Cerebrospinal fluid metallomics in cerebral amyloid angiopathy: an exploratory analysis.

Introduction: Cerebral amyloid angiopathy (CAA) is associated with symptomatic intracerebral haemorrhage. Biomarkers of clinically silent bleeding events, such as cerebrospinal fluid (CSF) ferritin and iron, might provide novel measures of disease presence and severity.

Methods: We performed an exploratory study comparing CSF iron, ferritin, and other metal levels in patients with CAA, control subjects (CS) and patients with Alzheimer's disease (AD).

Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy.

Background: Two cerebrospinal fluid (CSF) biomarkers specific for neurodegeneration have recently emerged - the neurofilament light (NfL, 68 kDa) and heavy (NfH, 190-210 kDa) chains. This study investigated whether the CSF NfH and NfL levels or their stoichiometric relationship changed over time in a neuroprotective treatment trial.

Methods: Serial CSF samples (n=95) from 42 patients with multiple system atrophy (MSA), half randomized to treatment with recombinant human growth hormone (r-hGH) and the other half to placebo, were collected at baseline, 6 and 12 months.

Phosphorylation and compactness of neurofilaments in multiple sclerosis: indicators of axonal pathology.

Aims: Axonal pathology extends to the axonal cytoarchitecture leaving its signature on axoskeletal proteins. This study investigated whether neurofilament (NfH) phosphorylation would relate to the dynamics of axonal pathology in multiple sclerosis (MS).

Methods: NfH phosphoforms (SMI32, SMI34, SMI35) were quantified by ELISA from microdissected samples of control and MS brain and spinal cord.

Discrepancies between qualitative and quantitative analysis of cerebrospinal fluid IgG: densitometric comparison of nephelometry-silver versus immuno-enzymes.

Background: Detection of local synthesis of IgG within the central nervous system is important for the diagnosis of brain inflammatory diseases such as multiple sclerosis. This is typically done by comparing the amounts of IgG in serum and parallel cerebrospinal fluid (CSF). Although there have been well-described problems with qualitative versus quantitative measurements of abnormal IgG, such as in myeloma paraproteins, similar difficulties are also found with CSF IgG.

Quantitative demonstration of intrathecal synthesis of high affinity immunoglobulin G in herpes simplex encephalitis using affinity-mediated immunoblotting.

Three paired serial samples of CSF and serum (from days 8, 13 and 22) were taken from a patient referred to the National Hospital for Neurology and Neurosurgery with what was duly confirmed as having herpes simplex encephalitis using PCR. The samples were investigated using affinity-mediated immunoblotting followed by incubation with sodium thiocyanate. Digitisation of the blots enabled further analysis.

The role of antibody affinity for specific antigens in the differential diagnosis of inflammatory nervous system disorders.

Affinity maturation has previously been shown with assays for total IgG for specific antigens using the technique of competition by chaotropic ions. We have extended this technique to individual clones and followed the maturation of clones during the course of herpes encephalitis. This has important implications for our understanding of the pathogenesis of multiple sclerosis.

From rabies to transmissible spongiform encephalopathies: an immune-mediated microbial trigger involving molecular mimicry could be the answer.

The concept of experimental allergic encephalomyelitis (EAE) being linked to both rabies post-vaccination encephalomyelitis and multiple sclerosis (MS) has raised the intriguing question whether animal studies carried out for the induction and transmission of transmissible spongiform encephalopathies (TSEs) using brain antigens including prions do have a similar immunopathogenetic mechanism. Although an essential link between autoimmunity and MS has been well established, its role in the pathogenesis of TSEs is generally lacking. However, auto-antibodies to myelin proteins and/or other neuronal antigens such as neurofilaments and prion proteins have been reported in animals with bovine spongiform encephalopathy (BSE) and scrapie as well as in patients with Creutzfeld-Jakob disease (CJD) and kuru.

Early identification of secondary brain damage in subarachnoid hemorrhage: a role for glial fibrillary acidic protein.

Secondary ischaemic deficit adversely affects outcome in patients with subarachnoid hemorrhage (SAH). Astrocytes are vulnerable to ischemia, releasing glial fibrillary acidic protein (GFAP) when challenged. In this study, we followed nine patients with SAH who underwent extra-ventricular drainage for the management of secondary hydrocephalus.

Measurement of high affinity antibodies on antigen-immunoblots.

We describe a semi-quantitative method for measuring the relative affinity of antigen-specific oligoclonal IgG bands separated by isoelectric focusing followed by blotting onto antigen-coated membrane and incubation with sodium thiocyanate. When the developed blot is digitised in greyscale, densitograms can be made and peak areas calculated using ImageJ freeware. By expressing peak area as a percentage of the total area under the curve we have shown that there is a statistically significant rise in percentage of peak area for a given band which persists with increasing molarities of sodium thiocyanate.

