Case report: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion: an autopsy case

Abstract

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion is a clinicoradiological syndrome characterized by transient neuropsychiatric symptoms and hyperintensity of the splenium of the corpus callosum on diffusion-weighted MRI. Although intramyelinic edema and inflammatory cell infiltration can be predicted by MRI, the pathology of the splenium of the corpus callosum remains unknown. We encountered a case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion and hypoglycemia in a patient who died of sepsis, and an autopsy was performed. The postmortem pathological findings included intramyelinic edema, myelin pallor, loss of fibrous astrocytes, microglial reactions, and minimal lymphocytic infiltration in the parenchyma. Based on these findings, transient demyelination following cytotoxic edema in the splenium of corpus callosum was strongly considered a pathogenesis of "clinically mild encephalitis/encephalopathy with a reversible splenial lesion" associated with hypoglycemia, and it could be generalized for the disease associated with the other causes. As cytotoxic edema could be the central pathology of the disease, the recently proposed term cytotoxic lesions of the corpus callosum may be applicable to this syndrome.

Keywords: autopsy: MRI; clinically mild encephalitis/encephalopathy with reversible splenial lesions; corpus callosum splenium; cytotoxic edema; hypoglycemia.

Figure 1

Diffusion-weighted brain MRIs (DWI). On day 2 of admission, hyperintensity was noted in the bilateral deep white matter and the corpus callosum splenium (A,D). On days 3 (B,E) and 6 (C,F), the hyperintensities were attenuated gradually.

Figure 2

Apparent diffusion coefficient maps brain MRI on day 2 of admission. Hypointensity was in the bilateral deep white matter (A) and the corpus callosum (B). This hypointensity was consistent with DWI hypointensity areas.

Figure 3

Pathology of the corpus callosum splenium. Pathological changes in the area of myelin pallor (A,C,E,G,I,K) are compared to those in the unaffected area of myelin unpallor (B,D,F,H,J,L) in corpus callosum splenium. Klüver-Barrera stain (A,B). Myelin is much paler (A) than that in the unaffected area (B). H&E stain (C,D). Intramyelinic edema is noticed (C). Immunoperoxidase for neurofilaments (E,F). Axons with phosphorylation are clearly visible (E,F). Immunoperoxidase for HLA-DR (G,H). Microglia increase in number and size (G). Immunoperoxidase for glial fibrillary acidic protein (GFAP) (I,J). Fibrous astrocytes decrease in number (I). Immunoperoxidase for CD8 (K,L). CD8-positive lymphocytes are infiltrated (K).

Figure 4

Pathology of the deep white matter. H & E stain (A). Vacuolization is marked. Klüver-Barrera stain (B). Myelin is pale. Immunoperoxidase for HLA-DR (C). Microglia increase in number and size. Immunoperoxidase for GFAP (D). Astrocytes decrease in number.