Cerebrospinal fluid cytology: differential diagnosis and prognostic value in demyelinating diseases of the central nervous system

Background Cerebrospinal fluid (CSF) examination provides useful diagnostic information in many central nervous system (CNS) diseases, such as inflammatory, neoplastic and demyelinating. The aim of the study was to assess the role of CSF cytology in the differential diagnosis of CNS pathology and its prognostic value in CNS demyelinating diseases. The study consists of 2 parts: 1. Evaluation of the role of CSF cytology in diagnosing neoplastic, infectious and demyelinating CNS diseases and their differential diagnosis. 2. Assessment of the predictive value of CSF cytology as early risk stratification for conversion to MS. Materials and methods We reviewed the CSF analysis of 86 patients: 4 patients with neoplastic meningitis, 2 patients with infectious meningitis, 57 patients with clinically isolated syndrome (CIS), 20 patients with MS, 2 patients with neuromyelitis optica (NMO) and 1 patient with anti-TNF-α-related CNS demyelination. Results CSF cytological analysis in patients with neoplastic meningitis revealed malignant cells, characterized by the presence of following characteristics: large size and/or nuclei; increased nucleus/cytoplasm ratio in favor of the nucleus; multiple nuclei; prominent or multiple nucleoli; variation in the size and shape of the cells and nuclei; high mitotic count, frequent atypical mitosis; irregular nuclear edges, hyperchromasia and irregular distribution of the nuclear chromatin. When appropriate, malignancy of the CSF atypical cells in these patients was also confirmed by immunophenotypic markers. CSF analyses in bacterial meningitis and viral meningitis demonstrated the typical CSF cytological characteristics: the increased white blood cell count (WBC) with more than 90% neutrophils in bacterial meningitis, and less elevated WBC count with small mature and reactive lymphocytes in viral meningitis. In a group of patients with CNS demyelinating diseases, CSF analysis demonstrated the same degree of activation of both lymphocytic and monocytic lineages in MS and CIS groups (MS: 48% and 52% respectively, CIS: 54.5% and 43.5%, respectively). These figures were quite different from the findings in anti-TNF-α-related enkephalomyelitis in acute phase (11% and 89%, respectively), characterized by prominent activation of monocyte/macrophage lineage with large kidney-like shaped nuclei. CSF cytology in 2 patients with NMO during the relapse phase (n=3) showed increased number of granulocytes (77%). Role of CSF analysis in predicting the conversion from CIS to clinically definite MS (CDMS). During a median follow-up of 86 months, 43 (75.4%) patients with CIS converted to CDMS. CSF analysis revealed more than 4 WBC/mm3 in 28 (49.3%) patients and CSF Ig oligoclonal bands (IgOB) in 41 (71.9%) patients. Median WBC count in patients with CIS who developed CDMS was 5 (range, 0-45) WBC/mm3, and in patients that have not still had CDMS at the end of follow-up was 2.5 (1-12) WBC/mm3 (p=0.03). All CIS patients (n=24) with both WBC>5/mm3 and IgOB positive developed CDMS after median period of 10.6 months (range, 3.4-61.8) after CIS. Conclusions 1. CSF cytological examination is an essential part of the armamentarium of routine techniques for the examination of CNS diseases, such as neoplastic, infectious and demyelinating diseases, thus permitting an adequate and reliable differential diagnosis them. 2. CSF analysis with assessment of WBC and IgOB at the time of CIS improves the prediction of CDMS outcome in patients.