01 December 2025 : Review article
A Review of the Role of Neuroimaging in Neurotoxicity Monitoring in Children with Acute Lymphoblastic Leukemia
Agata Rocka
ABEF 1*, Łucja Justyna Walczak ABCEF 2, Wiktoria Herbut BEF 3, Maria Leśniak BEF 4, Patrycja Majka BCEF 4, Justyna Lipniarska BEF 4, Monika Lejman ABCDEF 5, Joanna Zawitkowska ABCDEF 6, Magdalena Maria Woźniak ABCDEF 1
DOI: 10.12659/MSM.948914
Med Sci Monit 2025; 31:e948914
Table 1 Case reports including complications during methotrexate chemotherapy treatment of ALL in children.
| No. | Diagnosis | Age | Sex | Genetics | Treatment protocol | Neurological symptoms | Neuroimaging findings | Suspected drug | Rescue treatment |
|---|---|---|---|---|---|---|---|---|---|
| 1 | ALL []35 | 14y | M | NR | NOPHO-ALL-08 protocol | Altered mental status/encephalopathy | MRI: a small subdural hematoma | IT-MTX 240 mg (overdose) | Diazepam |
| Fosphenytoin | |||||||||
| Dexamethasone | |||||||||
| Meningeal signs/neuroinflammation | |||||||||
| Folinic acid | |||||||||
| Seizures | |||||||||
| Glucarpidase-IT | |||||||||
| 2 | ALL []35 | 14y | M | NR | Altered mental status/encephalopathy | No imaging | IT-MTX 240 mg (overdose) | Diazepam | |
| Fosphenytoin | |||||||||
| Dexamethasone | |||||||||
| Seizures | |||||||||
| Folinic acid | |||||||||
| Glucarpidase-IT | |||||||||
| 3 | B-ALL []36 | 7y | M | NR | Sensory hallucinations/visual disturbances | multifocal leukoencephalopathy with ischemia. diffuse vascular constriction of middle cerebral, posterior communicating, inferior cerebellar, and anterior cerebral arteries | IT-Cytarabine 70 mg | Citicoline | |
| LMWH | |||||||||
| Systemic symptoms | |||||||||
| Anti-thrombin III | |||||||||
| FFP | |||||||||
| Saline hydration | |||||||||
| 4 | T-ALL []37 | 7y | M | NR | COG-AALL0434 | Systemic symptoms | No imaging | IT-MTX 12 mg, vincristine | Observation |
| 5 | B-ALL []37 | 4 | M | NR | Systemic symptoms | No imaging | IT-MTX 12 mg | Observation | |
| 6 | B-ALL []37 | 4y | M | NR | NR | No imaging | IT-MTX 12 mg | Observation | |
| 7 | B-ALL []37 | 6y | F | NR | NR | No imaging | IT-MTX 12 mg | Observation | |
| 8 | ALL []38 | 12y | F | NR | NR | Seizures | widespread hyperintense subcortical LE in the frontal and parietal regions with areas of restricted diffusion consistent with leukoencephalopathy | IT-MTX | Benzodiazepine |
| Altered mental status/encephalopathy | Levetiracetam | ||||||||
| Focal neurological deficits | Dexamethasone | ||||||||
| 9 | B-ALL []39 | 17y | F | NR | COG-AALL1131 | Systemic symptoms | diffuse abnormal hyperintensities within the white matter of the frontal and parietal lobes bilaterally | IT-MTX | Aminophylline |
| Steroids | |||||||||
| Plasmapheresis | |||||||||
| Sensory hallucinations/visual disturbances | |||||||||
| Rituximab | |||||||||
| 10 | B-ALL []40 | 11y | M | CCCG-ALL-2015 | Seizures | increased densities associated with multiple hematomas in the left frontal, parietal, and temporal lobes and the centrum semiovale intracranial aneurysm | HD-MTX | Symptomatic treatment | |
| Altered mental status/encephalopathy | |||||||||
| ICH | |||||||||
| 11 | ALL []41 | 18y | F | NR | NR | Systematic symptoms | no lesions no lesions | IT-MTX | Dextromethorphan |
