Radiation-Induced Multiphasic Demyelination

Wong, Oi Yean; Tham, Yih-Horng; Lai, Michelle; Davagnanam, Indran; Bremner, Fion

doi:10.1097/wno.0000000000000735

Cited by 3 publications

(6 citation statements)

References 5 publications

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“…Previous reports indicate mean time to onset of symptoms is 1-4 months after radiotherapy, and affected areas tend to correlate with radiation targets. 8 The timing of symptoms differed for these 2 pediatric patients, with 1 patient experiencing symptoms 9 months postradiation and no imaging findings of multiple sclerosis until 5 years later. The other had symptoms and abnormal imaging consistent with multiple sclerosis at initial diagnosis, prior to surgery and radiation.…”

Section: Discussionmentioning

confidence: 96%

“…Scarce case reports have been described in the adult literature, including 2 involving radiation treatment for macroadenoma. 7,8 In one case, 7 weeks after radiotherapy, a 36-year-old female patient presented with temporal and spatial dissemination of T2/fluid-attenuated inversion recovery hyperintense lesions correlating with focal deficits. 7 Lumbar puncture yielded polyclonal IgG, negative myelin oligodendrocyte glycoprotein, and aquaporin-4 protein.…”

Section: Discussionmentioning

confidence: 99%

“…Sparse cases of multifocal and multiphasic demyelination have been documented in the literature. 7,8 Furthermore, it is quite rare for patients who undergo radiation to develop multiple sclerosis symptoms. It has previously been hypothesized that only individuals prone to developing de novo multiple sclerosis present with a relapsing disease course.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, there have been incidental case reports of multifocal, multiphasic demyelinating conditions presenting after ionizing radiation for cancer therapy. 7,8 No previous link between ionizing radiation and multiple sclerosis has been shown, although the proposed pathophysiology for radiation-induced brain injury and multiple sclerosis shares a common pathway. Furthermore, the immunogenic effects of tumor burden on peripheral inflammation serves as another mechanism to undermine the integrity of the blood-brain barrier, promoting vascular leak and a microclimate of inflammation, which may prompt demyelinating disorders.…”

mentioning

confidence: 99%

“…To date, there have only been a small number of case reports in the adult literature on multiple sclerosis as a differential diagnosis of postradiation brain lesions. 7,8 Here we discuss 2 pediatric patients with multifocal and multiphasic demyelination concurrent and after radiation for ependymoma.…”

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confidence: 99%

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Multifocal and Multiphasic Demyelinating Lesions After Radiation for Ependymoma in a Pediatric Population

et al. 2022

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Radiation treatment is widely used to address unresectable intracranial tumors. Owing to the nature of therapy, healthy tissue and diseased regions will be affected. New insights have shown that not only does this impact brain parenchyma but it causes changes in fluid status, myelination, and the integrity of the blood-brain barrier. This alters how peripheral and central immune systems interact, perpetuating neuroinflammation. Rare case reports in the adult literature have described multifocal, multiphasic demyelinating lesions after radiation. Here we describe 2 pediatric cases of relapsing demyelination after and in conjunction with radiation therapy for ependymoma, consistent with a multiple sclerosis phenotype. Insights into the underpinnings of multiple sclerosis show peripheral inflammation, blood-brain barrier disruption, and antigenic mimicry stimulate neuroinflammation. Here we investigate the roll that radiation, tumor burden, and systemic inflammation may play in creating demyelinating disorders. We strive to elucidate common pathophysiology between radiation-induced brain injury and multiple sclerosis.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Multifocal and Multiphasic Demyelinating Lesions After Radiation for Ependymoma in a Pediatric Population

et al. 2022

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Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

Clausi

Stessin

Zhao

et al. 2021

Sci Rep

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The efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

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Multiple Sclerosis-like Lesions Induced by Radiation: A Case Report and Systematic Review of the Literature

Sterpi,

Triantafyllou,

Tzanetakos

et al. 2024

JCM

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Background/Objectives: Radiotherapy (RT) remains crucial in treating both primary and metastatic central nervous system cancer. Despite advancements in modern techniques that mitigate some toxic adverse effects, magnetic resonance imaging (MRI) scans still reveal a wide range of radiation-induced changes. Radiation can adversely affect neuroglial cells and their precursors, potentially triggering a demyelinating pattern similar to multiple sclerosis (MS). The aim of the current review is to investigate the occurrence and characteristics of such cases presented in the literature. Methods: We present the case of a 37-year-old female patient with multiple white matter lesions on a brain MRI, mimicking MS, after the completion of RT sessions. Additionally, a systematic review of the literature (PROSPERO id: CRD42024624053) was performed on 4 January 2024. The databases of MEDLINE and SCOPUS were searched. Case reports or case series of adult patients with white matter lesions in a brain MRI, consistent with the MAGNIMS criteria for MS plaques, after RT, were included in our final synthesis. The PRISMA guidelines were applied. Results: The systematic search of the literature revealed 1723 studies, 7 of which conformed to our inclusion criteria, including seven patients in our final analysis. Four of them were female and the mean age was 39 ± 11 years. Several intracranial and extracranial RT types were performed. The symptoms occurred 3 ± 0.8 months after the completion of RT. Lesions were revealed in infratentorial, periventricular and subcortical white matter regions, but not in the spinal cord. All patients who received corticosteroids (83%) showed clinical improvement. Clinical and radiological recurrence occurred in two of the patients during the follow-up period. Fingolimod and Interferon beta-1a were administered to these two patients. Conclusions: Radiation-induced demyelination is a critical clinical and radiological entity that requires attention from both oncologists and neurologists. Comprehensive follow-up is essential to identify patients who may benefit from disease-modifying therapies and to distinguish them from those with pre-existing demyelinating conditions.

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Radiation-Induced Multiphasic Demyelination

Cited by 3 publications

References 5 publications

Multifocal and Multiphasic Demyelinating Lesions After Radiation for Ependymoma in a Pediatric Population

Multifocal and Multiphasic Demyelinating Lesions After Radiation for Ependymoma in a Pediatric Population

Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

Multiple Sclerosis-like Lesions Induced by Radiation: A Case Report and Systematic Review of the Literature

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