Antibody-mediated LGI1 Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Chronic Phase of the Disease

NCT ID: NCT06515106

Last Updated: 2024-07-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-18
• Study Completion Date: 2026-12-31

Brief Summary

The encephalitis mediated by antibodies against Leucine-rich, glioma inactivated 1 protein (anti-LGI1 encephalitis) predominantly affects men (M:F, 6:4) and mostly older than 60 years. The disease has two distinct clinical phases: The acute phase in which the majority of patients develop severe short-term memory deficits (unable to remember events or experiences that occurred a few minutes earlier). This memory impairment can be preceded or accompanied by one or more of the following: hyponatremia (60% of patients), a highly distinctive type of seizures called facio-brachial dystonic seizures (~40% of patients), along with confusion, irritability and other types of focal seizures or less frequently, generalized seizures. In addition, many patients at this stage have symptoms of REM sleep behavior disorder. In this stage, the CSF may show pleocytosis or mild increase of proteins, the EEG is usually abnormal, and in ~60% of the patients the MRI shows typical increased FLAIR signal in medial temporal lobes (11). There is a clinical sub-phenotype (~13% of patients) in which the disease presents as a rapidly progressive cognitive decline without the indicated FLAIR MRI changes. About 70% of patients improve rapidly with corticosteroids and immunotherapy (eg, intravenous immunoglobulins and/or plasma exchange), but the improvement is often partial. After the acute phase, there is a chronic or residual phase which represents the interval from improvement of initial symptoms until the disease is considered no longer active and the remaining symptoms are thought to be irreversible. This chronic phase may take several months (it has been less well studied), and is characterized by the absence of CSF pleocytosis and inflammatory MRI changes (albeit this may show residual hippocampal atrophy), and very low or undetectable titers of serum antibodies. Most patients are unable to return to their job or previous activities due to residual (irreversible) memory or cognitive deficits accompanied by signs of moderate brain atrophy. In addition, we and others have shown that about 27-35% of patients have relapsing symptoms after improving from the acute phase (. Although acute symptomatic seizures (facio-brachial dystonic and others) occur in ~90% of patients during the acute phase of the disease, less than 10% of patients develop chronic epilepsy often associated with hippocampal sclerosis. Therefore, the prevailing concept on this disease suggests a syndrome and clinical course in which the acute phase shows rapid, albeit partial, response to immunotherapy, and the symptoms of the chronic phase represent a burnout or irreversible process, in which the disease is no longer active, and the potential improvement of remaining symptoms is uncertain.

Here investigators postulate that a better knowledge of this stage will improve treatment decisions and outcome.

In Aim 1, the post-acute stage will be clinically characterized.

In Aim 2, the impact of cognitive rehabilitation will be assessed.

In Aim 3, a mouse model of anti-LGI1 encephalitis will be used to determine the underlying mechanisms and treatment of the postacute stage.

Conditions

Limbic Encephalitis With LGI1 Antibodies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Antibody-mediated LGI1 encephalitis patients

Participants of a prospective cohort in post-acute phase of the Antibody-mediated NMDA Receptor Encephalitis that will received a behavioral treatment.

Group Type: EXPERIMENTAL

Remote cognitive rehabilitation program

Intervention Type: BEHAVIORAL

Behavioral: Remote cognitive rehabilitation program Remote cognitive rehabilitation program will be performed through an online validated platform (Guttmann NeuroPersonalTrainer: https://gnpt.es/) run by the psychologists team. This is a Sanitary Product with CE certification (Sanitary Product RPS/430/2014; International Patent \[PCT/ES2008/00677\]) and here will be used within its approved indications. The rehabilitation program will increase in difficulty and decrease in frequency during the first year of follow-up (V1-V3).

Interventions

Remote cognitive rehabilitation program

Behavioral: Remote cognitive rehabilitation program Remote cognitive rehabilitation program will be performed through an online validated platform (Guttmann NeuroPersonalTrainer: https://gnpt.es/) run by the psychologists team. This is a Sanitary Product with CE certification (Sanitary Product RPS/430/2014; International Patent \[PCT/ES2008/00677\]) and here will be used within its approved indications. The rehabilitation program will increase in difficulty and decrease in frequency during the first year of follow-up (V1-V3).

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Patients with Antibody-mediated LGI-1 encephalitis in the post-acute stage of the disease;
• Patients has been discharged from hospital (acute phase).

Exclusion Criteria

• Inability to obtain informed consent;
• Inability to travel to the center.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundacion Clinic per a la Recerca Biomédica

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Josep Dalmau, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clínic

Lorena Rami, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundacion Clinic per a la Recerca Biomédica

Locations

Hospital Clínic de Barcelona

Barcelona, Catalonia, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Josep Dalmau, MD,PhD

Role: CONTACT

jdalmau@clinic.cat

34 93 227 1738

Facility Contacts

Josep Dalmau, MD, PhD

Role: primary

jdalmau@clinic.cat

+34 93 227 1738

Victor Patricio, MS

Role: backup

vpatricio@recerca.clinic.cat

+34 93 227 1738

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Provided Documents

Document Type: Study Protocol

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Document Type: Informed Consent Form

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Other Identifiers

PI23/00858

Identifier Type: -

Identifier Source: org_study_id