Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody

Study Overview
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Brief Summary
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The purpose of the study is to investigate effect of immunotherapy in intractable cryptogenic epilepsy patients with autoimmune antibody.

Detailed Description
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Cryptogenic epilepsy is an epilepsy of presumed symptomatic nature but the cause has not been identified. It account for at least 40% of adult-onset epilepsy. Autoimmune encephalitis including classic paraneoplastic syndrome and autoimmune synaptic encephalitis is a new category of immune-mediated disorders which often has favorable outcome. Recent studies reported that immunotherapy improves seizure outcome in medically intractable epilepsy patients with clinical and serological evidence of an autoimmune basis. Neural autoantibodies were detected in 22% of epilepsy due to unknown cause in a study, mostly from the antiepileptic drug(AED)-resistant epilepsy group. Of the patients who received immunotherapy, 75% archived >50% reduction in seizure frequency. Many patients with cryptogenic epilepsy are refractory to AED and significant percent of cryptogenic epilepsy harbor neural autoantibody. In those cases, immunotherapy is suggestive based on favorable outcome of immunotherapy in autoimmune encephalitis and autoimmune epilepsy. Investigators aim to investigate the response to immunotherapy in intractable cryptogenic epilepsy patients with neural autoantibodies.

Official Title
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Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody

Conditions
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Epilepsy, Unspecified, Intractable

Intervention / Treatment
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* Other: IVIG
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of cryptogenic epilepsy according to the International League Against Epilepsy's Classification of Epilepsy. Intractable epilepsy: Complete seizure control is not achieved with trials of two appropriate antiepileptic drugs At least 1 seizure within the past 8 weeks Presence of autoimmune antibody (NMDAR, LGI1, CASPR2, AMPA1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/CRMP5, -amphiphysin, GAD) in serum or cerebrospinal fluid Written informed consent signed by the subject or legal guardian prior to entering the study Exclusion Criteria: Clinical evidence of autoimmune encephalitis such as autoimmune limbic encephalitis History of severe head trauma Presence of structural abnormality which is thought to be epileptogenic in brain MRI Epilepsy of predominantly genetic or presumed genetic origin An active CNS infection, demyelinating disease, degenerative neurologic disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results History of immunotherapy A history of nonepileptic or psychogenic seizures within past 1 year Any clinically significant laboratory abnormality that in the opinion of the Investigator would exclude the subject from the study Any clinically significant psychiatric illness, psychological, or behavioral problems that, in the opinion of the Investigator, would interfere with the subject's ability to participate in the study Recent (within 4 weeks) change or dose adjustment of anti-epileptic drug (1 to 2 doses of rescue benzodiazepine is permitted) Refuse to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunotherapy<br>Intravenous immunoglobulin (IVIG) and oral prednisolone. IVIG and oral prednisolone are administered simultaneously: IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day). | Other: IVIG<br>* IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)<br>Drug: Prednisolone<br>* IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)<br>|
| No Intervention: Control<br>No immunotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent seizure reduction |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure free rate |  | 3 months | 
| Responder rate |  | 3 months | 
| Treatment failure rate |  | 3 months | 
| Quality of life scores as measured by QOLIE-31 |  | 3 months | 
| Quality of life scores as measured by BDI-2 |  | 3 months | 
| Cognition scores as measured by K-MMSE |  | 3 months | 
| Amount of epileptiform discharge measured by EEG |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intractable cryptogenic epilepsy with autoimmune antibody, Immunotherapy