Neural Autoantibody Prevalence in New-onset Focal Seizures of Unknown Etiology

Neural Autoantibody Prevalence in Patients With New-onset Focal Seizures of Unknown Etiology and a Predictive Scoring Scale

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.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy; Encephalitis Autoimmune

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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Chun-Hong Shen; Phone Number: +86 0571 87783872; Email: shen_neurology@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
      • Contact: Chun-Hong Shen; Phone Number: +86 0571 87783872; Email: shen_neurology@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detectable serum neural autoantibodies	such as NMDAR、AMPAR1、AMPAR2、LGI1、lg LON5、DPPX、GAD65、mGluR5、MOG	at baseline
Neuronal surface antibodies-mediated autoimmune- encephalitis	diagnosed according to the 2016 diagnostic criteria	at baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of seizure freedom	We defined seizure freedom according to the International League Against Epilepsy (ILAE) definition	through study completion, an average of 1 year
The proportion of drug-resistent epilepsy	We defined drug-resistent epilepsy according to the International League Against Epilepsy (ILAE) definition	through study completion, an average of 1 year
Clinical severity and recovery	modified Rankin scale, ranging from 0-6, higher scores mean a worse outcome	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Ningbo Medical Center Lihuili Hospital; Sir Run Run Shaw Hospital; Shaoxing People's Hospital
• Investigators: Principal Investigator: Chunhong Shen, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuroinflammatory Diseases; Encephalitis; Seizures
• Other Study ID Numbers: Yan2022-0336