Cerebrospinal Fluid Interleukin-6 Research Articles

Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome.

Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. We hypothesized that cohort heterogeneity, temporal inflammatory profiles, and concurrent inflammatory marker associations are critical to characterize when targeting subpopulations for anti-inflammatory therapies. Toward this objective, we used serial cerebrospinal fluid (CSF) samples to generate temporal acute IL-6 trajectory (TRAJ) profiles in a prospective cohort of adults with severe TBI (n=114). We examined the impact of injury type on IL-6 profiles, and how IL-6 profiles impact sub-acute (2weeks-3months) serum inflammatory marker load and long-term global outcome 6-12months post-injury. There were two distinct acute CSF IL-6 profiles, a high and low TRAJ group. Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale (GOS) scores at 6months (adjusted OR=3.436, 95% CI: 1.259, 9.380). Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ (p⩽0.05). The two groups did not differ with respect acute serum profiles; however, individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1β and IL-6 levels compared with the low TRAJ group (p⩽0.05). Lastly, injury type (isolated TBI vs. TBI+polytrauma) was associated with IL-6 TRAJ group (χ(2)=5.31, p=0.02). Specifically, there was 70% concordance between those with TBI+polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases are associated with increased odds for unfavorable global outcomes in the first year following TBI. Future studies should explore additional factors contributing to IL-6 elevations, and therapies to mitigate its detrimental effects on outcome.

Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis.

BackgroundTick-borne encephalitis (TBE) is a serious acute central nervous system infection that can result in death or long-term neurological dysfunctions. We hypothesize that changes in sphingosine-1-phosphate (S1P) concentration occur during TBE development.MethodsS1P and interleukin-6 (IL-6) concentrations in blood plasma and cerebrospinal fluid (CSF) were measured using HPLC and ELISA, respectively. The effects of S1P on cytoskeletal structure and IL-6 production were assessed using rat astrocyte primary cultures with and without addition of plasma gelsolin and the S1P receptor antagonist fingolimod phosphate (FTY720P).ResultsWe report that acute inflammation due to TBE virus infection is associated with elevated levels of S1P and IL-6 in the CSF of infected patients. This elevated concentration is observed even at the earliest neurologic stage of disease, and may be controlled by glucocorticosteroid anti-inflammatory treatment, administered to patients unresponsive to antipyretic drugs and who suffer from a fever above 39°C. In vitro, treatment of confluent rat astrocyte monolayers with a high concentration of S1P (5 μM) results in cytoskeletal actin remodeling that can be prevented by the addition of recombinant plasma gelsolin, FTY720P, or their combination. Additionally, gelsolin and FTY720P significantly decreased S1P-induced release of IL-6.ConclusionsTBE is associated with increased concentration of S1P and IL-6 in CSF, and this increase might promote development of inflammation. The consequences of increased extracellular S1P can be modulated by gelsolin and FTY720P. Therefore, blocking the inflammatory response at sites of infection by agents modulating S1P pathways might aid in developing new strategies for TBE treatment.

A safety study on intrathecal delivery of autologous mesenchymal stromal cells in rabbits directly supporting Phase I human trials.

There are no effective treatments that slow the progression of neurodegenerative diseases. A major challenge of treatment in neurodegenerative diseases is appropriate delivery of pharmaceuticals into the cerebrospinal fluid (CSF) of affected individuals. Mesenchymal stromal cells (MSCs-either naïve or modified) are a promising therapy in neurodegenerative diseases and may be delivered directly into the CSF where they can reside for months. In this preclinical study, we evaluated the safety of intrathecal autologous MSCs in a rabbit model. Autologous adipose-derived MSCs (or artificial CSF) were delivered intrathecally, either with single or with repeated injections into the foramen magnum of healthy rabbits and monitored for 4 and 12 weeks, respectively. Rabbits tolerated injections well and no definitive MSC-related side effects were observed apart from three rabbits that had delayed death secondary to traumatic foramen magnum puncture. Functional assessments and body weights were equivalent between groups. Gross pathology and histology did not reveal any abnormalities or tumor growth. Complete blood count data were normal and there were no differences in CSF interleukin-6 levels in all groups tested. Our data suggest that intrathecal delivery of autologous MSCs is safe in a rabbit model. Data from this study have supported two successful investigational new drug applications to the Food and Drug Administration, resulting in the initiation of two clinical trials using autologous MSCs in amyotrophic lateral sclerosis and multiple system atrophy.

