- Email: [email protected]
Herpes simplex (HSV-1) aseptic meningitis
CASE STUDIES IN INFECTIOUS DISEASE
Herpes simplex (HSV-1) aseptic meningitis Lawrence E. Eisenstein, MD, Anthony J. Calio, MD, and Burke A. Cunha, MD, Mineola and Stony Brook, New York
INTRODUCTION Herpes simplex virus type 1 (HSV-1) most frequently presents as mucocutaneous lesions. HSV-1 is common worldwide, and has a seroprevalence of as many as 80% in parts of the United States.1 HSV-1 also is the most common cause of viral encephalitis.2 Less frequently, HSV-1 can also cause meningoencephalitis and uncommonly, aseptic meningitis presents with headache, nuchal rigidity, vomiting, and photophobia.2-4 Patients with HSV-1 encephalitis usually present with fever, headache, seizures and mental confusion.2 In patients without encephalitis, HSV-1 is often not considered in the differential diagnosis of aseptic meningitis. In cerebral spinal fluid (CSF) of patients with HSV-1 encephalitis, findings include mononuclear predominance of cells, a variably elevated protein, a normal glucose and red blood cells (RBCs).5,6 Aseptic meningitis caused by HSV-1 is more likely to demonstrate higher CSF white blood cell counts and protein, and there are no CSF RBCs. For this reason, HSV-1 is not often considered in the differential diagnosis of aseptic meningitis. This illustrative case is a patient with HSV-1 aseptic meningitis diagnosed by CSF polymerase chain reaction (PCR).
CASE REPORT The patient was a 47-year-old woman who presented to the emergency department complaining of 3 days of fever to 103°F along with nausea, vomiting, severe head and neck pain, and photophobia. The patient was employed as a nurse and denied alcohol or tobacco use. She denied any recent illness and had only traveled to the eastern end of Long Island, denying any tick bites. On physical From the Infectious Disease Division, Winthrop-University Hospital, Mineola, New York, and State University of New York School of Medicine, Stony Brook, New York. Reprint requests: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. Heart Lung® 2004;33:196-7 0147-9563/$ – see front matter Copyright © 2004 by Elsevier Inc. doi:10.1016/j.hrtlng.2002.12.002
196
www.heartandlung.org
examination, the patient had a temperature of 98.9°F, and her other vital signs were normal. She was alert and oriented, and cranial nerves II-I were intact. The patient had nuchal rigidity and decreased range of flexion of her neck. A lumbar puncture was performed, and the CSF was clear; white blood cells ⫽ 714 cells per mm3 (polymorphonuclear neutrophils 1%, lymphocytes ⫽ 99%); glucose was 61 mg/dL; protein was 130 mg/dL; lactic acid was 3.1; and no RBCs were present. Other diagnostic studies included a negative Lyme titer and rapid plasma reagin. The diagnosis of aseptic meningitis was made and supportive care instituted. The remainder of the patient’s hospital stay was complicated by vomiting. She remained afebrile, and her headache and photophobia gradually improved. The patient was discharged after 4 days. After discharge, the PCR was reported as positive for HSV-1. She was treated with acyclovir as an outpatient and recovered completely.
DISCUSSION This is a case of HSV-1 causing aseptic meningitis. HSV-1 has been isolated as the cause of aseptic meningitis in as many as 3% of cases, and is much less common than enteroviruses or arboviruses as the cause of aseptic meningitis.5,7 HSV-1 aseptic meningitis often follows a recent episode of primary HSV-1 infection.2 Herpes simplex virus type 2 is more frequently the cause of aseptic meningitis than HSV-1 and is associated with primary genital herpes infection.3,4 In cases of HSV-1 encephalitis, the CSF often has RBCs present because of the hemorrhagic/necrotizing nature of the infection.4,8,9 Brain CT and electroencephalogram in HSV-1 encephalitis demonstrate the focal nature of the infection in the temporal lobe of the brain. In cases of HSV-1 encephalitis, there is almost always some mental status change present, which is a key distinguishing point from aseptic meningitis in which mental status remains intact. HSV-1 encephalitis often results in permanent neurologic sequelae. Aseptic meningitis usually resolves without residual
MAY/JUNE 2004
HEART & LUNG
Eisenstein, Calio, and Cunha
sequelae.2,7 HSV-1 encephalitis carries a high mortality of 20-50% when treated.2,4 This case serves to remind physicians that HSV-1 is a cause of aseptic meningitis, and CSF PCR testing should be included in otherwise unexplained cases of aseptic meningitis. PCR for HSV carry a sensitivity and specificity of 95 and 100%, respectively.5,6 Noninvasive diagnostics of HSV-1 aseptic meningitis has replaced brain biopsy as the gold standard for diagnosing HSV-1.5,7 Unlike the other causes of viral aseptic meningitis, for which there is no treatment except supportive care, acyclovir is useful in decreasing symptom duration and severity in HSV-1 aseptic meningitis.4 REFERENCES 1. Whitley RJ. Herpes simplex viruses. In: Knipe DM, Howley PM, Griffin DE, et al, eds. Fields’ Virology, 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 2461-98.
