Article
Increased detection of FAS ligand in cerebrospinal fluid in patients with degenerative cervical myelopathy – an indication of apoptosis as part of pathophysiology
Erhöhte Detektion des FAS-Ligand im Liquor bei Patienten mit degenerativer zervikaler Myelopathie – ein Hinweis auf Apoptose als Teil der Pathophysiologie
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Authors
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Christian Blume
- Rheinisch-Westfälische Technische Hochschule Aachen, Neurochirurgie, Aachen, Deutschland
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Lars Ove Brandenburg
- Rheinisch-Westfälische Technische Hochschule Aachen, Institut für Anatomie und Zellbiologie, Aachen, Deutschland
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Hans Rainer Clusmann
- Rheinisch-Westfälische Technische Hochschule Aachen, Klinik für Neurochirurgie, Aachen, Deutschland
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Verena Mainz
- Rheinisch-Westfälische Technische Hochschule Aachen, Klinik für Psychiatrie, Aachen, Deutschland
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Alexander Riabikin
- Rheinisch-Westfälische Technische Hochschule Aachen, Klinik für Neuroradiologie, Aachen, Deutschland
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Kerstin Jütten
- Rheinisch-Westfälische Technische Hochschule Aachen, Klinik für Neurochirurgie, Aachen, Deutschland
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Christian Andreas Mueller
- Rheinisch-Westfälische Technische Hochschule Aachen, Klinik für Neurochirurgie, Aachen, Deutschland
| Published: | June 26, 2020 |
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Outline
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Objective: Apoptosis plays an important role in determining neurological outcome in degenerative cervical myelopathy (DCM) based on clinically relevant animal models and cadaver studies. These show that FAS mediated apoptosis plays a role in demyelination and axonal dysfunction, leading to the development of neurological deterioration in DCM. The aim was to detect FAS ligand (FASL) in CSF, in vivo in patients with DCM.
Methods: Patients with DCM and indication for surgery were included. Patients were monitored for neurological symptoms (NDI/mJOA). CSF samples were taken pre- and 3 months postoperatively. A control group of patients with thoracic abdominal aortic aneurysm surgery (TAAA-group), who needed a lumbar drain for intraoperative CSF pressure monitoring was established. The control group was monitored to exclude neurological signs of DCM (NDI/mJOA). CSF samples were taken preoperatively. The samples were evaluated via ELISA. Protein-concentrations of FAS ligands (FASL) were measured in CSF pg/ml.
Results: Overall 21 patients (mean age 63y) and 32 controls (mean age 60 years; p=0.411) were included. In 21 cases FASL was preoperatively examined, in 8 patients postoperatively. Preoperative clinical scores: mJOA DCM group 10.15±2,9, TAAA group 17.3±1.2 (p<0.001); NDI DCM group 45.2±21.7, TAAA group 5.6±9.0 (p=<0.001). Significant differences of preoperative concentrations of FASL were detected in CSF: DCM group 179.5±73.9 pg/ml, TAAA group 138.5±35.1 pg/ml (p=0.009). In DCM patients, the preoperative FASL concentrations were reduced in each patient (179.5±73.9 pg/ml) versus postoperative values (73.5±30.5) but did not reveal statistically significant differences (p=0.074).
Conclusion: FASL initiates cytokine production by binding to FAS on microglia or astrocytes, which also lead to cell death in the lesion zone in animal model and cadaver study. This is the first time that FASL could be detected in DCM patients. We hypothesize, that blockade of FASL could be a therapeutic target in DCM to prevent apoptotic cell death. A larger postoperative cohort is necessary to determinate how far surgery in DCM is beneficial concerning FASL mediated cell death.
