Cerebrospinal Fluid Iron-Ferritin Ratio as a Potential Progression Marker for Parkinson's Disease.

Longitudinal PD CSF samples were subjected to ICP-MS and the total amount of iron and other bioelements was quantified. Additionally, ferritin and protein biomarkers of neurodegeneration were measured. Over time, mean iron levels significantly increased while levels of ferritin decreased.

Longitudinal CSF Iron Pathway Proteins in Posthemorrhagic Hydrocephalus: Associations with Ventricle Size and Neurodevelopmental Outcomes.

OBJECTIVE: Iron has been implicated in the pathogenesis of brain injury and hydrocephalus after preterm germinal matrix hemorrhage-intraventricular hemorrhage, however, it is unknown how external or endogenous intraventricular clearance of iron pathway proteins affect the outcome in this group. METHODS: This prospective multicenter cohort included patients with posthemorrhagic hydrocephalus (PHH) who underwent (1) temporary and permanent cerebrospinal fluid (CSF) diversion and (2) Bayley Scales of Infant Development-III testing around 2 years of age. CSF proteins in the iron handling pathway were analyzed longitudinally and compared to ventricle size and neurodevelopmental outcomes. RESULTS: Thirty-seven patients met inclusion criteria with a median estimated gestational age at birth of 25 weeks; 65% were boys. Ventricular CSF levels of hemoglobin, iron, total bilirubin, and ferritin decreased between temporary and permanent CSF diversion with no change in CSF levels of ceruloplasmin, transferrin, haptoglobin, and hepcidin. There was an increase in CSF hemopexin during this interval. Larger ventricle size at permanent CSF diversion was associated with elevated CSF ferritin (p = 0.015) and decreased CSF hemopexin (p = 0.007). CSF levels of proteins at temporary CSF diversion were not associated with outcome, however, higher CSF transferrin at permanent CSF diversion was associated with improved cognitive outcome (p = 0.015). Importantly, longitudinal change in CSF iron pathway proteins, ferritin (decrease), and transferrin (increase) were associated with improved cognitive (p = 0.04) and motor (p = 0.03) scores and improved cognitive (p = 0.04), language (p = 0.035), and motor (p = 0.008) scores, respectively. INTERPRETATION: Longitudinal changes in CSF transferrin (increase) and ferritin (decrease) are associated with improved neurodevelopmental outcomes in neonatal PHH, with implications for understanding the pathogenesis of poor outcomes in PHH. ANN NEUROL 2021;90:217-226.

Alteration of Iron Concentration in Alzheimer's Disease as a Possible Diagnostic Biomarker Unveiling Ferroptosis.

Proper functioning of all organs, including the brain, requires iron. It is present in different forms in biological fluids, and alterations in its distribution can induce oxidative stress and neurodegeneration. However, the clinical parameters normally used for monitoring iron concentration in biological fluids (i.e., serum and cerebrospinal fluid) can hardly detect the quantity of circulating iron, while indirect measurements, e.g., magnetic resonance imaging, require further validation. This review summarizes the mechanisms involved in brain iron metabolism, homeostasis, and iron imbalance caused by alterations detectable by standard and non-standard indicators of iron status. These indicators for iron transport, storage, and metabolism can help to understand which biomarkers can better detect iron imbalances responsible for neurodegenerative diseases.

Evidence for communication of peripheral iron status to cerebrospinal fluid: clinical implications for therapeutic strategy.

BACKGROUND: Iron is crucial for proper functioning of all organs including the brain. Deficiencies and excess of iron are common and contribute to substantial morbidity and mortality. Whereas iron's involvement in erythropoiesis drives clinical practice, the guidelines informing interventional strategies for iron repletion in neurological disorders are poorly defined. The objective of this study was to determine if peripheral iron status is communicated to the brain. METHODS: We used a bi-chamber cell culture model of the blood-brain-barrier to determine transcytosis of iron delivered by transferrin as a metric of iron transport. In the apical chamber (representative of the blood) we placed transferrin complexed with iron59 and in the basal chamber (representative of the brain) we placed human cerebrospinal fluid. Cerebrospinal fluid (CSF) samples (N = 24) were collected via lumbar puncture. The integrity of the tight junctions were monitored throughout the experiments using RITC-Dextran. RESULTS: We demonstrate that iron transport correlates positively with plasma hemoglobin concentrations but not serum ferritin levels. CONCLUSIONS: The clinical ramifications of these findings are several- fold. They suggest that erythropoietic demands for iron take precedence over brain requirements, and that the metric traditionally considered to be the most specific test reflecting total body iron stores and relied upon to inform treatment decisions-i.e., serum ferritin-may not be the preferred peripheral indicator when attempting to promote brain iron uptake. The future direction of this line of investigation is to identify the factor(s) in the CSF that influence iron transport at the level of the BBB.

