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Further potential targets are the mechanisms whereby CNS neurons lose regenerative ability as they mature. In the first decades of the 20th century, Ramón y Cajal[1] published observations on the response of neurons to injury, his own and from the work of others. He considered the lack of regeneration in the central nervous system (CNS) to be due to the absence of Schwann cells. [Extracted from the article]

The concept of the "Retinex" was introduced by Edwin Land in 1962. The aim of his theory of colour vision was to highlight the observations on colour perception that were at odds with the simple "Newtonian" concept that the colours that humans perceive when viewing narrow band light are directly related to perceived colours in the environment. There are, however, two particular observations which are at odds with this simple interpretation of the colours seen in the "spectrum" of light. One was emphasized by Gӧethe in his colour theory: namely that there are a range of named colours that are influenced by the luminance contrast (e.g. brown which is a darkened orange) or closeness of the colour to white. This was explored by Chevreul, Munsell and others who developed systems of colour based on the three dimensions: hue (colour category), saturation (closeness to white) and value (brightness). The second was the observation studied extensively by Land: namely that colours remain constant across a certain range despite a change in the spectral content of the illuminant. Thus despite a change in the pattern of cone excitation the colour appearance does not change. Land also emphasized that this phenomenon is influenced by other colours in the scene and introduced the study of natural scenes with natural illumination rather than narrow band light in the laboratory. So in this context Land decided to refer to the "Retinex" as it was clear that the various processes were taking place both at the retinal and cortical levels. I am adopting this term in my talk because clinical studies provide an opportunity to study the influence of damage at all levels in the visual pathway on colour perception. Beginning with congenital colour anomalies affecting the cone opsins all the way to damage to extra‐striate visual cortex clinical studies, such as those presented in this symposium, alterations in colour vision provide an insight into how damage at various levels in the "Retinex" influence colour perception. [ABSTRACT FROM AUTHOR]

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized. [ABSTRACT FROM AUTHOR]

The article presents a case wherein a 20-year-old female kitchen worker had a sudden onset right neck pain radiating to occipital region, after turning her head to the left whilst in bed and then awoke with vertigo, nausea and vertical diplopia. Neurological examination based on a triad of ocular signs, the saccadic lateropulsion, Horner's syndrome and horizontal-torsional jerk nystagmus, confirmed that the patient has an unsteady, wide-based ataxic gait.

Chromatic sensitivity was assessed in patients with pregeniculate and postgeniculate lesions. We examine changes in central vision along at foveal fixation and in each of the four paracentral quadrants of the visual field using the Colour Assessment and Diagnosis (CAD) test, a dynamic luminance contrast masking technique that isolates the use of Red / Green (RG) and Yellow / Blue (YB) colour signals. Because the extraction of colour signals in early visual processing involves opponent mechanisms, subjects with congenital RG loss of sensitivity exhibit symmetric increase in thresholds towards the long wavelength ("red") and middle wavelength ("green") regions of the spectrum locus. This is also frequently the case with acquired loss of chromatic sensitivity as a result of retinal or optic nerve disease. The findings from this study represent an exception to this rule. The patients investigated showed a marked asymmetry in colour thresholds. The study reveals how discrete, localized damage to visual pathways can cause selective loss of visual function and how the latter varies with retinal topography. The 36 pregeniculate patients investigated exhibited impairment in both RG and YB. Loss of colour vision was symmetrical for both RG and YB discrimination. Some pregeniculate patients exhibited substantial loss of colour vision in areas where perimetric loss was largely absent. All quadrants revealed similar symmetric loss of colour sensitivity. In 23 patients with postgeniculate lesions, patients with pre‐striate damage exhibited symmetric loss of chromatic sensitivity which affected either one or both chromatic mechanisms. Striate or extra‐striate lesions tended to exhibit general loss of colour vision within the area identified by visual field testing. More specific chromatic loss was associated with less impaired areas that were often normal on perimetric testing. Some patients with striate or extra‐striate lesions presented with asymmetric chromatic loss for one or more colour categories. When striate or extra‐striate lesions were also accompanied by underlying pre‐striate damage, chromatic sensitivity loss was always symmetric. The findings from this study show that the loss of chromatic sensitivity in cerebral achromatopsia depends strongly on the exact location and extent of the lesion with significant variation over the visual field. The same subject can exhibit loss of chromatic sensitivity that is either RG or YB specific, but also, spatially localized, non‐opponent loss of sensitivity for primary colours. [ABSTRACT FROM AUTHOR]

We report findings of monocular and binocular assessments of colour vision and thresholds for rod‐ and cone‐mediated sensitivity in two young patients (P1 and P2) diagnosed with monocular dyschromatopsia. Altered, monocular, colour perception with no clear diagnosis was reported in each patient based on results from a number of clinical visual assessment tests carried out over several years. Electrodiagnostic tests also revealed reduced Yellow / Blue (YB) chromatic sensitivity in P1. Both patients exhibited unexpected binocular interactions of colour signals. This abstract focuses mostly on the results obtained in P1, but similar results using the same visual assessment tests will also be presented for P2. P1 experienced visual discomfort, often manifested as differences between monocular and binocular viewing, noise‐like appearance of uniform fields and colours over the field, when viewed monocularly with either eye. As a result of these reports, we re‐examined P1's visual deficits using the Colour Assessment and Diagnosis (CAD) and the Flicker‐Plus (FP) tests (http://www.city-occupational.co.uk/). The FP test measures rod‐ and cone‐mediated rapid flicker sensitivity centrally (along the direction of gaze) and at 6 deg eccentricity in each of the four quadrants. Colour Vision. P1 shows significant loss of YB colour vision when tested monocularly in the right eye, but normal red‐green (RG) and YB colour vision in the left eye. When tested binocularly, P1 continues to show the same loss of YB colour vision observed when using only the right eye. These results were unexpected since P1 shows 'normal' binocular summation for both colour and flicker sensitivity, even when the thresholds are above the normal range. Rod‐ / Cone‐sensitivity. The patient's cone‐mediated, flicker sensitivity at all five locations investigated (under binocular viewing) was normal (with flicker detection thresholds, often under 2%), but only for the cone‐enhanced condition. When tested with rod‐enhanced stimuli, P1 shows much reduced sensitivity with larger thresholds in the periphery, but only in binocular viewing. Such responses have not been observed previously. In conclusion, P1 shows loss of YB colour vision in the right eye and also significant loss of rod‐mediated sensitivity at each of the five locations investigated. The patient's cone mediated thresholds, at every location tested, were consistently below the mean expected for normal trichromats, both binocularly and with each eye. The YB colour vision measured binocularly remained severely abnormal with thresholds similar to the right eye, in spite of normal colour vision in the left eye. Preliminary observations also suggest that the patient's colour and rapid flicker sensitivity can be affected by fatigue and other factors. Although patient, P2, varied significantly to P1 in monocular thresholds, a similar binocular, inhibitory interaction between the two eyes was observed when processing colour signals. These observations and the unusual interactions between signals derived from the two eyes point towards abnormal central processing of colour signals. [ABSTRACT FROM AUTHOR]

Background The clinical use of holotranscobalamin (holoTC) testing to evaluate vitamin B12 status has increased in recent years. We present two patients (African Caribbean and Indian heritage), in which the holoTC assay indicated severe B12 deficiency (< 5 pmol/L). Additional clinical tests revealed that these patients had normal levels of total vitamin B12 in blood and unremarkable levels of two other markers of vitamin B12 status, homocysteine and methylmalonic acid. We hypothesized that these patients carry a variant in the transcobalamin gene ( TCN2) that influences the most widely commercially available holoTC test - Active-B12 (Axis-Shield Diagnostics Ltd). Design Exon sequencing of the TCN2 gene was carried out. Protein characterization included total transcobalamin (TCN2) detection by Western blot, and holoTC by 57Co-labelled B12 binding followed by size fractionation. Results Exon sequencing of TCN2 revealed both patients were homozygous for the minor allele of rs35838082 (p.R215W). Western blot and chromatographic analyses revealed that the serum of these patients contains intact transcobalamin and that this variant-containing protein binds vitamin B12. The variant is rare in Caucasians (minor allele frequency (MAF) < 0·01) but more common in South Asians (MAF ~ 0·02) and those of African origin (MAF ~ 0·25). Conclusions The impeded ability to detect normal levels of holoTC in these two patients may be due to this variant interfering with the detection of holoTC by one or both of the monoclonal antibodies currently employed in the Active-B12 test. Laboratories should be aware of this variant and use confirmatory tests when applicable. [ABSTRACT FROM AUTHOR]

Objective: To determine a predictive factor for the risk of conversion from ocular myasthenia gravis (OMG) to generalized MG (GMG) in a prospective study. Methods: RNA was isolated from serum samples and detection of microRNA (miRNA) expression analyzed with qPCR. In the discovery set, 179 human miRNAs were assayed for profiling of five OMG patients and four age‐ and gender‐matched healthy controls. Based on the specific accumulation pattern of 19 miRNAs from the discovery set, in addition to miRNAs previously found elevated in generalized MG (GMG; miR‐150‐5p and miR‐30e‐5p), 21 miRNAs were subsequently analyzed in a validation cohort of 83 OMG patients (82 immunosuppression treatment naive; 49 male) within 3 months of diagnosis and at a follow‐up visit (median duration 28 months from first visit). Results: Thirteen patients generalized 14.8 ± 12.0 months after the diagnosis and the majority (85%) belonged to the late onset MG group. Two miRNAs were significantly higher in secondary GMG (SGMG) patients compared to OMG patients with late onset MG: miR‐30e‐5p (9.1 ± 0.5 vs. 6.3 ± 0.9; P < 0.0001) and miR‐150‐5p (7.4 ± 1.1 vs. 6.4 ± 1.1; P = 0.01). The sensitivity for miR‐30e‐5p in differentiating OMG and SGMG was 96% in all OMG patients and 100% in late onset OMG patients. Interpretation: This is the first study to describe a potential predictive factor associated with the risk of generalization for patients with OMG. Raised levels (>8) of miR‐30e‐5p at initial presentation in patients with ocular MG symptoms, give a predictive cut‐off for subsequent generalization of 96–100%. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate prespecified and post hoc analyses in RENEW subgroups to identify participants more likely to benefit from opicinumab. Methods: RENEW assessed the efficacy/safety of opicinumab versus placebo in participants with a first unilateral acute optic neuritis (AON) episode. Difference in visual evoked potential (VEP) latency of the affected eye at 24 weeks versus the fellow eye at baseline was the primary endpoint. Interactions between the primary endpoint and prespecified baseline variables (including age, timing of treatment initiation, and visual impairment) using the median as cut‐off were evaluated in the per protocol population using analysis of covariance (ANCOVA); subgroups based on preexisting brain T2 lesion volume were also analyzed. Interactions between the primary endpoint and retinal ganglion cell layer/inner plexiform layer (RGCL/IPL) and retinal nerve fiber layer (RNFL) thickness were assessed post hoc as was weight gain by treatment. Results: Treatment benefit of opicinumab (n = 33) over placebo (n = 36) on the primary endpoint was greatest in participants older than the median age at baseline (≥33 years); the difference versus placebo for baseline age ≥33 years was −14.17 msec [P = 0.01] versus −0.89 msec for baseline age <33 years, [P = 0.87]). Post hoc analysis showed that VEP latency recovery was significantly associated with less RGCL/IPL thinning (P = 0.0164), occurring early on. Interpretation: Age was the strongest prespecified baseline characteristic associated with a treatment effect of opicinumab. A strong association between VEP latency recovery at week 24 and early RGCL/IPL preservation was observed. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "True polycoria or pseudo-polycoria?," that was published in the previous issue.

Objective: Acute optic neuritis due to an inflammatory demyelinating lesion of the optic nerve is often seen in association with multiple sclerosis. Although functional recovery usually follows the acute episode of visual loss, persistent visual deficits are common and are probably due to axonal loss. The mechanisms of axonal loss and early features that predict it are not well defined. We investigated clinical, electrophysiological, and imaging measures at presentation and after 3 months as potential markers of axonal loss following optic neuritis. Methods: We followed 21 patients after their first attack of acute unilateral optic neuritis for up to 18 months. Axonal loss was inferred from optical coherence tomography measures of retinal nerve fiber layer (RNFL) thickness at least 6 months following the episode. Visual function, visual evoked potential, and optic nerve magnetic resonance imaging measures obtained during the acute episode and 3 months later were investigated for their association with later axonal loss. Results: After multivariate analysis, prolonged visual evoked potential latency and impaired color vision, at baseline and after 3 months, were significantly and independently associated with RNFL thinning. Low-contrast acuity measures exhibited significant univariate associations with RNFL thinning. Interpretation: The association of RNFL loss with a prolonged visual evoked potential (VEP) latency suggests that acute and persistent demyelination is associated with increased vulnerability of axons. VEP latency and visual function tests that capture optic nerve function, such as color and contrast, may help identify subjects with a higher risk for axonal loss who are thus more suitable for experimental neuroprotection trials. ANN NEUROL 2011;70:955-963 [ABSTRACT FROM AUTHOR]

Objectives To determine whether lateral occipital complex (LOC) activation with functional magnetic resonance imaging (fMRI) predicts visual outcome after clinically isolated optic neuritis (ON). To investigate the reasons behind good recovery following ON, despite residual optic nerve demyelination and neuroaxonal damage. Methods Patients with acute ON and healthy volunteers were studied longitudinally over 12 months. Structural MRI, visual evoked potentials (VEPs), and optical coherence tomography (OCT) were used to quantify acute inflammation, demyelination, conduction block, and later to estimate remyelination and neuroaxonal loss over the entire visual pathway. The role of neuroplasticity was investigated using fMRI. Multivariable linear regression analysis was used to study associations between vision, structure, and function. Results Greater baseline fMRI responses in the LOCs were associated with better visual outcome at 12 months. This was evident on stimulation of either eye ( p = 0.007 affected; p = 0.020 fellow eye), and was independent of measures of demyelination and neuroaxonal loss. A negative fMRI response in the LOCs at baseline was associated with a relatively worse visual outcome. No acute electrophysiological or structural measures, in the anterior or posterior visual pathways, were associated with visual outcome. Interpretation Early neuroplasticity in higher visual areas appears to be an important determinant of recovery from ON, independent of tissue damage in the anterior or posterior visual pathway, including neuroaxonal loss (as measured by MRI, VEP, and OCT) and demyelination (as measured by VEP). ANN NEUROL 2010;67:99-113 [ABSTRACT FROM AUTHOR]

The article discusses the cases of a 28-year-old female nurse and a 37-year-old gentleman with epilepsy. It states that these cases depict the development of significant bilateral visual loss after grand mal seizures. It suggests that clinicians should understand post-ictal visual reduction, a rare complication of generalized grand mal seizures or status epilepticus, to offer reassurance to patients and avoid unnecessary investigations.