Acute Toxic Leukoencephalopathy: Etiologies, Imaging Findings, and Outcomes in 101 Patients

Fellows’ Journal Club

Of 101 included patients, the 4 subgroups of >6 were the following: chemotherapy (n = 35), opiates (n = 19), acute hepatic encephalopathy (n = 14), and immunosuppressants (n = 11). Other causes (n = 22 total) notably included carbon monoxide (n = 3) metronidazole (n = 2), and uremia (n = 1). Acute hepatic/hyperammonemic encephalopathy clinically resolved in 36%, with severe outcomes in 23% (coma or death, 9/16 deaths from fludarabine). Notable laboratory results were elevated CSF myelin basic protein levels in 8/9 patients and serum blood urea nitrogen levels in 24/91. Acute toxic leukoencephalopathy is an imaging appearance that can arise from various etiologies, with potentially reversible reduced diffusion predominately affecting the periventricular WM. Given the shared DWI appearance among this heterogeneous array of etiologies, their outcomes may differ. Thus, the neurologic symptoms completely resolved in 36%, while severe outcomes occurred in 23%. The clinical outcome was most severe with chemotherapy-related ATL.

Abstract

BACKGROUND AND PURPOSE

Prior studies regarding acute toxic leukoencephalopathy (ATL) are either small, or preliminary. Our aim was to evaluate etiologies of and differences in imaging severity and outcomes among various etiologies of ATL.

Example of grade 1 DWI-FLAIR ATL severity. A 16-year-old girl with acute leukemia after 5 days of high-dose cytarabine and clofarabine combined chemotherapy, presented with acute right upper extremity weakness. An initial head CT (not shown) was unremarkable. On DWI (A) and ADC (B), unilateral diffusion reduction was present in the left PVWM with 60% ADC loss compared with NAWM and corresponding faint FLAIR hyperintensity (C). Accompanying MRA study (not shown) was normal. D, On follow-up MR imaging at 2 weeks after withdrawal of the chemotherapy, there was normalization of diffusion reduction with faint residual hyperintensity on DWI (not shown), ADC map (D, black arrow), and FLAIR (not shown), with a resultant T2-shinethrough effect on DWI. The symptoms had resolved at long-term clinical follow-up with both the ATLOS and mRS clinical scores being 0.
Example of grade 1 DWI-FLAIR ATL severity. A 16-year-old girl with acute leukemia after 5 days of high-dose cytarabine and clofarabine combined chemotherapy, presented with acute right upper extremity weakness. An initial head CT (not shown) was unremarkable. On DWI (A) and ADC (B), unilateral diffusion reduction was present in the left PVWM with 60% ADC loss compared with NAWM and corresponding faint FLAIR hyperintensity (C). Accompanying MRA study (not shown) was normal. D, On follow-up MR imaging at 2 weeks after withdrawal of the chemotherapy, there was normalization of diffusion reduction with faint residual hyperintensity on DWI (not shown), ADC map (D, black arrow), and FLAIR (not shown), with a resultant T2-shinethrough effect on DWI. The symptoms had resolved at long-term clinical follow-up with both the ATLOS and mRS clinical scores being 0.

MATERIALS AND METHODS

MRIs of patients with suspected ATL over 15 years were retrospectively reviewed; inclusion criteria were: MRI <3 weeks of presentation with both DWI and FLAIR. These were jointly graded by two neuroradiologists via a previously described score of severity. Clinical outcome was evaluated via both modified Rankin (mRS) and ATL outcome (ATLOS) scores, each being correlated with the DWI and FLAIR scores. Etiologic subgroups of n > 6 patients were statistically compared.

RESULTS

Of 101 included patients, the 4 subgroups of n > 6 were the following: chemotherapy (n = 35), opiates (n = 19), acute hepatic encephalopathy (n = 14), and immunosuppressants (n = 11). Other causes (n = 22 total) notably included carbon monoxide (n = 3) metronidazole (n = 2), and uremia (n = 1). The mean DWI/FLAIR severity scores were 2.6/2.3, 3.3/3.3, 2.1/2.1 and 2.0/2.5 for chemotherapeutics, opiates, AHE and immunosuppressants, respectively, with significant differences in both imaging severity and outcome (P = .003–.032) among subgroups, particularly immunosuppressant versus chemotherapy-related ATL and immunosuppressants versus opiates (P = .004–.032) related ATL. DWI and FLAIR severity weakly correlated with outcome (ρ = 0.289–.349, P < .005) but correlated stronger in the chemotherapy (ρ = 0.460–.586, P < .010) and opiate (ρ =.472–.608, P < .05) subgroups, which had the worst outcomes. ATL clinically resolved in 36%, with severe outcomes in 23% (coma or death, 9/16 deaths from fludarabine). Notable laboratory results were elevated CSF myelin basic protein levels in 8/9 patients and serum blood urea nitrogen levels in 24/91.

CONCLUSIONS

Clinical outcomes of ATL vary on the basis of etiology, being worse in chemotherapeutic- and opiate-related ATL. Uremia may be a predisposing or exacerbating factor.

Read this article: http://bit.ly/2HTfZ24

Acute Toxic Leukoencephalopathy: Etiologies, Imaging Findings, and Outcomes in 101 Patients
Tags:
Jeffrey Ross
Fatal error: Uncaught Error: Call to undefined function get_cimyFieldValue() in /home2/ajnrblog/public_html/wp-content/themes/ample-child/author-bio.php:13 Stack trace: #0 /home2/ajnrblog/public_html/wp-content/themes/ample-child/content-single.php(35): include() #1 /home2/ajnrblog/public_html/wp-includes/template.php(812): require('/home2/ajnrblog...') #2 /home2/ajnrblog/public_html/wp-includes/template.php(745): load_template('/home2/ajnrblog...', false, Array) #3 /home2/ajnrblog/public_html/wp-includes/general-template.php(206): locate_template(Array, true, false, Array) #4 /home2/ajnrblog/public_html/wp-content/themes/ample/single.php(21): get_template_part('content', 'single') #5 /home2/ajnrblog/public_html/wp-includes/template-loader.php(106): include('/home2/ajnrblog...') #6 /home2/ajnrblog/public_html/wp-blog-header.php(19): require_once('/home2/ajnrblog...') #7 /home2/ajnrblog/public_html/index.php(17): require('/home2/ajnrblog...') #8 {main} thrown in /home2/ajnrblog/public_html/wp-content/themes/ample-child/author-bio.php on line 13