Two Blood Monocytic Biomarkers (CCL15 and p21) Combined with the Mini-Mental State Examination Discriminate Alzheimer's Disease Patients from Healthy Subjects

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. In AD, monocytes migrate across the blood-brain barrier and differentiate into microglia, are linked to inflammatory responses and display age-dependent decreases in telomere lengths. Methods: Six monocyte-specific chemokines and the (telomere-associated) tumor suppressor proteins p53 and p21 were determined by multiplex immunoassay in plasma and monocyte extracts of patients with AD or mild cognitive impairment, and levels were compared between patients and controls (without cognitive impairment). Results: CCL15 (macrophage inflammatory protein-1δ), CXCL9 (monokine-induced by interferon-γ) and p21 levels were decreased in monocytes of AD patients compared with controls. Conclusion: The combination of monocytic CCL15 and p21 together with the Mini-Mental State Examination enables to differentiate AD patients from controls with high specificity and sensitivity

The Cerebrospinal Fluid in Multiple Sclerosis

Investigation of cerebrospinal fluid (CSF) in the diagnostic work-up in suspected multiple sclerosis (MS) patients has regained attention in the latest version of the diagnostic criteria due to its good diagnostic accuracy and increasing issues with misdiagnosis of MS based on over interpretation of neuroimaging results. The hallmark of MS-specific changes in CSF is the detection of oligoclonal bands (OCB) which occur in the vast majority of MS patients. Lack of OCB has a very high negative predictive value indicating a red flag during the diagnostic work-up, and alternative diagnoses should be considered in such patients. Additional molecules of CSF can help to support the diagnosis of MS, improve the differential diagnosis of MS subtypes and predict the course of the disease, thus selecting the optimal therapy for each patient

Nodding syndrome in Tanzania may not be associated with circulating anti-NMDA- and anti-VGKC receptor antibodies or decreased pyridoxal phosphate serum levels-a pilot study

Background: Nodding syndrome (NS) is a seemingly progressive epilepsy disorder of unknown underlying cause. We investigated association of pyridoxal-phosphate serum levels and occurrence of anti-neuronal antibodies against N-methyl-D-aspartate (NMDA) receptor and voltage gated potassium channel (VGKC) complex in NS patients.Methods: Sera of a Tanzanian cohort of epilepsy and NS patients and community controls were tested for the presence of anti-NMDA-receptor and anti-VGKC complex antibodies by indirect immunofluorescence assay. Furthermore pyridoxal-phosphate levels were measured.Results: Auto-antibodies against NMDA receptor or VGKC (LG1 or Caspr2) complex were not detected in sera of patients suffering from NS (n=6), NS plus other seizure types (n=16), primary generalized epilepsy (n=1) and community controls without epilepsy (n=7). Median Pyridoxal-phosphate levels in patients with NS compared to patients with primary generalized seizures and community controls were not significantly different. However, these median pyridoxal-phosphate levels are significantly lower compared to the range considered normal in Europeans.Conclusions: In this pilot study NS was not associated with serum anti-NMDA receptor or anti-VGKC complex antibodies and no association to pyridoxal-phosphate serum levels was found.Key words: nodding syndrome, epilepsy, anti-neuronal antibodies, pyridoxal-phosphat

IgG-index predicts neurological morbidity in patients with infectious central nervous system diseases

<p>Abstract</p> <p>Background</p> <p>Prognosis assessment of patients with infectious and neoplastic disorders of the central nervous system (CNS) may still pose a challenge. In this retrospective cross-sectional study the prognostic value of basic cerebrospinal fluid (CSF) parameters in patients with bacterial meningitis, viral meningoencephalitis and leptomeningeal metastases were evaluated.</p> <p>Methods</p> <p>White blood cell count, CSF/serum glucose ratio, protein, CSF/serum albumin quotient and Immunoglobulin indices for IgG, IgA and IgM were analyzed in 90 patients with bacterial meningitis, 117 patients with viral meningoencephalitis and 36 patients with leptomeningeal metastases in a total of 480 CSF samples.</p> <p>Results</p> <p>In the initial spinal tap, the IgG-index was the only independent predictor for unfavorable outcome (GOS < 5) in patients with infectious CNS diseases but not in patients with leptomeningeal metastases. The sensitivity and specificity of an IgG-index of 0.75 and higher for predicting unfavorable outcome was 40.9% and 80.8% in bacterial meningitis and 40% and 94.8% in viral meningoencephalitis, respectively. No significant associations between CSF parameters and outcome could be observed in follow-up CSF samples.</p> <p>Conclusion</p> <p>The present study suggests that in infectious CNS diseases an elevated IgG-Index might be an additional marker for the early identification of patients at risk for neurological morbidity.</p

