An Unusual Presentation of HSV Encephalitis in a Patient with Schizophrenia


Saurabh Agarwal, BA
Institution: University of Chicago, Pritzker School of Medicine

Marie Tobin, MD
Institution: University of Chicago, Department of Psychiatry


Address for Correspondence:
The University of Chicago
Department of Psychiatry
5841 South Maryland Avenue. MC 3077
Chicago Illinois 60637



Herpes simplex encephalitis is a potentially fatal condition that affects patients of all ages. Despite the various diagnostic tests available accurate diagnosis of HSE can be difficult because of differing clinical presentations. Accurate diagnosis of HSE can be further complicated in the presence of co-morbid psychiatric illness. Delay in diagnosis and treatment can result in severe neurological complications and even death. Presented here is a case report of a 52 year old male with concomitant schizophrenia in whom the diagnosis of HSE was particularly challenging given his unusual presentation.


Herpes simplex encephalitis (HSE) is the most common cause of sporadic fatal encephalitis in the western world (Rowlye et al, 1990). It has no predilection for sex and can occur at all ages (Fredricks et al, 1999). Over 90% of cases of HSE are caused by herpes simplex virus HSV 1; the remaining cases are caused by HSV2, which usually occurs in the neonatal period (Gumus et al, 2007). HSE primarily affects the temporal lobes of the brain. The mortality rate of HSV1 approaches 70% if untreated. Survivors develop severe neurological deficits (Whitley et al, 1986). Prompt initiation of antiviral therapy significantly improves outcomes. Reports show mortality rates decreased to 30%, with 38% of affected individuals regaining normal function (Whitley et al, 1977). Others show that the use of acyclovir specifically reduces the six-month mortality rate of HSE to 15-20%; with 50% of patients being able to return to normal life (Raschilas et al, 2002). For this reason, rapid and accurate diagnostic procedures are essential for management of the disease. Additionally, it is important to distinguish HSV from other forms of viral encephalitis because it is the only form of viral encephalitis for which an effective proven treatment exists (Billingsley et al, 2002).
In the following, we present an unusual presentation of HSE in a patient with a complicated medical background. We hope to add to the literature on the many different ways in which HSE can present and highlight the various techniques that can be used in diagnosis. Furthermore, we aim to emphasize that a negative HSV polymerase chain reaction (PCR) does not rule out the diagnosis of HSE if the rest of the clinical picture is consistent with a diagnosis of HSE.

Case Report:

A 52 year-old African American male with a history of schizophrenia, diabetes mellitus (type II) and hypertension presented to the emergency room with acute renal failure and bacteremia. He had been admitted to the psychiatric ward of an outside hospital. His schizophrenia had been stable for twelve years prior to this hospitalization. On this occasion, however, he presented with paranoia, auditory hallucinations, and delusions. After one week in the psychiatric ward, his schizophrenic symptoms showed significant improvement; however he was found to have acute renal failure, and was started on hemodialysis. A few days later, he developed fever with nausea and vomiting and was found to be bacteremic.The source of infection was found to be the access catheter placed in his right internal jugular vein. He was transferred to our emergency room. On admission; the patient was minimally alert and oriented only to self. His vital signs indicated only elevated BP at 160s/90s. His physical exam was notable for his pupils being minimally reactive to light, muddy sclera bilaterally, abdominal tenderness, right arm edema and warmth, and bilateral thigh pain. Laboratory values were significant for low sodium at 128 (normal 134-149 mEq/L), high BUN at 34 (normal 7-20 mg/dl), and a high creatinine at 4.5 (normal 0.5-1.4).
During the next few days, the patient’s inputs and outputs were within normal range. Relevant imaging studies included a noncontrast brain CT scan, which showed right temporal encephalomalacia and inflammation of the left mastoid air cells. Renal ultrasound showed mildly increased echogenicity consistent with medical renal disease.
Over the course of a week, the patient’s mental state worsened as he remained minimally alert and became disoriented. The patient’s demeanor was characterized by lethargy, inattentiveness, and perseveration of speech. The patient also had a characteristic grimace which he performed several times a minute consisting of contracting his orbicularis oris and orbicularis oculi muscles to scrunch up his face. He also often showed right hemi-neglect and a Babinski’s sign was unable to be elicited first on his left side, and then over the course of a few days, on his right side as well. Furthermore, despite aggressive fluid restriction, the patient’s hyponatremia worsened to 119. He also developed anemia and his creatinine levels remained high at 4.5. Lower lip lesions were also noted. The patient’s bilateral leg pain remained and the patient began to complain of lower back and neck pain and stiffness. His blood cultures also remained MRSA positive despite vancomycin and daptomycin therapy.
Given the complaints, further testing was done. A lumbar puncture showed high opening pressure, a normal glucose of 59 (normal 50-70 mg/dL), a slightly elevated protein level of 39 (normal 15-45), lymphocytic pleiocytosis and a high RBC count. Fungal and bacterial cultures were negative. An MRI showed bilateral temporal enhancement and an EEG showed diffuse slowing. HSV PCR, however, was negative, but given the clinical evidence for herpes simplex encephalitis, acyclovir was started.
Over the next week, the patient’s state improved significantly. He became much more alert and oriented and his physical and neurological exam was noted to be normal. His renal function also stabilized and he was no longer bacteremic. Electrolyte abnormalities were corrected and the sodium returned to normal levels. The patient was discharged to a nearby hospital specifically for patients with complex medical conditions who require an extended hospital stay for follow up care.


