CLINICAL REPORT MRI Deterioration in Herpes Simplex Encephalitis Despite Clinical Recovery Sofia Markoula, MD,* Sotirios Giannopoulos, MD,* Sigliti-Henrietta Pelidou, MD,* Maria Argyropoulou, MD,† Georgios Lagos, MD,* and Athanassios P. Kyritsis, MD* Objectives: Herpes simplex virus type 1 is a sporadic cause of viral encephalitis. Relapse of encephalitis occurs in up to 10% of patients, manifested by recurrent symptoms, clinical and MRI findings, and the presence of herpes simplex virus type 1 DNA in the cerebrospinal fluid (CSF). Methods: We describe the clinical features, MRI findings and outcome in 2 patients with herpes simplex encephalitis during the acute phase and 6 months after the onset of encephalitis. Results: Both patients had a good response to treatment and an excellent recovery. Despite clinical recovery, in a 6-month follow-up MRI lesions consistent with recurrence were disclosed, without any clinical findings or CSF abnormalities. Conclusions: The mechanism underlying this MRI deterioration is un- clear and an immune-mediated mechanism may be involved. Thus, MRI deterioration after herpes simplex encephalitis should be interpreted with caution and it does not always represent a relapse, especially when the imaging studies do not correlate with the clinical and CSF findings. Key Words: herpes simplex encephalitis, RI findings, outcome, immune-mediated mechanism (The Neurologist 2009;15: 223–226) H erpes simplex virus (HSV) type 1 is a sporadic cause of viral encephalitis. Magnetic resonance imaging (MRI) is a useful tool for the detection of the morphologic abnormalities in HSE, 1 revealing gray and white matter lesions at an early stage of the infection when computed tomography (CT) is typically unable to detect them. 2 When antiviral therapy is initiated in the early stages of the infection, the prognosis is favorable compared with late stages. Neurologic sequelae may be present in many treated patients and mortality is much higher in untreated patients. Recurrent enceph- alitis may occur in up to 10% of patients, most frequently in infants and children in a period frame from 2 months to many years. 3–5 In relapsing cases, there is clinical deterioration, neuropsychological deficits, expan- sion of the lesions in MRI, 6,7 and presence of viral replication or reactivation in the cerebrospinal fluid (CSF) proven by polymerase chain reaction (PCR) for HSV-1 DNA. In some cases, as the cases reported in this study, MRI may reveal chronic progressive nonvirus- mediated changes despite clinical recovery. CASE REPORTS We retrospectively studied 2 patients, a 46-year-old female and a 52-year-old male, who were hospitalized in the Neurology department with the diagnosis of herpes simplex encephalitis (HSE). Symptoms at onset, neurologic findings, treatment, imaging find- ings, and outcome at discharge were recorded. The female patient presented with headache, fever, general- ized seizures, and left hemiparesis. CT scan of the brain in the acute phase was normal. Brain MRI revealed high intensity abnormalities on T2-weighted images in the right temporal lobe and right insular cortex (Fig. 1A). The T1-weighted images, after administration of contrast, showed gyriform enhancement in the right temporal lobe and right insula (Fig. 1B). CSF examination showed a mononuclear cell pleocytosis (40 cells/mm 3 ) with mildly elevated protein con- centration (78 mg/dL) and normal glucose. Electroencephalogram demonstrated high voltage slow waves activity in the right temporal lobe. The diagnosis of HSE was confirmed by PCR for HSV-1 DNA in the CSF. Therapy with intravenous acyclovir was initiated at a daily dosage of 30 mg/kg for 10 days. She was discharged 12 days after admission, while asymptomatic, and with normal neurologic findings. A follow-up MRI and visit were scheduled after a period of 6 months for re-evaluation. Although the patient was asymptomatic, the T2-weighted scans revealed an increase of high intensity lesions in the insula and periventricular white matter adjacent to the horns of the lateral ventricle (Fig. 1C). The irregular contrast enhance- ment, although decreased, was still present in the right temporal lobe on the postcontrast T1-weighted scans, which showed no remarkable atrophy (Fig. 1D). Patient was hospitalized for 1 day, and a new lumbar puncture revealed normal cell count, mildly elevated protein, and normal glucose. PCR for presence of HSV-1 DNA was negative. The male patient presented with fever, headache, nausea, focal seizures, and minor alteration of consciousness. CT scan of the brain in the acute phase showed hypointense areas with slight enhancement after contrast administration in the right temporal lobe. Brain MRI, on T2-weighted images, showed high intensity lesions on the right temporal lobe, right insular cortex, and cingulate gyrus (Figs. 2A, B), with irregular contrast enhancement on postcontrast images (Fig. 2C). CSF examination showed a mononuclear cell pleocytosis (55 cells/mm 3 ) with protein concentration of 90 mg/dL and normal glucose. Electroencephalogram demonstrated high volt- age slow waves activity in the right temporal lobe. The diagnosis of HSE was confirmed by PCR for HSV-1 DNA in the CSF of the patient. Therapy with intravenous acyclovir was initiated at a daily dosage of 30 mg/kg for 10 days, and the patient was discharged asymptomatic with excellent clinical recovery. From the Departments of *Neurology and †Radiology, University of Ioannina, Medical School, Ioannina, Greece. Reprints: Sofia Markoula, MD, Department of Neurology, University of Ioannina School of Medicine, University Campus 45110, Ioannina, Greece. E-mail: me01415@cc.uoi.gr. Copyright © 2009 by Lippincott Williams & Wilkins ISSN: 1074-7931/09/1504-0223 DOI: 10.1097/NRL.0b013e3181921abc Recurrent encephalitis may occur in up to 10% of patients. The Neurologist • Volume 15, Number 4, July 2009 www.theneurologist.org | 223