Distinct serum and cerebrospinal fluid cytokine and chemokine profiles in autoantibody-associated demyelinating diseases

Background: Demyelinating diseases of the central nervous system associated with autoantibodies against aquaporin-4 and myelin-oligodendrocyte-glycoprotein are mediated by different immunopathological mechanisms compared to multiple sclerosis. Objective: The purpose of this study was to evaluate serum and cerebrospinal fluid cytokine/chemokine profiles in patients with autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein-associated demyelination compared to multiple sclerosis and autoimmune encephalitis. Methods: Serum and cerebrospinal fluid cytokine/chemokine levels were analysed using Procartaplex Multiplex Immunoassays. First, we analysed a panel of 32 cytokines/chemokines in a discovery group (nine aquaporin-4-antibody seropositive, nine myelin oligodendrocyte glycoprotein-antibody seropositive, eight encephalitis, 10 multiple sclerosis). Significantly dysregulated cytokines/chemokines were validated in a second cohort (11 aquaporin-4-antibody seropositive, 18 myelin oligodendrocyte glycoprotein-antibody seropositive, 18 encephalitis, 33 multiple sclerosis). Results: We found 11 significantly altered cytokines/chemokines in cerebrospinal fluid and serum samples in the discovery group (a proliferation-inducing ligand, fractalkine=CX3CL1, growth-regulated oncogene-\u3b1, interleukin-1 receptor antagonist, interleukin-6, interleukin-8=CXCL8, interleukin-10, interleukin-21, interferon-&3-induced protein-10=CXCL10, monokine induced by interferon-&3=CXCL9, macrophage inflammatory protein-1 f=CCL4). Most of these cytokines/chemokines were up-regulated in autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein positive patients compared to multiple sclerosis. We confirmed these results for cerebrospinal fluid interleukin-6 and serum interleukin-8, growth-regulated oncogene-\u3b1, a proliferation-inducing ligand and macrophage inflammatory protein-1\u3b2 in the validation set. Receiver-operating characteristic analysis revealed increased levels of cerebrospinal fluid interleukin-6, serum interleukin-8 and growth-regulated oncogene-\u3b1 in most patients with autoantibody-associated neurological diseases. Conclusion: This study suggests that distinctive cerebrospinal fluid and serum cytokine/chemokine profiles are associated with autoantibody-mediated demyelination, but not with multiple sclerosis

Cerebrospinal fluid analyses for the diagnosis of subarachnoid haemorrhage and experience from a Swedish study. What method is preferable when diagnosing a subarachnoid haemorrhage?

Subarachnoid haemorrhage (SAH) has a high mortality and morbidity rate. Early SAH diagnosis allows the early treatment of a ruptured cerebral aneurysm, which improves the prognosis. Diagnostic cerebrospinal fluid (CSF) analyses may be performed after a negative computed tomography scan, but the precise analytical methods to be used have been debated. Here, we summarize the scientific evidence for different CSF methods for SAH diagnosis and describe their implementation in different countries. The principle literature search was conducted using PubMed and Scopus with the search items "cerebrospinal fluid”, "subarachnoid haemorrhage”, and "diagnosis”. CSF analyses for SAH include visual examination, red blood cell counts, spectrophotometry for oxyhaemoglobin or bilirubin determination, CSF cytology, and ferritin measurement. The methods vary in availability and performance. There is a consensus that spectrophotometry has the highest diagnostic performance, but both oxyhaemoglobin and bilirubin determinations are susceptible to important confounding factors. Visual inspection of CSF for xanthochromia is still frequently used for diagnosis of SAH, but it is advised against because spectrophotometry has a superior diagnostic accuracy. A positive finding of CSF bilirubin is a strong indicator of an intracranial bleeding, whereas a positive finding of CSF oxyhaemoglobin may indicate an intracranial bleeding or a traumatic tap. Where spectrophotometry is not available, the combination of CSF cytology for erythrophages or siderophages and ferritin is a promising alternativ