When diagnosing HSE, one must have a high index of suspicion as there are no specific signs or symptoms (Razavi et al, 2001). HSE can have a number of clinical presentations consisting of any combination of fever, depressed level of consciousness, confusion, disorientation, olfactory and gustatory hallucinations, personality change, seizures, dysphagia, or other focal neurological signs (Jablkowski et al, 2004). Symptoms may vary in intensity early in the disease, but tend to progress rapidly.
There are also several tests that one can do to aid in the diagnosis of HSE. One of these is magnetic resonance imaging or MRI, which is currently the diagnostic imaging study of choice. It shows temporal lobe abnormalities in approximately 90% of cases of HSE (Tyler, 2004). Electroencephalography (EEG) is also commonly used and in over 80% of HSE patients generalized slowing or focal slowing and occasionally periodic lateralized epileptiform discharges are seen (Rose et al, 1992). Other signs are lymphocytic pleiocytosis, increased number of erythrocytes in 84% of cases, and elevated protein (McGrath et al, 1997).
The most sensitive and specific of all the generally used tests is HSV PCR. In our case, however, it was negative. One possible reason for this is that the test was done too early in the disease course (Puchhammer-Stöckl et al, 1993). Another reason for the negative PCR could be due to the presence of inhibitors of PCR such as hemoglobin degradation products from the red blood cells (Aurelius et al, 1991). Furthermore, one study found PCR to be only 75% sensitive and 100% specific. They concluded that although a positive PCR result establishes the diagnosis of HSE, a negative result does not by any means exclude the diagnosis (Troendle-Atkins et al, 1993). The rapid improvement in sensorium and resolution of neurological symptoms with acyclovir support a diagnosis of HSE in this case.
Undetected, herpes simplex encephalitis is frequently fatal. It can also result in enduring, disabling neurological sequelae despite the availability of effective treatment. Consequently, it is crucial to include HSE in the differential diagnosis of altered mental state. Additionally, patients with immunosuppression and complex medical problems are at greater risk of HSE. In our case the co-morbid diagnosis of schizophrenia delayed the diagnosis of HSE as the primary team attributed the observed stereotypic movements to his schizophrenic process.
We suggest that in cases of severe mental illness, the treating clinician should not be so quick to dismiss atypical symptoms as necessarily due to the underlying psychiatric illness and rather still complete a thorough work-up as even minor delays in diagnosis and treatment can often have drastic consequences.


Aurelius E, Johansson B, Sköldenberg B, Staland A, Forsgren M. (1991) Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet. Vol. 337, 189-92.

Billingsley ED, Hovland A, Agcaoili D, Long D, Borne D. (2002) A 39-year-old man with acute mental status changes. Journal of the Louisiana State Medical Society. Vol. 154, 230-3.

Fredricks D, Relman D. (1999) Application of Polymerase Chain Reaction to the Diagnosis of Infectious Diseases. Clinical Infectious Diseases. Vol. 29, 475-88.

Gumus H, Kumandas S, Per H, Tahan F, Koklu E, Karakukcu M. (2007) Unusual presentation of herpes simplex virus encephalitis: bilateral thalamic involvement and normal imaging of early stage of the disease. The American Journal of Emergency Medicine. Vol. 25, 87-9.

Jablkowski M, Kolasa P, Szubert W, Bialkowska J. (2004) Herpes simplex encephalitis: a case report. Medical Science Monitor. Vol. 10, CS41-45.

McGrath N, Anderson NE, Croxson MC, Powell KF. (1997) Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. Journal of Neurology, Neurosurgery & Psychiatry. Vol. 63, 321–26.

Puchhammer-Stockl E, Heinz FX, Kundi M, Popow-Kraupp T, Grimm G, Millner MM, Kunz C. (1993) Evaluation of the polymerase chain reaction for diagnosis of herpes simplex virus encephalitis. Journal of Clinical Microbiology. Vol. 31, 146-8.

Raschilas F, Wolff M, Delatour F, Chaffaut C, De Broucker T, Chevret S, Lebon P, Canton P, Rozenberg F. (2002) Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clinical Infectious Diseases. Vol. 35, 254-60.

Razavi B, Razavi M. (2001) Herpes simplex encephalitis--an atypical case. Infection. Vol. 29, 357-8.

Rose JW, Stroop WG, Matsuo F, Henkel J. (1992) Atypical herpes simplex encephalitis: clinical, virologic, and neuropathologic evaluation. Neurology. Vol. 42, 1809-12.

Rowlye AH, Whitley RJ, Lakeman FD, Wolinsky SM. (1990) Rapid detection of herpes-simplex-virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis. Lancet. Vol. 335, 440-41.

Troendle-Atkins J, Demmler GJ, Buffone GJ. (1993) Rapid diagnosis of Herpes Simplex virus encephalitis by using the Polymerase Chain Reaction. The Journal of Pediatrics. Vol. 123, 376-80.

Tyler KL. (2004) Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret’s. Herpes. Vol. 11, 57A-64A.

Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, Hanley D, Nahmias AJ, Soong SJ. (1986) Vidarabine versus acyclovir therapy in herpes simplex encephalitis. The New England Journal of Medicine. Vol. 314, 144-149.

Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Ch'ien LT, Alford CA. (1977) Adenine arabinoside therapy of biopsy-proven herpes simplex encephalitis: National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study. The New England Journal of Medicine. Vol. 297, 289-94.

Click on these links to visit our Journals:
Priory Bookshop | Search for papers and articles  | Psychiatry On-Line 
Dentistry On-Line
 |  Vet On-Line | Chest Medicine On-Line 
GP On-Line | Pharmacy On-Line | Anaesthesia On-Line | Medicine On-Line
Family Medical Practice On-Line

Home • Journals • Search • Rules for Authors • Submit a Paper • Sponsor us
Rules for Authors
Submit a Paper
Sponsor Us

Google Search

Advanced Search



Default text | Increase text size