Quantification of cerebrospinal fluid ferritin as a biomarker for CNS malignant infiltration / Quantificação de ferritina no líquido cefalorraquidiano como biomarcador para o diagnóstico de infiltração maligna no SNC

Several markers have been studied for their ability to make the CNS infiltration diagnosis earlier and more precise; previous studies showed that CSF ferritin concentrations were higher in patients with malignant invasion of CNS. The objective was to determine the importance of CSF ferritin as a biomarker for the diagnosis of CNS neoplasic infiltration. This study is based on 93 CSF samples, divided into five groups: malignant cells present (n13); malignant cells not present (n26); inflammatory neurological diseases (n16); neurocysticercosis (n20); acute bacterial meningitis (n18). CSF ferritin values were determined by micro particle enzyme immunoassay. CSF ferritin level (mean±SD) in the group with neoplasic cells in the CSF was 42.8±49.7 ng /mL, higher than in the other groups (p<0.0001). We conclude that CSF ferritin with the cut off 20 ng/mL could be an adjuvant biomarker to the diagnosis of CNS malignant infiltration.

Diversos marcadores foram estudados com a finalidade de avaliar sua capacidade de diagnosticar a infiltração neoplásica no SNC precocemente e de forma mais precisa. Estudos anteriores mostraram que as concentrações de ferritina no LCR eram mais elevadas nos pacientes com infiltração neoplásica no SNC. O objetivo foi determinar a importância da ferritina no LCR como biomarcador para o diagnóstico de infiltração neoplásica no SNC. Este estudo é baseado em 93 amostras do LCR, divididas em cinco grupos: células malignas presentes (n13); células malignas ausentes (n26); doenças neurologicas inflamatórias (n16); neurocisticercose (n20); meningites bacterianas agudas (n18). Os valores de ferritina no LCR foram determinados por ELISA de microparticulas. O nível de ferritina no LCR (média±desvio padrão) no grupo com células neoplásicas no LCR foi 42,8±49,7 ng/mL, mais elevado do que nos outros grupos (p<0.0001). Concluímos que a ferritina no LCR com cut off de 20 ng/mL pode ser um biomarcador para o diagnóstico de infiltração maligna no SNC.

Níveis de ferritina liquórica como marcadores da infiltraçäo leucêmica do sistema nervoso central / Levels of ferritin in cerebrospinal fluid as an indicator of central nervous system leukemic infiltration

A freqüência de células blásticas no líquor, ao diagnóstico das leucemias agudas, é de 10 a 15 por cento. A leucemia do sistema nervoso central propcia a recaída medular, tornando-se um fator de mau prognóstico. A sua identificaçao é feita, rotineiramente, através do exame citomorfológico - por vezes, nao satisfatório. A determinaçao da ferritina em amostras de líquor pode servir como marcador para a leucemia do sistema nervoso central. Níveis de ferritina acima de 5ng/ml no líquor mostraram associaçao com a infiltraçao leucêmica e com a possibilidade de progressao da leucemia medular ou nao, mesmo na ausência de blastos na amostra. O Serviço de Hematologia do Hospital de Clínicas de Porto Alegre, no período de março/90 a dezembro/94, estudou 106 pacientes: em 94/106 (88 por cento), o diagnóstico foi leucemia linfoblástica; e em 12/106 (12 por cento), leucemia mieloblástica. O exame citomorfológico do líquor, no momento do diagnóstico, foi positivo para blastos em 17/106 (16 por cento), dos quais 15/17 eram portadores de leucemia linfoblástica e 2/17 de leucemia mieloblástica. A dosegem da ferritina liquórica foi acima de 5 ng/ml em 31/106 (29 por cento) dos pacientes, onde 11/31 apresentaram presença de blastos no exame citológico, enquanto 20/31 tinham líquor negativo. Em 7/20 pacientes com líquor negativo para blastos, mas com a ferritina liquórica elevada, houve recaída precoce da leucemia. A ferritina liquórica parece ser um indicador da leucemia, tanto do sistema nervoso central, quanto da hematológica: níveis elevados, além de 5 ng/ml, sao um sinal de alerta para a evoluçao da leucemia, com recidiva entre os primeiros 12 e 18 meses de diagnóstico. A alteraçao na dosagem de ferritina do líquor sugere que o especialista realize punçoes lombares freqüentes, com o intuito de detectar o mais precocemente possível o acometimento leucêmico do sistema nervoso central ou de considerar a possibilidade de intensificaçao das profilaxias com esquemas quimioterápicos e/ou radioterápicos adequados.

value of estimation of cerebrospinal fluid ferritin level in the diagnosis of acute meningitis

The outcome of acute meningitis depends mainly on its early diagnosis and prompt treatment. We aimed to test the reliability of C.S.F. ferritin level in early diagnosis of acute meningitis and in the differentiation between septic and aseptic types. For this purpose, 58 patients were subjected to thorough physical and neurological examination. Lumber puncture was done and C.S.F. was examined bacteriologically, cyto logically, biochemically, in addition to ferritin estimation. According to the bacteriological results of C.S.F. examination, the patients were classified into 4 groups: acute septic meningitis [22 patients], acute purulent [10 patients], acute aseptic [13 patients] and the control group [13 patients]. Clinical manifestations were similar in all groups. Also, biochemical and cytological results were overlapping between different types. C.S.F. ferritin level was significantly elevated in all meningitis groups than the control one. Also, there was highly significant difference in C.S.F. ferritin level between different types of acute meningitis, the highest level was among the septic group [mean 197.12 +/- 97.5] followed by the purulent group [mean 101 +/- 24.5] and lastly the aseptic type [mean 24.3 +/- 12.7]. It is concluded/from the study that ferritin estimation in C.S.F. is not only a rapid test for early diagnosis of acute meningitis, but also is a good differential test between its various types

Serum and cerebrospinal fluid ferritin level in patients with meningoencephalitis

Thirty patients with meningoencephalitis and 10 patients with non infectious neurological diseases in addition to normal controls were the material of this study. All the selected cases were submitted to careful neurological assessment, routine cerebrospinal fluid [CSF] examination and ferritin determination in CSF and serum. The mean CSF ferritin concentration in normal subjects was 3.7 ug/L. [ranged from 1 - 7.5 ug/L]. Modest elevations ranging from 12 - 35 ug/L were observed in patients with strokes and presenile dementia. Also, modest elevations, ranging from 12 - 25 ug/L with a mean of 18.3 ug/L, were observed in patients with suspected viral meningoencephalitis. Marked elevations ranging from 35 - 300 ug/L with mean value of 115.4 ug/L, were observed in patients with bacterial meningoencephalitis. No correlation was observed between CSF ferritin and serum ferritin concentration whereas there is positive significant correlation between CSF protein and CSF ferritin concentration in patients with raised CSF protein. It can be concluded that CSF ferritin concentration is significantly increased in patients with meningoencephalitis with marked difference between viral and bacterial infections and hence its measurement is an early method for diagnosis and differentiation of patients presenting with infection of CSF or meningism