| Background:Intracranial infection can be divided into bacterial infection and specific infection. The pathogens classification of specific infection were tuberculosis, viruses and parasites, viral encephalitis is an infectious disease often found in children. with the improvement of living standard, tuberculosis and parasite infects are also less common. Bacterial infection is the most common disease in clinic which include bacterial meningitis, ventriculitis and brain abscess.Intracranial infection is one of common complications after neurosurgery. The overwhelming majority of patients have no intracranial infection before craniotomy, the causes of postoperative infection care thought to be bacterial meningitis, ventriculitis. Early and timely diagnosis of intracranial infection is very important in the clinical work. If left untreated, they could influence the curative effect of operation and the prognosis of patients, increasing in-hospital time and economic burden.Calcitonin original (PCT) is a kind of human calcitonin precursors found recently. Since Assieot etc first reported the PCT can be used as early marker of bacterial infections in1993, PCT has been widely used in diagnosis of various types of infectious diseases. PCT has become a research hotspots in application of evaluation of the degree of illness, treatment effect and prognosis and guidance of antibiotics use in recent years. Under normal circumstances, PCT is mainly secreted by medulla cells of the thyroid gland, the levels of PCT is very low in plasma (less than0.10.1μμg/L). However, recent studies have shown that bacterial endotoxin is one of the important stimulating factor for PCT generation. When healthy volunteers received intravenous injection of small dose bacterial endotoxin, PCT can be detected in plasma after2h, peak after12～48h and returned to normal level after2～3d.Plasma PCT is very stable,24h after sera samples collected, it fell by12%at room temperature for24h after PCT levels, about drop in4℃about6%. Thus, PCT can be collected by conventional laboratory methods and required no special storage conditions. Now PCT is thought to be a kind of nonsteroidal anti-inflammatory, having anti-inflammatory effect, and plays an important role in the regulation of cytokine network. Several studies have found that PCT is a secondary inflammatory transmitter, perhaps the secondary inflammatory cytokines in inflammatory cascade reaction, PCT itself can’t start the inflammatory response but can magnify the inflammatory response.PCT level appeared to elevate earlier than c-reactive protein (CRP) and other inflammatory factors in patients with systemic bacterial infection. Serum PCT can appear to rise in2h after infection, risen sharply after6h, maintain a high level in8～24h, however, in serum samples of patients with virus infection, tumor and autoimmune diseases, it maintained in the normal range or slightly increased slightly. PCT is significant for early clinical diagnosis of intracranial infection, domestic and international studies have suggested that PCT was thought to be the most sensitive and biologically independent predictor for early diagnosis of bacterial meningitis and viral meningitis. Moreover, Research has shown the PCT has a guiding significance for evaluation of the disease and assessment of the curative effect. Once antibiotic become effective, PCT decreases before improvment clinical symptoms. The change of serum PCT level is a valuable parameters of evaluating the effect of antibiotics in acute bacterial meningitis. If PCT level continue to rise, it means the infection is on the way up or the illness is aggravated, and it is necessary to inspect further and change the treatment program. On the contrary, the descending of PCT often indicates the improvement of decease, inflammation and infection have been controlled and antibiotic treatment is effective.The research of PCT level in cerebrospinal fluid (CSF) of patients with intracranial infection are more focused on the identification of viral infection and bacterial infection. Some scholars believe that PCT has the important distinction significance, the level of CSF PCT often increases obviously. However, their results were not consistent with the smaller sample size, which make it still controversial that the CSF PCT level can be considered as an specific indicator of the intracranial infection. The research on the alteration of serum PCT and CSF PCT in patients with intracranial infection has been rarely reported.Objective:By measuring and comparatively studying the levels of the serum PCT,CSF-PCT, temperature, routine blood tests, routine test and biochemical indicators of CSF between patients with intracranial infection and controls, we tried to find out a sensitive and reliable indicator for diagnosis of intracranial infection after craniotomy to order to provide some reference for clinical practice.Method:We collected hospitalized patients undergoing craniotomy operation in the past two years in the Department of Neurosurgery, Zhujiang Hospital, Southern Medical University. The diagnosis of intracranial infection was based on "Nosocomial infection diagnostic criteria (trial)" issued by the Ministry of Health. First of all, we excluded those patients with pulmonary infection and urinary tract infection, the rest (22males,18females; average age43.5years old,2-68years old) were divided into infected group