MRI in Chemotherapy induced Leukoencephalopathy: Report of Two Cases and Radiologist’s Perspective

Sindhwani, Geetika; Arora, Manali; Thakker, Vishal; Jain, Abhinav

doi:10.7860/jcdr/2017/29164.10248

Cited by 20 publications

(20 citation statements)

References 8 publications

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“…Furthermore, in the neuron-oligodendrocyte co-culture, low dose of MTA treatment severely affected oligodendrocytes and induced dysmyelination or demyelination, while leaving the underlying axons relatively intact. Indeed, increasing lines of evidence suggest that chemotherapy-related cognitive impairment is related to white matter damages, implying dysregulation of oligodendrocyte-lineage cells [34][35][36]. Now, there is considerable attention to repurposing (or repositioning) of MTAs for the treatment of a variety of brain disorders, with some already in clinical trials [27,37].…”

Section: Discussionmentioning

confidence: 99%

A Role of Microtubules in Oligodendrocyte Differentiation

Lee

Hur

2020

IJMS

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Oligodendrocytes are specialized cells that myelinate axons in the central nervous system. Defects in oligodendrocyte function and failure to form or maintain myelin sheaths can cause a number of neurological disorders. Oligodendrocytes are differentiated from oligodendrocyte progenitor cells (OPCs), which extend several processes that contact, elaborate, and eventually wrap axonal segments to form multilayered myelin sheaths. These processes require extensive changes in the cytoarchitecture and must be regulated by reorganization of the cytoskeleton. Here, we established a simple protocol to isolate and differentiate mouse OPCs, and by using this method, we investigated a role of microtubules (MTs) in oligodendrocyte differentiation. Oligodendrocytes developed a complex network of MTs during differentiation, and treatment of differentiating oligodendrocytes with nanomolar concentrations of MT-targeting agents (MTAs) markedly affected oligodendrocyte survival and differentiation. We found that acute exposure to vincristine and nocodazole at early stages of oligodendrocyte differentiation markedly increased MT arborization and enhanced differentiation, whereas taxol and epothilone B treatment produced opposing outcomes. Furthermore, treatment of myelinating co-cultures of oligodendrocytes and neurons with nanomolar concentrations of MTAs at late stages of oligodendrocyte differentiation induced dysmyelination. Together, these results suggest that MTs play an important role in the survival, differentiation, and myelination of oligodendrocytes.

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Section: Discussionmentioning

confidence: 99%

A Role of Microtubules in Oligodendrocyte Differentiation

Lee

Hur

2020

IJMS

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“…This range of cognitive deficiencies referred to as chemotherapy-induced cognitive impairment, chemobrain or chemofog severely hampers quality of life of patients undergoing treatment as well as of survivors since it significantly impacts their daily activities, social interactions and ability to return to school or work, involving severe financial hardship 3 . Advanced neuroimaging analyses have identified structural white and gray matter damage following chemotherapy in patients treated for various types of cancer, including breast 4 , colon 5 , testicular 6 and lung cancer 7 . Cognitive deficits associated with platinum-based therapeutics such as cisplatin have been observed for 5-10 years post-diagnosis in ovarian cancer survivors 8 , at least 2 years post-chemotherapy in head and neck cancer survivors 9 and 10-26 years post-treatment in testicular cancer survivors 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Nasal administration of mitochondria reverses chemotherapy-induced cognitive deficits

