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'{{Infobox disease | Name = Mollaret's meningitis | Image = Meninges-en.svg | Caption = Meninges of the central nervous system: dura mater, arachnoid, and pia mater. | DiseasesDB = | ICD10 = | ICD9 = {{ICD9|047.9}} | MedlinePlus = | eMedicineSubj = neuro | eMedicineTopic = 697 | eMedicine_mult = | MeshID = D008582 }} '''Mollaret's meningitis''' is a recurrent or chronic [[inflammation]] of the protective membranes covering the [[brain]] and [[spinal cord]], known collectively as the [[meninges]]. Since Mollaret's meningitis is a recurrent, benign (non-cancerous), [[aseptic meningitis]], it is now referred to as '''benign recurrent lymphocytic meningitis'''.<ref>{{cite journal|last1=Shalabi|first1=M|last2=Whitley|first2=RJ|title=Recurrent benign lymphocytic meningitis.|journal=Clinical infectious diseases : an official publication of the Infectious Diseases Society of America|date=Nov 1, 2006|volume=43|issue=9|pages=1194–7|pmid=17029141|url=http://cid.oxfordjournals.org/content/43/9/1194.long|doi=10.1086/508281}}</ref><ref name= Helbok>{{cite journal |author= Raimund Helbok, Gregor Broessner, Bettina Pfausler, Erich Schmutzhard |title=Chronic meningitis |journal= J Neurol |volume=256 |issue=|pages=168–175 |year=2009 |pmid= |doi=10.1007/s00415-009-0122-0}}</ref> It was named for [[Pierre Mollaret]], the French neurologist who first described it in 1944.<ref>{{WhoNamedIt|synd|1537}}</ref><ref>P. Mollaret. Méningite endothélio-leucocytaire multirécurrente bénigne. Syndrome nouveau ou maladie nouvelle? (Documents cliniques). Revue neurologique, Paris, 1944, 76: 57–76.</ref><ref>La méningite endothélio-leukocytaire multi-récurrente bénigne. Rev Neurol (Paris) 1944;76:57–67.</ref> Although chronic meningitis has been defined as "irritation and inflammation of the meninges persisting for more than 4 weeks being associated with pleocytosis in the cerebrospinal fluid",<ref name=Helbok/> cerebrospinal fluid abnormalities may not be detectable for the entire time.<ref name=Willmann/> Diagnosis can be elusive, as Helbok et al. note: "in reality, many more weeks, even months pass by until the diagnosis is established. In many cases the signs and symptoms of chronic meningitis not only persist for periods longer than 4 weeks, they even progress with continuing deterioration, i. e. headache, neck stiffness and even low grade fever. Impairment of consciousness, epileptic seizures, neurological signs and symptoms may evolve over time." <ref name=Helbok/> ==Signs and symptoms== Mollaret's meningitis is characterized by chronic, recurrent episodes of headache, stiff neck, [[meningismus]], and fever; [[cerebrospinal fluid]] (CSF) [[pleocytosis]] with large "endothelial" cells, [[neutrophil granulocytes]], and lymphocytes; and attacks separated by symptom-free periods of weeks to months; and spontaneous remission of symptoms and signs. Many people have side effects between bouts that vary from chronic daily headaches to after-effects from meningitis such as hearing loss. Some patients report short bouts of 3–7 days of being sick while others have cases that can last for weeks or months. Symptoms may be mild or severe.<ref name=Helbok/> While herpes simples and varicella can cause rash, Mollaret's patients may or may not have a rash.<ref name= Ihekwaba>{{cite journal |author=Ugo K. Ihekwaba, Goura Kudesia, and Michael W. McKendrick|title= Clinical Features of Viral Meningitis in Adults: Significant Differences in Cerebrospinal Fluid Findings among Herpes Simplex Virus, Varicella Zoster Virus, and Enterovirus Infections |journal= Clinical Infectious Diseases |volume=47 |issue=|pages=783–9 |year=2008 |pmid=18680414 |doi=10.1086/591129}}</ref> ==Cause== Although for a long time, the cause of Mollaret's meningitis was not known, recent work has associated this problem with [[herpes simplex]] viruses, which cause cold sores and genital herpes.