Significance of cerebrospinal fluid matrix metalloproteinase-9, interleukin-6, and tumor necrosis factor-alpha protein in children with viral encephalitis

Objective To explore the significance of changes of matrix metalloproteinase-9(MMP-9), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) protein level in the cerebrospinal fluid (CSF) of children with viral encephalitis(VE). Methods The concentration of neuron-specific enolase(NSE), structural proteins 100B (S100B), and MMP-9, IL-6, TNF-α in the CSF of VE children were detected by an enzyme linked immunosorbent assay, and the correlations of them were analyzed. Results NSE, S100B, MMP-9, IL-6, TNF-α protein expression could be found significantly higher than those in the control group, and there were significant differences according to statistics expression trends(all P<0.05). The NSE protein expression was significantly positive related with S100B in the VE group (r=0.467, P=0.009), and the concentration was markedly negative related with the duration of viral encephalitis (r=-0.472, P=0.008). MMP-9, IL-6 protein expression were significantly positive related with NSE, S100B respectively (r=0.698, P=0.00; r=0.559, P=0.00; r=0.812, P=0.00; r=0.664, P=0.00). TNF-α protein expression was positive related with CSF S100B(r=0.363, P=0.049), but there was no correlation between TNF-α and NSE(r=0.245, P=0.193). Conclusions The neurons and the neuroglial cells are damaged in the viral encephalitis children.MMP-9, IL-6, TNF-α protein may participate in the pathological damage process of nerve cells in VE children in different degrees. Key words: Viral encephalitis; Structural proteins 100B; Matrix metalloproteinase-9; Interleukin-6; Tumor necrosis factor-alpha; Child

Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

BackgroundManifestations in neuropsychiatric systemic lupus erythematosus (NPSLE), especially active diffuse NPSLE syndromes, are some of the most difficult complications of the disease. For the evaluation and the diagnosis of central...

Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.

Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication.

High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide

The dysregulation of inflammation has been associated with depression and, more recently, with suicidal behaviors. The reports regarding the relationship between interleukin-6 (IL-6) and suicide attempts are inconsistent. Personality traits such as impulsivity and aggression are considered endophenotypes and important factors that underlie suicidal behaviors. The aim of the current study was to assess whether plasma and cerebrospinal fluid (CSF) levels of IL-6 are associated with personality traits among suicide attempters. We assessed the relationships among personality traits, IL-6 and violent suicide attempts. The plasma and CSF levels of IL-6 were measured in suicide attempters (plasma=58, CSF=39) using antibody-based immunoassay systems. Personality domains were assessed using the Karolinska Scale of Personality (KSP). IL-6 levels in plasma and CSF were used to predict personality domains via regression models. Plasma IL-6 was significantly and positively correlated with extraversion as well as the KSP subscales impulsivity and monotony avoidance. CSF IL-6 was positively correlated with monotony avoidance. Violent suicide attempts tended to be associated with high plasma IL-6 levels. Plasma and CSF levels of IL-6 were not significantly associated with each other. These results indicate that impulsivity and the choice of a violent suicide attempt method might be related to higher levels of IL-6 in individuals who attempt suicide. The neuroinflammation hypothesis of suicidal behavior on the basis of elevated IL-6 levels might be partly explained by the positive association between IL-6 and impulsivity, which is a key element of the suicidal phenotype.

Low IL-8 is associated with anxiety in suicidal patients: genetic variation and decreased protein levels.

