Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage.

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4-14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4-14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4-14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

Association between elevated cerebrospinal fluid D-dimer levels and delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage.

Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major contributor to morbidity and mortality. It is currently not possible to reliably predict patients at risk of DCI after aSAH. The aim of this study was to quantify cerebrospinal fluid (CSF) D-Dimer and plasminogen levels and to investigate any association with development of DCI. Cerebrospinal fluid (CSF) samples collected from 30 patients within 72 h post-aSAH (n = 13 DCI and n = 17 non-DCI patients) were analysed. DCI was diagnosed when angiographic vasospasm was detected in the presence of new onset neurological deficit. Enzyme-linked immunosorbent assays were used to quantify D-dimer concentrations while western blotting was used to quantify plasminogen levels. Significant differences in CSF proteins between DCI and non-DCI cohorts were verified using Mann-Whitney test. Sensitivity and specificity of these proteins for detecting DCI was examined using a ROC curve and verified with a Fischer's exact test. CSF levels of D-dimer within 72 h post aSAH were significantly elevated in DCI patients (54.29 ng/ml, 25.35-105.88 ng/ml) compared to non-DCI patients (26.75 ng/ml, 6.9-45.08 ng/ml) [p = 0.03]. In our sample population, D-dimer levels above 41.1 ng/ml had a sensitivity of 69.2% and specificity of 75% for predicting DCI. CSF levels of plasminogen (DCI: 0.50 signal-intensity/µl, 0.20-0.73 signal-intensity/µl, non-DCI: 0.28 signal-intensity/µl, 0.22-0.54 signal-intensity/µl) did not differ between the DCI and non-DCI cohort (p > 0.05). Our study suggests that elevated D-dimer in the first 72 h after aSAH may be a potential predictive biomarker for DCI.

Biomarkers of Cerebral Injury and Inflammation in Pediatric Tuberculous Meningitis.

Background: Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neurospecific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods: Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analyzed for the neuromarkers S100B, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), in addition to multiple inflammatory markers. Results were compared with 2 control groups: patients with (1) a fatty filum (abnormal filum terminale of the spinal cord); and (2) pulmonary tuberculosis (PTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results: Data were collected from 44 patients with TBM (cases; median age, 3.3 [min-max 0.3-13.1] years), 11 fatty filum controls (median age, 2.8 [min-max 0.8-8] years) and 9 PTB controls (median age, 3.7 [min-max 1.3-11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE, and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated interleukin (IL) 12p40, interferon-inducible protein 10, and monocyte chemoattractant protein 1 concentrations, whereas infarcts were associated with elevated tumor necrosis factor α, macrophage inflammatory protein 1α, IL-6, and IL-8. Conclusions: CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.

Automated quantification of cerebral edema following hemispheric infarction: Application of a machine-learning algorithm to evaluate CSF shifts on serial head CTs.

Although cerebral edema is a major cause of death and deterioration following hemispheric stroke, there remains no validated biomarker that captures the full spectrum of this critical complication. We recently demonstrated that reduction in intracranial cerebrospinal fluid (CSF) volume (∆ CSF) on serial computed tomography (CT) scans provides an accurate measure of cerebral edema severity, which may aid in early triaging of stroke patients for craniectomy. However, application of such a volumetric approach would be too cumbersome to perform manually on serial scans in a real-world setting. We developed and validated an automated technique for CSF segmentation via integration of random forest (RF) based machine learning with geodesic active contour (GAC) segmentation. The proposed RF + GAC approach was compared to conventional Hounsfield Unit (HU) thresholding and RF segmentation methods using Dice similarity coefficient (DSC) and the correlation of volumetric measurements, with manual delineation serving as the ground truth. CSF spaces were outlined on scans performed at baseline (< 6 h after stroke onset) and early follow-up (FU) (closest to 24 h) in 38 acute ischemic stroke patients. RF performed significantly better than optimized HU thresholding (p < 10- 4 in baseline and p < 10- 5 in FU) and RF + GAC performed significantly better than RF (p < 10- 3 in baseline and p < 10- 5 in FU). Pearson correlation coefficients between the automatically detected ∆ CSF and the ground truth were r = 0.178 (p = 0.285), r = 0.876 (p < 10- 6) and r = 0.879 (p < 10- 6) for thresholding, RF and RF + GAC, respectively, with a slope closer to the line of identity in RF + GAC. When we applied the algorithm trained from images of one stroke center to segment CTs from another center, similar findings held. In conclusion, we have developed and validated an accurate automated approach to segment CSF and calculate its shifts on serial CT scans. This algorithm will allow us to efficiently and accurately measure the evolution of cerebral edema in future studies including large multi-site patient populations.