Oligoclonal IgG bands in the cerebrospinal fluid of portuguese patients with multiple sclerosis: negative results indicate benign disease.

We assessed the frequency of cerebrospinal fluid (CSF) restricted oligoclonal IgG bands (IgG-OCB) in Portuguese multiple sclerosis (MS) patients and its relationship with outcome. Paired CSF/serum samples of 406 patients with neurological disorders were submitted to isoelectric focusing with immunodetection of IgG. Ninety-two patients had definite MS; non-MS cases were assembled in groups inflammatory/infectious diseases (ID, n=141) and other/controls (OD, n=173).

Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement.

New criteria for the diagnosis of multiple sclerosis (MS) were published as the result of an internationally formed committee. To increase the specificity of diagnosis and to minimize the number of false diagnoses, the committee recommended the use of both clinical and paraclinical criteria, the latter involving information obtained from magnetic resonance imaging, evoked potentials, and cerebrospinal fluid (CSF) analysis. Although rigorous magnetic resonance imaging requirements were provided, the "new criteria paper" fell short in terms of guidelines as to how the CSF analysis should be performed and simply equated the IgG index with isoelectric focusing, without any justification.

No evidence for production of intrathecal immunoglobulin G against Acinetobacter or Pseudomonas in multiple sclerosis.

The production of oligoclonal, polyspecific immunoglobulin G is characteristic of multiple sclerosis (MS), yet no pathogen has been identified as an infectious agent. Recent studies have proposed Acinetobactercalcoaceticus and Pseudomonas aeruginosa as candidate organisms, on the basis of a sequence homology between a bacterial enzyme and bovine myelin basic protein. To investigate this, we looked for specific, high-affinity immunoglobulin G against these pathogensin paired serum and cerebrospinal fluid from MS patients compared to other neurological diseases.

Cerebrospinal fluid nitrite/nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage.

The findings of various studies reporting temporal changes in CSF total nitrite/nitrate (NOx) levels after subarachnoid hemorrhage (SAH) vary considerably. The study group comprised 10 patients with SAH and 10 control subjects. Total nitrite/nitrate concentration was measured by a vanadium-based assay with the colorimetric Griess reaction.

Quality assurance for cerebrospinal fluid protein analysis: international consensus by an Internet-based group discussion.

A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This new approach respecting multicultural differences, common views, and minority opinions, is available in http://www.

The clinical significance of an intrathecal monoclonal immunoglobulin band: a follow-up study.

Background: Intrathecal oligoclonal band synthesis occurs in 95% of patients with clinically definite MS but may also occur in the context of CNS infection and other inflammatory conditions. By contrast, the significance of an intrathecal synthesis of a monoclonal band remains uncertain. Previously, an association between a single intrathecal band and CNS lymphoma has been reported but a relationship has also been shown with diagnoses more usually associated with an oligoclonal pattern.

Post-streptococcal autoimmune neuropsychiatric disease presenting as paroxysmal dystonic choreoathetosis.

Paroxysmal dystonic choreoathetosis (PDC) is an episodic, non-kinesogenic, extrapyramidal movement disorder. It is postulated that PDC is an ion channel disorder. We describe a sporadic case of paroxysmal dystonic choreoathetosis occurring after streptococcal pharyngitis.

Apolipoprotein E and other cerebrospinal fluid proteins differentiate ante mortem variant Creutzfeldt-Jakob disease from ante mortem sporadic Creutzfeldt-Jakob disease.

The ability to perform an ante mortem differential diagnosis of Creutzfeld-Jakob disease (CJD) is aided by several clinical and molecular tests. There is a need for molecular tests which can reliably distinguish ante mortem variant CJD (vCJD) from ante mortem sporadic CJD (spCJD). A proteomics approach employing two-dimensional protein electrophoresis is applied to the study of ante mortem CSF samples obtained in collaboration with the CJD Surveillance Unit and the National Hospital for Neurology and Neurosurgery.

Post-streptococcal autoimmune dystonia with isolated bilateral striatal necrosis.

Infantile bilateral striatal necrosis (IBSN) is characterized by a dystonic movement disorder and basal ganglia imaging abnormalities. Acute IBSN often occurs after upper respiratory tract infections although no specific micro-organism which may cause IBSN has been identified. We present 2 children (1 year 2 months and 4 years) with acute IBSN after clinical pharyngitis.