Delayed posthypoxic leukoencephalopathy: a case series and review of the literature

Abstract

Background: Delayed posthypoxic leukoencephalopathy (DPHL) is a rare and underrecognized entity where patients manifest a neurological relapse after initial recovery from an acute hypoxic episode. We sought to describe the magnetic resonance imaging (MRI) findings in a group of patients with DPHL and review the available literature.

Methods: Retrospective case series including patients who presented with neurological and/or psychiatric symptoms after recovery from an acute hypoxic episode. The history and clinical presentation were reviewed from the electronic medical records. MRI scans were evaluated from the picture archiving and communication system. We performed a comprehensive review of the English medical literature for prior published cases of DPHL and describe the key imaging findings that have been reported related to this condition.

Results: A total of five patients were identified, including four patients with respiratory failure due to drug overdoses from benzodiazepines, opioids, and/or barbiturates, and one patient who presented after cardiopulmonary arrest due to pulmonary embolism. All patients showed diffuse, extensive, and confluent white matter signal abnormalities including prominent restricted diffusion, extending to the subcortical white matter and respecting the U-fibers. There was no gyral edema or contrast enhancement. In one case histopathology was available, which highlighted patchy subcortical myelin loss with sparing of U-fibers and demonstrated prominent macrophage/microglial inflammation with extensive axonal damage. Of the other four patients, two were at their neurological baselines and two had persistent neurological deficits at the time of discharge.

Conclusions: The described constellation of MRI findings is highly suggestive of DPHL in the appropriate clinical setting.

Keywords: Hypoxia; MRI; leukoencephalopathy; myelin; white matter.

Figure 1

65-year-old male presenting after an acute hypoxic episode secondary to opioid and benzodiazepine overdose (case 4). Baseline MRI (A through D) demonstrate a few nonspecific subcortical T2 and FLAIR white matter hyperintensities (A and B) without restricted diffusion (C and D) probably representing chronic small vessel ischemic changes in a patient of this age. MRI after neurological relapse (E through H) shows diffuse confluent white matter abnormalities in the centrum semiovale involving the subcortical white matter. There is corresponding signal hyperintensity on DWI (G) with somewhat less extensive hypointensity on the calculated ADC maps (H), indicating some degree of T2-shine through superimposed on cytotoxic edema. FLAIR: TR = 9000, TE = 126, and IR = 2490; DWI: TR = 9000, TE = 98, number of excitations = 2, matrix = 192 × 192; field of view, 23 × 23 cm to 24 × 24 cm, slice thickness = 4 mm, and gap 4.

Figure 2

Cropped and digitally magnified region from Fig.1E demonstrates that the white matter signal abnormality (asterisk) involves the subcortical white matter but spares the U-fibers which appear as a curvilinear dark band (arrowhead). The adjacent gray matter is also visualized (arrow).

Figure 3

MRI and histologic sections from a 59-year-old female who developed DPHL after being found unresponsive in the setting of opioid overdose. Axial T2-weighted image demonstrates more patchy white matter lesions compared to the case in Fig1, with corresponding low apparent diffusion coefficient (B) indicating restricted diffusion. T2: TR = 2683 and TE = 103; DWI: TR = 10,000, TE = 80, number of excitations = 2, matrix = 128 × 128, field of view, 24 × 24 cm, slice thickness = 5 mm, and gap 5 mm. (C) Abundant reactive astroglia characterized by brightly eosinophilic cytoplasm and enlarged nuclei are numerous in subcortical white matter. The mildly vacuolated background neuropil demonstrates ubiquitous eosinophilic ‘blebs’ which impart a rough or stippled character. Occasional macrophages are appreciated, for example, at 9 o’clock position. Hematoxylin and eosin, original magnification 200×. (D) The subcortical u-fibers at the gray white junction exhibit normal myelin, but white matter beneath these shows marked patchy pallor. Hematoxylin and eosin with luxol fast blue, original magnification 20×. (E) CD68 stain highlights lysosome-enriched cells, microglia and macrophages, abundant in the neuropil. Immunohistochemistry for CD68, original magnification 100×. (F) Neurofilament stain highlights frequent axonal swelling, indicative of damage, in white matter. Immunohistochemistry for SM31, original magnification 200×.