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Recurrent Herpes Simplex Type 2 Virus (Mollaret) Meningitis

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Recurrent Herpes Simplex Type 2 Virus (Mollaret) Meningitis J Am Board Fam Pract: first published as 10.3122/jabfm.17.4.303 on 8 July 2004. Downloaded from Recurrent Herpes Simplex Type 2 Virus (Mollaret) Meningitis Beloo Mirakhur, MD, PhD, and Marc McKenna, MD Mollaret meningitis is a rare form of meningitis were unremarkable. Cerebrospinal fluid (CSF) that is recurrent, aseptic, mild, and self-limiting. from her spinal tap was colorless with a hazy ap- When initially described by Mollaret, this form of pearance, glucose was 75 mg/dL, and protein was aseptic meningitis had no identifiable infecting 116 mg/dL, red blood cell count was 2/mm3 with a agent.1 New sophisticated diagnostic tools have white blood cell count of 633. The differential now identified Herpes simplex type 2virus as the count of the white blood cells was 74% lympho- most commonly isolated agent.2 The case pre- cytes, 19% monocytes, and 6% neutrophiles. CSF sented in this article is of a patient with a history of was negative for acid fast bacteria and fungus. No frequent bouts of recurrent aseptic meningitis cryptococcal antigen or antibodies were present. spanning a period of 20 years. The Gram stain of the CSF did not show the presence of organisms but was positive for Herpes Case Report simplex type 2virus by polymerase chain reaction The patient was a 52-year-old woman who pre- (PCR). Serum C3, C4, and total complement levels sented with malaise, nausea, fever, vomiting, head- were within the normal range. Lyme serology was ache, and photosensitivity. Her past medical his- nonreactive. Complete blood count, electrolytes, tory was significant for 20 previous episodes of serum urea nitrogen, and creatinine were within documented aseptic meningitis; all the episodes had normal limits. There was a mildly elevated periph- required hospitalization. Her past medical history eral glucose. The patient was positive for anti- was also significant for arthritis, chronic obstructive cardiolipin IgA antibody. DS DNA antibody and pulmonary disease, lupus, obstructive sleep apnea, those for SS-A and SS-B were absent. carpal tunnel syndrome, sciatica, hypertension, di- At admission, the patient was initially treated abetes mellitus type II, and transient ischemic at- with ceftriaxone for possible bacterial meningitis. tacks. Symptoms from her earlier meningitis epi- When the laboratory tests were positive for Herpes http://www.jabfm.org/ sodes lasted 3 to 10 days and subsequently cleared simplex type 2virus, the antibiotic was changed to without any residual symptoms. Numerous spinal intravenous acyclovir. This admission was pro- taps performed on her during her previous hospi- longed because of complications from sleep apnea talizations for meningitis indicated no known spe- and chronic obstructive pulmonary disease, neces- cific infectious cause. sitating intubation of the patient. On recovery, the She presented to the emergency department patient had no neurological deficits and was dis- on 2 October 2021 by guest. Protected copyright. complaining of headache, fever, stiff neck, and pho- charged from the hospital on a prophylactic dose of tophobia. She had a temperature of 100.0°F, blood acyclovir. Acyclovir was dosed at 800 mg twice pressure of 138/83 mm/Hg, and a heart rate of 85 daily. Two years after initiation of acyclovir, the beats/min. Her physical examination was remark- patient remains symptom-free and has had no fur- able for a stiff neck and a mildly decreased senso- ther hospitalizations for recurrence of meningitis. rium but no other focal neurological signs. Com- puted tomography, magnetic resonance imaging, Discussion and magnetic resonance angiography of her brain Various viruses can cause aseptic meningitis.3 In the adult population, a variant of recurrent aseptic meningitis has been identified, and this syndrome is Submitted, revised, 19 January 2004. From the Chestnut Hill Hospital, Philadelphia, Pennsyl- known as the Mollaret syndrome. Mollaret de- vania. Address correspondence to Marc McKenna, MD, scribed this unique form of recurrent aseptic th Chestnut Hill Hospital, 8815 Germantown Avenue, 5 1 Floor, Philadelphia, PA 19118 (E-mail: mckennamw@ meningitis in 1944. The clinical presentation chh.org). of Mollaret meningitis is recurrent episodes of Recurrent HSV 2(Mollaret) Meningitis 303 J Am Board Fam Pract: first published as 10.3122/jabfm.17.4.303 on 8 July 2004. Downloaded from meningismus, headache, and fever, separated by Table 1. Characteristics of Mollaret Meningitis symptom free episodes. Each episode can last from Recurrent episodes of recurrent meningitis a few days to 3 weeks and generally resolves with- Episodes separated by symptom free periods out any clinical intervention. Transient neurologi- Spontaneous remission of symptoms cal symptoms may occur in some patients but the Transient neurological symptoms in 50% of cases symptoms resolve with the resolution of the infec- No