Discussion
The use of intrathecal administration of methotrexate is an essential component in the chemotherapeutic treatment of acute lymphoblastic leukaemia [1, 2] to prevent and treat the affection of the central nervous system [2].
Renal toxicity is the most common and significant side effect of methotrexate; other side effects include: diarrhoea, mucositis, leukopaenia, hepatotoxicity, dry eyes, pleuritis, osteoporosis, and occasionally interstitial pneumonitis [3].
Acute leukoencephalopathy is observed in 5-18% of children undergoing this therapy [1, 4, 5], though some authors reported it as a rare manifestation, aseptic meningitis being the most frequent acute complication in this case [3].
Risk factors for this neurotoxic effect include: high dose treatment, intrathecal administration, young age, and associated cranial irradiation [1, 4, 5].
The pathophysiology of methotrexate-related neurotoxicity is unclear, but it is believed that it has a direct neurotoxic effect, generating cytotoxic oedema [2, 4]. Although this is seen on early MR as areas of altered signal intensity on DWI images [1, 2, 3, 4, 5], this acute cellular injury is not always irreversible [1, 3, 4, 5]. In patients undergoing cranial irradiation, this adverse effect may be more severe and irreversible [1]. Some authors reported fatal cases of methotrexate-induced neurotoxicity [2].
Clinical manifestations of acute neurotoxicity often include: seizure, transient ischaemic attack, encephalopathy, ataxia, myelopathy [4, 5] and stroke-like focal deficits [3]. Nausea, vomiting, headache, somnolence and mental confusion have also been reported [2].
On MR images these lesions are not confined to typical vascular territories and usually appear as focal areas of restricted diffusion on DWI, with high signal intensity on Flair and T2-weighted images [1, 2, 3, 4, 5] and no gadolinium enhancement [1]. Generally they affect periventricular white matter, more often both centrum semiovale [4, 5] and both corona radiata [1]. It can also compromise the splenium of corpus callosum [1], as in our case, and the cerebellum [2, 3]. Many authors suggest that imaging findings change with time, with restricted diffusion seen only in the acute and subacute stages, followed by gliosis and encephalomalacia in the chronic phase [1, 4, 5]. So is the case of our patient.
Different reports demonstrate that the use of MR, and especially DWI images, is a helpful tool in the detection of early methotrexate white matter injury.