Case Report

February 1, 2007

A 49-year-old white man, in whom HIV infection had been newly diagnosed (CD4+ cell count, 25/µL; HIV-1 RNA level, 274,000 copies/mL), was transferred to our hospital for further workup and treatment of multiple neurologic deficits. He had presented to another hospital with a 4-day history of left-sided weakness and numbness, left-sided facial droop, dysphonia, and dysphagia that led to the initial diagnosis of an acute stroke.

A 49-year-old white man, in whom HIV infection had been newly diagnosed (CD4+ cell count, 25/µL; HIV-1 RNA level, 274,000 copies/mL), was transferred to our hospital for further workup and treatment of multiple neurologic deficits. He had presented to another hospital with a 4-day history of left-sided weakness and numbness, left-sided facial droop, dysphonia, and dysphagia that led to the initial diagnosis of an acute stroke. The patient denied any medical or surgical history. He was taking no medications before admission, and there were no known drug allergies. His social history was notable for heavy tobacco and alcohol use as well as intravenous drug use. A review of systems was remarkable for significant weight loss, a nonproductive cough, and draining lesions from his left ear for approximately 1 month before hospital presentation.

Abnormal physical findings were several crusted vesicular lesions in the left external auditory canal (no other skin lesions were noted) and multiple neuralgic deficits. These deficits included central left cranial nerve VII palsy and an absent gag reflex (cranial nerve IX). In addition, the patient was unable to open his mouth spontaneously (mandibular branch cranial nerve V), protrude his tongue (cranial nerves V and XII), or shrug his left shoulder (cranial nerve XI). Sensation was absent on the left side of his face. A motor examination revealed left-sided hemiplegia. His reflexes were 3+ throughout with an upgoing plantar reflex on the left.

Notable laboratory findings were a hematocrit level of 28.3% (normal, 37% to 50%) and a white blood cell (WBC) count of 4.9 3 109/L (normal, 4.5 to 11 3 109/L).

MRI revealed increased fluid-attenuated inversion recovery and T2 signal in the right globus pallidus and pons (Figure 1). These regions also had low signal intensity on T1-weighted imaging and significant diffusion abnormalities on apparent diffusion coefficient maps), which, because of their extent, likely represented encephalitis. There was minimal peripheral enhancement on postgadolinium images and bilateral leptomeningeal enhancement, compatible with meningitis. The bilateral ventricles were mildly prominent, but the remaining brain parenchyma was normal. Magnetic resonance angiography findings were normal.

A lumbar puncture (LP) was performed, and the cerebrospinal fluid (CSF) findings are shown in the Table. Gram stain and culture for bacterial organisms were negative. The CSF VDRL test was negative. Polymerase chain reaction (PCR) assay results were positive for herpes simplex virus type 2 (HSV-2). Results of PCR testing for HSV-1, varicella- zoster virus, Cytomegalovirus, Epstein-Barr virus, West Nile virus, and JC virus were negative.

A biopsy of the ear lesions showed multinucleated cells with clear, glassy nuclei in an area of epithelial ulceration (Figure 2). Immunohistochemical staining confirmed HSV-2 (Figure 3).

Treatment was started with intravenous acyclovir and prednisone. During the first week of the patient's hospital stay, antiretroviral therapy was also initiated. On repeated MRI 7 days later, a new focus of diffusion abnormality within the right frontal lobe was seen. Also, the previously noted leptomeningeal enhancement had diminished, but the pontine and right thalamic lesions remained unchanged (Figure 4). There was no evidence of cranial nerve involvement.

The patient had minimal neurologic improvement after 2 weeks of acyclovir therapy. A repeated LP, performed 18 days after beginning acyclovir therapy, showed a WBC count of 2/µL and a red blood cell count of 8/µL.

The patient was transferred to a rehabilitation center after completing 21 days of acyclovir therapy. Six months later, he had not made a significant recovery and remained hemiplegic but without cognitive deficits.

Herpes simplex encephalitis (HSE) is considered the most common cause of sporadic encephalitis and is typically due to infection with HSV-1, is localized in the temporal or frontal lobe, and presents classically with fever and acute mental status changes with or without concomitant skin findings. However, brain stem encephalitis caused by HSV-2 infection is very rare and has been reported more commonly in patients who were immunocompetent at the time of their presentation, with or without concomitant HSV-2 genital infections.1-3

Classically, HSV-2 infection is associated with sporadic aseptic meningitis and neonatal encephalitis. With the advent of HIV infection and other immunosuppressive states, as well as the improved technology for diagnosis, HSV-2 infection has increasingly been associated with encephalitis-like presentations.4 HIV-positive patients, however, are not at increased risk for HSE, and this disease is not considered an AIDS-defining illness.5

HSE in immunocompromised patients may have atypical manifestations4,6 and has been observed in patients with concomitant Cytomegalovirus infection.7 The earliest cases of HSV-2 encephalitis in patients with HIV/AIDS were described in 1984 at the beginning of the AIDS epidemic,8 but no large studies have been conducted to evaluate the role of HSV-2 in the etiology of AIDS-related encephalitis.