Recent studies indicate that inflammation may play a role in the pathophysiology of suicidality. Interleukin-8 (IL-8) is a chemokine that in addition to its function in the immune system also exert neuroprotective properties. The involvement of this chemokine in neuropsychiatric conditions is incompletely known. We measured plasma and cerebrospinal fluid (CSF) IL-8, as well as the genotype frequency of a single nucleotide polymorphism (-251A/T, rs4073) in the promoter region of the IL8 gene, in suicide attempters (n=206) and healthy controls (n=578). Plasma and CSF levels of IL-8 were significantly lower in suicide attempters with anxiety than in healthy controls. IL-8 in both plasma and CSF correlated negatively with symptoms of anxiety. Compared with the population-based cohort, the IL-8-251T allele was more prevalent among female suicide attempters. Furthermore, suicide attempters carrying this allele showed more severe anxiety. This correlative study warrants further mechanistic studies on the effects of IL-8 in the central nervous system. We suggest that IL-8 might be involved in the biological mechanisms mediating resilience to anxiety. Thus, our findings highlight the chemokine IL-8 as a potential target for future development of anti-anxiety treatments and suicide prevention.

Association of interleukin-6-572C/G gene polymorphism and serum or cerebrospinal fluid interleukin-6 level with enterovirus 71 encephalitis in Chinese Han patients with hand, foot, and mouth disease.

Interleukin-6 (IL-6), as one of pro-inflammatory cytokines, plays a key role in Enterovirus 71 (EV71) encephalitis. We investigated the association of IL-6-572C/G polymorphism and serum or cerebrospinal fluid (CSF) IL-6 level with EV71 encephalitis in patients with hand, foot, and mouth disease (HFMD). This study was carried out in 59 Chinese Han patients with EV71 encephalitis, 128 EV71-related HFMD without complications, and 232 controls. The IL-6-572C/G polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism gene analysis. Serum or CSF IL-6 levels were determined using a commercial enzyme-linked immunosorbent assay. The patients with EV71 encephalitis had a higher frequency of IL-6-572GG/GC genotype compared to the patients with EV71-related HFMD without encephalitis complications (40.7 vs. 15.6 %, odds ratio (OR)=3.70, 95 % confidence interval (CI)=1.83-7.50, p=0.001). Similarly, the frequency of IL-6-572 G allele among the patients with EV71 encephalitis was also higher than that of patients with EV71-related HFMD without encephalitis complications (23.7 vs. 8.6 %, OR=3.31, 95 % CI=1.80-6.08, p<0.001). Serum IL-6 levels in G carries (CG + GG) (195.1 ± 11.8 pg/ml) elevated significantly compared to CC homozygotes (167.7 ± 6.7 pg/ml) in EV71-infected patients (p<0.001), but no significant differences were observed in CSF IL-6 levels among different genotypes in patients with EV71 encephalitis. Furthermore, G carriers (GG + GC) (10.6 ±.29 mg/l) had significantly higher blood CRP levels compared to CC homozygotes (9.31 ± 1.93 mg/l) in patients with EV71 encephalitis (p=0.005). These findings suggested that IL-6-572 G allele was significantly associated with the susceptibility to EV71 encephalitis in Chinese Han patients, and IL-6-572 G allele might elevate the risk to EV71 encephalitis.

Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a pilot study.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Autoimmune inflammation is common in the early stages of MS. This stage is followed by the neurodegenerative process. The result of these changes is axon and myelin breakdown. Although MS is according to McDonald's revised diagnostic criteria primarily a clinical diagnosis, paraclinical investigation methods are an important part in the diagnosis of MS. In common practice, magnetic resonance imaging of the brain and spinal cord, examination of cerebrospinal fluid (CSF) and examination of visual evoked potentials are used. There are an increasing number of studies dealing with biomarkers in CSF and their role in the diagnosis and treatment of MS. We hypothesized that the levels of some markers could be changed in MS in comparison with controls. We studied five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10 (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of beta-2-microglobulin and interleukin-8 in CSF were found to be significantly higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels of all markers between both groups were found. The levels of two studied inflammatory markers were found to be increased at the time of first clinical symptoms of MS. Research on the role of inflammatory and neurodegenerative markers in MS should continue.