Hypocretin-1 levels in the cerebrospinal fluid of patients with Percheron artery infarction with or without midbrain involvement: A case series.

BACKGROUND: Bilateral paramedian thalamic infarctions (BPTIs) due to artery of Percheron occlusion are known to cause hypersomnia. However, the role of hypocretin-1, a wake-promoting peptide that is located at the lateral hypothalamus, in hypersomnia in these patients remains unclear. METHODS: To clarify the role of hypocretin-1 in hypersomnia in patients with BPTIs, hypocretin-1 levels in the cerebrospinal fluid (CSF) were measured in 6 patients with BPTIs: 2 with rostral midbrain involvement (BPT+RMI) and 4 without midbrain involvement (BPT-MI). RESULTS: CSF hypocretin-1 levels were decreased in 2 patients with BPT+RMI and were within normal ranges in 4 patients with BPT-MI. Hypersomnia was noted in all the patients. In one BPT+RMI patient, hypersomnia was improved within 2 weeks and decreased CSF hypocretin-1 levels were reversed (acute phase (on day 9), 109.2 pg/mL; chronic phase (at 3 months), 323 pg/mL), whereas another BPT+RMI patient who displayed coma in the acute phase had decreased CSF orexin levels (107 pg/mL) at day 49 and exhibited severe disability. CONCLUSION: Hypocretin deficiency was not involved in hypersomnia observed in BPT-MI patients; however, CSF hypocretin-1 levels were reduced in BPT+RMI patients. Reduced CSF hypocretin-1 levels in the chronic phase may possibly predict a poor clinical outcome in patients with Percheron artery infarction.

Massive Cerebrospinal Fluid Replacement Reduces Delayed Cerebral Vasospasm After Embolization of Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND Delayed cerebral vasospasm (DCVS) following aneurismal subarachnoid hemorrhage (SAH) is a leading cause of poor prognosis and death in SAH patients. Effective management to reduce DCVS is needed. A prospective controlled trial was conducted to determine if massive cerebrospinal fluid (CSF) replacement (CR) could reduce DCVS occurrence and improve the clinical outcome after aneurysmal SAH treated with endovascular coiling. MATERIAL AND METHODS Patients treated with endovascular coiling after aneurysmal SAH were randomly divided into a control group receiving regular therapy alone (C group, n=42) and a CSF replacement group receiving an additional massive CSF replacement with saline (CR group, n=45). CSF examination, head CT, DCVS occurrence, cerebral infarction incidence, Glasgow Outcome Scale prognostic score, and 1-month mortality were recorded. RESULTS The occurrence of DCVS was 30.9% in the C group and 4.4% in the CR group (P<0.005). The cerebral infarction incidences in the C and CR groups were 19.0% and 2.2% (P<0.05), respectively, 1 month after the treatments. Mortality was not significantly different between the 2 groups during the follow-up period. CONCLUSIONS Massive CR after embolization surgery for aneurysmal SAH can significantly reduce DCVS occurrence and effectively improve the outcomes.

The detection of surfactant proteins A, B, C and D in the human brain and their regulation in cerebral infarction, autoimmune conditions and infections of the CNS.

