Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes

OBJECTIVE: A 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. METHODS: To 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). RESULTS: The 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. CONCLUSIONS: Although 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 neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes.

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

Patients with CSF neopterin levels below 61/l (n = 550).

<p>Out of 550 patients with CSF neopterin levels below 61 nmol/l, 68 patients had altered CSF proteins, and nine had altered CSF leucocytes. CSF NP: cerebrospinal fluid neopterin. The results are shown as the median and interval in brackets.</p

Representation of the 606 neurological patients in the clinical groups.

<p>Each group shows the percentage of patients with high CSF WBC, high CSF proteins and high CSF neopterin. The inflammatory/immune-mediated group had a significantly elevated percentage of high CSF WBC (^*X² = 27.91, p<0.001), high CSF proteins (^ΨX² = 17.51, p<0.001) and high CSF NP (^ΦX² = 103.73, p<0.001) compared with the other groups.</p

CSF biochemical values from subjects with CNS infections and peripheral infections.

<p>*Significant values were observed in Total Group 1 vs Total Group 2 (U-Mann Whitney test). The data for the CSF variables are shown as median and range in brackets. CSF: cerebrospinal fluid, WBC: white blood cells.</p

Patients with CSF neopterin levels above 61/l (n = 56).

<p>*Inflammatory/immune-mediated group had significantly elevated CSF neopterin (X² = 35.01, p<0.001), CSF proteins (X² = 12.71, p = 0.002) and CSF leukocytes (X² = 6.23, p = 0.044) compared with the other groups. Moreover, up to 69.6% of the patients more frequently had CSF NP>61 nmol/L. Out of 56 patients with a CSF neopterin level above 61 nmol/l, 13 patients had altered CSF proteins and four had altered CSF leucocytes.</p><p>AGS: Aicardi-Goutières syndrome; ARCI: arthrogryposis, renal tubular dysfunction, cholestasis, ichthyosis syndrome; anti-NMDA encephalitis: anti-(N-methyl D-aspartate) receptor encephalitis; CINCA: chronic infantile neurological, cutaneous and articular syndrome; VLCAD: very long-chain acyl-CoA dehydrogenase; CSF NP: cerebrospinal fluid neopterin; WBC: white blood cells. Dist: disturbances. The results are shown as the median and interval in brackets.</p

ROC curve to determine the new CSF neopterin cut-off.

<p>The samples were classified into two groups according to the condition that they presented either bacterial/viral central infection (n = 68) or peripheral infection (n = 52). The area under the curve was 0.934 (range: 0.883–0.985) with 61 nmol/l as the new cut-off. The sensitivity was 91.3%, and the specificity was 88.5%.</p

Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes

OBJECTIVE: A 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. METHODS: To 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). RESULTS: The 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. CONCLUSIONS: Although 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

70º Aniversario de la declaración universal de derechos humanos. La protección internacional de los Derechos Humanos en cuestión

Segundo volúmen de la Colección Perspectivas Iberoamericanas sobre la justicia. La Declaración Universal de los Derechos Humanos de las Naciones Unidas cumple, el 10 de diciembre de 2018, setenta años. La simbólica fecha obliga a los investigadores en derechos humanos a reflexionar críticamente sobre los avances y límites de un complejo sistema de normas y, sobre todo, de valores culturales sustentados en la matriz liberal occidental. Desde entonces, ha habido indiscutibles avances institucionales y normativos, como la creación del Consejo de Derechos Humanos, varios pactos y declaraciones complementarias, órganos específicos, tribunales internacionales, jurisprudencia, constituciones estatales, una infinidad de instituciones basadas en esta “ética mínima universal” que, contradictoriamente, no logró evitar un conjunto de catástrofes humanitarias y de vulneración de derechos. La primera década del siglo XX trae un reflejo limitante al consenso de la posguerra, pues la agresividad de los Estados hegemónicos, en alianza con intereses privados transnacionales, pone en jaque la capacidad del sistema protector frente a guerras humanitarias e internacionales. tratados económicos de nueva generación aquellos que excluyen por completo a la democracia del proceso de negociación.A Declaração Universal dos Direitos Humanos das Nações Unidas completa, em 10 de diciembre de 2018, setenta años. A data simbólica exige dos pesquisadores em direitos humanos uma reflexão crítica a respeito dos avanços y dos limites de um sistema complexo de normas e, principalmente, de valores culturales apoiados na matriz liberal ocidental. De lá para cá, houve indiscutível avanço institucional e normativo, do qual é exemplo a criação do Conselho de Direitos Humanos, diversos pactos e declarações complementarios, órgão específicos, tribunais internacionais, jurisprudência, constituições dos States, uma infinidade de instituições pautadas nesse “mínimo ético universal” que, contraditoriamente, não conseguiu evitar um conjunto de catástrofes humanitárias e de violação de direitos. A primeira década do século XX traz uma reflexão limite para o consenso do pós-guerra, pois a agressividade dos States hegemônicos, em aliança com interesses private transnacionais, põe em check a capacidade do sistema protectivo diante das guerras humanitárias e dos tratados internacionais econômicos de nueva generación aqueles que excluem completamente a democracia do processo negociador