Mollaret Meningitis may be Caused by Reactivation of Latent Cerebral Toxoplasmosis

Abstract

Mollaret meningitis (MM) occurs mainly in females and is characterized by recurrent episodes of headache, transient neurological abnormalities, and the cerebrospinal fluid containing mononuclear cells. HSV-2 was usually identified as the causative agent. Recently, we found that recurrent headaches in non-HIV-infected subjects were due to acquired cerebral toxoplasmosis (CT). The aim of the study was therefore to focus on molecular pathomechanisms that may lead to reactivation of latent CT and manifest as MM. Literature data cited in this work were selected to illustrate that various factors may affect latent CNS Toxoplasma gondii infection/inflammation intensity and/or host defense mechanisms, i.e., the production of NO, cytokines, tryptophan degradation by indoleamine 2,3-dioxygenase, mechanisms mediated by an IFN-gamma responsive gene family, limiting the availability of intracellular iron to T. gondii, and production of reactive oxygen/nitrogen species, finally inducing choroid plexitis and/or vasculitis. Examples of triggers revealing MM and accompanying disturbances of IFN-gamma-mediated immune responses that control HSV-2 and T. gondii include: female predominance (female mice are more susceptible to T. gondii infection than males); HSV-2 infection (increased IFN-gamma, IL-12); metaraminol (increased plasma catecholamine levels, changes in cytokine expression favoring T(H)2 cells responses); probably cholesterol contained in debris from ruptured epidermoid cysts (decreased NO; increased TNF-alpha, IL-6, IL-8). These irregularities induced by the triggers may be responsible for reactivation of latent CT and development of MM. Thus, subjects with MM should have test(s) for T. gondii infection performed obligatorily.

The Importance of Toxoplasma Gondii Infection in Diseases Presenting With Headaches. Headaches and Aseptic Meningitis May Be Manifestations of the Jarisch-Herxheimer Reaction

“…Calcified cavernous hemangioma in the left occipital region had also been described in a 45-year-old woman with frequent episodes of disorientation, confusion, agitation, delusion, and multiple seizure-type changes in EEG. One may suggest that these and other cases of calcifications in the brain were the result of reactivation of latent CT (Prandota, 2009a(Prandota, , 2009b(Prandota, , 2009c. Also, reactivation of latent CT was probably associated with the development of anaplastic ependymoma in a 30-year-old woman hospitalized because of a one week history of persistent right-sided retro-orbital pain and blurred vision, and diagnosed with IIH (Rourke, Davies, & Samandouras, 2008).…”

Significant Reduction of Brain Cysts Caused by Toxoplasma gondii after Treatment with Spiramycin Coadministered with Metronidazole in a Mouse Model of Chronic Toxoplasmosis

“…In vitro studies that mimic an immunocompromised state have shown that the conversion occurs within 1 week regardless of the age of the brain cysts (5). In immunocompetent hosts, the presence of cysts caused by T. gondii (referred to here as "T. gondii cysts") in the brain seems to be associated with various neurological disorders (27), including cryptogenic epilepsy (37), migraine (25), schizophrenia (38), Malloret meningitis (26), and affective (36) and behavioral (11) disorders.…”

Unexplained Liver Damage, Cryptogenic Liver Cirrhosis, and Steatohepatitis May Be Caused by Latent Chronic Toxoplasmosis

“…In addition, pyrin appeared to have both inhibitory and potentiating effects on IL-1β production and played a role in regulating NF-κB activation and apoptosis [105,106] . It was suggested that in patients with FMF T. gondii infection plays an important role in the pathogenesis of Mollaret meningitis [107] . Moreover, in human astroglia cells and in murine mast cells infected with T. gondii tachyzoites, the parasite induced upregulation of profibrotic factors, such as matrix metalloproteinase-2 and -9 (MMPs) via Erk1/2-NF-κB pathway [108] , and MMPs are a family of the extracellular matrix-degrading enzymes that are generally synthesized and secreted as latent soluble enzymes requiring activation in the extracellular space [109] .…”