Surfactant proteins (SP) have been studied intensively in the respiratory system. Surfactant protein A and surfactant protein D are proteins belonging to the family of collectins each playing a major role in the innate immune system. The ability of surfactant protein A and surfactant protein D to bind various pathogens and facilitate their elimination has been described in a vast number of studies. Surfactant proteins are very important in modulating the host's inflammatory response and participate in the clearance of apoptotic cells. Surfactant protein B and surfactant protein C are proteins responsible for lowering the surface tension in the lungs. The aim of this study was an investigation of expression of surfactant proteins in the central nervous system to assess their specific distribution patterns. The second aim was to quantify surfactant proteins in cerebrospinal fluid of healthy subjects compared to patients suffering from different neuropathologies. The expression of mRNA for the surfactant proteins was analyzed with RT-PCR done with samples from different parts of the human brain. The production of the surfactant proteins in the brain was verified using immunohistochemistry and Western blot. The concentrations of the surfactant proteins in cerebrospinal fluid from healthy subjects and patients suffering from neuropathologic conditions were quantified using ELISA. Our results revealed that surfactant proteins are present in the central nervous system and that the concentrations of one or more surfactant proteins in healthy subjects differed significantly from those of patients affected by central autoimmune processes, CNS infections or cerebral infarction. Based on the localization of the surfactant proteins in the brain, their different levels in normal versus pathologic samples of cerebrospinal fluid and their well-known functions in the lungs, it appears that the surfactant proteins may play roles in host defense of the brain, facilitation of cerebrospinal fluid secretion and maintenance of the latter's rheological properties.

Changes in HIF-1α, VEGF, NGF and BDNF levels in cerebrospinal fluid and their relationship with cognitive impairment in patients with cerebral infarction.

This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=0.037 and P=0.000; P=0.023 and P=0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hypoxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.

Acute cerebral ischaemia: relationship between serum and cerebrospinal fluid orexin-A concentration and infarct volume.

OBJECTIVE: Orexins are hypothalamic neuropeptides that are involved in feeding, neuroendocrine regulation, sleep-wakefulness and sleep disorders (such as narcolepsy). This study investigated the relationship between serum and cerebrospinal fluid (CSF) orexin-A concentrations and infarct volume, in patients with ischaemic stroke. METHODS: Serum and CSF concentrations of orexin-A were determined 48-72 h after the onset of ischaemic stroke in patients, then compared with those of healthy control subjects of comparable age. Infarct volumes were measured using computerized tomography, 48-72 h after hospitalization. RESULTS: Mean serum and CSF orexin-A concentrations were significantly lower among ischaemic stroke patients (n = 29) compared with control subjects (n = 13). There was a significant inverse correlation between infarct volumes and CSF orexin-A concentrations in patients with ischaemic stroke. CONCLUSION: These data show that serum and CSF orexin-A concentrations decrease after cerebral ischaemia and may play a role in the development of brain injury. The orexin-A concentration in the CSF might be a useful biomarker for the assessment of progression of brain tissue damage during the early stages of ischaemic stroke.

[Neurological adverse events under anti-TNF alpha therapy]. / Évènements neurologiques sous traitement par anti-TNF alpha.

INTRODUCTION: Anti-TNF alpha treatments are increasingly prescribed in various rheumatological or gastroenterological inflammatory diseases. Several adverse events, including neurological episodes have been reported in the literature. Relation to treatment is a major concern and guidelines for management of those patients are not available. The aim of our study is to collect and analyze neurological adverse events occurring during anti-TNF alpha therapy, and to propose guidelines for diagnosis of demyelinating-induced diseases. METHODS: All patients treated with anti-TNF alpha drug, who were addressed in our department following a neurological event, were collected. We gathered clinical data including previous neurological history and immunosuppressive treatments. Paraclinical data included brain and spinal MRI, CSF study and outcome after anti-TNF therapy was collected. RESULTS: Nine patients were included in this study. Sex ratio was eight and mean age was 49±9 years. One patient had previous history of subarachnoïdian hemorrage. All the patients previously received immunosuppressive drugs, including methotrexate (nine) and leflunomide (four). Three patients had a brain MRI before initiation of anti-TNF treatment, which was normal. Clinical episode was stroke-like in three cases, clinically isolated syndrome (CIS) in five cases, and peripheral neuropathy in one case. MRI showed lesions suggestive of demyelinating T2 hyperintensities in four cases, vascular infarcts in two cases, and non-specific T2 hyperintensities in three cases. Barkhof and Tintore criteria were fulfilled in one of the four CIS cases. CSF study was available for six patients. It was normal (four cases), showed oligoclonal bands (one case) and lymphocytic meningitis (one case). Anti-TNF alpha discontinuation was decided in five cases. Outcome was favorable for eight patients. One patient, whom MRI fulfilled Barkhof and Tintore criteria, and CSF showed oligoclonal bands, further developed relapsing remitting multiple sclerosis. CONCLUSION: Our study is compatible with data found in the literature. Barkhof and Tintore criteria and CSF study are useful in clinical practice to diagnose a first demyelinating event. Standardized paraclinical neurological explorations should be proposed to physicians who are in charge of anti-TNF treated patients.

