Mollaret's Meningitis Research Articles

Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

Lifetime quality-adjusted life years lost due to genital herpes acquired in the United States in 2018: a mathematical modeling study

Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost. We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18-49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States. We estimated 0.05 (95% uncertainty interval (UI) 0.02-0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01-0.02) and 0.05 (95% UI 0.02-0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63-9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600-67,900) due to GH in adults and 3,140 (95% UI 2,260-4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences. GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH. The Center for Disease Control and Prevention.

Клінічний випадок поєднання вторинного головного болю з рецидивуючими генітальними висипаннями в iмунокомпетентної жінки

У статті наведено детальний аналіз клінічного випадку рецидивуючих епізодів вираженого головного болю з появою висипання в ділянці зовнішніх статевих органів у імунокомпетентної жінки. Описано особливості перебігу цiєї патології, наведено результати лабораторного обстеження з обґрунтуванням вибору методів і оцінкою ефективності терапії. Наведено аналіз і класифікацію можливих інфекційних та неінфекційних етіологічних причин головного болю відповідно до Міжнародного товариства головного болю. Подано історичну довідку про менінгіт Молларе, діагностичні критерії цього діагнозу, описано терапію і прогноз. Також проведено диференціальну діагностику інших причин доброякісного рецидивуючого асептичного менінгіту. У результаті диференціального підходу в наведеному клінічному випадку був діагностований менінгіт Молларе. У статті описано особ­ливості цієї патології і діагностичні критерії, обговорено можливі етіологічні причини і схеми терапії. Підкреслено необхідність і ефективність тривалої супресивної хіміотерапії для профілактики повторних епізодів клінічного загострення в терапії менінгіту Молларе.

Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis.

Recurrent lymphocytic meningitis, also referred to as Mollaret meningitis, is a rare neurological disease characterized mainly by reactivation of herpes simplex virus 2 (HSV-2) from sensory ganglia. However, the underlying host immune determinants and viral factors rendering some individuals unable to maintain HSV-2 latency are largely unknown. We collected a cohort of 15 patients diagnosed with Mollaret meningitis. By whole-exome sequencing we identified rare host genetic variants predicted to be deleterious in molecules involved in (1) ubiquitin-proteasome pathways, (2) the autophagy machinery, and (3) cell proliferation/apoptosis. Moreover, infection of patient cells with HSV-2 or stimulation by virus-derived double-stranded DNA ligands revealed reduced antiviral interferon responses in most patients. These findings may contribute to a better understanding of disease pathogenesis and protective immunity to HSV in the central nervous system, and may ultimately be of importance for identification of targets for development of improved prophylaxis and treatment of this disease.

Mollaret's Meningitis: CSF Cytology to the Rescue

Mollaret's meningitis refers to the classical description by Pierre Mollaret of recurrent episodes of fever and meningism lasting 2-5 days, followed by spontaneous recovery. It remains a rare entity and most often is attributed to reactivation of latent Herpes Simplex virus (HSV)-2 virus. Though considered self-limiting and innocuous, there are exceptional cases in which neurological sequelae have been reported. From a clinician's perspective, narrowing down the diagnosis may not be straightforward and would require judicious use of investigations. Here we report two cases of Mollaret's meningitis, both of whom had negative cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for HSV. These reports also highlight an unusual pattern of presentation of this rare entity and the utility of CSF cytology in clinching the diagnosis.

Benigh Reccurent Lymphocytic Meningitis (Mollaret Meningitis): a Case Report

The article reports a clinical case of a patient with four recurring episodes of headache, nausea and focal neurological symptoms (hemiparesis, sensorimotor aphasia, adversive epileptic seizures) with a rapid onset of remission. The clinical picture of the disease was supplemented with lymphocytic pleocytosis and cell-protein dissociation in the cerebrospinal fluid, which allowed to diagnose benign recurrent lymphocytic meningitis (Mollaret meningitis) and to conduct pathogenetic therapy. The aim of this work is to improve the diagnosis of rare Mollaret meningitis.

