Clinical trial NCT06388161: Neural Autoantibody Prevalence in New-onset Focal Seizures of Unknown Etiology
Official title: Neural Autoantibody Prevalence in Patients With New-onset Focal Seizures of Unknown Etiology and a Predictive Scoring Scale
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Epilepsy
Encephalitis Autoimmune
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Sir Run Run Shaw Hospital
name: Ningbo Medical Center Lihuili Hospital
name: Shaoxing People's Hospital
First posted: 2024-04-29
Enrollment: 300
Sex: ALL
Minimum age (years): 14
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who have new-onset focal seizure with unknown etiology; and focal seizure is considered according to the seizure seiology, electroencephalography findings and/or other relevant information.

Brief summary: Seizure is one of the most common symptoms in autoimmune encephalitis with neuronal surface-mediated antibodies. Interestingly, some patients may exhibit new-onset seizures as the initial manifestation without fulminant sign of encephalitis, particularly in the early stage.

It is essential to recognize these patients early and to perform antibody testing, as studies have reported early immunotherapy can improve their clinical outcomes. At the same time, it is important to limit the number of patients who require testing, for the sake of specificity and cost effectiveness. Thus, this prospective, multicenter study aims to identify neural antibodies in patients with focal seizures of unknown etiology, and to create a score to preselect patients requiring autoantibody testing.

Detailed description: 1. Focal epileptic seizure or epilepsy is defined according to seizure semiology, electroencephalography findings and/or other relevant information. If applicable, 24 hour video-electroencephalography is performed.
2. Clinical information is documented by specially-assigned persons, including patient demographics, age at onset, disease duration, seizure semiology, seizure frequency, clinical manifestations, underlying malignancy, hyponatremia, brain MRI, medications and other diseases.
3. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Depression Scale (HAMA), Hamilton Anxiety Scale (HAMA) and the modified Rankin Scale (mRS) at baseline were assessed and recorded.
4. Previous scoring scales, such as antibody prevalence in epilepsy and encephalopathy (APE2) score, antibodies contributing to focal epilepsy signs symptoms (ACES) score and the "Obvious" Indications for Neural Antibody Testing in Epilepsy or Seizures (ONES) checklist are evaluated at baseline.
5. Commercial cell-based assay (CBA; EUROIMMUN, Lübeck, Germany) was used to detect serum anti-N-methyl-D-aspartate receptor (anti-NMDAR), anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (anti-AMPAR), anti-γ-aminobutyric acid B receptor (anti-GABABR), anti-leucine-rich glioma-inactivated 1 (anti-LGI1), anti-contactin-associated protein-like 2 (anti-CASPR2), and anti-glutamic acid decarboxylase 65 (anti-GAD65), anti-metabotropic glutamate receptor 5 (mGluR5), anti-dipeptidyl peptidase-like protein 6 (DPPX), anti-myelin oligodendrocyte glycoprotein (MOG) and anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) antibodies. If serum neural autoantibodies are detected, cerebrospinal fluid should be tested.

Eligibility criteria: Inclusion Criteria:

* Patients have a diagnosis of new-onset focal epileptic seizure or epilepsy and present with their first seizure within the previous 12 months
* Patients are prospectively recruited from the routine practice of epileptologists in epilepsy centers and epilepsy clinics
* There is no obvious suspicion of autoimmune encephalitis
* Written informed consent and sera are obtained
* Cerebrospinal fluid test must be conducted, when patients have detectable serum autoantibodies

Exclusion Criteria:

* Patients have other etiology of seizures, such as structure, infection, genetics and metabolism.
* Written informed consent are not obtained
* Loss of follow-up

Primary outcomes:
measure: Detectable serum neural autoantibodies
timeFrame: at baseline
measure: Neuronal surface antibodies-mediated autoimmune- encephalitis
timeFrame: at baseline
Secondary outcomes:
measure: The proportion of seizure freedom
timeFrame: through study completion, an average of 1 year
measure: The proportion of drug-resistent epilepsy
timeFrame: through study completion, an average of 1 year
measure: Clinical severity and recovery
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Chunhong Shen
role: PRINCIPAL_INVESTIGATOR
References: