Neurofilament phosphoforms: Surrogate markers for axonal injury, degeneration and loss

This review on the role of neurofilaments as surrogate markers for axonal degeneration in neurological diseases provides a brief background to protein synthesis, assembly, function and degeneration. Methodological techniques for quantification are described and a protein nomenclature is proposed. The relevance for recognising antineurofilament autoantibodies is noted. Pathological implications are discussed in view of immunocytochemical, cell-culture and genetic findings. With reference to the present symposium on multiple sclerosis, the current literature on body fluid levels of neurofilaments in demyelinating disease is summarised. (c) 2005 Elsevier B.V All rights reserved

The Historical Origin of the Pulfrich Effect: A Serendipitous Astronomic Observation at the Border of the Milky Way

Interested in star movement the founder of Heidelberg's astronomy observatory, Max Wolf, faced the dilemma that the hitherto used 'Blinkmikrosop' of his Institution was damaged beyond repair following the first world war. He therefore used a new method, stereoscopy, to systematically classify 1053 moving stars between 1915 and 1918. The key problem Wolf identified with the new method was that variation in brightness of the same star on different photographic plates gave rise to an illusory movement. This was a particularly frequent problem with smaller stars close to the very bright Milky Way such as those in the proximity of Cygni or fade-out stars such as R Coronae Borealis. Carl Pulfrich, the world-leading expert on stereoscopy at the time, picked up immediately on the technical limitations Wolf published on stereoscopy in 1920. Pulfrich, who was blind in one eye, could not see the effect himself and designed a projection device to demonstrate Wolf's serendipitous observation to an audience which was equipped with a monocular neutral density filter. Pulfrich performed detailed investigations on the relationship of spatial perception and object movement, naming the phenomenon stereo effect, but it became widely known as the Pulfrich effect. The neuro-anatomical basis of the Pulfrich effect lies in the joint encoding of motion and depth within the visual cortex. Recognising Pulfrich effect is relevant for the management of patients in whom pathology of the visual pathways impairs judgment of object movement/position (e.g., in traffic or sport). Fitting a unilateral tinted lens or contact lens in front of the good eye can abolish the problem

Why human color vision cannot reliably detect cerebrospinal fluid xanthochromia

Background - Visual assessment of cerebrospinal fluid (CSF) for xanthochromia ( yellow color) is practiced by the majority of laboratories worldwide as a means of diagnosing intracranical bleeds.Methods - Colorimetric and spectrophotometric analysis of CSF samples for recognizing the presence of bilirubin either in low concentrations or in the presence of hemolysed blood.Results - The experiments provide the physiological and colorimetric basis for abandoning visual assessment of CSF for xanthochromia.Conclusion - We strongly recommend relying on spectrophotometry as the analytical method of choice

Amniotic fluid brain-specific proteins are biomarkers for spinal cord injury in experimental myelomeningocele

Myelomeningocele (MMC), the most severe form of spina bifida (SB), causes neurological deficit. Injury to the spinal cord is thought to begin in utero. We investigated whether brain-specific proteins (BSPs) would enable us to monitor the development of MMC-related tissue damage during pregnancy in an animal model with naturally occurring SB (curly tail/loop tail mouse; n = 256). Amniotic fluid levels of neurofilament heavy chain (NfH), glial acidic fibrillary protein (GFAP) and S100B were measured by standard ELISA techniques. The amniotic fluid levels of all BSPs were similar in SB and control mice on embryonic day (E) 12.5 and 14.5, whereas a significant increase was observed for GFAP in SB mice on E16.5. Levels of all BSPs were significantly increased in SB mice on E18.5. The rapid increase in GFAP, paralleled by a moderate increase in NfH and S100B, suggests that spinal cord damage starts to accelerate around E16.5. The macroscopic size of the MMC was related to NfH level on E16.5 and E18.5, suggesting that axonal degeneration is most severe in large MMC. Amniotic fluid BSP measurements may provide important information for balancing the risks and benefits to mother and child of in utero surgery for MMC

Axonal degeneration and inflammation in acute optic neuritis

Aims: To investigate whether plasma biomarkers for axonal injury and inflammation are related to loss and recovery of visual function in acute optic neuritis (ON).Methods: Eighteen patients with ON and 14 controls were investigated in a longitudinal, prospective study. Plasma phosphorylated neurofilament heavy chain ( NfH(SMI35); a surrogate marker of axonal injury), nitric oxide metabolites (NOx), and citrulline ( surrogate markers of inflammation) were measured.Results: Patients with ON had higher median plasma NfH(SMI35) values than controls (0.17 versus 0.005 ng/ml; p< 0.05) and higher NOx values (49 versus 35.5 mu M; p< 0.001). Plasma NfH(SMI35) values correlated inversely with visual acuity at presentation ( R = -0.67; p = 0.01). NfH(SMI35) was higher in patients with poor recovery of visual acuity than in those with good recovery (0.25 ng/ml versus 0.09 ng/ml; p< 0.05). Three of four patients with high NfH(SMI35) and high NOx values experienced a poor recovery as opposed to only one of five with high NOx but normal NfH(SMI35) values.Conclusions: NfH(SMI35), a surrogate marker for axonal damage, is a prognostic indicator and should be considered in the design of neuroprotective treatment strategies

Spectrophotometry for cerebrospinal fluid pigment analysis

The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed. The clinically relevant CSF pigments--oxyhemoglobin and bilirubin--are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables (the four T's: traumatic tap, timing, total protein, and total bilirubin). The practical laboratory aspects of spectrophotometry and automated techniques are presented in the context of analytical and clinical specificity and sensitivity. The perceptual limitations of human color vision are highlighted and the use of visual assessment of the CSF is discouraged in light of recent evidence from a national audit in the United Kingdom. Finally, future perspectives including the need for longitudinal CSF profiling and routine spectrophotometric calibration are outlined