Pathologic-MRI Findings in Atypical IIDD (IIDD)

A Pathologic-MRI Reappraisal of Patients With Atypical Idiopathic Inflammatory Demyelinating Disorders

Our objective is to describe the pathologic and MRI findings in a series of patients with presumed demyelinating lesion of the central nervous system.

Study Overview

• Status: Completed
• Conditions: Idiopathic Inflammatory Demyelinating Disorders of the Central Nervous System

Detailed Description

Idiopathic inflammatory demyelinating disorders (IIDD) are a group of diseases with distinct clinical and magnetic resonnance imaging (MRI) features, the most frequent being Multiple Sclerosis (MS). MS can present with atypical MRI features that can be misleading. Neuromyelitis Optica Spectrum Disorder (NMOSD) is the main differential diagnosis. It has been demonstrated that some patient with NMOSD can also present with brain lesion that is sometimes difficult to diagnose. In this context, a retrospective series identifies 18 patients with centreal nervous system atypical demyelination and 1) pathological evidence of astrocytopathy and 2) immunohistochemistry demonstrating decrease of aqp4 binding. The aim of the study is to describe the radiological and pathological characteristics of a series of patients with pathologicaly proven atypical demyelination that underwent biopsy for diagnostic uncertainties.

This is a retrospective multicenter study. Inclusion criteria are: 1) Acute or subacute onset of neurological deficit, 2) Brain biopsy performed for diagnostic uncertainties revealing an active demyelinating lesion, 3) no known diagnosis of MS or NMOSD at the time of the biopsy and 4) no alternative diagnosis identified during the disease course.

All the medical records of the patients will be reviewed and the following data will be recorded: previous medical history including previous neurologic relapses, gender, age at onset, clinical symptoms at onset and diagnosis at last follow-up according to current diagnosis criteria for MS and NMOSD.

Brain MRI scanners will be analysed. The investigators will mainly focus on T1-, T2-, T2 gradient echo-, fluid- attenuated inversion recovery- and diffusion-weighted images. The following data will be recorded: number of lesions, location (cortical, juxtacortical, juxtaventricular, corpus callosum involvement, posterior fossa involvement), presence of a peripheral hyperintense/hypointense rim (on T2 sequence), and type of gadolinium enhancement (peripheral open or closed ring, central homogeneous or heterogeneous). The presence of oedema will be recorded and mass effect will be analysed. According to the classification of atypical demyelinating lesions (MAGNIMS group), patients will be classified as having either infiltrative, megacystic, balo-like, ring-like lesions or unclassified. Three neuropathologists (BL, BL and VR) blinded to the MRI and clinical datas will perform all the pathologic evaluations. Paraffin-embedded sections have been stained using hematoxylin & eosin, Luxol fast blue. Primary antibodies specific fot GFAP, CD3, CD8, CD20 and CD68 were used in routine practice. Additional immunohistochemical studies will be done using primary antiobodies specific for IgG and Aquaporin-4. The investigators will specifically look at the presence of 1) morphologic features suggestive of either MS (Creutzfeldt cells) or NMOSD (dystrophic astrocytes, myelin vacuolation, vascular hyalinization) 2) negative aquaporin-4 staining (suggestive of NMOSD) and 3) macrophages containing GFAP positive or Luxol fast blue positive debris.

• Study Type: Observational
• Enrollment (Actual): 25

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

25 patients with cerebral MRI lesions suggestive of demyelinating lesions

Description

Inclusion Criteria:

• Presence of brain lesion in MRI suggestive of demyelinating lesions
• Biopsy analysis revealed active inflammation with active demyelination
• No known diagnosis of MS or Devic's disease or other diagnosis

Exclusion Criteria:

- NO

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological	pathological results: morphologic changes and specific immunostaining	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI (magnetic resonnance Imaging)	MRI results: characteristics of the MRI lesions	1 day

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Hospices Civils de Lyon; University Hospital, Strasbourg, France; University Hospital, Bordeaux; University Hospital, Limoges; Centre Hospitalier Universitaire de Nīmes; Rennes University Hospital; Colmar Hospital; Perpignan Hospital
• Investigators: Study Director: Xavier Ayrignac, MD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: April 14, 2017
• First Posted (Actual): April 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 7, 2018
• Last Update Submitted That Met QC Criteria: May 4, 2018
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: MRI; Multiple Sclerosis; Idiopathic Inflammatory demyelinating disorders of the central nervous system; Neuromyelitis Optica; pahtological
• Additional Relevant MeSH Terms: Nervous System Diseases; Demyelinating Diseases; Central Nervous System Diseases
• Other Study ID Numbers: RECHMPL17_0078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: NC

Drug and device information, study documents

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