In this study, the outcomes of patients receiving integrated blood purification (HP + CVVHDF) treatment with conventional treatment were compared with those who received only the CVVHDF and conventional treatment. It was found that the efficacy of HP combined with CVVHDF in the treatment of children with severe viral encephalitis was better than using CVVHDF only, particularly for improving motor function.

There was no significant difference in the GCS scores, speech function, swallowing function, 7-day and 14-day mortality between the experimental group and control group A. The results of this study showed that the GCS score improved significantly after treatment in two groups, i.e. those who had received HP + CVVHDF, as well as those who had received CVVHDF only. This was consistent with existing studies. Liu Min et al. [17] found that the GCS scores of children with severe viral encephalitis treated by continuous blood purification were better than those who received traditional treatment only. Ni Jingwen et al. [18] also found that blood purification in children with influenza-related nervous system injuries could result in improvement of the GCS score and nervous system function and relieve intracranial hypertension.

Compared with children with mild viral encephalitis (control group B), the CSF NPT levels in children with severe viral encephalitis (the experimental group and control group A) were significantly higher. A correlation between NPT concentration in CSF and the CSF viral load was previously described [19]. Molero-Luis M et al. [20] found that CSF NPT levels higher than 61 nmol/L were helpful for distinguishing inflammatory and non-inflammatory neurological diseases but could not identify the aetiology of neurological disease. They also found that CSF NPT levels were significantly increased in inflammatory neurological diseases caused by both bacterial and viral infections.

This study found that the extent of lesions on brain MRI in mild and severe viral encephalitis correlated positively with CSF NPT levels. Magnetic resonance imaging can detect the location of a specific lesion and its size. It is highly intuitive and has important reference value for the diagnosis and prognosis evaluation of children [21]. Studies have shown that CSF NPT levels are associated with the presence of inflammatory lesions on MRI scans [22]. The more abnormal an MRI scan appears for children with viral encephalitis, the more severe the disease will likely be. In this study, the CSF NPT levels were significantly higher in children for whom more extensive lesions were observed on brain MRI scans.

It has been reported that viral infections cause an immune response resulting in the production of inflammatory factors, which, in turn, accelerate the progression of the disease and cause major organ dysfunction [23]. Continuous blood purification is beneficial for reducing the levels of inflammatory mediators, thereby preventing the inflammatory response cascade [24]. Little is known about the efficacy of multiple blood purification modalities in children with severe viral encephalitis and the association of NPT levels with prognosis. Putz et al. [25] found that patients with end-stage renal disease had decreased plasma levels of NPT each time they underwent haemodialysis, and that the concentration of NPT in patients with end-stage renal disease was related to the length of haemodialysis treatment time [26]. Sadeghi et al. [27] also found that the plasma NPT concentrations in renal transplant patients decreased significantly after plasma exchange treatment.

This study found that NPT levels in serum significantly decreased after integrated blood purification treatment for severe viral encephalitis, while the levels in CSF were not affected by changes in the serum concentration. This result was corroborated in another study [28].

The main purpose of the present study was to observe the efficacy of HP combined with CVVHDF in the treatment of severe viral encephalitis in children. While CVVHDF only was effective for removing small and medium-sized harmful molecular substances in the blood, its effectiveness for removing endotoxins and inflammatory cytokines of larger molecular size was poor. In contrast, HP was significantly more successful than hemofiltration for removing concentrations of various medium-sized molecules, including inflammatory cytokines. Using the advantages of two different blood purification modes to complement one another, it is possible to reduce the level of cytokines in the blood and thereby reduce the damage to organ function caused by inflammatory mediators [15]. The results of the current study showed that the improved outcome may have been related to the removal of inflammatory mediators in the body by blood purification technology. A possible mechanism for the better outcome after blood purification may be a decrease in demyelination of the nervous system and cerebrovascular and perivascular damage induced by the inflammatory response. At present, there are few studies on the combination of two or more blood purification modes in the treatment of children with critical illnesses. Further research is thus needed in this regard.

Both swallowing and motor dysfunction correlated positively with NPT levels in CSF before and after treatment. According to Ghisoni et al. [29], neopterin is not an inert compound but a cytoprotective molecule synthesised and secreted by nerve cells as a response to injury or inflammation. That is, the more severe the brain damage or inflammatory response, the more neopterin will be synthesised and secreted by nerve cells. This study showed that the more severe the sequelae in the recovery period, the higher the CSF NPT levels will be. The correlation between disease prognosis and NPT levels requires further confirmation by a prospective study using a larger sample size.

This study includes some shortcomings, i.e. it did not continuously monitor the CSF NPT levels of the children during the recovery period. Furthermore, the CSF NPT levels were not monitored long-term to study their correlation with nervous system functions (motor function, language function, and swallowing function). Moreover, this research was a single-centre study, the conclusions of which require further confirmation by a large number of prospective studies.