Dataset Information

Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray-white matter junction correlates with iron-enriched macrophages.

ABSTRACT:

Objective

Describe magnetic resonance imaging (MRI) susceptibility changes in progressive multifocal leukoencephalopathy (PML) and identify neuropathological correlates.

Methods

PML cases and matched controls with primary central nervous system lymphoma (PCNSL) were retrospectively identified. MRI brain at 3 T and 7 T were reviewed. MRI-pathology correlations in fixed brain autopsy tissue were conducted in three subjects with confirmed PML.

Results

With PML (n = 26 total, n = 5 multiple sclerosis natalizumab-associated), juxtacortical changes on susceptibility-weighted imaging (SWI) or gradient echo (GRE) sequences were noted in 3/3 cases on 7 T MRI and 14/22 cases (63.6%) on 1.5 T or 8/22 (36.4%) 3 T MRI. Similar findings were only noted in 3/25 (12.0%) of PCNSL patients (odds ratio (OR) 12.83, 95% confidence interval (CI), 2.9-56.7, p < 0.001) on 1.5 or 3 T MRI. On susceptibility sequences available prior to diagnosis of PML, 7 (87.5%) had changes present on average 2.7 ± 1.8 months (mean ± SD) prior to diagnosis. Postmortem 7 T MRI showed SWI changes corresponded to areas of increased iron density along the gray-white matter (GM-WM) junction predominantly in macrophages.

Conclusion

Susceptibility changes in PML along the GM-WM junction can precede noticeable fluid-attenuated inversion recovery (FLAIR) changes and correlates with iron accumulation in macrophages.

SUBMITTER: Mahajan KR

PROVIDER: S-EPMC8455719 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray-white matter junction correlates with iron-enriched macrophages.

Mahajan Kedar R KR Amin Moein M Poturalski Matthew M Lee Jonathan J Herman Danielle D Zheng Yufan Y Androjna Caroline C Howell Mark M Fox Robert J RJ Trapp Bruce D BD Jones Stephen E SE Nakamura Kunio K Ontaneda Daniel D

Multiple sclerosis (Houndmills, Basingstoke, England) 20210322 14

<h4>Objective</h4>Describe magnetic resonance imaging (MRI) susceptibility changes in progressive multifocal leukoencephalopathy (PML) and identify neuropathological correlates.<h4>Methods</h4>PML cases and matched controls with primary central nervous system lymphoma (PCNSL) were retrospectively identified. MRI brain at 3 T and 7 T were reviewed. MRI-pathology correlations in fixed brain autopsy tissue were conducted in three subjects with confirmed PML.<h4>Results</h4>With PML (<i>n</i> = 26 t ...[more]

PMID: 33749379

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Project description:Although most of the progressive multifocal leukoencephalopathy cases in sarcoidosis patients are explained by the treatment with immunosuppressive drugs, it is also reported in treatment-naive sarcoidosis patients, which implies a general predisposition of sarcoidosis patients for progressive multifocal leukoencephalopathy. Indeed, it was shown that active sarcoidosis patients have increased regulatory T cell frequencies which could lead to a subsequent systemic immunosuppression. However, if sarcoidosis with systemic changes of T cell subsets frequencies constitute a risk factor for the development of progressive multifocal leukoencephalopathy, which could then be counteracted by sarcoidosis treatment, is not known. In this cohort study, we included, characterized and followed-up six patients with bioptically confirmed definite progressive multifocal leukoencephalopathy and definite or probable sarcoidosis presenting between April 2013 and January 2019, four of them had no immunosuppressive therapy at the time of developing first progressive multifocal leukoencephalopathy symptoms. Analysis of immune cell subsets in these patients revealed significant imbalances of CD4+ T cell and regulatory T cell frequencies. Due to the progression of progressive multifocal leukoencephalopathy in four patients, we decided to treat sarcoidosis anticipating normalization of immune cell subset frequencies and thereby improving progressive multifocal leukoencephalopathy. Notably, by treatment with infliximab, an antibody directed against tumour necrosis factor-α, three patients continuously improved clinically, JC virus was no longer detectable in the cerebrospinal fluid and regulatory T cell frequencies decreased. One patient was initially misdiagnosed as neurosarcoidosis and died 9 weeks after treatment initiation due to aspiration pneumonia. Our study provides insight that sarcoidosis can lead to changes in T cell subset frequencies, which predisposes to progressive multifocal leukoencephalopathy. Although immunosuppressive drugs should be avoided in progressive multifocal leukoencephalopathy, paradoxically in patients with sarcoidosis treatment with the immunosuppressive infliximab might restore normal T cell distribution and thereby halt progressive multifocal leukoencephalopathy progression.

Dataset Information

Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray-white matter junction correlates with iron-enriched macrophages.

Objective

Methods

Results

Conclusion

Publications

Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray-white matter junction correlates with iron-enriched macrophages.

Similar Datasets

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