<ref name= Willmann >{{cite journal |author= Olaf Willmann, Parviz Ahmad-Nejad, Michael Neumaier, Michael G. Hennerici, Marc Fatar |title= Toll-Like Receptor 3 Immune Deficiency May Be Causative for HSV-2-Associated Mollaret Meningitis |journal= Eur Neurol |volume=63 |issue=|pages=249–251 |year=2010 |pmid= |doi=10.1159/000287585}}</ref><ref>{{cite web |url=http://emedicine.medscape.com/article/1169489-overview |title=Aseptic Meningitis |author=Tarakad S Ramachandran, MBBS, FRCP(C), FACP |date=Feb 12, 2010 |work= |publisher=Emedicine |accessdate=9 January 2011}}</ref> Cases of Mollaret's resulting from Varicella zoster virus infection, diagnosed by polymerase chain reaction ([[PCR]]), have been documented. In these cases, PCR for herpes simplex was negative.<ref name=Ohmichi>{{cite journal |author= Ohmichi, T., Takezawa, H., Fujii, C., Tomii, Y., Yoshida, T., & Nakagawa, M. |title= Mollaret cells detected in a patient with varicella-zoster virus meningitis. |journal= Clinical Neurology and Neurosurgery, |volume=114 |issue=7 |pages=1086–7 |year=2012 |pmid= 22402203|doi= 10.1016/j.clineuro.2012.02.015}}</ref><ref name= Jhaveri >{{cite journal |author= Jhaveri, Ravi M.D.; Sankar, Raman M.D., Ph.D.; Yazdani, Shahram M.D.; Cherry, James D. M.D. |title= Varicella-zoster virus: an overlooked cause of aseptic meningitis |journal= Pediatric Infectious Disease Journal |volume=22 |issue=1 |pages=96–97 |year=2003 |pmid= 12553305 |doi= 10.1097/00006454-200301000-00026}}</ref> Some patients also report frequent [[Herpes zoster|shingles]] outbreaks.{{Citation needed|date=January 2011}} The chickenpox virus is part of the herpes family.<ref>[http://patient.info/doctor/mollarets-meningitis Mollaret's meningitis] at patient.info</ref> CNS [[epidermoid cyst]]s can give rise to Mollaret's meningitis especially with surgical manipulation of cyst contents. A familial association, where more than one family member had Mollaret's, has been documented.<ref name=Jones>{{cite journal |author= Jones CW, Snyder GE |title= Mollaret meningitis: case report with a familial association. |journal= Am J Emerg Med., |volume=29 |issue=7 |pages=840.e1–840.e2 |year=2011 |pmid= 20825883|doi= 10.1016/j.ajem.2010.02.008 }}</ref> ==Diagnosis== Diagnosis starts by examining the patients symptoms. Symptoms can vary. Symptoms can include headache, sensitivity to light, neck stiffness, nausea, and vomiting. In some patients, fever is absent. [[Neurological examination]] and MRI can be normal.<ref name="Willmann"/> Mollaret's meningitis is suspected based on symptoms, and can be confirmed by HSV 1 or HSV 2 on [[PCR]] of [[Cerebrospinal fluid]] (CSF), although not all cases test positive on PCR. PCR is performed on spinal fluid or blood, however, the viruses do not need to enter the spinal fluid or blood to spread within the body: they can spread by moving through the axons and dendrites of the nerves.<ref>{{cite journal |author= Tal Kramer, Lynn W. Enquist |title= Directional Spread of Alphaherpesviruses in the Nervous System |journal= Viruses |volume=5 |issue= |pages=678–707 |date=2013 |pmid=|doi=10.3390/v5020678}}</ref> During the first 24 h of the disease the spinal fluid will show predominant polymorphonuclear neutrophils and large cells that have been called endothelial (Mollaret’s) cells.<ref name=Khattab>{{cite journal |author=Mohammed Abu Khattab, Hussam Al Soub, Mona Al Maslamani, Jameela Al Khuwaiter, and Yasser El Deeb|title= Herpes simplex virus type 2 (Mollaret's) meningitis: A case report |journal= International Journal of Infectious Diseases |volume=13 |issue= |pages=e476-e479 |date=2009 |url= |doi=10.1016/j.ijid.2009.01.003}}</ref> A study performed on patients who had diffuse symptoms, such as persistent or intermittent headaches, concluded that although PCR is a highly sensitive method for detection, it may not always be sensitive enough for identification of viral DNA in CSF, due to the fact that viral shedding from latent infection may be very low. The concentration of viruses in CSF during subclinical infection might be very low.