Diffuse white matter lesions in a case of herpes simplex encephalitis.

Abstract

Sirs: Herpes simplex encephalitis (HSE) is a viral encephalitis whose symptoms, though treatable, can be severe. One of its early diagnostic hallmarks is bilateral, high signal intensity of the temporal gray matter depicted by magnetic resonance imaging (MRI). This MRI-detected gray matter lesion usually decreases in parallel with improvement in the clinical condition. We report a case in which diffuse white matter lesions developed after successful treatment of HSE. A 59-year-old man suffered a sudden convulsion of the right upper limb and lost consciousness. Upon admission to our hospital, coma and right hemiparesis were confirmed by neurological examination. Cerebrospinal fluid (CSF) study showed pleocytosis (45 cells/3 mm3) with lymphocyte dominance, a protein level of 44 mg/dl, and a glucose level of 91 mg/dl. Herpes simplex virus (HSV) DNA was detected in the CSF by polymerase chain reaction assay. Cranial MRI showed high-intensity lesions in both temporal lobes and the left corona radiata on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images (Fig. 1). The patient was diagnosed with HSE and was given acyclovir by intravenous injection for 10 days, but his neurological status did not improve. The patient then received a 7-day course of adenine arabinoside, and gradually regained consciousness. No other convulsive seizures were observed. Although the patient responded to treatment, he remained drowsy and totally aphasic. CSF obtained at 3 months after admission showed a normal cell count (4 cells/3 mm3) and slightly increased protein level (49 mg/dl); thus, treatment of the HSE was thought to be successful. Electroencephalography at 3 months after the onset of the disease showed almost normal wave activity with slightly nonparoxysmal slow waves. Follow-up MRI at this time, however, revealed diffuse white matter lesions (Fig. 2). The white matter lesions as well as the patient’s drowsiness and aphasia were still present at 7 months after diagnosis. There have been some reports of white matter involvement in association with HSE [1, 2, 5]. Takanashi et al. [5] reported HSE in an 11-year-old girl who showed diffuse white matter lesions upon MRI in the subacute stage. The lesions disappeared in the chronic stage, and the authors concluded that the white matter lesions represented edema due to infection. Koenig et al. [2] reported a patient with HSE who showed white matter lesions upon computed tomography after successful treatment with adenine arabinoside. Temporal lobe biopsy revealed cell-mediated demyelination without reactivation of the HSV infection. The white matter involvement in our case also appeared in the chronic phase of the disease without evidence of HSV reactivation. These findings suggest that the white matter involvement associated with HSE is a demyelination that occurs as an autoimmune response following viral infection. Some recent reports have shown a limited but marked cytotoxic T-lymphocyte response to HSV infection [4, 6]. There may be some relation between this cytotoxic T-lymphocyte response and the autoimmune reaction. More immunological investigations of LETTER TO THE EDITORS