Methotrexate-related Leukoencephalopathy Sungita
Description: Methotrexate-related Leukoencephalopathy Sungita Kumar 3032021 RAD 4001 Dr. Eliana Bonfante-Meija Clinical History The patient is a 16-year-old female with T cell ALL who presented with acute-onset right-sided weakness and slurred speech
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slide1. Methotrexate-related Leukoencephalopathy Sungita Kumar
3/03/2021
RAD 4001
Dr. Eliana Bonfante-Meija<br>
slide2. Clinical History The patient is a 16-year-old female with T cell ALL who presented with acute-onset right-sided weakness and slurred speech
2/17: the patient’s mother came to wake her up in the morning and found her unable to move her right side
Taken to MDA where MRI/MRA brain was taken due to concern for stroke
Overnight, the patient’s strength improved
2/18: the patient’s symptoms acutely worsen in the morning and she is transferred to MHH
Receives asparaginase, nelarabine, and intrathecal methotrexate (last injection 9 days ago)<br>
slide3. Clinical History cont. Vitals on admission: Temp 98ËšF, HR 89, RR 15, BP 115/78, SpO2 99%
Physical Exam
Awake and alert
Right facial droop, RUE strength 0/5, RLE strength 1/5
Dysarthric
Labs:
Methotrexate < 0.4 (low)
Hgb 9.1, WBC 0.1, Plt 60
Prior Imaging
MRI and MRA were done at MDA, but imaging had a lot of artifacts due to braces
CTV head showed no venous thrombosis<br>
slide4. Differential Diagnosis Stroke 2/2 to:
Asparaginase toxicity (pro-thrombotic state)
PFO
Viral infection – varicella, parvovirus 19, influenza A, or coxsackie
Bacterial meningitis, TB meningitis, or viral encephalitis (can cause local vasculitis and thrombosis)
AVM
Intracranial hemorrhage 2/2 thrombocytopenia
Methotrexate neurotoxicity
Nelarabine neurotoxicity<br>
slide5. CT Brain without contrast – 2/18/2021 No hemorrhage or acute ischemic change visible
CTA head and neck showed no areas of occlusion or stenosis<br>
slide6. MRI Brain – 2/18/2021 DWI ADC Area of restricted diffusion in the centrum semiovale of the left frontal lobe measuring 2.5cm in diameter<br>
slide7. MRI Brain – 2/18/2021 T1 FLAIR<br>
slide8. Centrum Semiovale The centrum semiovale is a mass of white matter located superior to the lateral ventricles and corpus callosum
This is the classic location to see restricted diffusion on MRI in methotrexate-related leukoencephalopathy https://www.myelinationmriatlas.com/3-months.html https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us<br>
slide9. Summary and Key Findings 16-year-old female with T-cell ALL presented with waxing and waning stroke-like symptoms (hemiparesis and dysarthria) 9 days after receiving intrathecal Methotrexate
Methotrexate level was low
CT head, CTA head and neck, and CTV negative
MRI of the brain showed an area of restricted diffusion in the centrum semiovale (high signal on DWI and low signal on ADC)
T1 and FLAIR sequences showed no abnormalities<br>
slide10. Differential Diagnosis Methotrexate-related leukoencephalopathy
Stroke
Infarct typically includes the cortex
Viral encephalitis
Typically presents with fever, headache, photophobia
Neoplasm
Symptom onset is usually gradual<br>
slide11. Discussion: Methotrexate-related leukoencephalopathy Methotrexate is an antifolate antimetabolite (inhibits dihydrofolate reductase) that is used in the treatment of certain cancers
Neurotoxicity most often occurs in pediatric patients who are being treated for ALL
Increased risk with higher doses and intrathecal administration
The mechanism is unclear, but it is possible that methotrexate increases the release of adenosine, which can dilate cerebral vessels, alter neuronal function, and cause transient cytotoxic edema<br>
slide12. Discussion: Methotrexate-related leukoencephalopathy Manifests 2-14 days after administration
Headache, confusion, disorientation, lethargy, seizures, or focal neurological deficits
Unlike other encephalopathies, symptoms can wax and wane
Acute toxicity is transient, while chronic toxicity can result in permanent deficits
Also associated with myelosuppression, mucositis, lung disease, nephrotoxicity, and hepatotoxicity<br>
