Mollaret's meningitis: Cytopathologic analysis of fourteen cases

Abstract

Mollaret's meningitis (MM) is a rare disease of benign nature characterized by recurrent episodes of aseptic meningitis. Cerebrospinal fluid (CSF) examination remains the sole diagnostic modality. Eighteen CSF samples from 14 patients were studied along with the clinical data. Specimens were prepared by cytocentrifugation and Millipore filtration and were stained with Diff-Quik and Papanicolaou stains. Eight patients were men and six were women, with an age range of 17-74 yr (mean age 37 yr). Most common clinical presentation was recurrent episodes of headaches and photophobia followed by a sustained mild fever lasting 5-7 days. The CSF showed markedly increased cellularity with pleocytosis. The differential count showed predominant monocytosis ranging from 84% to 100% (mean 96). In our series, two patients had herpes simplex virus type 2 (HSV-2) DNA detected by polymerase chain reaction (PCR) in the CSF. The monocytes were seen predominantly singly, but three cases showed a strong tendency to aggregate in small groups. Phenotypically, these cells had bean-shaped bilobed nuclei as well as multiple deep nuclear clefts depicting the so-called "footprint" appearance. In four cases, multiple blunt-tipped cytoplasmic pseudopods were noted. Degenerated monocytes with the appearance of the so-called "ghost cells" were noted in one-half of the cases. Background cells were mostly small mature lymphocytes; however, one-half of cases showed a significant amount of plasma cells and/or polymorphonuclear leukocytes (PMNs). Lysed blood with hemosiderin-laden macrophages and numerous leptomeningeal cells were seen in two cases. CSF examination of MM presents a spectrum of cytomorphologic features. When interpreted in light of the appropriate clinical setting. the latter, although nonspecific, provides an accurate diagnosis. The differential diagnosis includes various degenerative, inflammatory/infectious, and lymphoproliferative disorders of the central nervous system.

Recurrent Lymphocytic Meningitis Positive for Herpes Simplex Virus Type 2

“…Symptomatic episodes of RLM usually subside within 5 years, but the total number of episodes may reach 30. Patients are typically middle-aged, and women are more often affected than men ( 1 – 3 ). In addition to symptoms typical of meningitis, ≈50% of patients have transient hallucinations, seizures, cranial nerve palsies, or an altered level of consciousness ( 4 ).…”

Follow the Footprints to the Diagnosis in a Patient with Meningismus

“…Since then, electron microscopy and immunohistochemistry have confirmed this cell to be a monocyte [2]. Although our patient had a 4-day history of disease, Mollaret cells are usually present during the acute phase of the disease and are most prevalent during the first 24 h, and therefore they can be easily missed [2].…”

Mollaret Meningitis may be Caused by Reactivation of Latent Cerebral Toxoplasmosis

“…It was thought that over time, the number of recurrent episodes of MM decrease, but several cases of this entity reported in older patients (Monteyene et al, 1996;Ruben, 1994;Szabo et al, 1983;Chan et al, 2003;Tedder et al, 1999;Pisani, Fattorello, Leotta, Marcello, & Zuliani, 1999;Ikari, Kuzuya, Yoshimine, Sugita, & Kazuya, 1993) suggest that advancing age is not protective (Monteyene et al, 1996;Tedder et al, 1994;Dylewski & Bekhor, 2004). This phenomenon also may be explained by eventual reactivation of the CNS T. gondii infection/inflammation in these elderly subjects with MM, because general population studies performed in adult subjects showed that plasma levels of TNF-α, sTNF-R p55 and p75, and IL-6 are significantly increasing with age (Himmerich et al, 2006).…”

“…The cerebrospinal fluid (CSF) contains large friable mononuclear cells thought to be of endothelial origin (vasculitis?) (Szabo, Majtenyi, & Guseo, 1983;Bamborschke, Sandmann, & Wullen, 1990;Pampliega-Perez et al, 2003), with blunt pseudopods (a "footprint" appearance) and bean-shaped and bilobed nuclei (Evans, 1993;Chan, Parvani, Levi, & Ali, 2003;Sendi & Garber, 2006). These cells, observed for only the first 24 hr ("ghosts" cells) and now considered to be activated macrophages (Ginsberg, 2004), may comprise 60%-70% of cells in the CSF.…”