Acute toxic leukoencephalopathy

Etiologies, imaging findings, and outcomes in 101 patients

Can Ozutemiz, S. K. Roshan, N. J. Kroll, J. C. Benson, Jeffrey B Rykken, M. C. Oswood, Lei Zhang, Alexander M McKinney

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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. 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.

Original languageEnglish (US)
Pages (from-to)267-275
Number of pages9
JournalAmerican Journal of Neuroradiology
Volume40
Issue number2
DOIs
StatePublished - Feb 1 2019

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Leukoencephalopathies
Poisons
Opiate Alkaloids
Immunosuppressive Agents
Uremia
Drug Therapy
Myelin Basic Protein
Hepatic Encephalopathy
Blood Urea Nitrogen
Metronidazole
Carbon Monoxide
Coma

PubMed: MeSH publication types

  • Journal Article

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Acute toxic leukoencephalopathy : Etiologies, imaging findings, and outcomes in 101 patients. / Ozutemiz, Can; Roshan, S. K.; Kroll, N. J.; Benson, J. C.; Rykken, Jeffrey B; Oswood, M. C.; Zhang, Lei; McKinney, Alexander M.

In: American Journal of Neuroradiology, Vol. 40, No. 2, 01.02.2019, p. 267-275.

Research output: Contribution to journalArticle

Ozutemiz, Can ; Roshan, S. K. ; Kroll, N. J. ; Benson, J. C. ; Rykken, Jeffrey B ; Oswood, M. C. ; Zhang, Lei ; McKinney, Alexander M. / Acute toxic leukoencephalopathy : Etiologies, imaging findings, and outcomes in 101 patients. In: American Journal of Neuroradiology. 2019 ; Vol. 40, No. 2. pp. 267-275.
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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. 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.",
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AU - Ozutemiz, Can

AU - Roshan, S. K.

AU - Kroll, N. J.

AU - Benson, J. C.

AU - Rykken, Jeffrey B

AU - Oswood, M. C.

AU - Zhang, Lei

AU - McKinney, Alexander M

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N2 - 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. 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.

AB - 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. 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.

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