Galán L, Matías-Guiu J, Matias-Guiu J A, Yáñez M, Pytel V, Guerrero-Sola A, Vela-Souto A, Arranz-Tagarro J A, Gómez-Pinedo U, García A G
Department of Neurology, Institute of Neurosciences, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Madrid, Spain.
Department of Pharmacology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
Acta Neurol Scand. 2017 Sep;136(3):212-216. doi: 10.1111/ane.12717. Epub 2016 Dec 29.
Cerebrospinal fluid (CSF) from some patients with amyotrophic lateral sclerosis (ALS) has been demonstrated to significantly reduce the neuronal viability of primary cell cultures of motor neurons. We aimed to study the potential clinical consequences associated with the cytotoxicity of CSF in a cohort of patients with ALS.
We collected CSF from thirty-one patients with ALS. We analysed cytotoxicity by incubating it into the primary cultures of motor cortex neurons. Neural viability was quantified after 24 hours using the colorimetric MTT reduction assay. All patients were followed up from the moment of diagnosis to death, and a complete evaluation during disease progression and survival was performed, including gastrostomy and respiratory assistance.
Twenty-one patients (67.7%) presented a cytotoxic CSF. There were no significant differences between patients with and without cytotoxicity regarding mean time from symptom onset to the diagnosis, from the diagnosis to death, from the diagnosis to respiratory assistance with BIPAP, from diagnosis to gastrostomy and from the onset of symptoms to death. In Cox regression analysis, bulbar onset, but not cytotoxicity, gender or age at onset, was associated with a lower risk of survival.
Cerebrospinal fluid cytotoxicity was not associated with differential survival rates. This suggests that the presence of cytotoxicity in CSF, measured through neuronal viability in primary cultures of motor cortex neurons, could reflect different mechanisms of the disease, but it does not predict disease outcome.
已证实一些肌萎缩侧索硬化症（ALS）患者的脑脊液（CSF）能显著降低运动神经元原代细胞培养物的神经元活力。我们旨在研究ALS患者队列中与脑脊液细胞毒性相关的潜在临床后果。
我们收集了31例ALS患者的脑脊液。通过将其孵育到运动皮质神经元的原代培养物中来分析细胞毒性。使用比色法MTT还原试验在24小时后对神经活力进行定量。所有患者从诊断时刻起直至死亡都进行了随访，并在疾病进展和生存期间进行了全面评估，包括胃造口术和呼吸辅助。
21例患者（67.7%）的脑脊液具有细胞毒性。在有和没有细胞毒性的患者之间，从症状出现到诊断、从诊断到死亡、从诊断到使用双水平气道正压通气（BIPAP）进行呼吸辅助、从诊断到胃造口术以及从症状出现到死亡的平均时间没有显著差异。在Cox回归分析中，延髓起病而非细胞毒性、性别或起病年龄与较低的生存风险相关。
脑脊液细胞毒性与不同的生存率无关。这表明，通过运动皮质神经元原代培养物中的神经元活力来衡量的脑脊液中细胞毒性的存在，可能反映了疾病的不同机制，但它并不能预测疾病的结局。
