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

Mahajan, Kedar R; Amin, Moein; Poturalski, Matthew; Lee, Jonathan K.; Herman, Danielle; Zheng, Yufan; Androjna, Charlie; Howell, Mark; Fox, Robert J.; Trapp, Bruce D.; Jones, Stephen E.; Nakamura, Kunio; Ontaneda, Daniel

doi:10.1177/1352458521999651

Cited by 5 publications

(10 citation statements)

References 33 publications

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“…Hemorrhage, iron accumulation, and calcification are depicted in diverse tissues using GRE sequences with T2*-based contrast [ 12 ]. A recent study matched the observed changes with neuropathological findings and suggested that susceptibility changes are correlated with iron accumulation in macrophages [ 13 ]. Additionally, similar findings have been reported in progressive multifocal leukoencephalopathy and multiple sclerosis, suggesting blood–brain barrier dysfunction, decreased iron clearance owing to axonal dysfunction, and dysregulation of iron transport proteins as causes of iron deposition [ 14 , 15 ].…”

Section: Discussionsupporting

confidence: 62%

Juxtacortical White Matter Hypointensity on T2*Gradient Echo Image in Vanishing White Matter Disease: A Case Report

2023

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Patient: Female, 29-year-old Final Diagnosis: Vanishing white matter disease Symptoms: Weakness of upper and lower limb Clinical Procedure: — Specialty: Neurology Objective: Congenital defects/diseases Background: Vanishing white matter disease (VWMD) – also known as childhood ataxia with central nervous system hypomyelination – is one of the most commonly inherited white matter diseases in children. Notably, a course of chronic progressive disease with episodes of rapid and major stress-induced neurological deterioration, such as fever and minor head trauma, is a typical clinical feature of VWMD. The combination of clinical features with specific magnetic resonance imaging findings, including diffuse and extensive white matter lesions with rarefaction or cystic destruction, could recommend a genetic diagnosis. However, VWMD is phenotypically diverse and can affect individuals of all ages. Case Report: A 29-year-old female patient presented with recent aggravation in gait disturbance. She had progressive movement disorder, with symptoms ranging from hand tremors to upper- and lower-extremity weakness, for 5 years. Whole-exome sequencing was performed to confirm the diagnosis of VWMD, and it revealed a mutation in homozygous eIF2B2 gene. The temporal evolution of VWMD observed in the patient for 17 years (from the age of 12 to 29 years) indicated an increased extent of T2 white matter hyperintensity in the cerebrum into the cerebellum and an increased amount of dark signal intensities in the globus pallidus and dentate nucleus. Moreover, a T2*-weighted imaging (WI) scan revealed diffuse, linear, and symmetrical hypointensity along the juxtacortical white matter on the magnification view. Conclusions: This is the case report about rare and unusual finding of diffuse linear juxtacortical white matter hypointensity on T2*-WI scan as a potential radiographic marker for adult-onset VWMD.

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Section: Discussionsupporting

confidence: 62%

Juxtacortical White Matter Hypointensity on T2*Gradient Echo Image in Vanishing White Matter Disease: A Case Report

2023

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“…[3][4][5][6][7]9 Mahajan et al (2021) reported that juxtacortical lesions on MRI correlate with iron-enriched macrophages based on three autopsy cases in which PML developed after treatment with natalizumab for multiple sclerosis. 10 First, the background of PML is different. Second, they used diaminobenzidine-enhanced Turnbull staining to detect both ferric and ferrous non-heme iron as well as immunohistochemistry for the ferritin-light chain.…”

Section: Discussionmentioning

confidence: 99%

“…Mahajan et al (2021) reported that in three patients who developed PML after treatment with natalizumab for multiple sclerosis, susceptibility changes in MRI correlated with pathological accumulation of iron in macrophages. 10 Herein, we report a case of PML with massive hypointense changes in juxtacortical lesions in a 71-year-old woman who had been treated with rituximab-containing chemotherapy for follicular lymphoma for 16 months. Neuropathological examination revealed iron deposits with hemosiderin-phagocytic macrophages in the U-fibers of the occipital lobes.…”

Section: Introductionmentioning

confidence: 99%

“…2 As a PML marker, linear juxtacortical hypointense changes in susceptibilityweighted imaging (SWI) on magnetic resonance imaging (MRI) have recently been reported. [3][4][5][6][7][8][9][10] Little is known about the biological mechanisms that induce these changes. Mahajan et al (2021) reported that in three patients who developed PML after treatment with natalizumab for multiple sclerosis, susceptibility changes in MRI correlated with pathological accumulation of iron in macrophages.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10] Little is known about the biological mechanisms that induce these changes. Mahajan et al (2021) reported that in three patients who developed PML after treatment with natalizumab for multiple sclerosis, susceptibility changes in MRI correlated with pathological accumulation of iron in macrophages. 10 Herein, we report a case of PML with massive hypointense changes in juxtacortical lesions in a 71-year-old woman who had been treated with rituximab-containing chemotherapy for follicular lymphoma for 16 months.…”

Section: Introductionmentioning

confidence: 99%

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An autopsy case of progressive multifocal leukoencephalopathy with massive iron deposition in juxtacortical lesions

et al. 2023

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Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by JC virus infection of oligodendrocytes. Little has been reported on iron deposits in patients with PML. Herein, we report a case of PML with massive iron deposition in the juxtacortical regions attaching white matter lesions in a 71‐year‐old woman who developed bilateral visual disturbance and progressive aphasia after 16 months of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment for follicular lymphoma. Magnetic resonance imaging revealed white matter lesions in the left parietal and other lobes with massive iron deposition in the juxtacortical lesions. A PCR test for JC virus was positive, confirming the diagnosis of PML. Despite treatment with mefloquine and mirtazapine, the patient died six months later. At autopsy, demyelination was found dominantly in the left parietal lobe. Moreover, hemosiderin‐laden macrophages and reactive astrocytes containing ferritin were abundant in the juxtacortical regions adjacent to the white matter lesions. This is a previously unreported case of PML after lymphoma, in which iron deposition was confirmed both radiologically and pathologically.

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Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging

Yamada,

Toko,

Nakamori

et al. 2024

J. Neurovirol.

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Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML.

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

Cited by 5 publications

References 33 publications

Juxtacortical White Matter Hypointensity on T2*Gradient Echo Image in Vanishing White Matter Disease: A Case Report

Juxtacortical White Matter Hypointensity on T2*Gradient Echo Image in Vanishing White Matter Disease: A Case Report

An autopsy case of progressive multifocal leukoencephalopathy with massive iron deposition in juxtacortical lesions

Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging

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