Brain metastases of the mucoepidermoid lung carcinoma: a case report.

Mucoepidermoid carcinoma, a salivary gland tumor, rarely occurs in bronchial mucous glands. Brain metastases are rarely seen which makes for a challenging diagnosis and treatment approach. A 40-year-old woman presented with confusion, and ataxia, accompanied by a declining Glasgow Coma Score. Brain computerized tomography revealed two hyperdense, postcontrast-enhanced infra- and supratentorial lesions with perifocal edema. First causing obstructive hydrocephalus. The initial surgery involved external ventricular drainage system placement leading to the patient's clinical improvement. After radiological diagnostics, both lesions were resected without complications. Histopathological analysis revealed solid clusters of atypical, polygonal epithelial cells exhibiting mucin production, classified as a poorly differentiated mucoepidermoid carcinoma metastasis which originated from the upper lobe's apicoposterior segment and left lung. The correct treatment approach remains elusive due to the infrequent occurrence and challenging diagnosis. While new oncological and radiosurgery options promise improved overall survival rates, radical resection remains the preferred initial option.

Innovative statistical approaches: the use of neural networks reduces the sample size in the splenectomy-MCAO mouse model.

AIM: To compare the effectiveness of artificial neural network (ANN) and traditional statistical analysis on identical data sets within the splenectomy-middle carotid artery occlusion (MCAO) mouse model. METHODS: Mice were divided into the splenectomized (SPLX) and sham-operated (SPLX-sham) group. A splenectomy was conducted 14 days before middle carotid artery occlusion (MCAO). Magnetic resonance imaging (MRI), bioluminescent imaging, neurological scoring (NS), and histological analysis, were conducted at two, four, seven, and 28 days after MCAO. Frequentist statistical analyses and ANN analysis employing a multi-layer perceptron architecture were performed to assess the probability of discriminating between SPLX and SPLX-sham mice. RESULTS: Repeated measures ANOVA showed no significant differences in body weight (F (5, 45)=0.696, P=0.629), NS (F (2.024, 18.218)=1.032, P=0.377) and brain infarct size on MRI between the SPLX and SPLX-sham groups post-MCAO (F (2, 24)=0.267, P=0.768). ANN analysis was employed to predict SPLX and SPL-sham classes. The highest accuracy in predicting SPLX class was observed when the model was trained on a data set containing all variables (0.7736±0.0234). For SPL-sham class, the highest accuracy was achieved when it was trained on a data set excluding the variable combination MR contralateral/animal mass/NS (0.9284±0.0366). CONCLUSION: This study validated the neuroprotective impact of splenectomy in an MCAO model using ANN for data analysis with a reduced animal sample size, demonstrating the potential for leveraging advanced statistical methods to minimize sample sizes in experimental biomedical research.

Bilateral posterior fossa chronic subdural hematoma as a cause of hydrocephalus.

Background: Infratentorial chronic subdural hematoma (cSDH) is still a rather elusive neurosurgical entity, which, due to its proximity and likely compression of the cerebellum and brainstem, can lead to devastating consequences. To establish standardized treatment, more studies and reports regarding its therapy are needed. We report a case of a simultaneous unilateral supratentorial and bilateral infratentorial cSDH, with the latter causing hydrocephalus and successfully treated with a bilateral burr-hole trepanation of occipital bone and placement of subdural drains. Case Description: A 71-year-old man with gait disturbance, Glasgow Coma Scale 12, and a radiologically verified unilateral supratentorial and bilateral cSDH of the posterior fossa causing cerebellum, brainstem, and fourth ventricle compression with obstructive hydrocephalus, underwent surgical evacuation of infratentorial hematoma with a bilateral burr-hole trepanation. The postoperative course was uneventful, with a control head computed tomography scan showing the resolution of the hematoma and hydrocephalus. The patient was discharged with no newly acquired neurological deficits. Conclusion: Due to a limited number of reports and studies involving infratentorial cSDHs causing hydrocephalus, decision-making and optimal surgical treatment remain unclear. We recommend a timely surgical evacuation of the hematoma if the patient is symptomatic while avoiding placement of external ventricular drainage.