et al. 2021

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Up to seventy-five percent of patients treated for cancer suffer from cognitive deficits which can persist for months to decades, severely impairing quality of life. Although the number of cancer survivors is increasing tremendously, no efficacious interventions exist. Cisplatin, most commonly employed for solid tumors, leads to cognitive impairment including deficits in memory and executive functioning. We recently proposed deficient neuronal mitochondrial function as its underlying mechanism. We hypothesized nasal administration of mitochondria isolated from human mesenchymal stem cells to mice, can reverse cisplatin-induced cognitive deficits. Methods: Puzzle box, novel object place recognition and Y-maze tests were used to assess the cognitive function of mice. Immunofluorescence and high-resolution confocal microscopy were employed to trace the nasally delivered mitochondria and evaluate their effect on synaptic loss. Black Gold II immunostaining was used to determine myelin integrity. Transmission electron microscopy helped determine mitochondrial and membrane integrity of brain synaptosomes. RNA-sequencing was performed to analyse the hippocampal transcriptome. Results: Two nasal administrations of mitochondria isolated from human mesenchymal stem cells to mice, restored executive functioning, working and spatial memory. Confocal imaging revealed nasally delivered mitochondria rapidly arrived in the meninges where they were readily internalized by macrophages. The administered mitochondria also accessed the rostral migratory stream and various other brain regions including the hippocampus where they colocalized with GFAP + cells. The restoration of cognitive function was associated with structural repair of myelin in the cingulate cortex and synaptic loss in the hippocampus. Nasal mitochondrial donation also reversed the underlying synaptosomal mitochondrial defects. Moreover, transcriptome analysis by RNA-sequencing showed reversal of cisplatin-induced changes in the expression of about seven hundred genes in the hippocampus. Pathway analysis identified Nrf2-mediated response as the top canonical pathway. Conclusion: Our results provide key evidence on the therapeutic potential of isolated mitochondria - restoring both brain structure and function, their capability to enter brain meninges and parenchyma upon nasal delivery and undergo rapid cellular internalization and alter the hippocampal transcriptome. Our data identify nasal administration of mitochondria as an effective strategy for reversing chemotherapy-induced cognitive deficits and restoring brain health, providing promise for the growing population of both adult and pediatric cancer survivors.

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“…On imaging, chemotherapy-related leukoencephalopathy typically produces non-enhancing T2 hyperintensity in the frontoparietal white matter, but can sometimes demonstrate diffuse involvement of the periventricular and deep white matter, similar to radiation-induced leukoencephalopathy [ 51 ]. On DWI, focal or diffuse areas of reversible restricted diffusion may be seen in acute cases and typically show improvement over time after cessation of the offending drug [ 52 ].…”

Section: Chemotherapy-related Complicationsmentioning

confidence: 99%

Brain tumour post-treatment imaging and treatment-related complications

Kessler

Bhatt

2018

Insights Imaging

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PurposeThe imaging of primary and metastatic brain tumours is very complex and relies heavily on advanced magnetic resonance imaging (MRI). Utilisation of these advanced imaging techniques is essential in helping clinicians determine tumour response after initiation of treatment. Many options are currently available to treat brain tumours, and each can significantly alter the brain tumour appearance on post-treatment imaging. In addition, there are several common and uncommon treatment-related complications that are important to identify on standard post-treatment imaging.MethodsThis article provides a review of the various post-treatment-related imaging appearances of brain neoplasms, including a discussion of advanced MR imaging techniques available and treatment response criteria most commonly used in clinical practice. This article also provides a review of the multitude of treatment-related complications that can be identified on routine post-treatment imaging, with an emphasis on radiation-induced, chemotherapy-induced, and post-surgical entities.Summary/ConclusionAlthough radiological evaluation of brain tumours after treatment can be quite challenging, knowledge of the various imaging techniques available can help the radiologist distinguish treatment response from tumour progression and has the potential to save patients from inappropriate alterations in treatment. In addition, knowledge of common post-treatment-related complications that can be identified on imaging can help the radiologist play a key role in preventing significant patient morbidity/mortality.Teaching points• Contrast enhancement does not reliably define tumour extent in many low-grade or infiltrative gliomas.• Focal regions of elevated cerebral blood volume (rCBV) on dynamic susceptibility contrast (DSC) perfusion-weighted imaging are suggestive of tumour growth/recurrence.• Brain tumour treatment response criteria rely on both imaging and clinical parameters.• Chemotherapeutic agents can potentiate many forms of radiation-induced injury.• Ipilimumab-induced hypophysitis results in transient diffuse enlargement of the pituitary gland.

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MRI in Chemotherapy induced Leukoencephalopathy: Report of Two Cases and Radiologist’s Perspective

Cited by 20 publications

References 8 publications

A Role of Microtubules in Oligodendrocyte Differentiation

A Role of Microtubules in Oligodendrocyte Differentiation

Nasal administration of mitochondria reverses chemotherapy-induced cognitive deficits

Brain tumour post-treatment imaging and treatment-related complications

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