| Focal neurological deficits | |||||||||
| 12 | T-ALL []42 | 11y | M | NR | Language and motor speech disorders | ischemic lesion with edema, cytotoxicity, and diffusion restriction in the deep white matter in the region of the left precentral gyrus (which is part of Broca’s area) | IT-MTX | Heparin followed by aspirin | |
| Focal neurological deficits | |||||||||
| 13 | ALL []43 | 15y | F | NR | UK-ALL 2011 Regimen B | Focal neurological deficits | no lesions symmetric areas of restricted diffusion in the centrum semiovale bilaterally, low signal intensity abnormalities on ADC mapping with corresponding regions of hyperintensity | IT-MTX | Corticosteroids |
| Language and motor speech disorders | Antihistamines | ||||||||
| Altered mental status/encephalopathy | Physiotherapy | ||||||||
| 14 | B-ALL []49 | 7m | F | GenotypeC677T | CCCG-ALL-2015 | Systemic symptoms | no lesions failed | HD-MTX | Mannitol |
| Meningeal signs/neuroinflammation | Dexamethasone | ||||||||
| 15 | B-ALL []44 | 13y | F | EORTC 58081 | Focal neurological deficits | hyperintensity in dorsal (T9 and T10) posterior medullary columns | IT-MTX | Methylprednisolone | |
| Dextromethorphan | |||||||||
| Sensory disturbances/paresthesia | |||||||||
| HD vitamins | |||||||||
| 16 | B-ALL []45 | 15y | M | NR | NR | Seizures | no lesions | IT-MTX | Leucovorin |
| Altered mental status/encephalopathy | |||||||||
| Rehabilitation | |||||||||
| Sensory hallucinations/visual disturbances | |||||||||
| 17 | B-ALL []46 | 6y | F | NR | AALL1131 | Sensory disturbances/paresthesia | periventricular and subcortical white matter disease on fluid-attenuated inversion recovery imaging | IT-MTX | Dextromethorphan |
| Focal neurological deficits | |||||||||
| Dexamethasone | |||||||||
| Language and motor speech disorders | |||||||||
| 18 | ALL []47 | 18y | F | NR | NR | Seizures | hyperintensity of white matter of bilateral centrum semiovale and bilateral corona radiation, DWI and ADC sequence with no areas of restriction | IT-MTX | NR |
| 19 | ALL []87 | 11y | M | CCCG-ALL-2015 | Seizures | Multiple hematomas in the left frontal, parietal, and temporal lobes, and the centrum semiovale. | MTX | NR | |
| Systemic symptoms | |||||||||
| ALL – acute lymphocytic leukemia; B-ALL – B-cell acute lymphocytic leukemia; CCCG – Chinese Children’s Cancer Group; COG-AALL – Children’s Oncology Group AALL1331 study; CT – computed tomography; CTA – computed tomography angiography; DWI – diffusion-weighted MRI; EORTC – European Organisation for Research and Treatment of Cancer; F – female; FFP – fresh frozen plasma; FLAIR – fluid-attenuated inversion recovery (FLAIR); HD – high dose; ICH – intracranial hemorrhage; IT – intrathecal; IVIG – intravenous immunoglobulin G; LE – leukoencephalopathy; LMWH – low-molecular-weight heparin; M – male; MRI – magnetic resonance imaging; MRA – brain magnetic resonance angiography; MTX – methotrexate; m – months; NOPHO – Nordic Society of Paediatric Haematology and Oncology; NR – not reported; PEG – polyethylene glycol; PRES – posterior reversible encephalopathy syndrome; T-ALL – T-cell acute lymphocytic leukemia; UK-ALL – United Kingdom guidelines for ALL; y – years. |