Meningite de Mollaret

Introdução: Meningite de Mollaret consiste em uma forma de meningite asséptica, sendo considerada uma patologia rara, haja visto a revisão literária mundial apresentar aproximadamente 50 casos descritos até o momento. Objetivo: Descrição de caso de meningite asséptica decorrente de lesão expansiva epidermóide. Método: Mulher submetida à ressecção retrossigmoidéia de tumor epidermóide em ângulo ponto-cerebelar a direita evoluindo sem déficits no pós-operatório imediato, mas evoluindo, no pós-operatório tardio, com meningismo e deficit de nervos cranianos contralaterais à lesão primária. Exames de propedêutica liquórica evidenciaram meningite sem crescimento de microorganismos. Discussão: A cascatainflamatória sistêmica desencadeada por essa patologia pode gerar um estado toxêmico, assemelhando-se clinicamente a meningite bacteriana. O estudo liquórico não evidencia agente causador, a despeito da elevação de polimorfonucleares e a redução da glicorraquia. O risco de desenvolver meningite asséptica pode ser reduzido, evitando-se contaminação do conteúdo cístico no espaço subaracnóide, removendo cuidadosamente todo tecido cístico e administrando corticoterapia no perioperatório. Conclusão: Meningite asséptica é uma patologia rara, sem consenso a respeito de seu manejo, justificando a necessidade de acúmulo de conhecimentos a partirde relatos de casos em todo o mundo

Mollaret Meningitis with High Level of Cytokines in CSF Successfully Treated by Indomethacin

A rare case of Mollaret meningitis characterized by four recurrent episodes of aseptic meningitis during the 3-year periods were reported. The patient showed high fever and severe headache accompanied by high level of cerebrospinal fluid (CSF) cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alfa (TNF-a). The symptoms and high CSF cytokines were dramatically resolved immediately after inducing indomethacin treatment. Reactivation of the latent virus is considered to be the cause of this rare disease and indomethacin is estimated to inhibit periodic abnormal generation of eicosanoid in the brain resulting in reducing fever and subsequent inflammation.

Cerebrospinal fluid cytology in nonmalignant aseptic meningeal disorders.

Cerebrospinal fluid cytology examination is a common and reliable primary and/or complementary procedure for the diagnosis of central nervous system (CNS) disorders. This review provides an update of aseptic meningeal disorders that may be encountered in cytopathology practice. The article covers the cytological findings and helpful ancillary studies needed of nonmalignant aseptic CNS disorders such as viral, bacterial, fungal and parasitic infections, and other noninfectious diseases, such as Mollaret's meningitis (recurrent benign lymphocytic meningitis), Guillain-Barré syndrome, multiple Sclerosis, subarachnoid haemorrhage, and drug-induced disorders.

Ketamine-Induced Crystalline Gastritis

Ketamine is an anesthetic agent commonly used for various pain syndromes. It is also a recreational drug. It is rarely prescribed orally because of its poor oral bioavailability. Oral dosages range from 0.5 mg/kg/day to 21 mg/kg/day based on the indication. A recent retrospective analysis reported gastropathy and gastritis in 80% of oral and inhalational ketamine users. A 27-year-old man with Mollaret's meningitis was admitted for intractable neuropathic pain; only parenteral ketamine provided symptomatic relief. He was later transitioned to oral ketamine, and prescribed up to 28 mg/kg/day for symptom control. One week later, he developed acute burning mid-epigastric pain and nausea. EGD revealed multiple “Band-Aid®”- like superficial plaques in the gastric cardia (Figure 1). Biopsy specimens showed active inflammation and deposits of clear refractile crystals in the gastric mucosa (Figure 2). Our clinical impression was ketamine-induced gastritis. Ketamine was discontinued and then reintroduced at 4 mg/kg/day. The patient's epigastric symptoms resolved. Three weeks later, a repeat EGD confirmed mucosal healing and absence of plaque. Biopsy specimens revealed inactive gastritis without crystalline deposition.Figure 1Figure 2This report is the first description in the literature of a crystalline-associated reactive gastritis in a patient on oral ketamine. The clinical features that support causality with ketamine include abrupt symptom onset with initiation of ketamine, lack of clinical or endoscopic features to suggest an alternative diagnosis, and prompt histologic and clinical resolution with cessation of ketamine. We speculate that crystalline-associated reactive gastritis is a dose-dependent phenomenon, as our patient was on a higher total dosage of oral ketamine than described in the literature. There were no excipients in the ketamine capsules that may have crystallized in vivo, suggesting ketamine crystallization was responsible for the patient's reactive gastritis. To investigate this hypothesis, we suspended a 5% solution of ketamine in normal saline. The specimen was examined under white light and polarizing light microscopy. Clear refractile crystals (Figure 3), similar to our patient's gastric biopsy specimen, were noted.Figure 3Our analysis strongly supports a case of ketamine-induced crystalline gastritis. Practitioners should be aware of this previously undescribed complication of oral ketamine.