Psychometrische Prüfung des deutschsprachigen „Neurologischen Fragebogens zur Müdigkeit bei Multipler Sklerose (NFI-MS-G)“ bei Rehabilitanden mit Multipler Sklerose (Psychometric Evaluation of the ‘German Neurological Fatigue Index for Multiple Sclerosis (NFI-MS-G)’ in a Sample of Rehabilitation Patients with Multiple Sclerosis)

Purpose The purpose of this study was to provide a patient-reported outcome measure for people with multiple sclerosis (MS) comprehensively reflecting the construct of fatigue and developed upon the assumptions of the Rasch model. The Neurological Fatigue Index – Multiple Sclerosis (NFI-MS) is based on both a medical and patient-described symptom framework of fatigue and has been validated. Therefore, in this study the German version of the NFI-MS (NFI-MS-G) consisting of a physical and cognitive subscale and a summary scale was validated. Method In this bi-centre-study, 309 people with MS undergoing outpatient rehabilitation or being≥2 months before or after their inpatient rehabilitation completed the German NFI-MS-G twice within 14–21 days together with other questionnaires. Correlation with established questionnaires and Rasch analysis were used for its validation. Additionally, psychometric properties of known-groups validity, internal consistency, test-retest reliability, measurement precision and readability were tested. Finally, the English NFI-MS and German NFI-MS-G were compared with each other to equate the language versions. Results The NFI-MS-G showed good internal construct validity, convergent and known-groups validity and internal consistency (Cronbach’s alpha 0.84–0.93). The physical subscale showed minor local dependencies between items 1 and 7, 2 and 3 and 4 to 6, that could be treated by combining the respective items to testlets. Unidimensionality was found for the physical and cognitive subscales but not for the summary scale. Replacing the summary scale, a 2-domains subtest measuring the higher-order construct of fatigue was created. Good test-retest reliability (Lin’s concordance correlation coefficient of 0.86–0.90) and low floor and ceiling effects were demonstrated. The NFI-MS-G was found easily readable and invariant across groups of gender, age, disease duration, timepoint and centre. Conclusion The German version of the NFI-MS comprehensively represents the construct of fatigue and has adequate psychometric properties. The German version differs from the English original version with respect to a lack of unidimensionality of the summary scale and minor local dependencies of the physical subscale that could be canceled out using a testlet analysis

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear.</p> <p>Findings</p> <p>We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture.</p> <p>CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, <it>p </it>< 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters.</p> <p>Conclusions</p> <p>Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.</p

The characteristics of suicides within a week of discharge after psychiatric hospitalisation – a nationwide register study

BACKGROUND: The characteristics of victims of immediate post-discharge suicides are not well known. We explored these characteristics for the purposes of better recognition and preventive efforts of potential immediate post-discharge suicides. METHODS: Suicides from a Finnish nationwide register were linked with preceding periods of psychiatric inpatient treatment. Characteristics of suicides within a week of discharge were compared to those occurring later after discharge. RESULTS: Compared to other previously hospitalised suicide victims, those committing suicide within a week of discharge were more often female, unmarried, had a higher grade of education and a diagnosis of schizophrenia spectrum or affective disorder, tended to use more drowning and jumping from heights as the methods for suicide and had gained a smaller improvement in psychological functioning during hospitalization. CONCLUSION: These characteristics indicate a more severe psychopathology, relatively poorer level of functioning, less global response to hospitalisation, and a more frequent choice of lethal and easily available method for suicide. Potentially suicidal psychiatric patients should be better recognized and an immediate follow-up arranged if it is decided they be discharged