The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: The spleen, a substantial reservoir of non-differentiated monocytes, may play a crucial role in the pathophysiology of post-ischemic inflammation and influence outcomes after ischemic stroke. AIM OF THE STUDY: To analyze splenectomy as a preclinical intervention in murine models of ischemic stroke. METHODS: Following systematic searches of PubMed, Scopus and Web of Science, a qualitative synthesis of study characteristics was performed, and the effect of splenectomy estimated by a three-level random-effects meta-analysis of infarct volumes and a conventional two-level random-effects meta-analysis of neurological deficit scores. RESULTS: Database searches identified a total of 14 studies, 13 of which were used for meta-analysis. The ischemic lesion volumes were reduced in splenectomized animals compared to the control groups (difference in standardized mean differences: - 1.42; 95% CI [- 1.98, - 0.85]; 95% PI [- 2.03, - 0.80]; I2(2) = 19.04%; 95% CI [0.00%, 65.49%]; I2(3) = 47.24%; 95% CI [0.00%, 85.23%]) and neurological deficit scores were improved (- 1.20; 95% CI [- 2.20, - 0.20]; 95% PI [- 4.58, 2.18]; I2 = 77.5%; 95% CI [50.0%, 89.9%]). A subgroup analysis for infarct volumes showed that splenectomy performed prior to ischemia achieved a higher reduction of the ischemic lesion than when splenectomy was performed immediately prior or after stroke. Although the overall effect size of splenectomy could be classified as large, there was a significant presence of risks of bias, study heterogeneity, and a potential presence of publication bias. CONCLUSION: Despite limitations related to heterogeneity, risks of bias, and potential publication bias, this meta-analysis points to the spleen and its functional cell populations as promising targets for the therapeutic modulation of post-stroke inflammation.

Spontaneous spinal subdural hematoma in COVID-19 patient: Croatian national COVID hospital experience.

Background: Spontaneous spinal subdural hematoma (SSDH) is a rare condition and causes of acute spinal cord compression, with symptoms varying from mild to severe neurological deficit. SSDH could occur as a consequence of posttraumatic, iatrogenic, or spontaneous causes, including underlying arteriovenous malformations, tumors, or coagulation disorder. Due to its rarity, it is difficult to establish standardized treatment. We present a rare case of SSDH in COVID-19 patient and course of treatment in COVID hospital. Case Description: A 71-year-old female patient was admitted due to instability, weakness of the left leg, and intensive pain in the upper part of thoracic spine as well as mild respiratory symptoms of COVID-19. She was not on pronounced anticoagulant therapy and her coagulogram at admission was within normal range. MRI revealed acute subdural hematoma at the level C VII to Th III compressing the spinal cord. The patient underwent a decompressive Th I and Th II laminectomy and hematoma evacuation. Post-operative MRI revealed a satisfactory decompression and re-expansion of the spinal cord. COVID-19 symptoms remained mild. Conclusion: SSDH represents a neurological emergency, possibly leading to significant deficit and requires urgent recognition and treatment. One of the main difficulties when diagnosing is to consider such condition when there is no history of anticoagulant treatment or previous trauma. Since high incidence of coagulation abnormalities and thromboembolic events was described COVID-19 patients, when considering the pathology of the central nervous system, the bleeding within it due to COVID-19 should be taken into account, in both brain and spine.

FORAMEN OVALE AND FORAMEN ROTUNDUM: CHARACTERIZATION OF POSTNATAL DEVELOPMENT.

The sphenoid bone development occurs in both prenatal and postnatal periods. Sphenoid bone openings are used as surgical landmarks and are of great importance for neurosurgeons in everyday practice. The aim of this study was to identify morphological characteristics, postnatal development and remodeling, as well as clinical aspect of the sphenoid bone openings and to investigate their relationship and difference in size. The macerated sphenoid bones analyzed in this study were scanned by micro-computed tomography. Areas and distance in-between foramen ovale and foramen rotundum were measured. In addition, different shapes of foramen ovale were described. The most common shape of foramen ovale on both sides was oval, followed by the round, almond and elongated shapes. Modest to strong positive correlations between all foramina and age for the whole sample and both subsamples were presented, except for the right foramen rotundum area in the male subsample, which did not show significant correlation with age. Our study revealed changes in postnatal development and anatomy of foramen ovale and foramen rotundum, primarily in the aspects of size and shape, and should contribute to reducing the risk of damage to neurovascular structures during surgical procedures.

Glycemia and venous thromboembolism in patients with primary brain tumors - A speculative review.