White matter lesions and lacunar infarcts are independently and differently associated with brain atrophy: the SMART-MR study.

OBJECTIVE: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI. METHODS: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 +/- 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid and WML. Total brain volume, ventricular volume and cortical gray matter volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), ventricular fraction (VF) and cortical gray matter fraction (GMF). Location and number of infarcts were rated visually. RESULTS: Mean +/- SD BPF was 79.3 +/- 2.8%, mean +/- SD VF was 2.01 +/- 0.95%, and mean +/- SD GMF was 36.6 +/- 3.3%. Linear regression analyses, adjusted for age, sex, vascular risk factors, intima media thickness and LI showed that in patients with moderate to severe WML (upper quartile) BPF was lower (-0.51%; 95% CI -0.93 to -0.08%), VF was higher (0.48%; 95% CI 0.31-0.65%) and GMF was lower (-1.48%; 95% CI -2.07 to -0.88%) than in patients with few WML (lower quartile). Presence of LI was associated with lower BPF (-0.52%; 95% CI -0.96 to -0.07%) and higher VF (0.25%; 95% CI 0.07-0.42%), but not with GMF, independent of WML and other potential confounders. CONCLUSION: WML are associated with total, subcortical and cortical brain atrophy, whereas LI are associated with total and subcortical atrophy, but not with cortical atrophy, suggesting an independent role for WML and LI in the pathogenesis of brain atrophy.

The prognostic value of NSE and S100B from serum and cerebrospinal fluid in patients with spontaneous subarachnoid hemorrhage.

Neuron-specific enolase (NSE) and S100B protein have been shown to be increased in cerebrospinal fluid (CSF) and serum of patients suffering from subarachnoid hemorrhage. This study was designed to evaluate the accuracy of NSE and S100B from CSF and serum for the prognosis of outcome and the detection of cerebral infarction, vasospasm and intracranial hypertension. In 55 patients with spontaneous subarachnoid hemorrhage and requiring external ventricular drainage the concentrations of NSE and S100B were determined daily from the serum and the CSF from admission until day 8. At ICU discharge patients' outcome was assessed by the Glasgow outcome scale and occurrence of cerebral infarction, vasospasm and intracranial hypertension were registered. Mean and peak values of each parameter for each patient were calculated. For accuracy assessment receiver operating characteristics were used. Bad outcome (Glasgow outcome scale 1 to 3) was found in 33 patients. Cerebral infarction, vasospasm, and intracranial hypertension were found in 31 (56%), 34 (62%), and 36 (65%) patients. Mean and peak values of NSE CSF (P<0.001), S100B CSF (P<0.001), and S100B serum (P<0.001) but not of NSE serum provided the ability to distinguish between patients with good and bad outcome. The accuracy of NSE CSF and S100B CSF did not differ significantly from that of S100B serum. NSE CSF (P<0.001), S100B CSF (P<0.001), and S100B serum (P<0.001) allowed the detection of cerebral infarction and intracranial hypertension. Cerebral vasospasm was detected by none of the parameters. In conclusion, NSE CSF, S100B CSF, and S100B serum provide similar prognostic values for outcome, intracranial hypertension and cerebral infarction. Significantly lower accuracy was found for NSE serum.

Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome.

Body fluid biomarkers of central nervous system damage may help improve the prognostic and diagnostic accuracy in ischemic stroke. We studied 53 patients. Stroke severity and outcome was rated using the National Institutes of Health Stroke Scale and modified Rankin scale. Ferritin, S100B, and NfH were measured in cerebrospinal fluid (CSF) and serum. Infarct volume was calculated from T2W images. CSF S100B (median 1.00 ng/mL) and CSF ferritin (10.0 ng/mL) levels were elevated in patients with stroke compared with control subjects (0.62 ng/mL, P < .0001; 2.34 ng/mL, P < .0001). Serum S100B (0.09 ng/mL) was higher in patients with stroke compared with control subjects (0.01 ng/mL). CSF S100B levels were higher in patients with a cardioembolic stroke (2.88 ng/mL) than in those with small-vessel disease (0.89 ng/mL, P < .05). CSF S100B levels correlated with the National Institutes of Health Stroke Scale score on admission (R = 0.56, P < .01) and the stroke volume (R = 0.44, P = .01). CSF S100B and NfH-SMI35 levels correlated with outcome on the modified Rankin scale. CSF S100B levels were related to stroke severity and infarct volume and highest in cardioembolic stroke.