Mollaret's meningitis and enterovirus infection

Mollaret's meningitis is a rare form of meningitis characterised by recurrent episodes of aseptic lymphocytic meningitis in otherwise healthy individuals. These episodes are often mild and self-limiting, with symptom-free intervals and no long-term neurological sequelae. Herpes simplex virus infection is by far the most common infectious aetiology. We report a case of Mollaret's meningitis in an otherwise healthy 8-year-old girl who presented with three distinct episodes of aseptic meningitis and frequent headaches over a 2-year period. Polymerase chain reaction for enterovirus (EV) RNA in the cerebrospinal fluid (CSF) was positive during her first episode. Diff Quik stained CSF preparations were positive for Mollaret cells during her second and third episodes. This is the first reported case of Mollaret's meningitis from EV infection. Early identification of the condition can avoid extensive investigations during recurrent episodes.

Herpes simplex virus type 2-associated recurrent aseptic (Mollaret's) meningitis in genitourinary medicine clinic: a case report

IntroductionCases of idiopathic recurrent benign aseptic meningitis were first described by Mollaret. Today, herpes simplex virus (HSV) is considered the cause of most cases of Mollaret’s meningitis.Case reportA 40-year-old male was referred to our genitourinary medicine clinic with recurrent genital herpetic lesions. He had HSV-2-positive genital ulcers 8 years earlier. One year after the first infection, he developed severe recurrent attacks of headache associated with meningitis symptoms. The results of all radiological and biochemical tests were normal, but the patient reported a correlation between his attacks and genital herpes flare-ups. We diagnosed the patient with Mollaret’s meningitis and started him on continuous suppressive acyclovir therapy, which resulted in marked clinical improvement.DiscussionMollaret’s meningitis is a rare form of idiopathic recurrent aseptic meningitis that has a sudden onset, short duration, and spontaneous remission with unpredictable recurrence. We believe that the presence of concurrent or recurrent mucocutaneous herpetic lesions can aid its diagnosis, prior to which, affected patients usually have many unnecessary investigations and treatments. Therefore, detailed sexual history should be sought in all patients with aseptic meningitis, and clinicians should also ask about history of recurrent headaches in all patients with recurrent herpetic anogenital lesions. Continuous suppressive acyclovir therapy may reduce the frequency and severity of attacks and can dramatically improve lifestyle.

About the Need to Review the Fredericks and Bruyn Criteria for Mollaret's Meningitis Diagnosis

According to the recent World Health Organization’s large-scale studies, about a third of the adult worldwide population suUˆU´er from a mental disorder such as depression, anxiety and schizophrenia. If also taken together with neurological disorders, such as dementia and stroke, these “disorders of the brain” account for 13% of the global disease burden. Нis surpasses both cardiovascular diseases (5%) and cancer (10%). Countries with the highest rate of burden >650 Disability Adjusted Life Years [DALYs] per 100,000 population included the USA, UK, Russia, and Australia. Нe annual cost of taking care of patients with neurological disorders in the US alone approaches $400B of which $200B is for Alzheimer patients. We believe that this cost in 10 years could reach to $1T in the US alone. In China 975,000 people die annually from brain trauma alone and the Alzheimer population in the Australasia corridor is rapidly on the rise. Нus, European Union, China, India, Japan and Australia are not immune from such high cost of healthcare despite having 100% government insurance