Venous thromboembolism (VTE) is a significant public health issue causing severe morbidity and mortality. One of the most vulnerable populations for VTE development are cancer patients. And among them, patients with brain tumors have arguably the highest risk of developing this often fatal complication. Hyperglycemia is a well-known factor which leads to a wide variety of pro-thrombotic changes. In this article, we review the current literature on the topic of VTE in brain tumor patients. We also discuss the known correlation between VTE and glycemia, as well as the importance and frequency of glycemia dysregulation in brain tumor patients. Based on the already well-known importance of glucose metabolism in cancer patients, as well as the previous research of our group, we hypothesize that there is a significant number of brain tumor patients who have chronically elevated glycemia, a fact that so-far hasn't been reported. We argue that these patients carry a significantly higher risk of VTE development and would benefit greatly from strict glycemic control. We present our hypothesis, the ways in which to test it, as well as the possible counter-arguments against it. Our hope is that other investigators will be inspired by our article to continue this type of research, since we consider the topic of VTE in brain tumor patients highly important and urgent, primarily due to its prevalence and severity.

Clinical application of the RONNA G4 system - preliminary validation of 23 robotic frameless brain biopsies.

AIMS: To report the outcomes of robot-assisted brain biopsies performed using a novel RONNA G4 system. The system was developed by a research group from the Faculty of Mechanical Engineering and Naval Architecture and a team of neurosurgeons from Dubrava University Hospital, University of Zagreb School of Medicine. METHODS: This prospective study included 49 biopsies analyzed during one year: 23 robotic frameless and 26 frame-based Leksell stereotactic biopsies. We analyzed the presenting symptoms, tumor range and location, postoperative complications, pathohistological diagnosis, diagnostic yield, as well as operation and hospitalization duration. The target point error was calculated to assess the accuracy of the RONNA system. RESULTS: No postoperative mortality, morbidity, or infections were observed. In the frameless robotic biopsy group, only one pathohistological diagnosis was inconclusive. Therefore, the diagnostic yield was 95.6% (22/23), similar to that of the framebased Leksell stereotactic biopsy group (95.1% or 25/26). The average target point error in the frameless robotic biopsy group was 2.15±1.22 mm (range 0.39-5.85). CONCLUSION: The RONNA G4 robotic system is a safe and accurate tool for brain biopsy, although further research warrants a larger patient sample, comparison with other robotic systems, and a systematic analysis of the entry and target point errors.

Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation.

Disorders of consciousness (DOC) are one of the major consequences after anoxic or traumatic brain injury. So far, several studies have described the regaining of consciousness in DOC patients using deep brain stimulation (DBS). However, these studies often lack detailed data on the structural and functional cerebral changes after such treatment. The aim of this study was to conduct a volumetric analysis of specific cortical and subcortical structures to determine the impact of DBS after functional recovery of DOC patients. Five DOC patients underwent unilateral DBS electrode implantation into the centromedian parafascicular complex of the thalamic intralaminar nuclei. Consciousness recovery was confirmed using the Rappaport Disability Rating and the Coma/Near Coma scale. Brain MRI volumetric measurements were done prior to the procedure, then approximately a year after, and finally 7 years after the implementation of the electrode. The volumetric analysis included changes in regional cortical volumes and thickness, as well as in subcortical structures. Limbic cortices (parahippocampal and cingulate gyrus) and paralimbic cortices (insula) regions showed a significant volume increase and presented a trend of regional cortical thickness increase 1 and 7 years after DBS. The volumes of related subcortical structures, namely the caudate, the hippocampus as well as the amygdala, were significantly increased 1 and 7 years after DBS, while the putamen and nucleus accumbens presented with volume increase. Volume increase after DBS could be a result of direct DBS effects, or a result of functional recovery. Our findings are in accordance with the results of very few human studies connecting DBS and brain volume increase. Which mechanisms are behind the observed brain changes and whether structural changes are caused by consciousness recovery or DBS in patients with DOC is still a matter of debate.

Frameless stereotactic brain biopsy: A prospective study on robot-assisted brain biopsies performed on 32 patients by using the RONNA G4 system.