Detection of elastin derived peptides in cerebrospinal fluid of patients with first ever ischaemic stroke.

OBJECTIVE: We have previously reported the optimized methods for the detection of elastin derived peptides (EDP) in the serum, synovial fluid, and bronchoalveolar lavage. The aim of the present study was to investigate whether EDP are detectable in cerebrospinal fluid (CSF) of patients with acute brain ischaemia. PATIENTS AND METHODS: Twenty-seven first ever ischaemic stroke patients (mean age 61.5+/-10.8 years; age range 47-70 years; 12 women) were studied in acute phase (1-15 days after the onset) with clinical evaluations, radiological assessments, and the analysis of serum and CSF based on Western blot and ELISA for the detection and quantification of EDP. RESULTS: None of the serum EDP concentrations are significantly higher in stroke patients compared with 25 healthy control individuals. However, EDP levels in CSF are strongly (p<0.0001) elevated compared with healthy subjects. They correlated with total cholesterol (r=0.53; p=0.02), triglycerides (r=0.67; p=0.004) and retinopathy (r=0.24; p=0.03), and with the interval between the stroke onset and the time of lumbar puncture (r=0.35; p=0.02). CONCLUSION: EDPs are detectable in CSF of healthy subjects and patients with ischaemic stroke. Acute brain infarction is followed by increased levels of EDP in CSF.

Clinical and laboratory characteristics of cerebral infarction in tuberculous meningitis: a comparative study.

Cerebral infarction as a complication of tubercular (TB) meningitis is not uncommon, but an adequate comparison of patients with and without stroke has not been carried out. This study was performed to evaluate the clinical characteristics of cerebral infarction secondary to TB meningitis, and to investigate predictive factors for cerebral infarction in patients with TB meningitis. Patients with TB meningitis were recruited over a period of 56 months. They were divided into two groups, those with and those without stroke. Demographic features and clinical, laboratory, and neuroradiological findings were compared between the two groups. We classified strokes into subtypes using neuroimaging findings. Of the 38 patients who were diagnosed with TB meningitis, eight also experienced cerebral infarction. The percentage of cerebrospinal fluid leukocytes that were neutrophils was significantly higher in patients with stroke (68%) than in patients without stroke (31%; p=0.0001). Upon initial CT imaging, meningeal enhancement was found in 11 patients, and of these patients, six experienced stroke. There were no significant differences between the groups with respect to other clinical and laboratory features, including demographic features, time between meningitis onset and treatment initiation, peripheral white blood cell count, and cerebrospinal fluid findings. Five of the eight patients who developed stroke had lacunar infarcts. One of the three patients with territorial nonlacunar infarction died due to herniation. When treating patients with TB meningitis, the possibility of cerebral infarction should be considered when patients develop focal neurological signs, meningeal enhancement on a CT scan, and sustained polymorphic cerebrospinal fluid pleocytosis.

Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis.

OBJECTIVES: This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. METHODS: CSF was collected from 92 adults with community-acquired bacterial meningitis, who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. Levels of proteins involved in the coagulation cascade were determined by means of immunoassays. RESULTS: Bacterial meningitis was accompanied by local activation of coagulation, as shown by significantly higher CSF soluble tissue factor (P<0.001) and prothrombin fragment F1+2 concentrations (P<0.001) as compared to viral meningitis patients and controls. This was accompanied by a significantly higher D-dimer formation (P<0.001). In addition, in bacterial meningitis fibrinolysis was attenuated, since CSF plasminogen activator inhibitor (PAI)-1 levels were significantly higher as compared to the controls (P=0.02). In patients with bacterial meningitis who developed brain infarction, CSF PAI-1 levels were higher than in those without infarction (P=0.04). CONCLUSIONS: Activation of coagulation and attenuation of fibrinolysis in the CSF are important features of bacterial meningitis; the net effect on fibrin turnover may contribute to the development of brain infarction.

