Alternating hemiparesis and orolingual apraxia as manifestations of methotrexate neurotoxicity in a paediatric case of acute lymphoblastic leukaemia

Yap, Siew Mei; MacEneaney, Peter; Ryan, Clodagh; O’Toole, Orna

doi:10.1136/bcr-2016-214677

Cited by 4 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Methotrexate (MTX) is an important chemotherapeutic agent used in acute lymphoblastic leukemia (ALL) treatment. It is a folic acid antagonist, and in intravenous high-dose or intrathecal administration, it can be associated with demyelination, white matter necrosis, loss of oligodendroglia, axonal swelling microcystic encephalomalacia, and atrophy in the deep cerebral white matter [1][2][3]. The typical damage inflicted on the central nervous system (CNS) white matter is termed leukoencephalopathy [3].…”

Section: Introductionmentioning

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

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.

show abstract

Section: Introductionmentioning

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

“…It has a wide clinical spectrum, ranging from sub-clinical manifestations with complete recovery to a progressive encephalopathy. Methotrexate induced acute encephalopathy is a transient neurological dysfunction that should be considered in patients presenting with stroke-like hemiparesis, seizures, aphasia, dysphasia, dysphagia, and diplopia 5 to 14 days after MTX therapy [1][2][3] . Here, we report a 12-year-old male with ALL who developed transient left hemiparesis associated with dysphasia and central facial paralysis 14 days after high dose MTX (5g/m 2 ) and intrathecal (IT) MTX (12 mg according to age) treatment.…”

Section: Introductionmentioning

confidence: 99%

Stroke-Like Hemiparesis During Acute Lymphoblastic Leukemia Treatment

et al. 2020

View full text Add to dashboard Cite

In this case report; a 12-year-old male with ALL who developed transient left hemiparesis associated with dysphasia and central facial paralysis 14 days after high dose methotrexate (5g/m2) and intrathecal MTX (12 mg, according to age) treatment has been reported. Cranial magnetic resonance imaging (MRI) revealed restricted diffusion in bilateral centrum semiovale compatible with MTX-induced acute encephalopathy. All clinical symptoms resolved completely without any treatment. Clinical findings including headache, nausea, emesis, lethargy, altered mental status, blurred vision, aphasia, dysphasia, hemiparesis and cranial MRI findings of restricted diffusion that does not comply with the territory of any artery seizure should alert the physician for MTX-induced acute encephalopathy.

show abstract

“…In the pediatric oncology population, neurotoxicity may occur after high doses of intravenous and standard doses of intrathecal MTX with a spectrum of manifestations ranging from asymptomatic head magnetic resonance imaging (MRI) abnormalities to an acute encephalopathy. 1 – 5 Although discontinuing MTX and supportive measures including the addition of corticosteroids and folinic acid frequently result in resolution of symptoms, progression to death has been reported. 1 , 6 , 7 Dextromethorphan (DXM), a mu (µ) agonist and weak antagonist of the N -methyl d -aspartate (NMDA) receptor, may alleviate symptoms of MTX neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Methotrexate encephalopathy: Two cases in adult cancer patients, who recovered with pathophysiologically based therapy

Pastel

Davis

Bengtson

et al. 2017

SAGE Open Medical Case Reports

View full text Add to dashboard Cite

Background/Objectives:Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy.Results:Case 1: A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2: A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high-dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery.Conclusions:These two cases suggest that N-methyl d-aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity.

show abstract

Alternating hemiparesis and orolingual apraxia as manifestations of methotrexate neurotoxicity in a paediatric case of acute lymphoblastic leukaemia

Cited by 4 publications

References 13 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

Stroke-Like Hemiparesis During Acute Lymphoblastic Leukemia Treatment

Methotrexate encephalopathy: Two cases in adult cancer patients, who recovered with pathophysiologically based therapy

Contact Info

Product

Resources

About