Neopterin concentrations in cerebrospinal fluid and serum as an aid in differentiating central nervous system and peripheral infections in children

Abstract

Neopterin is a sensitive indicator for cellular immune activation. Its concentrations were determined in cerebrospinal fluid (CSF) and serum specimens from 91 children with no evidence of central nervous system (CNS) or peripheral inflammations, 43 with definite neuroborreliosis, 51 with other CNS infections, and 33 with peripheral infections. The aim of our study was (a) to establish a range of normal CSF neopterin concentrations in control children, and (b) to inquire into the diagnostic potential of neopterin measurements in both body compartments for aiding in differential diagnosis of inflammatory vs noninflammatory diseases, and CNS vs peripheral inflammations. CSF neopterin concentrations in controls were invariably low (up to 9.3 nmol/L), but in children with neuroborreliosis and, even more so, with other CNS infections neopterin concentrations were significantly (P <0.0001) increased. Children with peripheral infections, however, rarely showed raised CSF neopterin concentrations. Serum concentrations of neopterin, on the other hand, were not significantly different between controls and children with neuroborreliosis. Although serum concentrations were significantly different between controls and children with other CNS infections, diagnostic efficiency was poor for this comparison. Peripheral infections, in contrast, were associated with significantly higher (P <0.0001) serum neopterin concentrations when compared with controls. A classification tree was constructed on the basis of CSF and serum neopterin concentrations, allowing with high accuracy the discrimination between controls, children with CNS infections, and children with peripheral infections. Thus, on the basis of a comparatively large control group, our data underline the diagnostic validity of neopterin as an aid in differential diagnosis of inflammatory vs noninflammatory diseases, and confirm that CSF neopterin concentrations are not correlated with serum neopterin concentrations, and, therefore, CSF neopterin appears to be produced intrathecally.

Cerebrospinal fluid neopterin in paediatric neurology: a marker of active central nervous system inflammation

“…Previous investigators have shown that CSF neopterin is a sensitive marker of active inflammation and is produced by monocytes secondary to interferon species stimulation (particularly interferon-gamma and to a lesser extent interferon-alpha). 1,4 CSF neopterin appears to normalize quickly once inflammation has resolved. 2 As this cohort was heterogeneous, we first presented the findings according to the mode of presentation and disease course (acute, chronic progressive, chronic static, and 'febrile exacerbation of chronic static' disorders).…”

“…5,17 CSF neopterin is intrathecally produced and is not elevated in infectious disease peripheral to the CNS. 4,18 CSF neopterin therefore appears to be a specific marker of CNS immune activation.…”

Should children with cerebral palsy and normal imaging undergo testing for inherited metabolic disorders?

“…The child was afebrile and well at the time of lumbar puncture. Raised neopterin levels are described in inflammation of the central nervous system, including Aicardi–Goutieres syndrome 18–20 …”

Plasma neopterin level as a marker of peripheral immune activation in amnestic mild cognitive impairment and Alzheimer's disease

“…elevated levels of CSF neopterin have been detected in different CNS disease processes (Hagberg et al, 2010;Millner et al, 1998). Correlations of CSF and peripheral (blood) neopterin levels appear to vary depending on the disease processes, from those that correlate strongly such as in patients with HIV infection (Hagberg et al, 2010) to those that correlate poorly such as in pediatric patients with CNS infection (Millner et al, 1998). One study that examined CSF neopterin levels in AD compared with NC did not find differences between the two groups (Engelborghs et al, 1999).…”