Brain MRI Longitudinal Volumetric Characteristics Associated With Outcomes of CASPR2-Limbic Encephalitis (C2-MRI)

Anti-CASPR2 limbic encephalitis (CASPR2-LE) is a rare neurological disorder primarily affecting males over the age of 50. It is mediated by an autoimmune antibody response in the central nervous system (CNS) against the cellular adhesion molecule contactin-associated protein-like 2 (CASPR2). This protein plays an important role in the trafficking of KV1 channels under the myelin sheath in the juxtaparanodal region of myelinated axons. It is mostly present in the neurons of the limbic system, basal ganglia, and other motor related and sensation areas (Qin, Yang, Zhu, Wang, & Shan, 2021). This distribution explains the diverse clinical manifestations of the disease, primarily characterized by cognitive impairment. Other manifestations include cerebellar ataxia, hyperkinetic movement disorders (HMDs), seizures, and neuropathic pain, which all typically develop around 10.4 months after onset. At last visit, memory impairment is seen in 69% of the patients, cerebellar ataxia in 42% of the patients, and functional dependency in 25% of the patients. Even though most patients' symptoms improve with immune-active treatments, up to 69% of them have long-term memory impairments due to damage to hippocampal structures (Benoit et al., 2023). Research has primarily focused on understanding the disease's clinical features, underlying mechanisms, and potential treatment options. On the other hand, it is shown that MRIs performed at baseline show signal changes in the hippocampus in 62-71% of the patients, and these changes are subject to variations in subsequent follow-up scans, that differ widely among patients as mentioned before (Bien et al., 2017). And since the dynamics of hippocampal volume changes and its association with the development of hippocampal atrophy and long-term cognitive impairment are not well studied yet in CASPR2-LE, we primarily aim to examine the longitudinal changes of hippocampal volume in anti-CASPR2 Limbic Encephalitis (CASPR2-LE) patients to examine whether it correlates to the development of anterograde amnesia and hippocampal atrophy on follow-up.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Encephalitis Associated With Anti-CAPR2 Antibodies
• Intervention / Treatment: Other: Retrospective evaluation of specific brain MRI features

• Study Type: Observational
• Enrollment (Estimated): 27

Contacts and Locations

• Study Contact: Name: Bastien Joubert, professor; Phone Number: +334 78 86 15 53; Email: Bastien.joubert@chu-lyon.fr
• Study Contact Backup: Name: Marine Villard, doctor; Phone Number: +33 4 27 85 54 60; Email: marine.villard@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69677
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: Bastien Joubert, professor; Phone Number: +334 78 86 15 53; Email: Bastien.joubert@chu-lyon.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients will be included from the from the database of the French Reference Centre for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (Lyon, France)

Description

Inclusion Criteria:

• Patients with a definite diagnosis of CASPR2-antibody-associated encephalitis
• available MRI records
• Ascertained positivity for CASPR2-antibodies in CSF

Exclusion Criteria:

• Positivity for another antibody against neural or glial antigens
• MRI images not available
• Not enough clinical data to ascertain outcome

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CASPR2- Patients	Other: Retrospective evaluation of specific brain MRI features; Brain MRI changes in the acute stage, i.e. < 3 months from symptoms onset, including abnormal signal intensity, altered diffusion and/or contrast enhancement in the hippocampus (unilateral/bilateral), abnormal signal intensity in basal ganglia, insula, and/or perisylvian cortex, presence of global brain atrophy, presence of hippocampal atrophy and/or MTS, hippocampal volumetry; Brain MRI changes after acute phase resolution (> 6 months after symptoms onset) including abnormal signal intensity in the hippocampus (unilateral/bilateral), presence of global brain atrophy, presence of hippocampal atrophy and/or MTS, hippocampal volumetry
Patients affected by autoimmune encephalitis with antibodies against CASPR2	Other: Retrospective evaluation of specific brain MRI features; Brain MRI changes in the acute stage, i.e. < 3 months from symptoms onset, including abnormal signal intensity, altered diffusion and/or contrast enhancement in the hippocampus (unilateral/bilateral), abnormal signal intensity in basal ganglia, insula, and/or perisylvian cortex, presence of global brain atrophy, presence of hippocampal atrophy and/or MTS, hippocampal volumetry; Brain MRI changes after acute phase resolution (> 6 months after symptoms onset) including abnormal signal intensity in the hippocampus (unilateral/bilateral), presence of global brain atrophy, presence of hippocampal atrophy and/or MTS, hippocampal volumetry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional independance	Defined by a modified Rankin Scale (mRS) score ≤2	12 months after first treatment

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Autoimmune encephalitis, CASPR2 antibodies, MRI
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Immune System Diseases; Neoplasms; Autoimmune Diseases; Neoplasms by Site; Central Nervous System Viral Diseases; Central Nervous System Infections; Neurodegenerative Diseases; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuroinflammatory Diseases; Encephalitis; Autoimmune Diseases of the Nervous System; Limbic Encephalitis
• Other Study ID Numbers: 69HCL24_0106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No