To discuss inclusion criteria for sending cerebrospinal fluid(CSF)pathogen metagenomic next-generation sequencing(mNGS).

Although mNGS has shown diagnostic superiority in infection, due to its indifference nature,lacking of standards for sending samples bring false positivities.

From March 2017 to April 2020, Department of Neurology, Beijing Tongren Hospital parallelly sent CSF of 35 patients for pathogen mNGS and conventional pathogen testing. Sensitivities, specificities and Youden's indexes of mNGS and conventional testing were compared. Receiver operating characteristic (ROC) curves and areas under the curve (AUC) were used to compared diagnostic efficacies of two methods. Patients were then scored according to  inclusion criteria for sending CSF mNGS  based on diagnostic criteria for encephalitis proposed by international encephalitis consortium, one score for each item with maximum scores 7. Positive coincidence rates of CSF mNGS with clinical diagnoses of CNS infection of each score were calculated.

Nineteen of 35 patients were clinical diagnosed as CNS infection. Eighteen cases were positive with CSF mNGS, while seventeen cases were positive with conventional testing. Seventeen cases of clinical diagnosed CNS infection were CSF mNGS positive, with diagnostic sensitivity 17/19, specificity 15/16 and Youden index 0.832. Fourteen cases of clinical diagnosed CNS infection were conventional testing positive, with diagnostic sensitivity 14/19, specificity 13/16 and Youden index 0.612. AUC of CSF mNGS was 0.916 (95%CI: 0.822-1.000, P=0.000), and AUC of conventional testing was 0.806 (95%CI: 0.674-0.938, P=0.000). There was no difference in diagnostic efficacies between mNGS and conventional testing (Z= 1.245, P= 0.213). The positive coincidence rates of mNGS with clinical infection showed a trend of increase with scores, and notably cases ≥ 3 scores had higher positive coincidence rates than cases < 3 scores (P= 0.000).

Sending CSF according to objective inclusion criteria based on diagnostic criteria for encephalitis proposed by international encephalitis consortium may improve positive coincidence rate of pathogen mNGS.