An Explanation for Putaminal CT, MR, and Diffusion Abnormalities Secondary to Nonketotic Hyperglycemia

Wintermark et al (1) recently reported findings of high signal intensity on T1-weighted MR images and faint hyperattenuation of involved putamen on CT scans one month later. In addition, the putamen appeared hyperintense on the exponential diffusion-weighted (DW) images. The authors tried to propose an explanation by assuming that protein desiccation occurring in the course of Wallerian degeneration could explain the CT hyperattenuation and the MR imaging and DW imaging patterns in the early phase. I think this explanation is inadequate.

First, I had previously reported 10 cases of hemichorea-hemiballism with similar CT and MR imaging findings and collected 13 more cases to date (2). A key finding in my article was that there was a mismatch between the size of lesions detected on CT scans and on T1-weighted MR images, and also a mismatch between their evolutions over time. It appeared that the lesions on CT and on T1-weighted MR images resulted from two different pathophysiological mechanisms running in parallel. It is not appropriate to make an attempt to give one explanation for two pathologic processes, although they may be triggered by the same event.

Second, it is now clear that the high signal intensity lesions on T1-weighted MR images are related to manganese accumulation in the reactive astrocytes after ischemia. In their article published in 1999, Fujioka et al (3) reproduced the MR imaging finding in rats 7 days after 15-minute occlusion of the middle cerebral artery but not after 60-minute occlusion. Histologic examination revealed that this specific ischemic change disclosed by MR imaging corresponded to selective neuronal death and gliosis, with preservation of the macroscopic structure of the brain, a finding similar to what I reported after histologic analysis of a biopsy specimen obtained from my patient. We both agreed that the MR imaging finding resulted from a progressive pathologic reaction in an incomplete infarction, which confirmed my hypothesis proposed in the 1998 article; that is, the MR imaging finding was related more to vascular compromise than to petechial hemorrhage or hyperglycemia (4). In their latest paper, Fujioka et al demonstrated a similar time course of the appearance of high signal intensity on T1-weighted MR images and the accumulation of tissue manganese accompanied by Mn-superoxide dismutase and glutamine synthetase induction in reactive astrocytes (3).

Third, the restricted diffusion on the DW images reported by Wintermark et al provided additional evidence that ischemia did occur early in the disease course. It is not required to discard such a good explanation for the purpose of keeping one explanation for both findings.

Fourth, while the mechanism responsible for the hyperattenuation on CT scans remains inconclusive, protein desiccation during Wallerian degeneration appears not to be the best explanation. Protein breakdown usually occurs from 4 to 14 weeks after injury, whereas the hyperintense lesions on CT scans in many of these patients occur early in the disease course. To the best of my knowledge, manganese deposition in the brain is not associated with hyperattenuation on CT scans. Microbleeds or “reversible calcium deposition or influx” remains a possible explanation.