Low serum potassium in mid life associated with decreased cerebrospinal fluid Abeta42 in late life.

Low serum potassium increases risk of hypertension and stroke, and cardiovascular factors increase the risk of Alzheimer disease (AD). We examined the association between serum potassium and the biologic marker cerebrospinal fluid amyloid-beta (Abeta42), which is decreased in Alzheimer disease patients. Psychiatric examinations, laboratory and other tests were conducted on a population-based sample of 1080 women aged 46 to 60 in 1968, with follow-ups in 1974, 1980, and 1992. In 1992, cerebrospinal fluid Abeta42 levels were obtained from 81 women. Increasing serum potassium in 1968 was associated with increasing cerebrospinal fluid Abeta42 (beta = 153.9, P = 0.041) in 1992 using age-adjusted linear regression. Compared with the lowest tertile of potassium, the middle (beta = 95.3, P = 0.138) and highest tertiles (beta = 193.5, P = 0.004) had incrementally increased cerebrospinal fluid Abeta42 levels. Associations remained after controlling for blood pressure and other factors, and were similar among the 17 women in 1974 with available serum potassium. Potassium in 1980 and 1992 was not associated with cerebrospinal fluid Abeta42. Findings suggest low serum potassium in mid life, but not late life, is associated with low cerebrospinal fluid Abeta42 levels in late life. It is possible potassium co-varies with another variable that is associated with cerebrospinal fluid Abeta42. Nonetheless, serum potassium is a modifiable risk factor and further examination of the potassium-dementia relationship is warranted.

More accurate identification of reversible ischemic injury in human stroke by cerebrospinal fluid suppressed diffusion-weighted imaging.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC) derived from diffusion-weighted (DWI) MRI has been used to differentiate reversible from irreversible ischemic injury. However, the ADC can be falsely elevated by partial volume averaging of cerebrospinal fluid (CSF) with parenchyma, limiting the accuracy of this approach. This study tested the hypothesis that the accuracy of differentiating reversible from irreversible ischemic injury could be improved by CSF suppression at image acquisition. METHODS: Sixteen patients presenting within 6 hours from symptoms, and having partial reversal of the acute lesion on DWI were studied using conventional CSF-suppressed DWI. Lesions were segmented from coregistered acute DWI and follow-up fluid-attenuated inversion recovery (FLAIR) series. The segmented volumes were applied to conventional (ADC(C)) and CSF-suppressed ADC (ADC(FLIPD)) maps to classify each voxel as progressed to infarct or reversed. Individual voxel ADC values were pooled across all patients. Sensitivity to predict reversal, specificity, and accuracy were calculated for both methods. RESULTS: A total of 25 313 voxels were classified as progressed and 31 952 voxels reversed. Across all lesion voxels, ADC(FLIPD) values more accurately depicted tissue fate compared with ADC(C) values (P<0.0001). The largest difference in the two methods was in voxels with <75% parenchyma, where the accuracy of ADC(C) was only 50% compared with 62% for ADC(FLIPD.) CONCLUSIONS: CSF-suppressed ADC measurements gave a more accurate identification of reversible ischemic injury in this sample. We predict that multimodal MRI models of tissue viability in ischemic stroke will be more accurate if CSF-suppressed ADC measurements are used.

Elevated neurofilament levels in neurological diseases.

Neurofilaments, a major cytoskeletal constituent of neuronal cells, can be released into the cerebrospinal fluid during several neurodegenerative diseases. By means of a new sensitive ELISA capable of measuring 60 ng/l of neurofilament light, significant elevations were observed for different neurological disorders. Cerebral infarction presented levels of 19800+/-9100 ng/l, amyothropic lateral sclerosis 3600+/-1200 ng/l, 'relapsing-remitting' MS 2500+/-1500 ng/l, extrapyramidal symptoms 1100+/-300 ng/l, late onset AD 300+/-100 ng/l and vascular dementia 1400+/-800 ng/l. In patients with no signs of neurological diseases the upper normal level and cut-off values was determined to be below 100 ng/l. NF-L determinations will be a valuable complement in identifying neuronal degradation and can be used clinically for diagnostic and monitoring purposes.