Pomalidomide-associated progressive multifocal leukoencephalopathy in multiple myeloma: cortical susceptibility-weighted imaging hypointense findings prior to clinical deterioration

Ueno, Hiroki; Kikumto, Mai; Takebayashi, Yoshiko; Ishibashi, H.; Yasutomi, H; Umemoto, Kasane; Nakamichi, Kazuo; Saijo, Masayuki; Ichinohe, Tatsuo; Makino, Hírofumi

doi:10.1007/s13365-020-00845-0

Cited by 11 publications

(12 citation statements)

References 12 publications

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“…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 ]. Notably, recent studies on brain ion deposition used susceptibility-weighted imaging sequences, which are more sensitive to paramagnetic effect than T2*-WI, or quantitative susceptibility mapping, which can be quantitatively evaluated; these methodological differences limitations of the present study.…”

Section: Discussionsupporting

confidence: 63%

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: 63%

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

2023

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“…14,15 Using susceptibilityweighted imaging (SWI), linear juxtacortical hypointense (at the cortical-WM junction) changes are observed in association with PML lesions even prior to clinical manifestations in some individuals. [16][17][18][19][20][21] This is an attractive imaging biomarker of PML in the appropriate clinical context-patients on immunomodulatory/immunosuppressive therapies or an immunocompromised state. 22 PML paramagnetic changes have been interpreted as occurring in the cortex, deep cortical layers or adjacent U-fibers and its etiology has been enigmatic.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Case reports of IMiD-related neurotoxicity have been published for both lenalidomide and pomalidomide. [23][24][25][26][27] Peripheral neuropathy is a commonly reported adverse effect for IMiDs, but central neurotoxicity, including ataxia, amnesia, aphasia, and reversible comas, are rare, with only a few cases reported. 28 Notably, both of our patients were receiving IMiDs for many years during their previous therapies without significant central neurotoxicity and specifically without any white matter degenerative changes, as was seen in both baseline MRIs.…”

Section: Dovepressmentioning

confidence: 99%

Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma

Kareem¹,

Viswanathan²,

Sahebjam³

et al. 2022

OTT

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Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.

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Pomalidomide-associated progressive multifocal leukoencephalopathy in multiple myeloma: cortical susceptibility-weighted imaging hypointense findings prior to clinical deterioration

Cited by 11 publications

References 12 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

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

Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma

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