BACKGROUND: We present a novel robotic neuronavigation system (RONNA G4), used for precise preoperative planning and frameless neuronavigation, developed by a research group from the University of Zagreb and neurosurgeons from the University Hospital Dubrava, Zagreb, Croatia. The aim of study is to provide comprehensive error measurement analysis of the system used for the brain biopsy. METHODS: Frameless stereotactic robot-assisted biopsies were performed on 32 consecutive patients. Post-operative CT and MRI scans were assessed to precisely measure and calculate target point error (TPE) and entry point error (EPE). RESULTS: The application accuracy of the RONNA system for TPE was 1.95 ± 1.11 mm, while for EPE was 1.42 ± 0.74 mm. The total diagnostic yield was 96.87%. Linear regression showed statistical significance between the TPE and EPE, and the angle of the trajectory on the bone. CONCLUSION: The RONNA G4 robotic system is a precise and highly accurate autonomous neurosurgical assistant for performing frameless brain biopsies.

Hemoglobin A1c in Patients with Glioblastoma-A Preliminary Study.

BACKGROUND: Glioblastomas are among the most common primary brain tumors with an abysmal prognosis. The significance of glucose metabolism in glioblastoma cell metabolism and proliferation is well-known. However, a significant correlation between the systemic metabolic status of the patient and the cellular proliferation of the glioblastoma has not yet been established. METHODS: Our aim was to observe and analyze for a possible correlation between glioblastoma cellular proliferation and patients' glycated hemoglobin (HbA1c) levels as a marker of chronic systemic glycemia. We analyzed the data from 25 patients and compared their Ki-67 values with their preoperative HbA1c values. RESULTS: We observed a statistically significant correlation (P < 0.03) between chronic glycemia (measured using HbA1c) and the cellular proliferation of glioblastoma (measured by cellular Ki-67 expression). CONCLUSIONS: These results imply a possible positive correlation between glioblastoma cell proliferation and chronic systemic glycemia, a correlation that, to the best of our knowledge, has not yet been reported. Further research in this area could not only lead to a better understanding of glioblastoma but also have significant clinical applications in treating this devastating disease.

A biphasic tumor in posterior cranial fossa and the pineal region in young adult.

BACKGROUND: Biphasic tumors of the central nervous system are rarely described and mainly consisted out of the glial and mesenchymal component. The tumor originated out of both astrocytes and pinealocytes, best to our knowledge, has not been described. We present a case of a brain tumor consisted out of pilocytic astrocytoma (PA) and pineocytoma as components situated in the pineal region and posterior cranial fossa in young adult. CASE DESCRIPTION: We present a 21-year-old patient with a history of intermittent headache, followed by nausea and vomiting, double vision, and dextropulsion. Magnetic resonance imaging revealed an extensive cystic-solid expansive formation in the posterior cranial fossa with a solid part in the area of the pineal gland. The patient underwent surgical resection. The pathohistological analysis showed two types of tumor cells; the major part of tumor showed features of PA, while minor part corresponded to pineocytoma. CONCLUSION: PA accounts for 5% of all gliomas and is most common in children and young adults. It usually occurs in the cerebellum, the optic pathway, third ventricular region, etc. Pineocytomas are rare, accounting up to 1% of all intracranial tumors. Since tumors origin is different, there must be complex molecular events or mutations that can lead to cell rearrangements and generation of two histologically different tissues in the same tumor mass. The course of treatment options is different for PA and pineocytoma; therefore, the case of brain mass consisted out of two different tissues can be helpful when deciding about the treatment of tumors in posterior cranial fossa and pineal region.

Dynamics of inflammatory factors expression in ischemic brain tissue injury.

Ischemic stroke is one of the most common cause of mortality and disability in the modern world. Still, therapeutic options remain modest. Aim of the study was to present dynamics of inflammatory factors expression (C reactive protein, procalcitonin, interleukin 10) in patients after ischemic stroke. Our study included 101 patients divided in thrombolised and nonthrombolised groups. Inflammatory factors concentration in serum was determinate at admission, 24, 48 hours and seven days after the initial onset, while neurological assessment was measured at the admission, 24 hours, seven days and three months after the initial onset using National Institute of Health Stroke Scale and Rankin Scale. Certain pattern was observed in dynamics of inflammatory factors: intensive increase in first and second day after the stroke, followed by decrease till day seven in both groups. Additionally, thrombolised group showed significant neurological improvement. Although well investigated, the role of inflammatory factors in the ischemic stroke still stays controversial. High association of C reactive protein and interleukin 10 values suggest potential prognostic role in patient's follow-up, while the role of procalcitonin values still remains unclear.

The Dubrava Model-A Novel Approach in Treating Acutely Neurotraumatized Patients in Rural Areas: A Proposal for Management.