Acute phase response after fatal traumatic brain injury.

An inflammatory response occurring after fatal traumatic brain injury (TBI) initiates time-dependent cascades of acute phase response. This may offer the potential to monitor postmortem biomarker levels of several pro-inflammatory cytokines to gain information about the cause of death and the trauma survival time. Cerebrospinal fluid (CSF) and serum samples were collected from forensic autopsies of 95 adult cadavers after postmortem intervals up to 6 days. The cases were divided according to their cause of death into fatal TBI (n = 46) with different survival times and age- and gender-matching non-TBI fatalities as controls (n = 49). Quantitative marker levels of interleukin-6 (IL-6), ferritin, soluble tumor necrosis factor receptor type 1, C-reactive protein, and lactate dehydrogenase were analyzed using immunoassays. Standardized statistical tests were performed to differentiate causes of death and survival time of TBI cases. The CSF IL-6, ferritin, and LDH levels after TBI were significantly higher than those in the controls (p < 0.001). Only serum IL-6 values showed comparable differences (p < 0.05). Both CSF and serum ferritin levels were discriminative between early and delayed death after TBI (p < 0.05). There were partly distinctive correlations between marker levels in both fluids with rising values after longer survival. There were up to moderate correlation between the marker levels and the postmortem interval due to postmortem hemolysis. However, neither CSF nor serum level ranges were affected by the age or gender of the subjects. This study is the first to measure all five proteins systematically in postmortem trauma cases. Ferritin and IL-6 proved themselves to be interesting postmortem biomarkers to provide specific information on the injury pattern and the survival time of traumatic fatalities. Such forensic investigations could serve as inexpensive and fast laboratory tests.

Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study.

OBJECTIVE: To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF ß-amyloid (Aß) and tau. METHODS: Mixed-effects models of CSF Aß1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aß1-42 for up to 5 years. RESULTS: In subjects with biomarker-confirmed Alzheimer's pathology, high CSF ferritin (>6.2 ng/mL) was associated with accelerated depreciation of CSF Aß1-42 (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or Aß1-42 in subjects with low baseline pathology. In simulation modelling of the natural history of Aß deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF Aß from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF Aß over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical Aß levels to the average level of Alzheimer's subjects from 18.8 to 10.8 years. CONCLUSIONS: Iron might facilitate Aß deposition in Alzheimer's and accelerate the disease process.

Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis.

BACKGROUND: Meningeosis neoplastica is a diffuse metastatic spread of tumor cells in the subarachnoid space. Although first recognized in 1870, systematic investigations regarding cerebrospinal fluid (CSF) constituents in this condition are scarce. METHODS: Routine CSF samples analyzed from 2001 to 2012 at the Laboratory of Clinical Neurochemistry, University of Göttingen, were re-evaluated. Patients, whose CSF contained malignant cells were included in this study. RESULTS: Patients (n = 132, age 59.1 ± 29.1, 58% women) were identified, whose CSF contained malignant cells. The most frequent primary tumor was breast cancer (32.6%), followed by lung cancer (25.0%) and hematologic malignancies (21.2%). The most frequent clinical symptoms were affections of cranial nerves (41.7%), psychiatric abmormalities (32.6%) and radicular lesions of the lower extremities (20.5%). CSF cell counts ranged from 0 to 4692 cells/µl (median 4 cells/µl) and were elevated in 50%. The CSF-to-serum albumin ratio was abnormal in 69.4%. It ranged from 1.8 to 330 x 10-3 (median 17.5 x 10-3). Total CSF protein ranged from 166 to 15,840 mg/l (median 1012 mg/l). CSF lactate was elevated (>2.4 mmol/l) in 65.2% [3.6 mmol/l (1.3/15.6 mmol/l); median (minimum/maximum)]. In 50% of all patients CSF lactate was ≥3.5 mmol/l. The CSF cell counts correlated significantly with the CSF lactate levels and the CSF protein contents. In 56 of 118 CSF samples (47.5%) ferritin was elevated, and in 25 of 65 carcinoma patients (38.5%) an intrathecal production of carcinoembryonic antigen (CEA) was detected. Granulocytes were found in 52.7% of the CSF samples. The percentages of granulocytes and lymphocytes were higher in samples with an elevated cell count. CONCLUSION: In approximately 50% of CSF samples with meningeosis neoplastica the CSF cell count is not elevated. Diagnosis may be missed when only CSF samples with elevated cell counts are subjected to cytological analysis. CSF lactate and protein and the CSF-to-serum albumin ratio are frequently increased in meningeosis neoplastica. The differential diagnosis between meningeosis neoplastica and central nervous infections, in particular tuberculous or fungal meningitis, can be difficult.