OP0229 Correlation of the Integrated Cerebrospinal Fluid Interleukin-6 Level with Brainstem Atrophy in Chronic Progressive Neuro-BehÇEt's Disease

BackgroundCentral nervous system (CNS) involvement is a serious complication of Behçet's disease and is referred to as neuro-Behçet's disease (NB). NB is classified into acute type (ANB) and chronic progressive...

Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older women. Results from a population-based sample.

The literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6), interleukin-8 (IL-8) and depression in a population-based sample of older women who were followed for 17 years. 86 dementia-free women aged 70-84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992-3. CSF IL-6 and CSF IL-8 were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria. At baseline, women with ongoing major (n=10) or minor depression (n=9) had higher levels of CSF IL-6 (p=0.008) and CSF IL-8 (p=0.007) compared with those without depression (n=67). Higher CSF IL-8 was related to higher MADRS score (p=0.003). New cases of depression were observed in 9 women during follow-ups. No associations between CSF cytokine levels and future depression could be shown in women without depression at baseline. Higher levels of CSF IL-6 and IL-8 were associated with current depression in this population-based sample. CSF IL-6 and CSF IL-8 may play a role in depression in late life.

Shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage: the role of intrathecal interleukin-6.

Aneurysmal subarachnoid hemorrhage (SAH) has been reported to induce an intrathecal inflammatory reaction reflected by cytokine release, particularly interleukin-6 (IL-6), which correlates with early brain damage and poor outcome. The present study examines intrathecal IL-6 production together with clinical parameters, as a predictor of posthemorrhagic shunt dependency. Among 186 SAH patients admitted between July 2010 and December 2012, 82 received external ventricular drainage due to acute hydrocephalus. In these patients, cerebrospinal fluid (CSF) concentrations of IL-6 were measured within the first 14 days after SAH. Patients whose IL-6 values were not determined regularly and those who did not survive until discharge were excluded. The peak value of IL-6, ventricular infection during the hospital stay, microbial CSF culture, patient's age and sex, Hunt and Hess grade, and aneurysm location were assumed as predictive for shunt dependency. Sixty-nine patients were included, 24 of whom underwent shunt surgery. Peak IL-6 values of ≥10,000 pg/ml were significantly associated with a higher incidence of shunt dependency (p = 0.009). Additional risk factors were aneurysm location on the anterior cerebral artery and its branches or in the posterior circulation (p = 0.025), and age ≥60 years (p = 0.014). In a multivariate analysis, IL-6 ≥10,000 pg/ml appeared to be the only independent predictor for shunt dependency (p = 0.029) CONCLUSION: CSF IL-6 values of ≥10,000 pg/ml in the early post-SAH period may be a useful diagnostic tool for predicting shunt dependency in patients with acute posthemorrhagic hydrocephalus. The development of shunt-dependent posthemorrhagic hydrocephalus remains a multifactorial process.

Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men.

Interleukin-6 (IL-6) is a cytokine with pleiotropic actions in both the periphery of the body and the central nervous system (CNS). Altered IL-6 secretion has been associated with inflammatory dysregulation and several adverse health consequences. However, little is known about the physiological circadian characteristics and dynamic inter-correlation between circulating and CNS IL-6 levels in humans, or their significance. Simultaneous assessment of plasma and cerebrospinal fluid (CSF) IL-6 levels was performed hourly in 11 healthy male volunteers over 24h, to characterize physiological IL-6 secretion levels in both compartments. IL-6 levels showed considerable within- and between-subject variability in both plasma and CSF, with plasma/CSF ratios revealing consistently higher levels in the CSF. Both CSF and plasma IL-6 levels showed a distinctive circadian variation, with CSF IL-6 levels exhibiting a main 24h, and plasma a biphasic 12h, circadian component. Plasma peaks were roughly at 4 p.m. and 4 a.m., while the CSF peak was at around 7 p.m. There was no correlation between coincident CSF and plasma IL-6 values, but evidence for significant correlations at a negative 7-8h time lag. This study provides evidence in humans for a circadian IL-6 rhythm in CSF and confirms prior observations reporting a plasma biphasic circadian pattern. Our results indicate differential IL-6 regulation across the two compartments and are consistent with local production of IL-6 in the CNS. Possible physiological significance is discussed and implications for further research are highlighted.