slide13. Discussion: Methotrexate-related leukoencephalopathy Radiographic findings:
CT: low attenuation in the white matter of both cerebral hemispheres (non-specific)
MRI T2 and FLAIR: transient diffuse high signal in the centrum semiovale, initially sparing subcortical U-fibers – can be unilateral, bilateral, or alternate between both over the course of the disease
MRI DWI and ADC: restricted diffusion across multiple vascular territories in the centrum semiovale<br>
slide14. Discussion: Methotrexate-related leukoencephalopathy Treatment
There is currently no standard treatment
Case reports suggest that aminophylline (non-selective adenosine receptor antagonist) may be beneficial
Dextromethorphan showed benefit in a retrospective study of 18 patients
Patient received dextromethorphan on 2/18 and the right-sided weakness improved
She was discharged the next day back to MDA<br>
slide15. Final Diagnosis Methotrexate-related leukoencephalopathy
MRI shows restricted diffusion across multiple vascular territories in the centrum semiovale https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us DWI ADC<br>
slide16. ACR appropriateness Criteria<br>
slide17. Cost of Imaging Average cost of:
CT brain: $1,200
CTA head: $6,200
MRI brain: $2,625
TOTAL: $10,025
https://www.newchoicehealth.com/procedures<br>
slide18. Take Home Points In patients who present with acute neurological deficits and history of receiving methotrexate, consider methotrexate-related leukoencephalopathy
Look for restricted diffusion in the centrum semiovale on MRI
Treat the patient with dextromethorphan or aminophylline<br>
slide19. References https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us
https://radiopaedia.org/articles/centrum-semiovale-1?lang=us
https://www.annalsofoncology.org/article/S0923-7534(19)41115-0/fulltext
https://www.uptodate.com/contents/therapeutic-use-and-toxicity-of-high-dose-methotrexate#H6
https://www.uptodate.com/contents/overview-of-neurologic-complications-of-conventional-non-platinum-cancer-chemotherapy?sectionName=METHOTREXATE&topicRef=1155&anchor=H2&source=see_link#H7
https://www.acr.org/Clinical-Resources/ACR-Appropriateness-Criteria
https://www.newchoicehealth.com/procedures
https://www.ncbi.nlm.nih.gov/books/NBK556114/<br>
slide20. Questions?<br>
3/03/2021
RAD 4001
Dr. Eliana Bonfante-Meija<br>
slide2. Clinical History The patient is a 16-year-old female with T cell ALL who presented with acute-onset right-sided weakness and slurred speech
2/17: the patient’s mother came to wake her up in the morning and found her unable to move her right side
Taken to MDA where MRI/MRA brain was taken due to concern for stroke
Overnight, the patient’s strength improved
2/18: the patient’s symptoms acutely worsen in the morning and she is transferred to MHH
Receives asparaginase, nelarabine, and intrathecal methotrexate (last injection 9 days ago)<br>
slide3. Clinical History cont. Vitals on admission: Temp 98ËšF, HR 89, RR 15, BP 115/78, SpO2 99%
Physical Exam
Awake and alert
Right facial droop, RUE strength 0/5, RLE strength 1/5
Dysarthric
Labs:
Methotrexate < 0.4 (low)
Hgb 9.1, WBC 0.1, Plt 60
Prior Imaging
MRI and MRA were done at MDA, but imaging had a lot of artifacts due to braces
CTV head showed no venous thrombosis<br>
slide4. Differential Diagnosis Stroke 2/2 to:
Asparaginase toxicity (pro-thrombotic state)
PFO
Viral infection – varicella, parvovirus 19, influenza A, or coxsackie
Bacterial meningitis, TB meningitis, or viral encephalitis (can cause local vasculitis and thrombosis)
AVM
Intracranial hemorrhage 2/2 thrombocytopenia
Methotrexate neurotoxicity
Nelarabine neurotoxicity<br>
slide5. CT Brain without contrast – 2/18/2021 No hemorrhage or acute ischemic change visible
CTA head and neck showed no areas of occlusion or stenosis<br>
slide6. MRI Brain – 2/18/2021 DWI ADC Area of restricted diffusion in the centrum semiovale of the left frontal lobe measuring 2.5cm in diameter<br>
slide7. MRI Brain – 2/18/2021 T1 FLAIR<br>
slide8. Centrum Semiovale The centrum semiovale is a mass of white matter located superior to the lateral ventricles and corpus callosum
