In patients with global hypoxic-ischemic injury caused by cerebral hypoperfusion in the event of cardiac arrest, drowning, or asphyxiation, injury patterns are highly variable depending on brain maturity, severity, and length of cerebral hypoperfusion [7]. Mild-to-moderate cerebral hypoperfusion might cause watershed zone infarcts, and severe cerebral hypoperfusion might damage gray matter structures including the basal ganglia, thalami, cortex, cerebellum, and hippocampi. Typical for global hypoxic-ischemic injury is increased signal intensity on DWI in cerebellar hemispheres, basal ganglia, and cerebral cortex. In ischemic stroke and global hypoxic-ischemic injury, changes on DWI can be detected very early, sometimes several minutes after arterial occlusion or cerebral hypoperfusion and is primarily due to cytotoxic edema. DWI and ADC abnormalities may pseudonormalize by the end of the first week [8]. ADC pseudonormalization is a normal phase encountered in the subacute stage of ischemic stroke and represents an apparent return to normal healthy brain values on ADC maps, and does not represent true resolution of ischemic damage.
Changes on T2-weighted sequences are usually visible after a few hours in patients with hypoxic brain damage or ischemic stroke. Hyperintensities on FLAIR images can be used to identify acute ischemic strokes at 3 hours or less [9]. In the case of an acute ischemic stroke, hyperintensities intensify in the first 24 hours and are therefore still visible days after the event until scarring or the breakdown of the damaged tissue.
Since in our case the first MRI imaging was done on day 10 after the index event, DWI and ADC changes might not have been captured on MR images. However, hypoattenuation suggestive of ischemic changes were not detected on 24-hour follow-up NCCT. In addition, following acute ischemic stroke or manifest hypoxic brain damage, FLAIR hyperintensities should have already been visible on first MRI imaging on day 10 and not developed later to be visible on MR imaging on day 23.
Other disorders or imaging changes that may resemble DPHL, such as posterior reversible encephalopathy syndrome (PRES), progressive multifocal leukoencephalopathy (PML), or DWI and FLAIR hyperintensities associated with status epilepticus, should be ruled out. In PRES patchy T2/FLAIR hyperintensities sparing the cortex and usually located in parieto-occipital lobes and posterior cortical watershed zones can be observed most often [10]. Atypical PRES as a variant may include the frontal lobes [11]. However, our patient did not have any hypertensive phases and did not show any kind of intracranial hemorrhage on imaging, as it would be observed most often in patients with PRES.
PML is caused by a subacute opportunistic infection caused by DNA virus John Cunningham polyomavirus (JCV) [12]. On T2-weighted images, PML can typically induce hyperintensities, which are predominantly seen in subcortical and periventricular white matter, often involving subcortical U-fibers leading to a scalloped appearance [13]. Since our patient was undergoing treatment for AML, associated PML could have been the trigger of the FLAIR hyperintensities. However, the U-fibers were spared in our patient. In addition, the anatomical distribution of FLAIR hyperintensities is limited to the area downstream of the left internal carotid artery, which in turn makes DPHL more likely and isolated PML in this area less likely.
In status epilepticus, T2/FLAIR hyperintensities of the gray matter and/or subcortical white matter with or without mild mass effect may be observed, and are usually accompanied by acutely restricted diffusion. In some cases, it might be difficult to differentiate clinical symptoms and imaging changes of status epilepticus and ischemic stroke [14]. In our case, clinical course, imaging appearance, and EEG patter of the patient did not match theses differential diagnoses.
Metabolic or toxic disorders, for example, as a neurotoxic side effect of arsenic trioxide and all-trans-retinoic acid, that is, the patients’ chemotherapy for AML, would, if any, have caused more global, symmetrical changes on MR imaging, which is why they are not discussed further in this manuscript, although we have investigated them in clinical care of the patient.
Our publication has some limitations. On the one hand, the first MRI was performed on day 10, which means that no baseline MRI was performed before or 24 hours after acute ischemic stroke therapy. Performing CT initially and on 24-hour follow-up imaging is worldwide standard practice in the diagnostic workup of an acute ischemic stroke; however, as a result, possible early changes on DWI are beyond our knowledge.
Since this is an individual case, our findings cannot be directly transferred or reproduced, and are dependent on colleagues, in particular neurologists and (neuro-)radiologists, to confirm our observations. For this purpose, different distribution patterns and clinical manifestations might be documented according to the affected vascular territories. Therefore, this topic might not be referred to as unilateral DPHL, but territorial DPHL in the future.
