Cerebrospinal Fluid Neopterin Analysis in Neuropediatric Patients: Establishment of a New Cut Off-Value for the Identification of Inflammatory-Immune Mediated Processes

Abstract

ObjectiveA high level of cerebrospinal fluid (CSF) neopterin is a marker of central nervous system inflammatory-immune mediated processes. We aimed to assess data from 606 neuropediatric patients, describing the clinical and biochemical features of those neurological disorders presenting CSF neopterin values above a new cut-off value that was defined in our laboratory.MethodsTo establish the new CSF neopterin cut-off value, we studied two groups of patients: Group 1 comprised 68 patients with meningoencephalitis, and Group 2 comprised 52 children with a confirmed peripheral infection and no central nervous system involvement. We studied 606 CSF samples from neuropediatric patients who were classified into 3 groups: genetic diagnosis (A), acquired/unknown etiologic neurologic diseases (B) and inflammatory-immune mediated processes (C).ResultsThe CSF neopterin cut-off value was 61 nmol/L. Out of 606 cases, 56 presented a CSF neopterin level above this value. Group C had significantly higher CSF neopterin, protein and leukocyte values than the other groups. Sixteen of twenty-three patients in this group had a CSF neopterin level above the cut-off, whereas three and seven patients presented increased leukocyte and protein values, respectively. A significant association was found among CSF neopterin, proteins and leukocytes in the 606 patients. White matter disturbances were associated with high CSF neopterin concentrations.ConclusionsAlthough children with inflammatory-immune mediated processes presented higher CSF neopterin values, patients with other neurological disorders also showed increased CSF neopterin concentrations. These results stress the importance of CSF neopterin analysis for the identification of inflammatory-immune mediated processes.

Cerebrospinal fluid biomarkers in patients with central nervous system infections: a retrospective study

“…11,12 CNS levels of neopterin denote intrathecal production by microglia, as the BBB has a low permeability for peripheral neopterin, it represents a relevant index of local inflammation. 4,13,14 This marker shows higher values in herpesvirus group, suggesting an important role in the diagnosis of herpetic encephalitis, as assessed by Bociaga and Eisenhut in their works, and helping clinician to distinguish from other viral involvement of CNS, like enteroviral meningitis in which neopterin presents lower values, maybe for the less cytotoxic damage. 4,13 S100-β is a cytoplasmic calcium-binding protein, abundant in astroglial cells, represents an important marker of astrocytic damage.…”

Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases

“…It has been demonstrated that neopterin in the brain is independently produced, as there is no correlation between the concentrations of neopterin in the plasma and cerebrospinal fluid (CSF) of patients with immune-inflammatory disorders 5 – 8 . Regarding neopterin cellular sources in the brain, it has been suggested that microglia and astrocytes are candidates to produce neopterin since these cells respond to interferon-gamma 9 .…”

“…The elevation of neopterin in the CSF has been reported in several disorders, including acute viral and bacterial infections 10 – 15 and chronic neuroinflammatory diseases, among others 7 , 8 , 16 , 17 . A cut-off value of 61 nmol/L for neopterin in the CSF has been proposed to allow for discrimination between central nervous system inflammatory and non-inflammatory disorders in paediatric populations 8 . However, it is not expected that neopterin alone can discriminate among different neuroinflammatory aetiologies 8 .…”

A Rare Case of Aicardi-Goutières Syndrome Who Showed a Positive Evolution after Being Treated with Growth Hormone, High Doses of Melatonin and Neurorehabilitation

“…In turn, MT was given, preventively, because of its potent scavenging effects on the toxic reactive oxygen species (ROS) [33,34], to which the brain is particularly sensitive, most likely elevated because of the clinical situation of the patient and the work carried out in his neurorehabilitation. Moreover, the clinical history indicated that neopterin, a marker of inflammatory-immune processes [35], had been detected to be elevated in a CSF sample of the patient; therefore, given the anti-inflammatory effects of MT [36,37], we thought that the administration of this indolamine could add more beneficial effects to the patient.…”