Case Report

Mollaret meningitis: case report with a familial association Abstract

Mollaret meningitis is a syndrome characterized by recurrent bouts of meningitis that occur over a period of several years in an affected patient. Also known as recurrent lymphocytic meningitis, this entity involves repeated episodes of headache, stiff neck, fever, and cerebrospinal fluid pleocytosis. herpes simplex virus type 2 is the most frequently implicated causative agent, and treatment involves the use of Antiviral medications. We describe a case of Mollaret meningitis in a 47-year-old man who presented to the emergency department with his eighth episode of meningitis during a period of 20 years. Cerebrospinal fluid Polymerase chain reaction testing for herpes simplex virus type 2 was positive, and further testing excluded other common viral, bacterial, and inflammatory causes of meningeal irritation. The patient’s family history was significant for a brother who also had multiple episodes of Aseptic meningitis during a period of several years. This represents the first published report of a possible familial association involving Mollaret meningitis. It is likely that Mollaret meningitis is underrecognized among emergency physicians, and improved recognition of this entity may limit unwarranted antibiotic use and shorten or eliminate unnecessary hospital admission.

Recurrent lymphocytic meningitis was first described in 1944 by Pierre Mollaret [1]. The syndrome, also known as Mollaret meningitis, is a rare disorder that presents with Recurrent episodes of aseptic meningitis. Advances in diagnostic testing modalities have suggested that herpes simplex virus type 2 (HSV-2) is probably the causative agent in most cases [2]. This report represents the second description of Mollaret meningitis to be published in the emergency medicine literature and the first published description of a possible familial association involving Mollaret meningitis [3].

A 47-year-old man presented to the emergency depart- ment complaining of a headache and stiff neck. His symptoms began 2 days earlier and had been progressively worsening. The headache was severe and frontal in nature, with radiation down his spine. He had photophobia and

phonophobia, but denied fever, vomiting, or focal neurologic deficit. The patient reported that his current symptoms were identical to 7 previous episodes during the past 20 years. Per- patient report a lumbar puncture had been performed during every prior episode, leading to a diagnosis of aseptic meningitis each time. The patient’s brother has also had repetitive episodes of aseptic meningitis, with 5 distinct occurrences during the previous 6 years. Lumbar punctures had been performed on his brother during each of these episodes, with no evidence of Bacterial meningitis and no determination of a conclusive diagnosis.

The patient was afebrile, and initial vital signs were within normal limits. He was uncomfortable but alert and oriented. Pupils were equal and reactive. Cranial nerves II-XII were intact. Strength was 5/5 and symmetrical throughout his upper and lower extremities. Sensation was intact to fine touch. There was moderate pain with neck flexion, but no neck stiffness. The remainder of the physical examination was unremarkable.

A noncontrast head computed tomography was negative for acute pathology. Initial laboratory studies revealed a white blood cell count of 9.2, 73% PMNs; a chemistry panel and Coagulation studies were within normal limits. A lumbar puncture was performed, with an opening pressure of 25 cm H₂O. Moderate WBCs and no organisms seen on Gram stain. Tube 1 had 405 WBCs, 90% lymphocytes, and 10% monocytes, with 22 red blood cells. Tube 3 had 379 WBCs with 43 red blood cells. The cerebrospinal fluid protein was elevated at 111 mg/dL, and glucose was 55 mg/dL.

The patient received Empiric treatment with acyclovir, ceftriaxone, and vancomycin while awaiting lumbar puncture results. He was admitted to the hospital for further antibiotic therapy. Cerebrospinal fluid Bacterial cultures grew no organisms. Herpes simplex virus polymerase chain reaction performed on cerebrospinal fluid was positive for HSV-2. Further inpatient testing revealed a negative HIV test, negative rapid plasma reagin (RPR), negative antinuclear antibody and anti-DNA antibodies, and a sedimentation rate of 5 mm/h. A diagnosis of recurrent lymphocytic meningitis was made, and the patient was treated with acyclovir during his 3-day hospitalization, followed by 10 days of valacyclovir.

Mollaret meningitis is a rare disorder characterized by recurrent episodes of headache and meningismus. Fever is

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often present [4]. Seizures, altered mental status, hallucina- tions, and Visual disturbances have been reported as uncommon manifestations of the syndrome [5]. These self- limited episodes typically resolve after 3 to 5 days. The duration of time in between episodes varies from a few weeks to several years. Although most patients stop having recurrences after 3 to 5 years, the syndrome has been found to persist for as long as 28 years [6]. Advances in diagnostic testing have identified HSV-2 as the most frequent causative agent [2].

Mollaret meningitis remains a diagnosis of exclusion. Other entities that must be ruled out include congenital or acquired meningeal-cutaneous fistulae. Epidermoid cysts may repeatedly discharge their contents into the meningeal space resulting in aseptic meningitis. Atypical infectious agents should also be considered, including fungi, spir- ochetes, mycobacteria, and HIV, though it is unusual for infectious agents other than members of the herpes virus family to cause recurrent episodes. Vasculidities, including Behcet disease, have been associated with aseptic meningi- tis, as have systemic lupus erythematosis and sarcoidosis. Nonsteroidal Anti-inflammatory agents, antimicrobials, allo- purinol, and intrathecal agents have all been implicated as well [7].

Our patient required multiple physician encounters spanning 2 decades before the diagnosis of recurrent lymphocytic meningitis was made. Consequently, it is likely that this entity is underrecognized and, therefore, more common than currently suspected. Evidence-based treatment recommendations are limited by the rarity and self-limited nature of the disease process. Most authors recommend treatment of acute symptoms with acyclovir or valacyclovir [2,8,9]. In addition, several patients with frequent recur- rences have been successfully treated with long-term prophylaxis using acyclovir [8,10]. Further investigation is needed before antiviral prophylaxis can be routinely recommended. Increased awareness of this entity among emergency physicians may shorten or prevent unnecessary hospital stays or antibiotic administration. Improved aware- ness may also allow for further investigation into genetic or Environmental factors that could predispose patients to the

development of Mollaret meningitis and that may contribute to the familial relationship observed in this case.

Christopher W. Jones MD Department of Emergency Medicine University of North Carolina Chapel Hill, NC 27599-7594, USA

E-mail address: [email protected]

Graham E. Snyder MD Department of Emergency Medicine University of North Carolina Chapel Hill, NC 27599-7594, USA

WakeMed Health and Hospitals Department of Emergency Medicine

Raleigh, NC, USA

doi:10.1016/j.ajem.2010.02.008

References

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