CASE

A 43 year-old female with a past medical history of migraine headaches presented to the emergency department with a severe, diffuse headache. The headache started suddenly, waking her from sleep about two hours prior to arrival, and was described as the worst headache of her life. The headache was not improved with home ibuprofen or Tylenol, prompting her visit to the emergency department. Upon further questioning, the patient noted the headache was associated with neck stiffness, diaphoresis, and subjective fever.

When questioned about recent medications, she endorsed recently starting Cipro for a presumed urinary tract infection. She was particularly concerned about fluoroquinolone-induced tendinitis (which she had read about online), because she had been experiencing bilateral hip numbness and pain, which radiated into her thighs. However, these symptoms had ceased the day prior to presentation.

Review of the patient’s chart also showed that she had recently been seen in the emergency department several days before with a painful and itchy perineal rash, but was ultimately diagnosed with a fungal infection and started on nystatin. At that time, she denied sexual activity or known herpes virus infection.

On exam, the patient had normal vital signs. There was significant photophobia, which precluded fundoscopic exam, as well as pain with flexion or extension of the neck. There were also multiple discrete cratered excoriations found on genital exam; a sample was taken and sent for testing.

Bloodwork was unremarkable. A CT scan of the head was normal. A lumbar puncture was performed, showing an elevated white blood cell count (470) with lymphocytic predominance (82%) and mildly increased protein (104 mg/dL), but normal glucose. Gram stain was negative. All other results were pending.

DIAGNOSIS

Herpes meningitis

DISCUSSION

Herpes simplex viruses (HSVs) are double-stranded DNA viruses surrounded by a viral envelope. Classically, HSV-1 causes oral lesions, but skin and ocular involvement are possible, as well as encephalitis. HSV-2, on the other hand, is mostly associated with genital infections. Transmission occurs via direct contact, and after the initial infection, the virus becomes dormant in nearby neuronal cell bodies. Reactivation is common and may be subclinical, so recent direct/sexual contact or antecedent history of herpes infection may not always be apparent. [1]

Herpes can also cause aseptic meningitis, meaning that there is no growth on bacterial  culture of cerebrospinal fluid (CSF). In fact, HSV-2 accounts for 31% of aseptic meningitis, whereas HSV-1 is identified as the culprit in 4%. Of the patients who present with herpetic genital lesions, 13 - 36% will go on to develop meningeal signs; however, one may have herpes meningitis without any prior history of genital lesions. The differential diagnosis for aseptic meningitis also includes enteroviruses (most common), varicella, human immunodeficiency virus, mumps, and West Nile virus, among others. Thus, a history of travel, immunocompromised status, sexual activity, and vaccinations is important to elicit. [1] 

The presentation is similar to other causes of meningeal irritation, including bacterial meningitis and subarachnoid hemorrhage, and these more significant pathologies must be considered. Presenting symptoms may include headache, meningismus, photophobia, and fever. [2] Interestingly, a small proportion of patients with herpes meningitis will experience radiculo-myelitis as a paresthesia or weakness, and this may account for the lower extremity complaints of the patient in this case. Meningoencephalitis is an important consideration as well, particularly if the patient has altered mental status, reduced Glasgow Coma Scale, or associated neurological symptoms, such as seizures. [1]

CSF analysis will show a mononuclear pleocytosis, although neutrophils may predominate early in the disease course, confounding the diagnosis. Glucose should be within normal limits, and protein is mildly elevated. However, the only way to truly differentiate between the various causes of aseptic meningitis is to send samples for polymerase chain reaction (PCR). Unless a clear clinical context exists, such as the patient’s genital rash in this case, it is reasonable to evaluate for enteroviruses, varicella, and herpes, as these account for the vast majority of cases. [1]

Treatment consists of intravenous acyclovir based on the patient’s ideal, not actual, body weight. While there is only limited evidence regarding the effectiveness of this treatment, one case series found fewer neurological sequelae in immunocompromised patients with treatment. There was no difference in immunocompetent patients. [3] If meningoencephalitis is suspected, acyclovir should be given empirically. Although the history and exam may be highly consistent with herpes or other aseptic meningitis, a bacterial meningitis cannot be excluded without obtaining CSF, so it is also reasonable to initiate empiric antibiotic therapy, given the potentially disastrous consequences of an untreated bacterial meningitis.

CASE RESOLUTION

The patient was started on IV acyclovir, as well as vancomycin and ceftriaxone for empiric bacterial coverage pending definitive diagnosis. Ultimately, both her perineal and CSF cultures were positive for HSV-2, confirming the diagnosis of herpes meningitis.

TAKE-AWAYS

• The diagnosis of herpes meningitis requires a high index of suspicion, but sexual activity and recent cutaneous lesions can be important clues

• It is reasonable to provide empiric antibiotic and antiviral coverage, given the high morbidity and mortality associated with untreated bacterial meningitis or viral encephalitis

• Herpes meningitis may be associated with a lumbosacral radiculo-myelitis, resulting in lower extremity pain not associated with cutaneous findings.

Please see Dr. Kelly Wong’s post on herpes encephalitis for more information regarding the diagnosis and management of that condition.

AUTHOR: Daniel Coleman is a fourth-year emergency medicine resident at Brown University/Rhode Island Hospital.

FACULTY REVIEWER: Kristina McAteer is an Assistant Professor of Emergency Medicine and Clinician Educator at Brown/Rhode Island Hospital.

REFERENCES

1. Logan SA, MacMahon E. Viral meningitis. BMJ. 2008 Jan 5;336(7634):36-40.

2. Kupila L, Vuorinen T, Vainionpää R, Hukkanen V, Marttila RJ, Kotilainen P. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology. 2006 Jan 10;66(1):75-80.

3. Noska A, Kyrillos R, Hansen G, Hirigoyen D, Williams DN. The role of antiviral therapy in immunocompromised patients with herpes simplex virus meningitis. Clin Infect Dis. 2015 Jan 15;60(2):237-42.