a case is defined as the patient either fulfilling criteria of: 1) "definite PNS" according to Graus et. al 2004 with one of the following neurological syndromes; encephalomyelitis, limbic encephalitis, subacute cerebellar degeneration, opsoclonus-myoclonus, stiff person syndrome or 2) "definite autoimmune limbic encephalitis" according to Graus et al. 2016 or 3) "definite anti-NMDA receptor encephalitis" according to Graus et al. 2016.

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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Cumulative Incidence of Autoimmune Encephalitides and Paraneoplastic Neurological Syndromes in Sweden
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : November 2021


Group/Cohort Intervention/treatment
Extended Cohort: Patients tested for any neuronal antibody in the Swedish population
All patients tested for any neuronal antibody in serum or CSF between 2015 and 2019 in Sweden.
Other: Description and analysis
Collection of laboratory data.

Core Cohort: Patients with a positive neuronal antibody test belonging to the Uppsala-Örebro region
All patients belonging to the Uppsala-Örebro health care region (a region in the middle of Sweden with a population of approximately 2.1 million), that tested positive for any neuronal antibody in serum or cerebrospinal fluid between 2015-2019.
Other: Description and analysis
Collection of clinical, laboratory and radiological data from medical records.




Primary Outcome Measures :
  1. Cumulative incidence of autoimmune encephalitides in the Uppsala-Örebro health care region between 2015-2019 [ Time Frame: 5 years ]
    Cumulative incidence of autoimmune encephalitides in the Uppsala-Örebro health care region based on detection of neuronal antibodies in serum or CSF, with case ascertainment based on review of medical records and application of diagnostic criteria (Graus et al. 2004 and 2016).


Secondary Outcome Measures :
  1. Positivity rate [ Time Frame: 5 years ]
    Positivity rate - the number of positive tests divided by the number of total tests in the Swedish population for each year and for serum and CSF respectively.

  2. False positivity rate [ Time Frame: 5 years ]
    False positivity rate - the number of positive tests where case ascertainment fails divided by the total number of positive tests.

  3. Estimated cumulative incidence of autoimmune encephalitides and PNS in the Swedish population [ Time Frame: 5 years ]
    Cumulative incidence of autoimmune encephalitides and PNS in the Swedish population between 2015-2019 estimated from the cumulative incidence in the Uppsala-Örebro health care region as well as detection of neuronal antibodies in the entire Swedish population

  4. Incidence rates of autoimmune encephalitides and PNS [ Time Frame: 5 years ]
    Yearly age-and sex-adjusted incidence rates for autoimmune encephalitides in the Uppsala-Örebro health care region between 2015-2019



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Extended cohort: All patients in Sweden tested for any neuronal antibody (AMPA 1, AMPA 2, Amphiphysin, CARP VIII, CASPR2, CV2/CRMP5, DPPX, GABA B, GAD65 (>2000 IU/ml by ELISA in serum, or detected in CSF), glycine receptor, Homer 3, Hu, IgLON5, ITPR1, LGI-1, Ma2/Ta, NMDAR, PCA-2, Tr, Ri, SOX1, VGCC, Yo, Zic4), in serum or CSF between 2015 and 2019.

Core cohort: All patients belonging to the Uppsala-Örebro health care region (a region in the middle of Sweden with a population of approximately 2.1 million), that tested positive for any neuronal antibody (AMPA 1, AMPA 2, Amphiphysin, CARP VIII, CASPR2, CV2/CRMP5, DPPX, GABA B, GAD65 (>2000 IU/ml by ELISA in serum, or detected in CSF), glycine receptor, Homer 3, Hu, IgLON5, ITPR1, LGI-1, Ma2/Ta, NMDAR, PCA-2, Tr, Ri, SOX1, VGCC, Yo, Zic4), in serum or cerebrospinal fluid between 2015-2019. Patients will be identified by the only five laboratories that perform tests for neuronal antibodies in Sweden.

Criteria

Applicable only on Core Cohort:

Inclusion Criteria:

  • All ages, both sexes.
  • Neuronal antibody (AMPA 1, AMPA 2, Amphiphysin, CARP VIII, CASPR2, CV2/CRMP5, DPPX, GABA B, GAD65(>2000 IU/ml by ELISA in serum, or detected in CSF), glycine receptor, Homer 3, Hu, IgLON5, ITPR1, LGI-1, Ma2/Ta, NMDAR, PCA-2, Tr, Ri, SOX1, VGCC, Yo, Zic4), detected in serum or cerebrospinal fluid between 2015-2019
  • Antibody test was requested by a health care facility in the Uppsala-Örebro health care region
  • Signed informed consent. If the participant is deceased consent will be presumed

Exclusion Criteria:

  • Incomplete personal data or social security number making it impossible to identify and/or contact the patient to get written consent
  • Informed consent not signed. If the participant is deceased consent will be presumed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04708626


Contacts
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Contact: Sonja Kosek, MD +4654617941 sonja.kosek@neuro.uu.se

Locations
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Sweden
Uppsala University Recruiting
Uppsala, Uppland, Sweden, 75237
Contact: Sonja Kosek, MD    +4654617941    sonja.kosek@neuro.uu.se   
Sponsors and Collaborators
Uppsala University
Investigators
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Study Director: Joachim Burman, Assoc prof Uppsala University
Study Director: Anna Rostedt Punga, Professor Uppsala University
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Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT04708626    
Other Study ID Numbers: DNR2019-03068
First Posted: January 14, 2021    Key Record Dates
Last Update Posted: February 4, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Uppsala University:
autoimmune encephalitis
paraneoplastic neurological syndrome
neuronal antibody
cumulative incidence
epidemiology
Additional relevant MeSH terms:
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Encephalitis
Hashimoto Disease
Syndrome
Disease
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Thyroiditis, Autoimmune
Thyroiditis
Thyroid Diseases
Endocrine System Diseases