Severe, Fatal Methotrexate-related Neurotoxicity in 2 Adolescent Patients With ALL

Dabagh, Sarah; David, Henry; Young, Sarah P.; Doan, Andrew; Bhojwani, Deepa

doi:10.1097/mph.0000000000001706

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…As stated, this is typically transient, and most patients can receive subsequent MTX without recurrence of symptoms. Nevertheless, there are reports of very rare cases of poor neurologic outcomes and even fatalities with progressive encephalopathy [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Methotrexate-Induced Stroke-Like Syndrome: A Typical Presentation of a Rare Complication

Santos¹,

Silva²,

Moreira³

et al. 2023

Cureus

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Methotrexate (MTX) is one of the mainstay drugs used in acute lymphoblastic leukemia (ALL) management; however, it can cause damage to the central nervous system (CNS), typically to the subcortical white matter. Stroke-like syndrome is one particular form of MTX-related neurotoxicity that occurs within 21 days of methotrexate administration (intrathecal or high-dose intravenous treatment). The clinical picture comprehends fluctuating neurological symptoms evoking acute cerebral ischemia or hemorrhage (paresis or paralysis, speech disorders - aphasia and/or dysarthria, altered mental status, and occasionally seizures), with spontaneous resolution in the majority of cases, without other identifiable cause. The typical neuroimage includes areas of restricted diffusion on diffusion-weighted imaging and non-enhancing T2 hyper-intense lesions in the white matter, on brain MRI. We report a 12-year-old boy with low-risk B-ALL without CNS involvement, who presented to the emergency department with complaints of sudden paresis of the four limbs (more severe on the right side), aphasia, and confusion. He had received one dose of intrathecal MTX 11 days prior to this episode. An angio-MRI of the brain revealed bilateral restricted diffusion areas in the centrum semiovale, and symptoms fluctuated until complete neurological recovery without any medical intervention, which is very suggestive of MTX-related neurotoxicity. This case illustrates a rare complication of MTX administration that presented with typical clinical and radiological characteristics, in an adolescent with hematological malignancy who experienced swift and full neurological recovery.

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Section: Discussionmentioning

confidence: 99%

Methotrexate-Induced Stroke-Like Syndrome: A Typical Presentation of a Rare Complication

Santos¹,

Silva²,

Moreira³

et al. 2023

Cureus

View full text Add to dashboard Cite

show abstract

“…Studies showed that giving folinic acid in the first 24-36 hours after initiating MTX therapy can prevent neurotoxicity [17]. Secondly, after the onset of the neurological symptoms, Dextromethorphan, an N-methyl-D-aspartate receptor antagonist, and aminophylline, an adenosine receptor antagonist, have been helpful in the management of MTX-neurotoxicity [1], [11], [18].…”

Section: Discussionmentioning

confidence: 99%

Methotrexate-Induced Neurotoxicity in Paediatric Malignancies

Vodă

Stoia

Patran

et al. 2022

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Hematologic malignancies have a growing variety of therapeutic options, but many of these have both central and peripheral nervous system side effects, which may force the physician to discontinue or lower the dosage of the offending drug to prevent irreversible damage. Neurotoxicity is a common side effect of chemotherapy. Peripheral neuropathy is frequent with many medicines, but other complications such as seizures and encephalopathy may require immediate intervention. Early detection of undesirable neurological side effects may lead to more effective treatments and dosage changes. Furthermore, understanding typical toxicities may aid in distinguishing chemotherapy-related symptoms from cancer progression into the CNS. In this article, we discuss the potential side effects of Methotrexate use in childhood hematologic malignancies, with a focus on the difficulty of the differential diagnosis of newly onset neurological symptoms in pediatric oncology patients and potential interventions.

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“…However, cau tion is warranted as there are case reports of patients with poor neu ro logic out comes and rare fatal i ties after repeated epi sodes of meth o trex ate neu ro tox ic ity. 9,20 In these uncom mon sce nar ios, par tic u larly when patients do not make a full recov ery in the expected time frame or have recur rent severe meth o trex ate neu ro tox ic ity, com ple tion of CNS-directed ther apy with alter nate agents would require an indi vid u al ized approach based on the patient's risk of CNS relapse.…”

Section: Recurrence Of Meth O Trex Ate Neu Ro Tox Ic Itymentioning

confidence: 99%

Managing therapy-associated neurotoxicity in children with ALL

2021

Self Cite

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Several chemotherapeutic agents and novel immunotherapies provide excellent control of systemic and central nervous system (CNS) leukemia but can be highly neurotoxic. The manifestations of subacute methotrexate neurotoxicity are diverse and require vigilant management; nonetheless, symptoms are transient in almost all patients. As methotrexate is a crucial drug to prevent CNS relapse, it is important to aim to resume it after full neurologic recovery. Most children tolerate methotrexate rechallenge without significant delays or prophylactic medications. Neurotoxicity is more frequent with newer immunotherapies such as CD19– chimeric antigen receptor T (CAR T) cells and blinatumomab. A uniform grading system for immune effector cell–associated neurotoxicity syndrome (ICANS) and algorithms for management based on severity have been developed. Low-grade ICANS usually resolves within a few days with supportive measures, but severe ICANS requires multispecialty care in the intensive care unit for life-threatening seizures and cerebral edema. Pharmacologic interventions include anticonvulsants for seizure control and glucocorticoids to reduce neuroinflammation. Anticytokine therapies targeted to the pathophysiology of ICANS are in development. By using illustrative patient cases, we discuss the management of neurotoxicity from methotrexate, CAR T cells, and blinatumomab in this review.

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Severe, Fatal Methotrexate-related Neurotoxicity in 2 Adolescent Patients With ALL

Cited by 7 publications

References 20 publications

Methotrexate-Induced Stroke-Like Syndrome: A Typical Presentation of a Rare Complication

Methotrexate-Induced Stroke-Like Syndrome: A Typical Presentation of a Rare Complication

Methotrexate-Induced Neurotoxicity in Paediatric Malignancies

Managing therapy-associated neurotoxicity in children with ALL

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