"CHOICES": An acronym to aid in delineating potential causes of non-metabolic, non-infectious acute toxic leukoencephalopathy

Abstract

Purpose: To describe non-metabolic, non-infectious etiologies of acute toxic leukoencephalopathy (ATL) on DWI MRI, and provide a useful acronym to remember them.

Material and methods: Our PACS archive was reviewed, yielding 185 patients with suspected ATL per MRI reports and clinical follow up; infectious or metabolic causes were excluded.

Result/discussion: The 87 included non-infectious, non-metabolic ATL patients' etiologies are represented by the acronym 'CHOICES': chemotherapy ('C',n = 34); heroin-induced ('H',n = 6), opioid analogues ('O',n = 14); immunosuppressant ('I',n = 11) or imidazole (n = 2); cocaine ('C',n = 1); environmental or ethanol abuse ('E',n = 5), splenial lesions ('S',n = 9), and 'other' (n = 5).

Conclusion: The "CHOICES" acronym delineates various toxic etiologies of ATL.

Keywords: ADEM, Acute disseminated encephalomyelitis; AEDs, Anti-epileptic drugs; AHE, Acute Hepatic/Hyperammonemic Encephalopathy; AHL, Acute hemorrhagic leukoencephalitis; ATL, Acute toxic leukoencephalopathy; Acute toxic leukoencephalopathy; CO, Carbon monoxide; Diffusion-Weighted imaging; EPM, Extrapontine myelinolysis; EtOH, Ethanol; HIE, Hypoxic-ischemic encephalopathy; LE, leukoencephalopathy; MBD, Marchiafava-Bignami Disease; MERS, Mild encephalitis/encephalopathy with reversible splenial lesion; NAWM, Normal-appearing white matter; ODS, Osmotic demyelination syndrome; PML, Progressive multifocal leukoencephalopathy; PRES, Posterior reversible encephalopathy syndrome; PVWM, Periventricular white matter; Periventricular white matter; RIS, Radiology information system; RSL, Reversible splenial lesions.

Fig. 1

A 62 year old acutely encephalopathic female with acute toxic leukoencephalopathy (ATL), who had been administered fludarabine 3 weeks prior to imaging for treatment of multiple myeloma. She expired 19 days after MRI. 1A-C: there was bilateral, symmetric PVWM hyperintensity (arrows) on FLAIR (A), with reduced diffusion on DWI (B) and on ADC map (C).

Fig. 2

A 57 year old male with ATL on 5-Fluorouracil (5-FU) for esophageal cancer, who presented with altered mental status 5 days prior to MRI. 2A-C: The initial MRI showed reduced diffusion within the PVWM (arrows) on DWI (A) and ADC map (B); however, there was no evident abnormal signal on FLAIR (C). 2D-F: The MRI findings of ATL and symptoms nearly entirely resolved 19 days later on MRI, as shown on follow up DWI (D), ADC (E) and FLAIR (F) performed at that time.

Fig. 3

A 24 year old female was found unresponsive and quadriplegic from ATL after heroin inhalation (aka “chasing the dragon”). 3A-D: Reduced diffusion involves the PVWM relatively diffusely and symmetrically on DWI MRI (A) and ADC map (B), also with bilateral, symmetric periventricular hyperintensity on FLAIR (C), characteristic of ATL. Her paresis mostly resolved by 1 year, but there were residual PVWM abnormalities with severe cerebral atrophy on FLAIR (D).

Fig. 4

A 19 year old male with oral methadone overdose-related ATL presented with acute left sided weakness and upper motor neuron signs. 4A-C: The reduced diffusion bilaterally involves the PVWM (arrows) on DWI MRI (A) and ADC map (B), with bilateral symmetric periventricular hyperintensity on FLAIR (C). 4D-F: There is also reduced diffusion within the optic radiations on DWI MRI (D) and ADC map (E), also having abnormal signal on FLAIR (F).

Fig. 5

A 37 year old male with myelodysplastic syndrome underwent a normal-appearing baseline brain MRI prior to bone marrow transplantation (BMT), which was nearly normal on FLAIR (A), DWI (B) and ADC map (C). Nineteen days post-BMT, while the patient was on cyclosporine therapy (an immunosuppressant medication), regions of hyperintensity (arrows) from ATL developed within the bilateral posterior PVWM on FLAIR (D) and DWI (E); note mild, asymmetric reduced diffusion in the left posterior PVWM on the ADC map (F, arrow). The patient’s symptoms promptly resolved over several days after the cessation of cyclosporine.

Fig. 6

A 69 year old female with acutely altered mental status developed ATL after receiving high doses of metranidazole for over 2 months, prescribed for a recto-vaginal fistula. Her symptoms resolved after cessation of metronidazole. 6A-D: The reduced diffusion was symmetric and bilateral within the centrum semiovale (arrows) on DWI MRI (A) and ADC map (B), with hyperintensity on T2WI (C). Also, there was bilateral abnormal signal within the posterior limbs of the internal capsules (D, arrows) and midline callosal splenium (D, dotted arrow) on DWI. Notably, the dentate nuclei were normal in this patient (not shown); hence, this represents an atypical case of metronidazole toxicity causing ATL.