Effect of exercise intensity on cerebrospinal fluid interleukin-6 concentration during recovery from exhaustive exercise in rats

The purpose of this study was to investigate the possible role of moderate and strenuous swimming training on plasma and cerebrospinal fluid (CSF) IL-6 (interleukin-6) levels during recovery from exhaustive exercise in rats. Wistar rats were divided into three groups: sedentary control (C), moderately trained (MT) and strenuously trained (ST). MT rats underwent swimming exercise for one hour/day and 5 days/week for 8 weeks. Animals in the ST group began swimming with 1 h/day and swimming duration was progressively increased by 30 min/wk, reaching 2.5 h/day by week 4 and stayed constant for an additional 4 weeks. After all animals underwent an acute exhaustive swimming exercise, animals were divided into 3 groups, and decapitated immediately, 24 and 48 hours after exhaustion to obtain tissue samples. Muscle citrate synthase activity, plasma and CSF IL-6 levels were determined. The citrate synthase activity was found to be higher in MT and ST groups compared to the C group. Although plasma IL-6 levels were found unaltered among all groups, the CSF IL-6 concentration was found to be increased 24 hours after exhaustive exercise of the ST group. We conclude that exercise training intensity is an important factor determining cerebrospinal IL-6 concentration after exhaustive exercise.

Reversible basal ganglia lesions in neuropsychiatric lupus: a report of three pediatric cases

Central nervous system involvement represents a serious and common complication of systemiclupus erythematosus (SLE). We describe the characteristics of patients with neuropsychiatric (NP) SLE complicated with reversible basal ganglia lesions. We describe the cases of three NPSLE patients. They presented with NP manifestations such as headache, cognitive dysfunction, tremors, seizures, and mood disorder. The levels of autoantibodies to NMDA (N-methyl-d-aspartate) receptor antibodies and antiribosomal-P antibodies were elevated, indicating the presence of an acute phase. Marked elevation of interleukin-6 in cerebrospinal fluid was noted when these patients showed NP symptoms. Moreover, the patients presented with high-intensity lesions in the basal ganglia on T2-weighted images, fluid-attenuated inversion recovery (FLAIR) images, diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps. Following immunosuppressive treatment, almost complete improvement of the lesions was noted. The reported cases indicate that reversible vasculopathies represent vasogenic edema localized in basal ganglia lesions and that activation of the autoimmune system and inflammation could lead to NP manifestations in SLE.

痛みをともなわず1日で横断性脊髄症を生じ広範な脊髄病変を呈した神経Behçet病の1例

A 64-year-old man had transverse myelopathy that rapidly progressed without pain over the course of 1 day. The cerebrospinal fluid interleukin-6 (CSF IL-6) level was extremely high (1,120 pg/dl). Spinal cord magnetic resonance imaging (MRI) showed a longitudinal extensive lesion extending from Th8 to the conus medullaris. Despite treatment with steroids and cyclophosphamide, the symptoms worsened, and the range of sensory disturbance spread. MRI showed that the lesion expanded to Th3 over the course of 2 months. Neuro-Behçet disease (NBD) was diagnosed on basis of the high CSF IL-6 level and HLA-B51 positivity, and treatment with infliximab was begun. The sensory disturbance improved slightly, and the CSF IL-6 level fell to the normal range (7.0 pg/ml). It is important to include NBD, which rarely presents with extensive spinal cord lesion, in the differential diagnosis when patients present with acute transverse myelopathy without pain.

