Recurrent herpes simplex encephalitis

Recurrent herpes simplex encephalitis

European Journal of Internal Medicine 16 (2005) 513 – 514 Brief report Recurrent herpes simplex encephalitis Zvi Landau...

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European Journal of Internal Medicine 16 (2005) 513 – 514

Brief report

Recurrent herpes simplex encephalitis Zvi Landau, Edward B. Miller*, Marina Roif Department of Internal Medicine D, Kaplan Medical Center, PO Box 1, Rehovot 76100, Israel1 Received 10 May 2004; received in revised form 13 January 2005; accepted 5 September 2005

Abstract Recurrent herpes simplex virus (HSV) encephalitis is a rare disorder with only a few cases reported. We report a case of HSV encephalitis with documented recurrence in the same anatomic location, lending support to the theory of reactivation as the mechanism of disease. D 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. Keywords: Encephalitis; Herpes; Viral reactivation

1. Introduction Herpes simplex virus (HSV) is a common cause of acute viral encephalitis and of relapsing mucocutaneous infections. Encephalitis relapses are rare with reactivation, inadequate treatment, and re-infection proposed as mechanisms of recurrence [1]. We report an individual who experienced three episodes of HSV encephalitis involving the same area of the brain over a 2-year period despite adequate treatment with intravenous acyclovir, suggesting local reactivation as the causative mechanism.

2. Case report A 64-year-old man was first hospitalized in May 2002 with a 3-day history of headache, fever, vomiting, and mental confusion. Physical and neurological examinations were unremarkable except for fever (38.5 -C) and disorientation to place and time. Baseline laboratory studies, chest X-ray, and ECG were unremarkable. Lumbar puncture revealed an elevated opening pressure of 22 mm H2O, glucose 62 mg/dl, protein 45 mg/dl, and WBC 120 cells/ml * Corresponding author. Tel.: +972 8 9441 901; fax: +972 8 9441 866. E-mail address: edward [email protected] (E.B. Miller). 1 Affiliated with the Hebrew University School of Medicine, Jerusalem, Israel.

with 65% PMNs. CSF serologic studies for enterovirus, west nile virus, and tuberculosis were all negative. IgG serology for HSV was positive, but CSF PCR was negative. Two CTs of the brain were normal, although EEG revealed focal abnormalities in the left frontal region. Following a generalized seizure, the patient was treated with intravenous ceftriaxone, ampicillin, acyclovir (14-day course), and phenytoin with defervescence. CSF gram stain and bacterial cultures were negative and antibiotics were discontinued. He returned to baseline mental status and was discharged without residual neurological deficits. Postdischarge MRI revealed a hypo-intense area in the left temporal lobe compatible with encephalitis. One year later (July 2003), the patient was readmitted with complaints of headache, blurred vision, lethargy, and disorientation. Physical and neurological examinations were unremarkable except for the presence of alexia. Laboratory studies, chest X-ray, and ECG were normal. A CT of the brain showed a hypodense area in the left temporal area consistent with a prior infarction. EEG was normal. Lumbar puncture revealed a normal opening pressure, an absence of WBCs, but with RBCs 356/ml. CSF protein was 66 mg/dl and glucose 84 mg/dl. PCR for HSV was negative, but serum and CSF antibody titers suggested an active HSV infection (Table 1). An MRI scan again revealed a hypo-intense area in the left temporal region and a technetium brain scan (SPECT) showed inflammatory changes in the same area. Blurred

0953-6205/$ - see front matter D 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2005.09.003


Z. Landau et al. / European Journal of Internal Medicine 16 (2005) 513 – 514

Table 1 Titers of HSV-1 IgG antibodies Date a

July 30, 2003 August 12, 2003 October 10, 2003 August 15, 2004b



1:16 1:8 N/A 1:8

1:256 1:128 1:64 1:256

N/A= not available. a Second admission. b Third admission.

vision, alexia, and headache resolved following a 2-week course of intravenous acyclovir. In August 2004, the patient presented a third time with disorientation, headache, diplopia, and agitation. Physical and neurological examinations were unremarkable, and LP revealed protein 60 mg/dl, glucose 75 mg/dl, and WBC 3 cells/ml. PCR for HSV was positive. He completed an additional 2-week course of acyclovir again with complete resolution of his neurological symptoms. He has since been followed as an outpatient without further neurological symptoms or sequelae.

3. Discussion This patient suffered three episodes of apparent HSV encephalitis over a 2-year period. The first two episodes were non-diagnostic according to PCR, but clinical response to acyclovir along with characteristic MRI and SPECT findings were highly suggestive of active HSV infection. The second episode was clinically similar to the first, and HSV infection was confirmed by positive serologic studies. The third episode, also similar clinically, was associated with a positive PCR for HSV. Although PCR is considered the gold standard for HSV infection and is present in the vast majority of cases, PCR-

negative infections have been described [2,3]. Negative PCR appears to be correlated with low CSF protein and WBC levels, as well as with the presence of anti-HSV antibodies in the CSF, as occurred in our patient [4]. Relapsing HSV encephalitis is a rare event and has been reported primarily in children following discontinuation of anti-viral therapy, suggesting inadequate eradication [5]. In our patient, recurrences occurring a full year apart and in the same anatomic area of the brain suggested reactivation of latent HSV. HSV virus is known to lie dormant in brain cells [6] but, for unknown reasons, encephalitis relapses are quite rare. Periodic relapses, common in other organ systems, are particularly rare in adult encephalitis patients. As this case demonstrates, periodic reactivation of latent HSV infection, however rare, is a possible consequence of HSV encephalitis.

References [1] Yamada S, Kameyama T, Nagaya S, Hashizume Y, Yoshida M. Relapsing herpes simplex encephalitis: pathologic confirmation of viral reactivation. J Neurol Neurosurg Psychiatry 2003;74:262 – 4. [2] Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis 2002;34:1154 – 7. [3] Puchhammer-Stockl E, Presterl E, Croy C, Abrie S, Popow-Kraupp T, Kundi M, et al. Screening for possible failure of herpes simplex virus PCR in cerebrospinal fluid for the diagnosis of herpes simplex encephalitis. J Med Virol 2001;64:531 – 6. [4] De Tiege X, Heron B, Lebon P, Ponsot G, Rozenberg F. Limits of early diagnosis of herpes simplex encephalitis in children: a retrospective study of 38 cases. Clin Infect Dis 2003;36:1355 – 9. [5] Barthez-Carpentier MA, Rozenberg F, Dussaix E, Lebon P, Goudeau A, Billard C, et al. Relapse of herpes simplex encephalitis. J Child Neurol 1997;10(5):363 – 8. [6] Fraser NW, Lawrence WC, Wroblewska Z, Gilden DH, Koprowski H. Herpes simplex type 1 DNA in human brain tissue. Proc Natl Acad Sci 1981;78(10):6461 – 5.