permanent neurological sequelae tion. The episodes of meningitis may not be asso- Probable causative agent is Herpes simplex type 2virus ciated with active herpetic lesions on the skin or mucous membranes. The course of the disease, although protracted, is benign, and does not pose a has spontaneous resolution. The rarity of Mollaret threat to the patient. In general, the symptoms tend syndrome precludes well-documented clinical trials to reoccur over a period of 3 to 5 years, although a studying the efficacy of various antiviral drugs. Al- 4 case lasting more than 28 years has been reported. though acyclovir is a safe, effective, and specific Recurrent attacks of Mollaret meningitis usually anti-Herpes drug,10,11 it has not been shown to 5 resolve after a period of 3 to 5 years. definitively alter the natural history of the disease, This patient fulfilled the criteria proposed by whereas other therapies, including estrogen, ste- 6 Bruyn et al for the clinical diagnosis: recurrent roids, antihistamine, phenylbutazonum, and colchi- attacks separated by symptom-free weeks or cine have been unsuccessful in the treatment of months, spontaneous remission of symptoms and Mollaret meningitis.12,13 The case we present is an signs, recurrent episodes of severe headache, men- interesting case of Mollaret meningitis, with nu- ingismus, and fever. Clinical and pathologic evi- merous reoccurrences spanning a period of 20 dence of infectious meningitis were absent. Mag- years. To our knowledge, this is the largest number netic resonance imaging, magnetic resonance of recurrent episodes documented to occur in an angiography, computed tomography, and electro- individual patient. In our patient, it took more than encephalographic studies ruled out the possibility 21 hospitalizations before the diagnosis of Mollaret of a lupus neuropsychiatric illness. The absence of syndrome was made. Several hospital admissions lupus CNS manifestation was further ruled out by could not have been prevented in this patient but the presence of normal levels of complement C3 the earlier diagnosis of this disorder might have and C4. avoided extensive diagnostic investigations associ- Recent data suggest that Herpes Simplex type 2 ated with each admission. http://www.jabfm.org/ virus is identified as the most common agent caus- 2,7,8 ing Mollaret syndrome. After the primary in- Conclusion fection, Herpes simplex type 2virus becomes dor- Mollaret syndrome, although rare, should be con- mant, most commonly within the sensory neurons sidered in all persons with recurrent aseptic men- of the sacral dorsal root ganglia. It is believed that ingitis (Table 1). It can be diagnosed by PCR anal- the retrograde seeding of the CSF by the Herpes ysis of spinal fluid for the presence of viruses, in on 2 October 2021 by guest. Protected copyright. simplex type 2virus results in meningitis. With the particular Herpes simplex type 2.14 The diagnosis advent of new diagnostic procedures, such as the of this syndrome could prevent various hospital PCR, which is now widely available, it has become admissions for patients, and short-term attacks easy to identify the presence of Herpes simplex could be treated with acyclovir.15 The efficacy of type 2virus in patients with Mollaret syndrome, long-term antiviral prophylaxis is unknown; it suggesting that it is a causative agent of benign might prove to be of some benefit in decreasing the 9 recurrent meningitis. The detection of Herpes vi- number of recurrences as it did in our patient, who ral DNA in the CSF does not require any addi- has remained symptom-free on acyclovir, as of this tional procedures; it is a simple test that can be writing, for the last 2years. done on the CSF that has already been collected. Detection of Herpes DNA in the CSF will allow References the clinician to use abortive and preventive antiviral 1. Mollaret P. La me´ningite endothe´lio-leukocytaire therapy. multi-re´currente be´nigne. Rev Neurol (Paris) 1944; The major problem in assessing the efficacy of 76:57–67. any drug therapy is the nature of the disease, which 2. Tedder G, Ashley R, Tyler K, Levin M. Herpes 304 JABFP July–August 2004 Vol. 17 No. 4 J Am Board Fam Pract: first published as 10.3122/jabfm.17.4.303 on 8 July 2004. Downloaded from simplex virus infection as a cause of benign recurrent 9. Jackson A. Acute viral infections. Curr Opin Neurol lymphocytic meningitis. Ann Intern Med 1994;121: 1995;8:170–4. 334–8. 10. Whitley R, Lakeman F. Herpes simplex virus infec- 3. Beghi E, Nicolosi A, Kurland L, Mulder D, Hauser tions of the central nervous system: therapeutic and W, Shuster L. Encephalitis and aseptic meningitis, diagnostic considerations. Clin Infect Dis 1995;20: Olmsted county, Minnesota, 1950–1981: I. Epide- 414–20. miology. Ann Neurol 1984;16:283–94. 11. Townsend G, Scheld W. Infections of the central 4. Tyler K, Adler D. Twenty-eight years of benign nervous system. Adv Intern Med 1996;43:403–47. recurring Mollaret meningitis. Arch Neurol 1983; 40:42–3. 12. Stamm A, Livingston W, Cobbs C, Dismukes W.
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