<ref>{{cite journal |author= Birgitta Sundén, Marie Larsson, Tina Falkeborn, Jakob Paues, Urban Forsum, Magnus Lindh, Liselotte Ydrenius, Britt Åkerlind and Lena Serrander |title= Real-time PCR detection of Human Herpesvirus 1–5 in patients lacking clinical signs of a viral CNS infection|journal= BMC Infectious Diseases |volume=11|pages=220|date=2011 |pmid= 21849074|doi=10.1186/1471-2334-11-220|url=http://www.biomedcentral.com/1471-2334/11/220}}</ref> Investigations include [[blood test]]s (electrolytes, liver and kidney function, inflammatory markers and a [[complete blood count]]) and usually [[X-ray]] examination of the chest. The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid (fluid that envelops the brain and the spinal cord) through [[lumbar puncture]] (LP). However, if the patient is at risk for a cerebral mass lesion or elevated [[intracranial pressure]] (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a lumbar puncture may be [[contraindicated]] because of the possibility of fatal [[brain herniation]]. In such cases, a [[Computed tomography|CT]] or [[Magnetic resonance imaging|MRI]] scan is generally performed prior to the lumbar puncture to exclude this possibility. Otherwise, the CT or MRI should be performed after the LP, with MRI preferred over CT due to its superiority in demonstrating areas of cerebral edema, ischemia, and meningeal inflammation. During the lumbar puncture procedure, the opening pressure is measured. A pressure of over 180&nbsp;mm H₂O is suggestive of bacterial meningitis. It is likely that Mollaret meningitis is underrecognized by physicians, and improved recognition may limit unwarranted antibiotic use and shorten or eliminate unnecessary hospital admission.<ref name=Jones/> [[File:PCR tests of Mollaret's Meningitis patient from Kojima et al, 2002.jpg|thumb|This shows the results of polymerase chain reaction tests on a chronic Mollaret's meningitis patient, along with symptoms.]] PCR testing has advanced the state of the art in research, but PCR can be negative in individuals with Mollaret's, even during episodes with severe symptoms. For example, Kojima et al. published a case study for an individual who was hospitalized repeatedly, and who had clinical symptoms including genital herpes lesions. However, the patient was sometimes negative for HSV-2 by PCR, even though his meningitis symptoms were severe. Treatment with acyclovir was successful, indicating that a herpes virus was the cause of his symptoms.<ref name=Kojima>{{cite journal |author=Yuki Kojima, Hideyuki Hashiguchi, Tomoko Hashimoto, Sadatoshi Tsuji, Hiroshi Shoji, and Yukumasa Kazuyama|title= Recurrent Herpes Simplex Virus Type 2 Meningitis: A Case Report of Mollaret's Meningitis |journal= Jpn. J. Infect. Dis. |volume=55 |issue= |pages=85–88 |date=2002 |url=http://www0.nih.go.jp/JJID/SC-29.pdf }}</ref> ==Treatment== ===Initial treatment=== [[Acyclovir]] is the treatment of choice for Mollaret's meningitis. Some patients see a drastic difference in how often they get sick and others don't. Often treatment means managing symptoms, such as [[pain management]] and strengthening the immune system. ==See also== * [[Encephalitis]] * [[Meningitis]] * [[Herpes simplex virus]] * [[Varicella zoster virus]] ==References== {{reflist|2}} {{Viral diseases}} {{Diseases of the nervous system}} {{DEFAULTSORT:Mollaret's Meningitis}} [[Category:Disorders of fascia]] [[Category:Medical emergencies]] [[Category:Meningitis]] [[Category:Herpes simplex virus-associated diseases]] [[Category:Varicella zoster virus-associated diseases]]'