The present case was complicated because the patient presented with signs and symptoms that led to the initial diagnosis of a cerebrovascular event. He also lacked other typical signs of infection, such as fever; and owing to the atypical localization of his lesions, he did not display any of the neurologic features classically associated with temporal lobe HSE, such as fluctuating mental status and behavioral changes.

In addition, the vesicles found on the external auditory canal may have resulted from antegrade migration of HSV-2 particles to the skin (as is the case with herpes zoster oticus). Latency of herpesviruses usually occurs in trigeminal sensory ganglia, and reactivation is associated with temporal and frontal invasion of the brain via the rami meningeales of the ganglion or the trigeminal nerve.

Ramsay Hunt syndrome, associated with varicella-zoster virus, differs from the other herpesvirus-associated cranial nerve syndromes because this syndrome is a constellation of unilateral facial palsy, hearing loss, sensory abnormalities, and vesicles in the external auditory canal as a result of reactivation of the virus in the geniculate ganglion.

Infection with HSV-2 causes similar skin eruptions following dormancy in nerve roots, notably in the genital area, and in the terminal nerve distribution of the fifth cranial nerve on the face. HSV-2 infection has also been implicated in cases of herpes gladiatorum, which typically involves the earlobes. In addition, HSV DNA has been found in CNS tissue of asymptomatic patients, suggesting that herpesvirus latency may sometimes occur in the brain itself.9

One case report has described a Ramsey Hunt–like syndrome due to HSV-2 infection in an immunocompetent woman who had recurrent lesions in the ear associated with facial sensory abnormalities.10 Yet, auditory canal vesicles following or preceding the occurrence of encephalitis in an immunocompromised patient and subsequent facial palsy have not been reported before.

Historically, the mortality associated with HSE due to HSV-1 infection when left untreated is approximately 70%.11 Intravenous acyclovir decreases this mortality rate to about 20% and significantly decreases morbidity as well, with minor or no neurologic impairment observed in more than 50% of treated patients.12,13 Treatment duration in adults for HSE due to HSV-2 infection in the setting of HIV/AIDS is unclear. Most recommendations arise from studies conducted in neonates, in which outcomes were improved with longer durations of treatment, usually up to 21 days of acyclovir.14

In a retrospective study of 45 patients, the administration of corticosteroids was an independent predictor of improved outcome.15 Furthermore, a simplified acute physiological score II (which is used to quantify severity of illness and is based on various hemodynamic and laboratory values) of 27 or greater at admission and a delay of more than 2 days between admission to the hospital and initiation of therapy, as was the case with this patient,are independent predictors of poor outcome.16

The widespread availability of newer diagnostic tests, such as PCR tests, may lead to an increase in the recognition of atypical presentations of HSE as in this Case Report. Further research into the diverse presentations of HSV-2 encephalitis as well as into optimal treatment regimens is warranted given that many CNS infections present atypically and may be mistaken for cerebrovascular events in immunocompromised patients.

No potential conflict of interest was reported by the authors.



1. Chu K, Kang DW, Lee JJ, Yoon BW. Atypical brainstem encephalitis caused by herpes simplex virus 2. Arch Neurol. 2002;59:460-463.
2. Dennett C, Cleator GM, Klapper PE. HSV-1 and HSV-2 in herpes simplex encephalitis: a study of sixty-four cases in the United Kingdom. J Med Virol. 1997;53:1-3.
3. Tang JW, Coward LJ, Davies NW, et al. Brain stem encephalitis caused by primary herpes simplex 2 infection in a young woman. J Neurol Neurosurg Psychiatry. 2003;74:1323-1325.
4. Fodor PA, Levin MJ, Weinberg A, et al. Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF. Neurology. 1998;51:554-559.
5. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):1-19.
6. Harrison NA, MacDonald BK, Scott G, Kapoor R. Atypical herpes type 2 encephalitis associated with normal MRI imaging. J Neurol Neurosurg Psychiatry. 2003;74:974-976.
7. Cinque P, Vago L, Marenzi R, et al. Herpes simplex virus infections of the central nervous system in human immunodeficiency virus-infected patients: clinical management by polymerase chain reaction assay of cerebrospinal fluid. Clin Infect Dis. 1998;27: 303-309.
8. Dix RD, Waitzman DM, Follansbee S, et al. Herpes simplex virus type 2 encephalitis in two homosexual men with persistent lymphadenopathy. Ann Neurol. 1985;17:203-206.
9. Baringer JR, Pisani P. Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction. Ann Neurol. 1994;36:823-829.
10. Diaz GA, Rakita RM, Koelle DM. A case of Ramsay Hunt-like syndrome caused by herpes simplex virus type 2. Clin Infect Dis. 2005;40:1545-1547.
11. Whitley RJ, Soong SJ, Dolin R, et al. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med. 1977;297:289-294.
12. Skoldenberg B, Forsgren M, Alestig K, et al. Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet. 1984;2:707-711.
13. Whitley RJ, Alford CA, Hirsch MS, et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986;314:144-149.
14. Kimberlin DW, Lin CY, Jacobs RF, et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics. 2001;108:230-238.
15. Kamei S, Sekizawa T, Shiota H, et al. Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry. 2005;76:1544-1549.
16. Raschilas F, Wolff M, Delatour F, et al. Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis. 2002;35:254-260.