HEART & LUNG
VOL. 33, NO. 3
Herpes simplex (HSV-1) aseptic meningitis 2. Whitley JR, Kimberlin DW. Viral encephalitis. Pediatr Rev 1999; 20:192-7. 3. Corey L. Herpes simplex virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Disease. 5th ed. New York: Churchill Livingston; 2000. p. 1564-75. 4. Simko JP, Caliendo AM, Hogle K, Versalovic J. Differences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) documented by detection of HSV DNA. Clin Infect Dis 2002;35:414-9. 5. Thomson RB Jr, Bertram H. Laboratory diagnosis of central nervous system infections. Infect Dis Clin North Am 2001;15: 1047-71. 6. Zunt JR, Marra C. Cerebrospinal fluid testing for the diagnosis of central nervous system infections. Neurol Clin 1999;17: 75-82. 7. Corey L. Herpes simplex viruses. In: Fauci A, Braunwald E, Longo E, et al, eds. Harrison’s: Principles of Internal Medicine. 14th ed. New York: McGraw-Hill; 1998. p. 1080-6. 8. Cunha BA. Infectious Disease in Critical Care Medicine, New York: Marcel Dekker; 1998. p. 161-3. 9. Nath A, Berger JR. Acute viral meningitis and encephalitis and the herpesviruses. In: Goldman L, Bennett JC (eds). Cecil Textbook of Medicine. 21st ed. Philadelphia: W.B. Saunders; 2000. p. 2123-6, 2128-32.
www.heartandlung.org
197
Herpes simplex (HSV-1) aseptic meningitis Lawrence E. Eisenstein, MD, Anthony J. Calio, MD, and Burke A. Cunha, MD, Mineola and Stony Brook, New York
INTRODUCTION Herpes simplex virus type 1 (HSV-1) most frequently presents as mucocutaneous lesions. HSV-1 is common worldwide, and has a seroprevalence of as many as 80% in parts of the United States.1 HSV-1 also is the most common cause of viral encephalitis.2 Less frequently, HSV-1 can also cause meningoencephalitis and uncommonly, aseptic meningitis presents with headache, nuchal rigidity, vomiting, and photophobia.2-4 Patients with HSV-1 encephalitis usually present with fever, headache, seizures and mental confusion.2 In patients without encephalitis, HSV-1 is often not considered in the differential diagnosis of aseptic meningitis. In cerebral spinal fluid (CSF) of patients with HSV-1 encephalitis, findings include mononuclear predominance of cells, a variably elevated protein, a normal glucose and red blood cells (RBCs).5,6 Aseptic meningitis caused by HSV-1 is more likely to demonstrate higher CSF white blood cell counts and protein, and there are no CSF RBCs. For this reason, HSV-1 is not often considered in the differential diagnosis of aseptic meningitis. This illustrative case is a patient with HSV-1 aseptic meningitis diagnosed by CSF polymerase chain reaction (PCR).
