Mollaret's meningitis

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Mollaret's meningitis
Other namesBenign recurrent lymphocytic meningitis
Meninges-en.svg
Meninges of the central nervous system: dura mater, arachnoid, and pia mater.
Specialty Neurology

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 also referred to as benign recurrent lymphocytic meningitis. [1] [2] It was named for Pierre Mollaret, the French neurologist who first described it in 1944. [3] [4]

Contents

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", [2] cerebrospinal fluid abnormalities may not be detectable for the entire time. [5] 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." [2]

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 years; 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 and visual impairment, nerve pain and twitches. Symptoms may be mild or severe. [2] Some cases may be short, lasting only 3–7 days, while others last for weeks to months.[ citation needed ]

While herpes simplex and varicella can cause rash, Mollaret's patients may or may not have a rash. [6] Herpes simplex virus is likely the most common cause of Mollaret's meningitis. [7]

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, particularly HSV-2. [5] [8]

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. [9] [10] Some patients also report frequent shingles outbreaks.[ citation needed ] Varicella zoster virus, which causes chickenpox and shingles is part of the herpes family, and is sometimes called "herpes zoster virus". [11] CNS epidermoid cysts (a type of cholesteatoma) can give rise to Mollaret's meningitis especially with surgical manipulation of cyst contents.[ citation needed ]

A familial association, where more than one family member had Mollaret's, has been documented. [12]

Diagnosis

Diagnosis starts by examining the patient's 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. [5]

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. [13]

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. [14]

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. [15]

Investigations include blood tests (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 CT or 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.[ citation needed ]

During the lumbar puncture procedure, the opening pressure is measured. A pressure of over 180 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. [12]

This shows the results of polymerase chain reaction tests on a chronic Mollaret's meningitis patient, along with symptoms. PCR tests of Mollaret's Meningitis patient from Kojima et al, 2002.jpg
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. [16]

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.[ citation needed ]

The IHMF recommends that patients with benign recurrent lymphocytic meningitis receive intravenous acyclovir in the amount of 10 mg/kg every 8 hours, for 14–21 days. More recently, the second-generation antiherpetic drugs valacyclovir and famciclovir have been used to successfully treat patients with Mollaret's. Additionally, it has been reported that Indomethacin administered in the amount of 25 mg 3 times per day after meals, or 50 mg every 4 hours, has resulted in a faster recovery for patients, as well as more extended symptom-free intervals, between episodes. [1]

Prognosis

Recurring Mollaret meningitis attacks generally resolve within 3 to 5 years after the first occurrence, but some patients live with the disease for much longer. [1] With suppressive antiviral therapy, some patients who have Mollaret's report experiencing fewer attacks. However, there are some that have flare ups all throughout the year. [1]

See also

Related Research Articles

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<span class="mw-page-title-main">Viral meningitis</span> Medical condition

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<span class="mw-page-title-main">Varicella zoster virus</span> Herpes virus that causes chickenpox and shingles

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<span class="mw-page-title-main">Lumbar puncture</span> Procedure to collect cerebrospinal fluid

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<span class="mw-page-title-main">Aseptic meningitis</span> Medical condition

Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycobacteria, spirochetes, fungi, medications, and cancer malignancies. The testing for both meningitis and aseptic meningitis is mostly the same. A cerebrospinal fluid sample is taken by lumbar puncture and is tested for leukocyte levels to determine if there is an infection and goes on to further testing to see what the actual cause is. The symptoms are the same for both meningitis and aseptic meningitis but the severity of the symptoms and the treatment can depend on the certain cause.

<span class="mw-page-title-main">Viral encephalitis</span> Medical condition

Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.

<span class="mw-page-title-main">Herpetic gingivostomatitis</span> Medical condition

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<span class="mw-page-title-main">Meningoencephalitis</span> Medical condition

Meningoencephalitis, also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain tissue.

Herpes gladiatorum is one of the most infectious of herpes-caused diseases, and is transmissible by skin-to-skin contact. The disease was first described in the 1960s in the New England Journal of Medicine. It is caused by contagious infection with human herpes simplex virus type 1 (HSV-1), which more commonly causes oral herpes. Another strain, HSV-2 usually causes genital herpes, although the strains are very similar and either can cause herpes in any location.

