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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Chasing shadows: Cytologically detected shadow cells in the cerebrospinal fluid of patients with multiple sclerosis
Klaus Berek1, Franziska Di Pauli1, Michael Auer1
1Department of Neurology, Neuroimmunology Laboratory, Medical University of Innsbruck, Innsbruck, Austria.
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/µl and a red blood cell (RBC) count ≤500/µl. 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 (β [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.
Insights
Shadow cells in cerebrospinal fluid (CSF) did not differ between multiple sclerosis (MS) and other neurological diseases (OND). Their presence correlates with white blood cell count, not MS-specific factors, indicating inflammation drives their occurrence.
Area of Science:
- Neuroscience
- Cell Biology
- Clinical Neurology
Background:
- Multiple sclerosis (MS) pathophysiology involves inflammation and neurodegeneration.
- Regulated cell death, including apoptosis, is implicated in MS.
- Shadow cells in cerebrospinal fluid (CSF) are hypothesized to be apoptotic cells.
Purpose of the Study:
- To investigate the prevalence of shadow cells in the CSF of MS patients.
- To compare shadow cell occurrence in MS versus other neurological diseases (OND).
Main Methods:
- Cytological examination of CSF samples from 114 MS patients and 125 OND patients.
- Standardized microscopic analysis by two blinded investigators.
- Inclusion criteria: CSF white blood cell (WBC) count ≤50/µl and red blood cell (RBC) count ≤500/µl, with rapid laboratory processing (≤0.5 h).
Main Results:
- No statistically significant difference in shadow cell counts between MS and OND groups (p=0.106).
- Multivariable regression identified CSF WBC count as a significant predictor of shadow cells (p<10⁻⁹).
- Disease group (MS vs. OND) did not impact shadow cell presence (p=0.466).
Conclusions:
- Shadow cell occurrence in CSF is associated with the level of inflammatory cells.
- The presence of shadow cells is not specific to multiple sclerosis.
- Inflammation, rather than MS-specific mechanisms, appears to drive shadow cell formation.
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