Introduction Neurotrauma is one of the leading causes of death and disabilities nowadays and represents one of the largest socioeconomic problems in rich countries, as well as developing ones. A satisfying, medically viable, and cost-effective model of managing acutely neurotraumatized patients, especially ones who come from distant and/or rural areas, has yet to be found. Patient outcome after acute neurotrauma depends on many factors of which the possibility of urgent treatment by an experienced specialist team has a crucial role. Here, we present our own way of managing acutely neurotraumatized patients from distant places which is unique in Croatia, the Dubrava model. Methods We present our 5-year experience cooperating with general hospitals in four neighboring cities (Cakovec, Bjelovar, Sisak, and Koprivnica) in managing, operating, and taking care of acutely neurotraumatized patients. Results More than 300 surgeries have been performed in these hospitals through the Dubrava model. Our experience so far provides encouraging results that this system could also be successfully implemented in other institutions. Furthermore, we recorded an increased number of surgeries each year, as well as a good mutual cooperation with the local general hospitals. Discussion This trauma managing model is one of a kind in Croatia. We argue that it is not only better for the patients, providing them with better chances of survival, and disability-free recovery, but is also far superior in many ways to the dominant and currently prevalent way of treating these patients in other parts of Croatia. Conclusion The Dubrava model of treating patients in rural and distant areas is a reliable and proven model with many benefits and as such its implementation should be considered in other institutions as well.

Intracranial Mature Teratoma in an Adult Patient: A Case Report.

Introduction : Primary intracranial teratoma is a subtype of germ cell tumors, classified into three subtypes. They occur very rarely, with only several reported individual cases in adults. Case Description We present a patient with an intermittent headache in the right frontal region. Magnetic resonance imaging (MRI) revealed a right sided high frontal parasagittal mass that compressed the falx, the right lateral ventricle, as well as the brain parenchyma. Patient underwent surgical treatment. Histopathological analysis described mature teratoma. Four months after the surgical treatment there were no signs of residual intracranial mass or relapse. Discussion Primary intracranial teratoma in adults has a nonspecific clinical presentation. MRI reveals a solitary irregular mass with multilocularity and mixed signals derived from different tissues. The patients age, biochemical markers, and patohistological analysis are necessary to confirm the diagnosis. Conclusion Teratoma treatment strategy still remains controversial. It includes radical resection whenever possible. Since the residual portion of mature teratoma may contain part of immature or malignant tissue, tumor recurrence after surgical removal is possible. Also, new tumor mass could occur at other sites intracranial after the initial one was removed. Thus, although patients usually recover, they should be followed-up for a long period of time.

Primary dural lymphoma mimicking meningioma: a clinical and surgical case report.

INTRODUCTION: Primary central nervous system lymphoma and its subtype, primary dural lymphoma, are types of non-Hodgkin's lymphoma that only occur in the central nervous system without any dissemination. They are extremely rare cases of extra nodal lymphomas accounting for 1--5% of intracranial tumors. CASE REPORT: We present a patient diagnosed with primary dural lymphoma in right frontal brain region who underwent surgical resection. Histopathological analysis revealed diffuse B-type large cell non-Hodgkin lymphoma. Patient underwent four cycles of R-CHOP and intrathecal methotrexate protocol. Six months postoperative, no signs of newly onset infiltration were present. DISCUSSION: Primary dural lymphoma most likely presents with unusual radiological signs, which can easily be mistaken for meningioma, the main differential diagnosis. A thorough immunological, histopathological and clinical patients profile should be conducted in order to establish the certainty of diagnosis. Although there are few treatment options: surgery, radiotherapy or chemotherapy, there is no established treatment protocol.

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset.

OBJECTIVES: Our study focused on the RANKL (receptor activator of nuclear factor-κB ligand)/RANK/OPG (osteoprotegerin) axis and selected proinflammatory/immunoregulatory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. METHODS: PBL and CSF were collected from healthy controls (n = 35) and MS patients at the clinical onset of the disease (n = 33). In addition, PBL samples were obtained from relapse-remitting (RR)-MS patients (n = 30). Patients were assessed by means of the expanded disability status scale (EDSS) and routine laboratory parameters. Soluble (s)RANKL and OPG were measured in the CSF and plasma; gene expression was detected for RANKL, RANK, OPG, and selected cytokines/chemokines (interleukin [IL]-4, IL-10, IL-17, CCL2, and CXCL12) in PBL mononuclear cells. RESULTS: The OPG level in the CSF was lower in MS patients at clinical onset than in controls. Moreover, the sRANKL/OPG ratio was higher in the CSF of MS patients at clinical onset and in the plasma of RR-MS patients than in controls. Gene expression of RANKL/RANK/OPG in PBL mononuclear cells was higher only in RR-MS patients. IL-4, CCL2, and CXCL12 were positively correlated and IL-10 was negatively correlated with RANKL/RANK expression. OPG was negatively correlated with EDSS and alkaline phosphatase level. CONCLUSION: Our study revealed that changes of RANKL/RANK/OPG axis are associated with MS, particularly the decreased OPG level in the CSF at disease onset. Therefore, these factors may serve as disease biomarkers and molecular targets of novel therapeutic approaches.