Fig. 7

A 44 year old male presented with an altered and decreased level of consciousness for 2–3 days following a reported large amount of “crack” cocaine inhalation, which caused ATL. An initial MRI demostrated bilateral, symmetric reduced diffusion throughout the PVWM (arrows) on DWI MRI (A) and ADC map (B), also with PVWM hyperintensity on FLAIR (C). Four months later, the areas of reduced diffusion within the PVWM evolved into predominantly “T2 shine-through” (i.e. bright on ADC), as shown on DWI MRI (D), ADC map (E), and FLAIR (F).

Fig. 8

A 33 year old male with ATL from carbon monoxide (CO) poisoning, in which the symptoms and imaging findings later improved, having severely elevated serum CO levels. 8A-B: an MRI demonstrates reduced diffusion in bilateral PVWM (arrows) on DWI (A) and ADC map (B), these abnormalities had mostly resolved 9 months later (arrows), as shown on DWI (C) and with mild resultant diffuse cerebral atrophy on FLAIR (D).

Fig. 9

A 37 year old male with alcohol abuse presented with visual changes, who was ultimately diagnosed with ATL from Marchiafava-Bignami disease. 9A-C: On the initial MRI, reduced diffusion is noted in the body (dotted arrows) and the splenium (arrows) of the corpus callosum on DWI MRI (A) and ADC map (B), while these same areas are hyperintense on FLAIR (C). On a follow up MRI 2 months later, subsequent focal atrophy was present within the callosal splenium (arrows), having elevated diffusion that appears dark on DWI (D) that is less visible on SWI (E); focal atrophy is also noted within the callosal body (dotted arrow) on sagittal FLAIR (F).

Fig. 10

A 20 year old male with ganglioglioma on anti-epileptic therapy for 5 years presented with confusion, eventually being diagnosed with RSL-ATL. 10A-C: There is reduced diffusion within the callosal splenium (arrows) on DWI (A) and ADC map (B), with hyperintensity on FLAIR (C). 10C-D: The lesions resolved after 3 months, as on DWI (D), ADC (E) and FLAIR (F) sequences.

Fig. 11

A 57 year old male with a Na⁺ level of 115mEq/L, corrected over 1-2days, with osmotic demyelination syndrome affecting the PVWM and basal ganglia. Mildly reduced diffusion is noted within the PVWM bilaterally (arrows) on DWI (A) and the ADC map (B), with basal ganglial hyperintensities also present on FLAIR (arrows, C), but sparing the pons on FLAIR (D). Hence, as the basal ganglia are additionally involved, this is not characteristic of ATL.

Fig. 12

A 53 year old male with chronic hepatic failure presented with acute confusion from acute hepatic/hyperammonemic encephalopathy (AHE). The patient had an elevated serum level of NH₄⁺ 101 ug/dl (normal: <20-40 ug/dl). 12A-D: bilateral symmetric PVWM involvement of the centrum semiovale is present on DWI (A) and FLAIR (B), also with involvement of the thalami (D arrows); involvement of the internal capsules’ posterior limbs (D dotted arrows) is noted on the ADC map (C) and FLAIR (D), being characteristic of AHE.

Fig. 13

A 38 year old female with acute pulmonary and cardiac failure and arrest causing hypoxic-ischemic encpehalopathy (HIE). 13A-C: an MRI the day after the insult shows gyriform reduced diffusion (arrows) on DWI (A), ADC map (B) and hyperintensities on FLAIR (C) within the parietal cortices bilaterally. 13D-F: Six days later, in the subacute phase, the reduced diffusion is symmetric and bilateral within the centrum semiovale of the PVWM on DWI (D) and ADC map (E), with slight hyperintensities on FLAIR (F), consistent with delayed PVWM anoxic injury from HIE, which could mimic ATL if the initial MRI was not obtained. However, ATL usually lacks the mild cortical hyperintensity as noted here (arrows, 13C).

Fig. 14

A 5 year old male with ADEM. Multifocal and asymmetric hyperintensities on FLAIR (A) have only very minimal reduced (and mostly elevated) diffusion (arrows) on DWI (B) and ADC map (C), and multifocal enhancement (arrows) on post-contrast T1WI (D). After 6 weeks, the hyperintensities have mostly regressed on FLAIR (E), and there is resolution of enhancement on postcontrast T1-WI (F). The multifocal contrast enhancement is not typical for ATL.

Fig. 15

A 62 year old immunocompromised male, with PML, has “T2-shine through” (i.e. highly elevated diffusion) on DWI (A) and elevated diffusivity on ADC map (B); typically asymmetric lesions of PML are also seen (arrows) on FLAIR (C). Such multifocal lesions usually have an incomplete rim of enhancement (arrows) on postcontrast T1WI, suggestive for PML-IRIS (D).

Fig. 16

A 37 year old female with acute confusion was diagnosed with AHL, having histopathologic confirmation. Reduced diffusion is noted within the cortex unilaterally on DWI (A) and ADC map (B), with accompanying hyperintensity on FLAIR (C) and mild cortical enhancement on postcontrast T1WI (D). The unilaterality, asymmetry, mild enhancement, and mass effect are not typical of ATL, as well as the lack of PVWM reduced diffusion. Although no hemorrhage was noted on T2WI, diffuse microhemorrhages were confirmed on histopathology.