Answer of March 2016

 

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Clinical History:


A 15 year old child with history of acute lymphoblastic leukemia on chemotherapy presenting with acute lower limb weakness.


Plain CT Brain

Plain CT Brain


MRI Brain T1W  MRI Brain T2W

MRI Brain T1W                                                    MRI Brain T2W


MRI Brain DWI  MRI Brain ADC map

MRI Brain DWI                                                    MRI Brain ADC map


MRA  MRI Brain FLAIR

MRA                                                                  MRI Brain FLAIR



 

Diagnosis


Methotrexate induced neurotoxicity


Discussion


The incidence of acute CNS neurotoxicity associated with therapy for acute lymphoblastic leukemia is 5-18%. Methotrexate is often the major cause of acute neurotoxicity. 


The clinical presentation and the type of neurotoxicity depend on the route and dose of methotrexate. They can present with aseptic meningitis and transverse myelopathy when methotraxate is given intrathecally. Or they can present with acute and chronic encephalopathy as well as stroke-like syndrome with either intravenous and intrathecal methotraxate. Risk facts include high-dose treatment, intrathecal treatment, young age and associated cranial irradiation. In particular stroke-like syndrome usually has onset between 3-10days after administration. 


The pathophysiology is unclear. Mechanisms include increased adenosine accumulation, homocysteine elevation and its excitatory effects on the NMDA receptor and alterations of biopterin metabolism. 


On MRI, features include T2/FLAIR hyperintensities in the periventricular white matter particularly in the centrum semiovale. Restricted diffusion is present when the disease is detected early. These changes reflect cytotoxic edema. 


Treatment includes aminophylline, an adenosine antagonist and dextromethorphan an antagonist of NMDA. 

Patients often recover spontaneously from neurotoxic events. 


In our patient the changes were vaguely seen on CT scan at the left centrum semiovale which were FLAIR/T2 hyperintense on MRI where as the lesion at right centrum semiovale was only seen on DWI in the MRI. MRA was normal. The patient was given aminophylline and had neurological recovery.