Idiopathic Inflammatory Demyelinating Disorders of the Central Nervous System Clinical Trial
Official title:
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.
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.
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