An usual case of vasculo- and neuro-Behçet's disease with &lt;i&gt;MEFV&lt;/i&gt; mutations

A 35-year-old man had a 2-year history of uveitis and arterial wall thickening of an aortic branching artery detected by magnetic resonance imaging. He was admitted to our hospital because of mental exaltation. He had been treated with a moderate dose of prednisolone (30 mg/ml) plus methotrexate (6 mg/week) under the diagnosis of Takayasu arteritis for 2 years. Neurological examinations and brain magnetic resonance imaging taken on admission showed no abnormal findings. Although cerebrospinal fluid showed four cells/mm3 and 45 mg/dl of protein, cerebrospinal fluid interleukin-6 levels were markedly elevated (65.4 pg/mL), suggesting the neuro-Behçet's disease. The diagnosis of coexistence of vasculo- and neuro-Behçet's disease was made because vascular lesions are considered as a complication of Behçet's disease. We performed DNA testing using direct sequencing of all exons of the MEFV gene because of the patient's history of periodic fever since 30 year-old. The E148Q/L110P compound heterozygous mutation was found. His neurological symptoms and periodic fever were well controlled after the administration of infliximab (5 mg/kg every 2-month interval). Although occurrence by chance cannot be ruled out, the unusual findings of this patient suggest that MEFV mutations have some etiopathogenic mechanisms of an atypical phenotype of Behçet's disease.

Influenza A (H1N1)-induced ischemic stroke in a child: case report and review of the literature

Ischemic stroke is an important cause of death and long term morbidity in children. Viral respiratory infections are emerging as important risk factors responsible for ischemic stroke in this age group. The direct action of virus against cerebral vessels, autoimmune reactivity, and increased production of cytokines are advocated as the main factors for causing ischemic stro-ke. This study can be useful for clarifying some molecular aspects of H1N1 virus infection in children.We report on the case of a H1N1-induced ischemic stroke in a Caucasian 2 year-old female. The cerebrospinal fluid samples showed the positivity of polymerase chain reaction for influenza A (H1N1) infection, confirmed also by pharyngeal swab culture. Increased levels of cerebrospinal fluid interleukin 6 and interleukin 1β were also detected.&nbsp;&nbsp;H1N1 virus infection has been identified as an important cause of neurological involvement in children. The findings of increased levels of Interleukin 6 and interleukin 1β in the cerebrospinal fluid of this child with H1N1 induced-ischemic stroke seems to validate the role of pro-inflammatory cytokines as crucial mediators of cerebral thrombus formation.&nbsp;&nbsp

Quantitative analysis of brainstem atrophy on magnetic resonance imaging in chronic progressive neuro-Behçet's disease

ObjectivesTo examine whether quantitative analysis of the brainstem areas on magnetic resonance imaging (MRI) scans is useful for diagnosis as well as evaluation of disease activity in chronic progressive neuro-Behçet's disease (CPNB). MethodsMRI scans in patients with acute neuro-Behçet's disease (ANB) (n=10), CPNB (n=10), Behçet's disease with neurological manifestations non-attributable to NB (non-NB) (n=8), and control patients with non-inflammatory neurological diseases (NID) (n=10) were studied. The areas of midbrain tegmentum and pons were measured on mid-sagittal sections of T1-weighted images of MRI using software NIH Image J ver.1.45. ResultsThe areas of midbrain tegmentum as well as those of pons were significantly decreased in CPNB compared with those in the other three groups. On receiver operating characteristic (ROC) analysis, the sensitivity and specificity of the areas of brainstem combining midbrain tegmentum and pons for diagnosis of CPNB against non-CPNB (ANB+non-NB) were 80.0% and 94.4%, respectively, at cut-off value of 614.9mm2. Brainstem atrophy progressed most markedly during the first 2years during the course of CPNB. Moreover, the progression rate of atrophy was closely correlated with the elevation of cerebrospinal fluid interleukin-6. ConclusionThese results indicate that quantitative analysis of the brainstem areas on MRI scans is effective for diagnosis as well as for evaluation of the disease activity in CPNB. Moreover, it is suggested that an appropriate therapeutic intervention to reduce CSF IL-6 would be required as early as possible upon diagnosis of CPNB.