Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 35-year-old woman is evaluated for a 1-day history of fever, headache, myalgia, arthralgia, and neck stiffness. The patient is sexually active. She had a similar episode 2 years ago, at which time results of cerebrospinal fluid (CSF) analysis showed lymphocytic meningitis. All culture results were negative, and her symptoms resolved over the next 3 days.

On physical examination, temperature is 38.3 °C (101.0 °F), blood pressure is 110/70 mm Hg, pulse rate is 90/min, and respiration rate is 12/min. There are no oral or genital ulcers. There is mild neck stiffness. Remaining physical examination findings, including mental status evaluation and complete neurologic examination, are normal. Funduscopic examination is normal.

Examination of the CSF shows a leukocyte count of 90/µL (90 × 10⁶/L) with 95% lymphocytes, a glucose level of 68 mg/dL (3.8 mmol/L), and a protein level of 70 mg/dL (700 mg/L). A Gram-stained CSF specimen is negative.

Which of the following diagnostic studies will most likely establish the cause of this patient’s meningitis?

A: CSF cytology
B: CSF IgM assay for West Nile virus
C: CSF polymerase chain reaction for herpes simplex virus type 2
D: MRI of the brain

MKSAP Answer and Critique

The correct answer is C: CSF polymerase chain reaction for herpes simplex virus type 2.

This patient most likely has benign recurrent lymphocytic meningitis, and the most appropriate study to confirm the diagnosis is cerebrospinal fluid (CSF) polymerase chain reaction for herpes simplex virus type 2 (HSV-2). Benign recurrent lymphocytic meningitis, formerly known as Mollaret meningitis, is most often caused by HSV-2, although some cases have been associated with HSV-1 and Epstein-Barr virus. Patients usually experience 2 to 3 to at least 10 episodes of meningitis (most often characterized by headache, fever, and stiff neck) that last for 2 to 5 days and are followed by spontaneous recovery. About 50% of patients may also have transient neurologic manifestations, such as seizures, hallucinations, diplopia, cranial nerve palsies, or an altered level of consciousness. Disease occurs in patients without symptoms or signs of genital or cutaneous infection. Nucleic acid amplification tests, such as CSF polymerase chain reaction to detect the DNA of HSV-2, will establish the diagnosis. Patients usually recover without therapy; it is not clear whether antiviral agents alter the course of mild infection.

Given the recurrent nature of this patient’s illness, it is unlikely to be caused by a malignancy. Cytologic studies are therefore unnecessary at this time. Cytology may reveal Mollaret cells, which are large atypical monocytes, but they are not seen in all cases, and their presence does not establish the etiologic diagnosis.

The recurrent episodes that this patient has experienced also make West Nile virus infection unlikely.

MRI of the brain would be appropriate if the patient had the clinical presentation of encephalitis (fever, hemicranial headache, language and behavioral abnormalities, memory impairment, cranial nerve deficits, and seizures), which is most often caused by HSV-1 rather than HSV-2.

Key Point

• Herpes simplex virus type 2 is the most common cause of benign recurrent lymphocytic meningitis, and the diagnosis is established by cerebrospinal fluid polymerase chain reaction.

This content is excerpted from MKSAP 16 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.