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<span class="mw-page-title-main">Meningitis</span> Inflammation of the membranes around the brain and spinal cord

Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasionally photophobia.

Herpesviral meningitis is meningitis associated with herpes simplex virus (HSV).

<span class="mw-page-title-main">Herpes simplex encephalitis</span> Encephalitis associated with herpes simplex virus

Herpes simplex encephalitis (HSE), or simply herpes encephalitis, is encephalitis due to herpes simplex virus. It is estimated to affect at least 1 in 500,000 individuals per year, and some studies suggest an incidence rate of 5.9 cases per 100,000 live births.

Neurovirology is an interdisciplinary field which represents a melding of clinical neuroscience, virology, immunology, and molecular biology. The main focus of the field is to study viruses capable of infecting the nervous system. In addition to this, the field studies the use of viruses to trace neuroanatomical pathways, for gene therapy, and to eliminate detrimental populations of neural cells.

<span class="mw-page-title-main">Lymphocytic pleocytosis</span> Increase in lymphocytes within cerebrospinal fluid

Lymphocytic pleocytosis is an abnormal increase in the amount of lymphocytes in the cerebrospinal fluid (CSF). It is usually considered to be a sign of infection or inflammation within the nervous system, and is encountered in a number of neurological diseases, such as pseudomigraine, Susac's syndrome, and encephalitis. While lymphocytes make up roughly a quarter of all white blood cells (WBC) in the body, they are generally rare in the CSF. Under normal conditions, there are usually less than 5 white blood cells per µL of CSF. In a pleocytic setting, the number of lymphocytes can jump to more than 1,000 cells per µL. Increases in lymphocyte count are often accompanied by an increase in cerebrospinal protein concentrations in addition to pleocytosis of other types of white blood cells.

<span class="mw-page-title-main">Chronic meningitis</span> Inflammation of the membranes surrounding the brain and spinal cord lasting longer than 4 weeks

Chronic meningitis is a long-lasting inflammation of the membranes lining the brain and spinal cord. By definition, the duration of signs, symptoms and inflammation in chronic meningitis last longer than 4 weeks. Infectious causes are a leading cause and the infectious organisms responsible for chronic meningitis are different than the organisms that cause acute infectious meningitis. Tuberculosis and the fungi cryptococcus are leading causes worldwide. Chronic meningitis due to infectious causes are more common in those who are immunosuppressed, including those with HIV infection or in children who are malnourished. Chronic meningitis sometimes has a more indolent course than acute meningitis with symptoms developing more insidiously and slowly. Also, some of the infectious agents that cause chronic infectious meningitis such as mycobacterium tuberculosis, many fungal species and viruses are difficult to isolate from the cerebrospinal fluid making diagnosis challenging. No cause is identified during initial evaluation in one third of cases. Magnetic resonance imaging (MRI) of the brain is more sensitive than computed tomography and may show radiological signs that suggest chronic meningitis, however no radiological signs are considered pathognomonic or characteristic. MRI is also normal in many cases further limiting its diagnostic utility.

