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
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|
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).
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.
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.
- 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.
|Study Type :||Observational|
|Estimated Enrollment :||150 participants|
|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|
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.
- 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).
- 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.
- 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.
- 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
- 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
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
|Contact: Sonja Kosek, MDemail@example.com|
|Uppsala, Uppland, Sweden, 75237|
|Contact: Sonja Kosek, MD +4654617941 firstname.lastname@example.org|
|Study Director:||Joachim Burman, Assoc prof||Uppsala University|
|Study Director:||Anna Rostedt Punga, Professor||Uppsala University|