Cerebrospinal fluid ferritin concentration in patients with purulent, bacterial meningitis ­ own observations / Stezenie ferrytyny w plynie mózgowo-rdzeniowym chorych z ropnymi, bakteryjnymi zapaleniami opon i mózgu - obserwacje wlasne

THE AIM: The aim of the study was to evaluate the usefulness of cerebrospinal fluid (CSF) ferritin concentration assessment in adults with purulent, bacterial meningoencephalitis. MATERIAL AND METHODS: The investigation was performed in 18 subjects hospitalized at the Clinical Ward of Infectious Diseases, Medical University of Silesia in Bytom from 2008 through 2012, for purulent, bacterial meningoencephalitis. The patients were divided into two groups, according to severity of their clinical condition: Group I ­ very severe course of the disease, group II ­ moderate and mild course of the disease. In all the individuals, CSF interleukin-6 concentration was evaluated during the first 24 hours of hospitalization. RESULTS: Mean CSF ferritin concentration in patients in very severe clinical condition (group I) was 314.71 ng/mL as compared to 162.13 ng/mL in subjects of group II with moderate and mild course of the disease. The difference between CSF mean concentration of this cytokine was statistically significant (p<0.01). Correlations between CSF ferritin and CSF protein and lactate were determined. The control assays performed in 6 patients from group I revealed only slightly decrease of CSF ferritin level in the fatal course of the disease. In survivals with recovery CSF concentration of this protein was decreased markedly as compared to the initial level. CONCLUSIONS: The obtained results indicate the usefulness of CSF ferritin concentration assessment in estimation of intensity of inflammation in the subarachnoid space, and indirectly, of severity of the patient's clinical condition. The level of this protein concentration also seems to be helpful as a prognostic marker in purulent, bacterial meningoencephalitis.

Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation After Traumatic Brain Injury in Children.

OBJECTIVES: The magnitude and role of the cellular immune response following pediatric traumatic brain injury remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric traumatic brain injury by measuring cerebrospinal fluid levels of soluble cluster of differentiation 163 and ferritin and soluble interleukin-2 receptor α, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome. DESIGN: Retrospective analysis of samples from an established, single-center cerebrospinal fluid bank. SETTING: PICU in a tertiary children's hospital. PATIENTS: Sixty-six pediatric patients after severe traumatic brain injury (Glasgow Coma Scale score < 8) who were 1 month to 16 years old and 17 control patients who were 1 month to 14 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α were determined by enzyme-linked immunosorbent assay at two time points (t1 = 17 ± 10 hr; t2 = 72 ± 15 hr) for each traumatic brain injury patient. Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α after traumatic brain injury were compared with controls and analyzed for associations with age, patient sex, initial Glasgow Coma Scale score, diagnosis of abusive head trauma, the presence of hemorrhage on CT scan, and Glasgow Outcome Scale score. Cerebrospinal fluid level of soluble cluster of differentiation 163 was increased in traumatic brain injury patients at t2 versus t1 and controls (median, 95.4 ng/mL [interquartile range, 21.8-134.0 ng/mL] vs 31.0 ng/mL [5.7-77.7 ng/mL] and 27.8 ng/mL [19.1-43.1 ng/mL], respectively; p < 0.05). Cerebrospinal fluid level of ferritin was increased in traumatic brain injury patients at t2 and t1 versus controls (8.3 ng/mL [<7.5-19.8 ng/mL] and 8.9 ng/mL [<7.5-26.7 ng/mL] vs <7.5 ng/mL below lower limit of detection, respectively; p < 0.05). Cerebrospinal fluid levels of soluble interleukin-2 receptor α in traumatic brain injury patients at t2 and t1 were not different versus controls. Multivariate regression revealed associations between high ferritin and age 4 years or younger, lower Glasgow Coma Scale score, abusive head trauma, and unfavorable Glasgow Outcome Scale score. CONCLUSIONS: Children with traumatic brain injury demonstrate evidence for macrophage activation after traumatic brain injury, and in terms of cerebrospinal fluid ferritin, this appears more prominent with young age, initial injury severity, abusive head trauma, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses and whether inflammation represents a therapeutic target after traumatic brain injury.