This is the classic location to see restricted diffusion on MRI in methotrexate-related leukoencephalopathy https://www.myelinationmriatlas.com/3-months.html https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us<br>
slide9. Summary and Key Findings 16-year-old female with T-cell ALL presented with waxing and waning stroke-like symptoms (hemiparesis and dysarthria) 9 days after receiving intrathecal Methotrexate
Methotrexate level was low
CT head, CTA head and neck, and CTV negative
MRI of the brain showed an area of restricted diffusion in the centrum semiovale (high signal on DWI and low signal on ADC)
T1 and FLAIR sequences showed no abnormalities<br>
slide10. Differential Diagnosis Methotrexate-related leukoencephalopathy
Stroke
Infarct typically includes the cortex
Viral encephalitis
Typically presents with fever, headache, photophobia
Neoplasm
Symptom onset is usually gradual<br>
slide11. Discussion: Methotrexate-related leukoencephalopathy Methotrexate is an antifolate antimetabolite (inhibits dihydrofolate reductase) that is used in the treatment of certain cancers
Neurotoxicity most often occurs in pediatric patients who are being treated for ALL
Increased risk with higher doses and intrathecal administration
The mechanism is unclear, but it is possible that methotrexate increases the release of adenosine, which can dilate cerebral vessels, alter neuronal function, and cause transient cytotoxic edema<br>
slide12. Discussion: Methotrexate-related leukoencephalopathy Manifests 2-14 days after administration
Headache, confusion, disorientation, lethargy, seizures, or focal neurological deficits
Unlike other encephalopathies, symptoms can wax and wane
Acute toxicity is transient, while chronic toxicity can result in permanent deficits
Also associated with myelosuppression, mucositis, lung disease, nephrotoxicity, and hepatotoxicity<br>
slide13. Discussion: Methotrexate-related leukoencephalopathy Radiographic findings:
CT: low attenuation in the white matter of both cerebral hemispheres (non-specific)
MRI T2 and FLAIR: transient diffuse high signal in the centrum semiovale, initially sparing subcortical U-fibers – can be unilateral, bilateral, or alternate between both over the course of the disease
MRI DWI and ADC: restricted diffusion across multiple vascular territories in the centrum semiovale<br>
slide14. Discussion: Methotrexate-related leukoencephalopathy Treatment
There is currently no standard treatment
Case reports suggest that aminophylline (non-selective adenosine receptor antagonist) may be beneficial
Dextromethorphan showed benefit in a retrospective study of 18 patients
Patient received dextromethorphan on 2/18 and the right-sided weakness improved
She was discharged the next day back to MDA<br>
slide15. Final Diagnosis Methotrexate-related leukoencephalopathy
MRI shows restricted diffusion across multiple vascular territories in the centrum semiovale https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us DWI ADC<br>
slide16. ACR appropriateness Criteria<br>
slide17. Cost of Imaging Average cost of:
CT brain: $1,200
CTA head: $6,200
MRI brain: $2,625
TOTAL: $10,025
https://www.newchoicehealth.com/procedures<br>
slide18. Take Home Points In patients who present with acute neurological deficits and history of receiving methotrexate, consider methotrexate-related leukoencephalopathy
Look for restricted diffusion in the centrum semiovale on MRI
Treat the patient with dextromethorphan or aminophylline<br>
slide19. References https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us
https://radiopaedia.org/articles/centrum-semiovale-1?lang=us
https://www.annalsofoncology.org/article/S0923-7534(19)41115-0/fulltext
https://www.uptodate.com/contents/therapeutic-use-and-toxicity-of-high-dose-methotrexate#H6
https://www.uptodate.com/contents/overview-of-neurologic-complications-of-conventional-non-platinum-cancer-chemotherapy?sectionName=METHOTREXATE&topicRef=1155&anchor=H2&source=see_link#H7
https://www.acr.org/Clinical-Resources/ACR-Appropriateness-Criteria
https://www.newchoicehealth.com/procedures
https://www.ncbi.nlm.nih.gov/books/NBK556114/<br>
slide20. Questions?<br>