1. Possible causes of acute neurological deterioration in children during treatment of haematological malignancies (especially, Acute Lymphoblastic Leukemia-ALL-) :
- cerebrovascular disease (arterial or venous thrombosis)
- CNS invasion by neoplastic cells
- CNS infection
- metabolic or electrolytic disturbances
- drug neurotoxicity
- Clinical findings in these patients are not sufficient specific to establish an accurate diagnosis. In addition, quite different treatment guidelines are used for each of these entities. In order of history, clinical, biological and imaging findings, neoplastic, infectious, metabolic and vascular diseases may be excluded.
- MRI has a crucial role because of its high sensitivity to detect brain parenchymal and vascular lesions. It may exclude neoplastic and infectious disease or a venothrombotic event. Based on MRI fndings, a suspected diagnosis of acute drug neurotoxicity can be confirmed.
2. Methotrexate (MTX) neurotoxicity
![](https://epos.myesr.org/posterimage/esr/ecr2006/736/media/3544?maxheight=300&maxwidth=300)
Fig.: MRI study performed during the acute onset of symptoms in acute methotrexate neurotoxicity.
- Although MTX is almost always used with other drugs, however MTX is assumed to play the main role in the developement of neurotoxic effects.
- High-dose methotrexate and intratecal methorexate have improved the prognosis for ALL and are effective in preventing recurrences of central nervous system, but they are frequently associated with neurotoxicity.
- Different possible explanations for its neurotoxicity have been proposed including demyelination, white matter necrosis, loss of oligodendroglia, axonal swelling, microcystic encephalomalacia, and atrophy relatively selective for the deep cerebral white matter.
- Chronic leukoencephalopathy: (10% of patients)
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- Hyperintense areas in the cerebral deep white matter on T2-weighted sequences without contrast enhancement in asymptomatic patients.
- It can be produced by many chemotherapeutic agents as well as of radiation therapy, and usually occur insidiously after several months
- Associated with mild cognitive deficits rather than focal neurological abnormalities.
- Acute neurotoxicity: (5-7% of patients).
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- Symptoms are usually found 7-10 days after intrathecal MTX administration.
- It causes a strokelike event including symptoms like seizures, affective disturbance or sudden onset of focal neurologic deficits as sided hemiparesis or aphasia.
- Bilateral hyperintensities in centrum semiovale of the posterior frontal and parietal white matter bilaterally in DWI, with normal T2-weighted images.
- Cytotoxic edema is the likely cause of her symptoms and the associated diagnostic imaging changes. It canbe related to late swelling of glial cells.
- Clinical symptoms usually are transient with complete recovery and should not necessarily prompt modification of potentially curative chemotherapeutic regimens.
- Radiological normalization is slower with increased signal in T2 images during several months, in the same areas where the prior diffusion-weighted study showed restricted diffusion.
3. Diffusion-weighted MR imaging (DWI)
- DWI detects restricted motion of protons in the intracellular space providing a differential diagnosis between vasogenic and cytotoxic edema.
- Restricted diffusion can be encountered in (reduced list version)
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- Ischemic infarction
- Acute demyelination
- Head trauma
- Brain abscess.
- Lesions with restricted diffusion show:
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- high signal intensity on DWI
- diminished signal intensity on ADC maps.
- DWI abnormalities are usually indicative of irreversible cytotoxic injury. However, some lesions identifiable on DWI and not associated with T2 abnormalities can resolve and disappear like patients with sustained seizure activity or patients with ischaemic stroke events who underwent satisfactory rapid thrombolytic therapy.
- Acute neurotoxicity associated with intrathecal MTX is another entity in which diffusion abnormalities are not necessarily associated with irreversible cell death.
![](https://epos.myesr.org/posterimage/esr/ecr2006/736/media/16690?maxheight=300&maxwidth=300)
Fig.
4. Differential diagnosis of bilateral parietal white matter lesion
- Acute methotrexate neurotoxicity, closely related to clinical history. MRI shows hyperintense lesions on DWI.
- Posterior reversible encephalopathy syndrome (PRES) related to acute hypertension but also with an increasing number of medical conditions including tacrolimus, cyclosporin-A. MRI shows hyperintensity on T2-weighted and FLAIR images. DWI showed isointensity and increased signal intensity on ADC values, indicating vasogenic edema.
- Acute ischaemic stroke of both posterior cerebral arteries, with hyperintense signal on DWI
- Chronic diffuse ischaemia of white matter, observed in elderly people
- Acute demyelination disease
- Progressive multifocal leukoencephalopathy, immunocompromised patients, AIDS.
![](https://epos.myesr.org/posterimage/esr/ecr2006/736/media/16501?maxheight=300&maxwidth=300)
Fig.: Progressive multifocal leukoencephalopathy in patient with AIDS. This lesions are characterized by increased diffusion showing Hyperintense on ADC, and hypointensities on DWI