CASE REPORT The patient was a 47-year-old woman who presented to the emergency department complaining of 3 days of fever to 103°F along with nausea, vomiting, severe head and neck pain, and photophobia. The patient was employed as a nurse and denied alcohol or tobacco use. She denied any recent illness and had only traveled to the eastern end of Long Island, denying any tick bites. On physical From the Infectious Disease Division, Winthrop-University Hospital, Mineola, New York, and State University of New York School of Medicine, Stony Brook, New York. Reprint requests: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. Heart Lung® 2004;33:196-7 0147-9563/$ – see front matter Copyright © 2004 by Elsevier Inc. doi:10.1016/j.hrtlng.2002.12.002
196
www.heartandlung.org
examination, the patient had a temperature of 98.9°F, and her other vital signs were normal. She was alert and oriented, and cranial nerves II-I were intact. The patient had nuchal rigidity and decreased range of flexion of her neck. A lumbar puncture was performed, and the CSF was clear; white blood cells ⫽ 714 cells per mm3 (polymorphonuclear neutrophils 1%, lymphocytes ⫽ 99%); glucose was 61 mg/dL; protein was 130 mg/dL; lactic acid was 3.1; and no RBCs were present. Other diagnostic studies included a negative Lyme titer and rapid plasma reagin. The diagnosis of aseptic meningitis was made and supportive care instituted. The remainder of the patient’s hospital stay was complicated by vomiting. She remained afebrile, and her headache and photophobia gradually improved. The patient was discharged after 4 days. After discharge, the PCR was reported as positive for HSV-1. She was treated with acyclovir as an outpatient and recovered completely.
DISCUSSION This is a case of HSV-1 causing aseptic meningitis. HSV-1 has been isolated as the cause of aseptic meningitis in as many as 3% of cases, and is much less common than enteroviruses or arboviruses as the cause of aseptic meningitis.5,7 HSV-1 aseptic meningitis often follows a recent episode of primary HSV-1 infection.2 Herpes simplex virus type 2 is more frequently the cause of aseptic meningitis than HSV-1 and is associated with primary genital herpes infection.3,4 In cases of HSV-1 encephalitis, the CSF often has RBCs present because of the hemorrhagic/necrotizing nature of the infection.4,8,9 Brain CT and electroencephalogram in HSV-1 encephalitis demonstrate the focal nature of the infection in the temporal lobe of the brain. In cases of HSV-1 encephalitis, there is almost always some mental status change present, which is a key distinguishing point from aseptic meningitis in which mental status remains intact. HSV-1 encephalitis often results in permanent neurologic sequelae. Aseptic meningitis usually resolves without residual
MAY/JUNE 2004
HEART & LUNG
Eisenstein, Calio, and Cunha
sequelae.2,7 HSV-1 encephalitis carries a high mortality of 20-50% when treated.2,4 This case serves to remind physicians that HSV-1 is a cause of aseptic meningitis, and CSF PCR testing should be included in otherwise unexplained cases of aseptic meningitis. PCR for HSV carry a sensitivity and specificity of 95 and 100%, respectively.5,6 Noninvasive diagnostics of HSV-1 aseptic meningitis has replaced brain biopsy as the gold standard for diagnosing HSV-1.5,7 Unlike the other causes of viral aseptic meningitis, for which there is no treatment except supportive care, acyclovir is useful in decreasing symptom duration and severity in HSV-1 aseptic meningitis.4 REFERENCES 1. Whitley RJ. Herpes simplex viruses. In: Knipe DM, Howley PM, Griffin DE, et al, eds. Fields’ Virology, 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 2461-98.
HEART & LUNG
VOL. 33, NO. 3
Herpes simplex (HSV-1) aseptic meningitis 2. Whitley JR, Kimberlin DW. Viral encephalitis. Pediatr Rev 1999; 20:192-7. 3. Corey L. Herpes simplex virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Disease. 5th ed. New York: Churchill Livingston; 2000. p. 1564-75. 4. Simko JP, Caliendo AM, Hogle K, Versalovic J. Differences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) documented by detection of HSV DNA. Clin Infect Dis 2002;35:414-9. 5. Thomson RB Jr, Bertram H. Laboratory diagnosis of central nervous system infections. Infect Dis Clin North Am 2001;15: 1047-71. 6. Zunt JR, Marra C. Cerebrospinal fluid testing for the diagnosis of central nervous system infections. Neurol Clin 1999;17: 75-82. 7. Corey L. Herpes simplex viruses. In: Fauci A, Braunwald E, Longo E, et al, eds. Harrison’s: Principles of Internal Medicine. 14th ed. New York: McGraw-Hill; 1998. p. 1080-6. 8. Cunha BA. Infectious Disease in Critical Care Medicine, New York: Marcel Dekker; 1998. p. 161-3. 9. Nath A, Berger JR. Acute viral meningitis and encephalitis and the herpesviruses. In: Goldman L, Bennett JC (eds). Cecil Textbook of Medicine. 21st ed. Philadelphia: W.B. Saunders; 2000. p. 2123-6, 2128-32.
www.heartandlung.org
197