Cerebrospinal fluid ferritin--unspecific and unsuitable for disease monitoring.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage is sometimes difficult to diagnose radiologically. Cerebrospinal fluid (CSF) ferritin has been proposed to be highly specific and sensitive to detect hemorrhagic central nervous system (CNS) disease. We analyzed here the specificity of CSF ferritin in a large series of various CNS diseases and the influence of serum ferritin. MATERIALS AND METHODS: CSF ferritin, lactate, protein and total cell count were analyzed in 141 samples: neoplastic meningitis (n=62), subarachnoid hemorrhage (n=20), pyogenic infection (n=10), viral infection (n=10), multiple sclerosis (n=10), borreliosis (n=5) and normal controls (n=24). Cerebrospinal fluid ferritin was measured with a microparticle immunoassay. In addition, serum and CSF ferritin were compared in 18 samples of bacterial and neoplastic meningitis. RESULTS: In CNS hemorrhage, median ferritin was 51.55µg/L (sensitivity: 90%) after the second lumbar puncture. In neoplastic meningitis, the median CSF ferritin was 16.3µg/L (sensitivity: 45%). Interestingly, ferritin was higher in solid tumors than that in hematological neoplasms. In 90% of pyogenic inflammation, ferritin was elevated with a median of 53.35µg/L, while only 50% of patients with viral infection had elevated CSF ferritin. In ventricular CSF, median ferritin was 163µg/L, but only 20.6µg/L in lumbar CSF. Ferritin was normal in multiple sclerosis and borreliosis. CONCLUSIONS: Ferritin was elevated not only in hemorrhagic disease, but also in neoplastic and infectious meningitis. Ferritin was not a reliable marker of the course of disease. The influence of serum ferritin on CSF ferritin is negligible. We conclude that elevated CSF ferritin reliably, but unspecifically indicates severe CNS disease.

Therapeutic strategies to prevent Alzheimer's disease pathogenesis using a fluorescent conjugated polyelectrolyte.

Toxic metals accumulation in brain has a significant role in the pathogenesis of Alzheimer's disease (AD) by accelerating amyloid ß (Aß) peptide aggregation. Aß has high affinity for iron and copper resulting in the generation of neurotoxic hydrogen peroxide, oxidative stress and free radical formation. Water-soluble conjugated polyfluorene derivative poly(9,9-bis(6-sulphate hexyl) fluorene-alt-1,4-phenylene) sodium salt (P1) binds Fe(3+) heme proteins selectively in cerebrospinal fluid (CSF), including ferritin in the Aß fibrils and diminishes their accumulation. Hence, therapeutic strategies involving clearance of Aß from brain plaques, metal removal, structurally modifying the aggregates, and preventing them from aggregating again into toxic polypeptides are vital strategies to control AD pathogenesis.

Lower molecular weight intravenous iron dextran for restless legs syndrome.

BACKGROUND: Various techniques used to assess brain iron concentrations have demonstrated the presence of low iron stores in patients with restless legs syndrome (RLS). Previous open-label and randomized studies generally support the value of iron treatment for RLS symptoms. Only one of these studies assessed iron therapy response to changes in brain iron status. The current study was designed to assess the effect of iron therapy on RLS symptoms and on CSF measures of brain iron status. METHODS: Idiopathic RLS patients drawn from the Korean population received four weekly intravenous (IV) doses of 250 mg low-molecular weight iron dextran for a total dose of 1g. One week after the last dose, any subject on RLS medication tapered off the RLS medications. Blood and CSF samples were taken to measure iron parameters at baseline and again, three weeks after the last dose. We have been following their response to the drug for two years after treatment. RESULTS: Twenty-five patients (age 55.2 ± 9.3, 18 female) enrolled in this study without serious adverse reactions. Seventeen of the 25 patients (68%) showed moderate or complete improvement of all RLS symptoms after treatment based on the Korean-translated versions of the International RLS Severity scale (K-IRLS). Changes in the K-IRLS did not correlate significantly with changes in CSF ferritin. The response to IV iron could not be predicted by patients' demographics, or by blood or CSF iron baseline characteristics. RLS symptom improvement started between one and six weeks after treatment and the treatment benefits lasted from one month to 22 months. Fourteen patients, (56%) completely stopped all medications, for a mean duration of 31.3 ± 33.1 weeks. These results are comparable to those from a prior study with high molecular weight dextran. CONCLUSIONS: Intravenous low-molecular weight iron dextran produced significant improvement of RLS symptoms in a majority of patients without any significant adverse effects. Serious anaphylaxis occurs with high molecular weight, but rarely, if ever, with this low molecular weight dextran. Given apparent comparable efficacy the low molecular weight and not the high molecular weight iron dextran, should be considered for RLS treatment. Although changes in CSF ferritin were seen following therapy, these changes were not related to clinical improvements.

