Chasing shadows: Cytologically detected shadow cells in the cerebrospinal fluid of patients with multiple sclerosis

Background: Pathophysiology of multiple sclerosis (MS) is dominated by both inflammation and neurodegeneration. A correlation between inflammation and regulated cell death has been suggested previously. Shadow cells in the cerebrospinal fluid (CSF) are considered apoptotic cells. Objective: To assess the occurrence of shadow cells in MS patients in comparison to other neurological diseases (OND).Methods: We conducted cytological examination of CSF in 114 MS patients and 125 patients with OND, who had diagnostic lumbar puncture at the Department of Neurology, Medical University of Innsbruck, with time to laboratory processing <= 0.5 h, showed a CSF white blood cell (WBC) count <= 50/mu l and a red blood cell (RBC) count <= 500/mu l. Shadow cells were counted by two blinded, independent, experienced investigators, using a standardized approach on microscopic slides.Results: The number of shadow cells did not statistically significantly differ between patients with MS (median: 12, IQR: 0-85) and OND (median 6, IQR: 0-94; p = 0.106). Multivariable regression analysis including age, sex, time to laboratory processing, CSF WBC and RBC count, CSF/serum glucose ratio, CSF/serum albumin quotient and disease group as independent variables, identified WBC count as significant predictor of shadow cells (beta [ln WBC count]=0.73, p<10-9), whereas the disease group had no impact (p = 0.466).Conclusions: Occurrence of shadow cells in the CSF seems to depend on the extent of inflammatory cells rather than MS disease-specific mechanisms.