Brain biopsy performed with the RONNA G3 system: a case study on using a novel robotic navigation device for stereotactic neurosurgery.

BACKGROUND: Robotic neuronavigation is becoming an important tool for neurosurgeons. We present a case study of a frameless stereotactic biopsy guided by the RONNA G3 robotic neuronavigation system. METHODS: A 45 year-old patient with a history of vertigo, nausea and vomiting was diagnosed with multiple periventricular lesions. Neurological status was unremarkable. A frameless robotic biopsy of a brain lesion was performed. RESULTS: Three tissue samples were obtained. There were no intraoperative or postoperative complications. Histological analysis showed a B-cell lymphoma. After merging the preoperative CT scan with the postoperative MRI and CT scans, the measured error between the planned and the postoperatively measured entry point was 2.24 mm and the measured error between the planned and postoperatively measured target point was 2.33 mm. CONCLUSIONS: The RONNA G3 robotic system was used to navigate a Sedan brain biopsy needle to take tissue samples and could be a safe and precise tool for brain biopsy.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio help identify patients with lung cancer, but do not differentiate between lung cancer subtypes.

AIM: To assess the diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in lung cancer (LC). We compared the ratios between healthy participants and all LC patients, as well patients with different pathohistological LC subtypes. METHODS: We retrieved the data on neutrophil, lymphocyte, and platelet levels in 449 patients with different pathohistological LC subtypes (non-small cell LC, small-cell LC, atypical or metastatic LC, neuroendocrine, and sarcomatoid carcinoma) and 47 healthy controls. NLR and PLR were calculated by dividing the absolute number of neutrophils or platelets with the absolute number of lymphocytes. RESULTS: There were significant differences in both NLR and PLR (P<0.001) between all LC patients and the control group, but there were no differences between patients with different LC subtypes. Reciever operating characteristics analysis for NLR showed the optimal cut-off value of 2.71, with a sensitivity of 77.05% and specificity of 87.23%. The optimal cut-off value for PLR was 182.31, with a sensitivity of 51.09% and specificity of 91.49%. CONCLUSION: The results showed that the NLR and PLR may have added value in the early diagnosis of LC, but further research is needed to confirm these results.

Decreased level of sRAGE in the cerebrospinal fluid of multiple sclerosis patients at clinical onset.

OBJECTIVES: Receptor for advanced glycation end products (RAGE) ligands/RAGE interactions have been proposed to have a pathogenic role in neuroinflammatory disorders. Our study aimed to assess changes in high-mobility group box (HMGB)1 and its receptor RAGE in peripheral blood (PBL) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) at the disease onset compared with control subjects. METHODS: PBL and CSF were collected from control subjects (n = 30) and MS patients (n = 27) at clinical onset. Soluble RAGE (sRAGE), HMGB1, S100 calcium-binding protein A12 (S100A12), interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured in the CSF and plasma by enzyme-linked immunosorbent assay. Gene expression in PBL mononuclear cells (PBMCs) was detected by quantitative PCR for RAGE, HMGB1, S100A12 and several proinflammatory/immunoregulatory cytokines. RESULTS: We found a significantly lower expression of IL-10 (p = 0.031) in the PBMCs of MS patients. The level of sRAGE in the CSF of MS patients was lower (p = 0.021), with the ability to discriminate between MS patients and control subjects. Moreover, PBMC gene expression for HMGB1 and S100A12 positively correlated with IL-6. CONCLUSIONS: Our study confirmed that the cytokine network is disturbed in PBL and CSF at MS clinical onset. The deregulated HMGB1/RAGE axis found in our study may present an early pathogenic event in MS, proposing sRAGE as a possible novel therapeutic strategy for MS treatment.