and disinfected group (n=20). Patients including23cases of spontaneous intracerebral hemorrhage,16cases of intracranial tumors,1cases of arachnoid cyst.Body temperature, cerebrospinal fluid and blood samples were collected from each patient. Temperature was detected every4h and the highest temperature were recorded. Specimens of infected group were collected after confirmation of intracranial infection. We reserved specimens for examination from uninfected patients24-48h after operation and continue to track72h exclude intracranial infection. The temperature is axillary temperature detection, measurement time>5min. Cerebrospinal fluid samples obtained by the following ways:lumbar puncture, the lumbar cistern drainage, ventricle drainage and ventricle endoscopy. Samples were collected with aseptic operation and without cerebrospinal fluid replacement. If there was a drainage tube, get rid of cerebrospinal fluid from death lumen and then collect the samples. Blood samples were divided into two copies, one copy for a routine blood test and the other for detection for PCT level. Cerebrospinal fluid samples (6ml) were divided into three copies, one for routine test, another for biochemical examination and the last for PCT level detection. Briefly, the total of white blood cell (WBC) were counted by electric resistance method, the absolute value of neutrophils was obtained using cell chemical dyeing/multi-angle laser light scattering method and then neutrophil percentage was calculated. The sandwich plus automatic quantitative fluorescence method was used to detect PCT level while the cerebrospinal fluid samples were centrifuged. For CSF routine test, Pandy test method and manual method were applied to analyse protein quality, cerebrospinal fluid cell classification and cell count. For biochemical examination, glucose level was determined with enzyme electrode method and chloride with ion selective electrode analysis.All data are presented as mean x±SD. Groupwise comparisons of continuous data were performed using Student’s t-test. Rate comparation was done using four table chi-square test. The sensitivity, specificity, positive predictive value and negative predictive value for the various diagnostic tests were derived from the receiver operator characteristic (ROC) curve. For statistical analyses, SPSS software, version13.0for Windows (SPSS Inc., Chicago, USA) was used. p<0.05was considered significant.Result:PCT level of cerebrospinal fluid (CSF PCT), WBC count of cerebrospinal fluid (CSF WBC), serum PCT and the body temperature of patients from infection group was significantly higher than those of non infection group (p<0.05). CSF chloride and glucose levels of infection group were significantly lower when compared with those of uninfected group (p<0.05). The peripheral blood WBC count and neutrophil percentage between infected group and unfected group show no difference (p>0.05).The areas under the ROC curves were used to compare the usefulness of various diagnostic tests to detect intracranial infection. The under-curve area of CSF PCT, CSF WBC count, serum PCT, peripheral blood WBC count, peripheral blood neutrophil percentage, CSF chloride, CSF Glucose and body temperature were:0.964,0.869,0.804,0.681,0.694,0.843,0.755and0.720respectively. Except for peripheral blood WBC count, other indicators are significant in the diagnosis of intracranial infection (p<0.05). The under-curve area of CSF PCT was the largest, indicating the CSF PCT is the most effective in diagnosis of intracranial infection.With a cut off level for PCT of>0.05μg/L, the sensitivity of CSF PCT was100.0%, which is significant higher than peripheral blood WBC count, peripheral blood neutrophil percentage, CSF chloride, CSF Glucose and body temperature (p<0.01), however, its specificity is65.0%, the low specificity leads to a high misdiagnosis rate. When we increase the cut off level of PCT to0.01μg/L, we found that the sensitivity of the CSF PCT, specific degree, positive predictive value and negative predictive value were95.0%,90.0%,90.5%and94.7%respectively, the sensitivity of CSF PCT is higher than the serum PCT, serum WBC, and its specificity is higher than that of CSF WBC and serum WBC, the difference was statistically significant (p<0.05).Cerebrospinal fluid PCT (CSF PCT) is significantly correlated with serum PCT, cerebrospinal fluid WBC (CSF WBC) and cerebrospinal fluid chloride (CSF Cl), their correlation coefficients were r=0.729, r=0.679and r=-0.636respectively (p<0.01). The correlation coefficient between CSF PCT and cerebrospinal fluid glucose (CSF Glu), CSF PCT and body temperature were r=-0.457and r=0.440respectively, both p value<0.01, suggesting that CSF PCT showed mild associated with CSF Glu and body temperature. No correlation was found between CSF PCT and peripheral WBC, CSF PCT and percentage of peripheral blood neutrophil (p>0.05).Conclusion:Cerebrospinal fluid PCT (CSF PCT) can be served as an early diagnosis indicator of intracranial infection, CSF PCT for the diagnosis of intracranial infection has good sensitivity and specificity. The diagnostic value of CSF PCT is superior to those traditional indicators such as CSF WBC, CSF chloride, CSF glucose, peripheral blood WBC and body temperature. The combined use of these indicators will be able to improve the early-diagnosis rate of intracranial infection. |
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