References

  1. 1 2 3 4 Shalabi, M; Whitley, RJ (Nov 1, 2006). "Recurrent benign lymphocytic meningitis". Clinical Infectious Diseases. 43 (9): 1194–7. doi: 10.1086/508281 . PMID   17029141.
  2. 1 2 3 4 Raimund Helbok; Gregor Broessner; Bettina Pfausler; Erich Schmutzhard (2009). "Chronic meningitis". J Neurol. 256 (2): 168–175. doi:10.1007/s00415-009-0122-0. PMID   19224317. S2CID   6218001.
  3. ↑ synd/1537 at Who Named It?
  4. ↑ Mollaret P (1944). "Méningite endothélio-leucocytaire multirécurrente bénigne. Syndrome nouveau ou maladie nouvelle? (Documents cliniques)". Revue neurologique, Paris. 76: 57–76.
  5. 1 2 3 Olaf Willmann; Parviz Ahmad-Nejad; Michael Neumaier; Michael G. Hennerici; Marc Fatar (2010). "Toll-Like Receptor 3 Immune Deficiency May Be Causative for HSV-2-Associated Mollaret Meningitis". Eur Neurol. 63 (4): 249–251. doi: 10.1159/000287585 . PMID   20375513.
  6. ↑ Ugo K. Ihekwaba; Goura Kudesia; Michael W. McKendrick (2008). "Clinical Features of Viral Meningitis in Adults: Significant Differences in Cerebrospinal Fluid Findings among Herpes Simplex Virus, Varicella Zoster Virus, and Enterovirus Infections". Clinical Infectious Diseases. 47 (6): 783–9. doi: 10.1086/591129 . PMID   18680414.
  7. ↑ Kasper, Dennis L.; Larry Jameson, J.; Hauser, Stephen L.; Loscalzo, Joseph; Fauci, Anthony S.; Longo, Dan L. (2015-04-08). Harrisons Principles of Internal Medicine (19th ed.). p. 1179. ISBN   9780071802154.
  8. ↑ Tarakad S Ramachandran, MBBS, FRCP(C), FACP (Feb 12, 2010). "Aseptic Meningitis". Emedicine. Retrieved 9 January 2011.
  9. ↑ Ohmichi, T.; Takezawa, H.; Fujii, C.; Tomii, Y.; Yoshida, T. & Nakagawa, M. (2012). "Mollaret cells detected in a patient with varicella-zoster virus meningitis". Clinical Neurology and Neurosurgery. 114 (7): 1086–7. doi:10.1016/j.clineuro.2012.02.015. PMID   22402203. S2CID   41674924.
  10. ↑ Jhaveri, Ravi M.D.; Sankar, Raman M.D.; Yazdani, Shahram M.D.; Cherry, James D. M.D. (2003). "Varicella-zoster virus: an overlooked cause of aseptic meningitis". Pediatric Infectious Disease Journal. 22 (1): 96–97. doi: 10.1097/00006454-200301000-00026 . PMID   12553305.
  11. ↑ Mollaret's meningitis at patient.co.uk
  12. 1 2 Jones CW, Snyder GE (2011). "Mollaret meningitis: case report with a familial association". Am J Emerg Med. 29 (7): 840.e1–840.e2. doi:10.1016/j.ajem.2010.02.008. PMID   20825883.
  13. ↑ Tal Kramer; Lynn W. Enquist (2013). "Directional Spread of Alphaherpesviruses in the Nervous System". Viruses. 5 (2): 678–707. doi: 10.3390/v5020678 . PMC   3640521 . PMID   23435239.
  14. ↑ Mohammed Abu Khattab; Hussam Al Soub; Mona Al Maslamani; Jameela Al Khuwaiter; Yasser El Deeb (2009). "Herpes simplex virus type 2 (Mollaret's) meningitis: A case report". International Journal of Infectious Diseases. 13 (6): e476–e479. doi: 10.1016/j.ijid.2009.01.003 . PMID   19329344.
  15. ↑ Birgitta Sundén; Marie Larsson; Tina Falkeborn; Jakob Paues; Urban Forsum; Magnus Lindh; Liselotte Ydrenius; Britt Åkerlind; Lena Serrander (2011). "Real-time PCR detection of Human Herpesvirus 1–5 in patients lacking clinical signs of a viral CNS infection". BMC Infectious Diseases. 11: 220. doi: 10.1186/1471-2334-11-220 . PMC   3176207 . PMID   21849074.
  16. ↑ Yuki Kojima; Hideyuki Hashiguchi; Tomoko Hashimoto; Sadatoshi Tsuji; Hiroshi Shoji; Yukumasa Kazuyama (2002). "Recurrent Herpes Simplex Virus Type 2 Meningitis: A Case Report of Mollaret's Meningitis" (PDF). Jpn. J. Infect. Dis. 55 (3): 85–88. PMID   12195049. Archived from the original (PDF) on 2013-01-22. Retrieved 2014-09-21.
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