コルヒチンが有効なMollaret髄膜炎で，<i>MEFV</i>遺伝子変異をみとめた1例

A 66-year-old woman was admitted to our hospital with recurrent meningitis. She presented with 10 episodes of meningitis in 10 months. Examination of cerebrospinal fluid demonstrated pleocytosis, with neutrophils dominant at the early stage, and lymphocytes dominant at the late stage. Mollaret cells were found and the level of IL-6 was increased in cerebrospinal fluid. Several antibiotics and antiviral agents failed to prevent relapse. However, colchicine therapy successfully prevented the recurrence of meningitis. Genetic testing for familial Mediterranean fever (FMF) showed a mutation in the MEFV gene. It is difficult to diagnose the cause of Mollaret's meningitis in some patients. FMF, neuro-Behçet's disease, and neuro-Sweet disease should be included in the differential diagnosis of recurrent meningitis. In addition, colchicine therapy can prevent the relapse of meningitis in such cases.

Recurrent aseptic (Mollaret's) meningitis in a young girl

Abstract Mollaret's meningitis is a recurrent benign aseptic meningitis mainly occurring in adults. We report a 9-year-old female child with three episodes of recurrent aseptic meningitis with periods of complete normalcy in between the episodes. Her neuroimaging findings were normal. The investigations for immunodeficiency and for the presence of structural nervous system anomaly were also normal. Herpes simplex virus (HSV) deoxyribonucleic acid (DNA) polymerase chain reaction test was negative in the cerebrospinal fluid (CSF). The patient was diagnosed with Mollaret's meningitis on the basis of the clinical course, CSF findings, and absence of other causes for the meningitis.

Mollaret cells detected in a patient with varicella-zoster virus meningitis

Mollaret cells, which are observed in recurrent aseptic meningiis (Mollaret meningitis), have a unique bean-shaped nucleus with uclear clefts and are extremely fragile and difficult to detect for ore than 24 h after the appearance of symptoms [1]. The presnce of herpes simplex virus-2 (HSV-2) in the cerebrospinal fluid CSF), as detected by polymerase chain reaction (PCR), has recently een associated with Mollaret meningitis [2,3]. We present the rst report of a patient diagnosed with varicella-zoster virus (VZV) eningitis with Mollaret cells in CSF.

Rezidivierende Kopfschmerzepisoden

Mollaret's meningitis is a recurrent meningitis, usually caused by Herpes simplex virus type 2. Symptoms are typical for meningitis, but other causes for recurrent and chronic meningitis have to be excluded in the cerebrospinal fluid. Usually Mollaret's meningitis is a benign form of meningitis without sequelae. There are no evidence-based data about therapy because of few reported cases.

A case of recurrent benign lymphocytic (Mollaret's) meningitis and review of the literature

Mollaret's meningitis is a rare form of benign recurrent aseptic meningitis first described in 1944. We report a case of Mollaret's meningitis due to Herpes Simplex Virus type 2 (HSV2), diagnosed with Polymerase Chain Reaction (PCR) implementation in the Cerebrospinal fluid (CSF) of the patient and treated successfully with acyclovir. To our knowledge, this is the first case of Mollaret's meningitis reported in Greece. We reviewed the literature since PCR has become widely available. Herpes Simplex Virus type 2 has been the most commonly identified causative agent of Mollaret's meningitis.

Mollaret meningitis: a case report

Mollaret meningitis is characterized by three or more episodes of benign recurrent aseptic meningitis in which symptoms and signs resolve spontaneously within two to five days. Severe headache with an acute onset, fever and meningismus are the main clinical features. We report a case of Mollaret meningitis in a seven-year-old girl who presented with four aseptic meningitis episodes in one year.

Mollaret meningitis: case report with a familial association

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.