Acute toxic encephalopathy

Case contributed by Kavitha Nair
Diagnosis probable


Recently diagnosed case of metastatic colorectal cancer and received one cycle of neoadjuvant chemotherapy (5-FU) five days ago, now presented to the emergency department with acute onset vertigo and bilateral lower limb weakness. CT brain without contrast was normal. Referred for urgent MRI brain without contrast due to renal impairment.

Patient Data

Age: 50 years
Gender: Male
  • Note: This case has been tagged as "legacy" as it no longer meets image preparation and/or other case publication guidelines.

from 5-FU


Axial MRI DWI image (b=1000) at initial presentation shows symmetric areas of increased signal in bilateral centrum semiovale, bilateral frontoparietal periventricular and deep white matter, as well as in the corpus callosum and bilateral middle cerebellar peduncles, with corresponding low signal on the ADC map suggestive of restricted diffusion. No abnormal FLAIR signal was noted in these areas. The abnormal areas are isointense to the white matter on T1W images and do not show any contrast enhancement in the post-contrast T1W images (not shown).

FU MRI after 15 days after...


FU MRI after 15 days after stopping the drug

Follow up MRI after 15 days of discontinuation of 5-FU shows near total resolution of the areas of diffusion restriction, with minimal facilitated diffusion seen in the splenium of the corpus callosum and bilateral centrum semiovale. This correlated with complete resolution of the patient's neurological symptoms.

Case Discussion

Acute toxic leukoencephalopathy is a term used to denote the damage to cerebral white matter caused by many agents, e.g., chemotherapeutic agents, environmental toxins, organ failure (liver/kidneys), etc. The chemotherapy drugs that are known to cause toxic encephalopathy include methotrexate, 5-FU and cyclosporine. Prompt recognition and appropriate management, including stopping the offending drug, can reverse the neurological manifestations in these patients before irreversible damage occurs.

The regions commonly affected are the periventricular and deep white matter of the frontal, parietal, or occipital lobes and the corpus callosum which typically show significant diffusion restriction, and increased T2-FLAIR signal, which is bilateral, confluent and symmetric.  

DWI plays a significant role, both during the acute episode and during follow-up, to demonstrate reversibility after therapy. 

Differential diagnosis:

  • posterior reversible encephalopathy syndrome (PRES): can also occur due to chemotherapeutic drugs, however there is more commonly a parieto-occipital distribution of lesions, which is mainly involving the cortex and the subcortical white matter, without diffusion restriction

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