[Cerebrospinal fluid-based diagnostics of CT-negative subarachnoid haemorrhage]. / Liquordiagnostik bei CT-negativer Subarachnoidalblutung.

The diagnostic investigation of CT-negative subarachnoid haemorrhage (SAH) is a particular challenge in clinical neurology. Cerebrospinal fluid (CSF) analysis via lumbar puncture is the method of choice. The diagnosis of SAH in CSF is based on a bloody or xanthochromic discoloration of the CSF as well as on findings in non-automated CSF cytology including the detection of erythrophages and siderophages. The automated determination of CSF ferritin concentrations or spectrophotometric detection of xanthochromia may contribute to the diagnosis but are only useful with regard to the overall clinical picture. Generally, the knowledge of the time flow of CSF changes associated with SAH is essential for a correct interpretation of CSF findings.

CSF tau protein is a useful marker for effective treatment of superficial siderosis of the central nervous system: two case reports.

We report two cases of superficial siderosis (SS) of the central nervous system (CNS), which is caused by chronic haemorrhaging into the subarachnoid space with haemosiderin deposition in the superficial portion of the CNS. Patient 1 had fluid collection in the spinal canal, which was reported as the source of the chronic bleeding. Patient 2 was bleeding from thickened dura at the level of the sacral vertebrae. Both of the patients had xanthochromic cerebrospinal fluid. We surgically repaired the sources of bleeding. Subsequently the cerebrospinal fluid (CSF) cleared and their symptoms were not aggravated for about 1 year. We measured several CSF markers of SS before and after surgery. Total tau protein (CSF-t-tau), phosphorylated tau protein (CSF-p-tau), iron (CSF-iron) and ferritin (CSF-ferritin) in the CSF were highly elevated at diagnosis. After surgery, the levels of CSF-t-tau and CSF-p-tau were markedly reduced while CSF-iron and CSF-ferritin had not decreased. It is suggested that CSF-t-tau and CSF-p-tau reflected the neural damage in SS and were useful to evaluate the effectiveness of SS therapies.

A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome.

OBJECTIVE: The aim of this study was to ascertain whether high-dose intravenous (IV) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS. METHODS: The study was a randomized, parallel-group double-blind study of 1000mg iron sucrose given IV versus placebo. Primary measures of the clinical status were global rating scale (GRS) and periodic leg movements of sleep (PLMS). Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra. RESULTS: At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects. At 2-weeks post-treatment, iron treatment resulted in a small but significant increase in CSF ferritin and a decrease in RLS severity (GRS) but did not change PLMS or MRI iron index. None of the secondary outcomes changed with treatment. There was no single case of clear treatment benefit in any of the patients. This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes. The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinically significant benefit. CONCLUSIONS: High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies. Differences in iron formulation, dosing regiment, and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies.

Quantification of cerebrospinal fluid ferritin as a biomarker for CNS malignant infiltration.

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 neoplastic 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 neoplastic 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.

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.

CSF iron, ferritin and transferrin levels in restless legs syndrome.

The aim of this study is evaluating iron, ferritin, and transferrin in both serum and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that iron deficiency in the central nervous system (CNS) causes the symptoms as a result of the dysfunction of dopaminergic systems. These parameters, polysomnographic sleep measures, and subjective evaluation of the sleep quality were compared in 10 patients of idiopathic RLS (RLS group) and 10 age-matched patients of psychophysiological insomnia without RLS symptoms (non-RLS group). With sleep patterns, sleep latency was longer and sleep efficiency was lower in the RLS group than those in the non-RLS group. Periodic leg movement index in the RLS group was higher than that of the non-RLS group. With serum examination, there were no significant differences for the iron, ferritin, and transferrin values between the both groups. With CSF examination, the iron and ferritin values were lower and the transferrin values were higher in the RLS group than those in the non-RLS group. There was positive correlation between the serum and CSF ferritin levels in the both groups, but the slope of the regression lines for the RLS group was lower than that for the non-RLS group. These results indicate low brain iron concentration caused by the dysfunction of iron transportation from serum to CNS in patients with idiopathic RLS.