Clinical trial NCT04708626: Epidemiology of Autoimmune Encephalitides and Paraneoplastic Neurological Syndromes in Sweden
Official title: Epidemiology of Autoimmune Encephalitides and Paraneoplastic Neurological Syndromes in Sweden
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Autoimmune Encephalitis
Paraneoplastic Neurological Syndrome
Keywords: autoimmune encephalitis
paraneoplastic neurological syndrome
neuronal antibody
epidemiology
incidence rate
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2021-01-14
Enrollment: 110
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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 in serum or cerebrospinal fluid between 2015 and 2019. Patients will be identified by the only five laboratories that perform tests for neuronal antibodies in Sweden.

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 study the investigators aim to estimate the incidence rate 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.

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 2021 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.

Eligibility 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

Primary outcomes:
measure: Incidence rate of autoimmune encephalitides and paraneoplastic neurological syndromes in the Uppsala-Örebro health care region between 2015-2019
timeFrame: 5 years
Secondary outcomes:
measure: Positivity rate
timeFrame: 5 years
measure: False positivity rate
timeFrame: 5 years
measure: Estimated incidence rate of autoimmune encephalitides and paraneoplastic neurological syndromes in the Swedish population
timeFrame: 5 years
measure: Incidence rates of autoimmune encephalitides and paraneoplastic neurological syndromes
timeFrame: 5 years
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University
state: Uppland
Study officials:
affiliation: Uppsala University
name: Joachim Burman, Assoc prof
role: STUDY_DIRECTOR
affiliation: Uppsala University
name: Anna Rostedt Punga, Professor
role: STUDY_DIRECTOR
References: