Search

A young woman presented with blurred vision due to anticholinergic syndrome. We highlight the importance of considering this condition in the context of multiple medications and increased anticholinergic burden. The documented pupil abnormality gives an opportunity to review the syndrome of the reverse (inverse) Argyll Robertson pupil (preserved pupil light response with loss of accommodation). We review other situations in which the reverse Argyll Robertson pupil may occur and its possible mechanism in this case. [ABSTRACT FROM AUTHOR]

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]

To describe the frequency and characteristics of intraretinal and subretinal fluid in nonarteritic anterior ischemic optic neuropathy (NAAION) and to assess the influence on the visual deficit and optic nerve fiber/ganglion cell loss. A retrospective, single-center study. Thirty-two patients with NAAION referred to our Neuro-ophthalmology Department between 2014 and 2021. The study was carried out at the University Hospital of Liège, Belgium. For participants in whom subretinal fluid was identified on standard OCT (Carl Zeiss Meditec) an additional macular OCT (Spectralis Heidelberg) had been performed. The pattern and the maximal height of the retinal fluid were determined manually, and thicknesses of retinal layers were obtained using the OCT protocol analysis. The mean age of the cohort was 60 years (standard deviation, ±12.5; range, 22–88 years), and 65.6% were male. In the 21 eyes (46.7%) in which retinal fluid was observed, macular OCT findings were categorized according to fluid localization: 19 cases had parafoveal fluid (of whom 9 also had subfoveal fluid). One patient had subfoveal fluid alone, and 1 patient had peripapillary subretinal fluid alone. Specific patterns of optic disc (OD) swelling were associated with the occurrence and distribution of retinal edema. Visual acuity, visual field loss, and foveal thresholds were stable over the period of observation (P = 0.74, P = 0.42, and P = 0.36, respectively). No difference was found in visual function at 6 months between patients with retinal fluid treated (n = 10) or not treated (n = 11) with corticosteroids (visual acuity, P = 0.13; foveal threshold, P = 0.59; mean deviation, P = 0.66). Subretinal fluid is found in a high proportion of cases of NAAION. Visual function remained largely stable from presentation in this cohort. Corticosteroid intake at presentation did not influence visual recovery or timing of the resorption of tissue edema. Our findings do not support treatment of NAAION with corticosteroids with or without evidence of subretinal fluid acutely. With regard to pathogenesis, we propose that the volume of transudate generated at the OD is the critical factor rather than dysfunction of retinal mechanisms subserving reabsorption. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

We emphasise that all three tests are to be used for screening; the tests are designed so that healthy subjects would make few or no errors, no scoring system is provided and if errors are made further investigation is indicated. Declaration of interest statement MJ-G has a personal financial interest in the VOSP test, but neither the CORVIST nor the QSVD tests. We remain grateful to her for suggesting to Elizabeth Warrington (EW) and to one of us (MJ-G) that a companion to the existing Queen Square Screening Test for Cognitive Deficits (QSCD) be produced, which became the Queen Square Screening Test for Visual Deficits (QSVD). [Extracted from the article]

A brainstem lesion of any type that involves the medial longitudinal fasciculus (MLF) can cause internuclear ophthalmoplegia (INO). This primarily affects conjugate horizontal gaze and classically manifests as impaired adduction ipsilateral to the lesion and abduction nystagmus contralateral to the lesion. Here, we describe the anatomy of the MLF and review the clinical features of INO. We also describe conjugate horizontal gaze palsy and some of the 'INO-plus' syndromes. [ABSTRACT FROM AUTHOR]

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]

Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists. [ABSTRACT FROM AUTHOR]

The article presents simplified checklists to help neurologists to interpret Humphrey and Goldmann visual fields, emphasizing the importance of correlating the visual field outputs with careful patient history and clinical examination. Topics discussed include the useful aspects of eye anatomy, what happens during a Goldmann field test and a Humphrey field test, and the keys to interpreting both tests. It also mentions what perimetry results provide and when they change.

Abstract: The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica (NMO) spectrum disorder, multiple sclerosis associated optic neuritis (MSON) and unclassified optic neuritis (UCON) forms. Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies. [Copyright &y& Elsevier]

The adult neuro-ophthalmologist may see patients presenting for the first time with symptoms and signs classically associated with paediatric conditions. Therefore a literature review combined with case descriptions from the author's clinic is presented here, divided into problems of the optic nerve, ocular motility or visual function. Though such a review cannot be comprehensive nor cover every paediatric condition that has ever presented to an adult clinic, the authors hope that it will provide some useful insights and interesting clinical vignettes to assist clinicians in their own practice. [ABSTRACT FROM AUTHOR]

Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n = 20), chronic relapsing inflammatory optic neuritis (CRION, n = 19), neuromyelitis optica (NMO, n = 9), and healthy controls (n = 28). Serum NfH-SMI35 levels were quantified by ELISA. Findings. SerumNfH-SMI35 levels were highest in patients with NMO (mean 0.79±1.51 ng/mL) compared to patients with CRION (0.13± 0.16 ng/mL, P = 0.007), MSON (0.09 ± 0.09, P = 0.008), and healthy controls (0.01 ± 0.02 ng/mL, P = 0.001). High serum NfHSMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions. [ABSTRACT FROM AUTHOR]

Abstract: Visual aura is a common presenting symptom of migraine to both neurologists and ophthalmologists. Features such as photopsia, fortification spectra, and the slow propagation of a scintillating scotoma across the visual field are usually considered diagnostic features of the visual aura of migraine. In the vast majority of cases, the diagnosis can be made without the need for further investigations. We present 9 patients and a further 31 cases from the literature who experienced visual aura fulfilling the diagnostic criteria for migraines but caused by focal occipital pathology. Key clinical features that could help to differentiate between the visual aura of migraine and those suggestive of a structural lesion are outlined. We review current scientific theories into the pathophysiology of visual aura, drawing on clinical and basic science research, including human functional imaging studies of migraine aura and advances in the genetic characterization of familial channelopathies, in order to explain the overlap which occurs in the clinical features of visual aura associated with migraine, cortical lesions, and epilepsy. We conclude that any disease process that is able to create a state of neuronal hyperexcitability can therefore increase an individual’s susceptibility to the development of cortical spreading depression, the electrophysiological correlate of the visual aura. [Copyright &y& Elsevier]

Damage to ventral occipito-temporal extrastriate visual cortex leads to the syndrome of prosopagnosia often with coexisting cerebral achromatopsia. A patient with this syndrome resulting in a left upper homonymous quadrantanopia, prosopagnosia, and incomplete achromatopsia is described. Chromatic sensitivity was assessed at a number of locations in the intact visual field using a dynamic luminance contrast masking technique that isolates the use of colour signals. In normal subjects chromatic detection thresholds form an elliptical contour when plotted in the Commission Internationale d'Eclairage, (x-y), chromaticity diagram. Because the extraction of colour signals in early visual processing involves opponent mechanisms, subjects with Daltonism (congenital red/green loss of sensitivity) show symmetric increase in thresholds towards the long wavelength ('red') and middle wavelength ('green') regions of the spectrum locus. This is also the case with acquired loss of chromatic sensitivity as a result of retinal or optic nerve disease. Our patient's results were an exception to this rule. Whilst his chromatic sensitivity in the central region of the visual field was reduced symmetrically for both 'red/green' and 'yellow/blue' directions in colour space, the subject's lower left quadrant showed a marked asymmetry in 'red/green' thresholds with the greatest loss of sensitivity towards the 'green' region of the spectrum locus. This spatially localized asymmetric loss of 'green' but not 'red' sensitivity has not been reported previously in human vision. Such loss is consistent with selective damage of neural substrates in the visual cortex that process colour information, but are spectrally non-opponent. [ABSTRACT FROM AUTHOR]

Douglas Argyll Robertson (1837–1909) was the first surgeon in Scotland to practice entirely in the field of ophthalmology. He completed his medical education under von Arlt in Prague and Albrecht von Graefe in Berlin. He made major contributions to ophthalmic surgery. He described that in cases of spinal cord disease there may be loss of the pupil light reflex but retention of the response to accommodation. This condition was named the “Argyll Robertson pupil” which has become one of the best known physical signs in Neurology. Argyll Robertson can be credited with a large number of other original observations in neuro-ophthalmology and he made a particular contribution to the management of glaucoma both from the discovery of the action of physostigmine (extract of the Calabar bean) and as the first to recommend trephining the sclera in those cases of glaucoma where extensive degenerative changes in the iris made an iridectomy impracticable. Less widely known was the importance of his father (John Argyll Robertson) as a likely influence on his choice of career. Current understanding of the pathophysiological basis of the “Argyll Robertson pupil” is discussed. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is a common disorder which remains an important cause of permanent visual loss. Early corticosteroid treatment at an appropriate dose is effective, but two retrospective studies have also suggested that aspirin should be added to corticosteroid treatment in order to reduce thrombotic complications. Recent editorial and opinion articles have supported this suggestion, and prescription of aspirin to patients with GCA is common in general clinical practice. Here we review the evidence for the use of aspirin in the treatment of GCA, and indicate where there may be a lack of data to support its widespread prescription. [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 cites a case of a 25-year-old female secretary who was diagnosed of acute optic neuritis. The patient complained a blurry vision in her right eye and experienced color blindness. White matter abnormalities were found by magnetic resonance imaging. The patient undergone a course of intravenous corticosteroids followed by the initiation of interferon beta-1a therapy.

Photophobia is a complex disorder that can involve aversion not simply to bright light but to spatial patterns, colour and flicker. The use of tinted lenses to reduce photophobia in neurological diseases has a long history. Rarely has the possibility that different individuals might require lenses individually tailored to their needs been considered. Here we explore this possibility using the Intuitive Colorimeter system. The colorimeter illuminates text with coloured light and permits the colour, strength of colour and brightness to be manipulated separately. Many individuals find that a colour other than white is comfortable for viewing text. This colour is optimized in the colorimeter by a search strategy that allows for colour adaptation. Spectacle lenses are then individually tinted so that the chosen colour is experienced under conventional lighting. In this article, we review the use of the Intuitive Colorimeter in photosensitive epilepsy, autism, migraine, cluster headache, visual snow, stroke, multiple sclerosis and concussion; these are disorders in which individually coloured tints have featured in scientific and clinical reports. The evidence is preliminary rather than conclusive, but it suggests that precision tints can reduce photophobia. In patients with autism, the perception of emotion in facial expression is improved. Occasionally, the clinical benefit extends to the reduction of seizures and headaches and to an increase in reading speed. [ABSTRACT FROM AUTHOR]

Examination of a lady who presented with diplopia revealed unilateral exophthalmos. An orbital CT scan showed thickening of the extraocular muscles. Biopsy of skin lesions demonstrated histological features of sarcoidosis. Her eye signs resolved with systemic steroid treatment. [ABSTRACT FROM AUTHOR]

Focuses on the development of the fortification spectra of migraine. Discussion of principle; Background history; Presentation of the nineteenth century knowledge of fortification.

Previous studies have recommended skin biopsy (the immunofluorescent “band” test) as a valuable tool in the identification of cases of optic neuritis which are autoimmune. However in recent years the diagnostic spectrum of optic neuritis not associated with multiple sclerosis (MS) has considerably expanded both following the description of specific syndromes and also the discovery of other means of identifying autoimmune optic neuritis (such as detecting antibodies to Aquaporin 4). Furthermore the value of the immunofluorescent band test in the diagnosis of systemic autoimmune disorders such as systemic lupus erythematosis (SLE) has been questioned. However the test could still be useful if it can be shown that there are cases of autoimmune optic neuritis patients who have a positive skin biopsy but have serological evidence for neither SLE nor for neuromyelitis optica (NMO). [ABSTRACT FROM AUTHOR]

A 24-year-old male was referred for unilateral visual loss and papilloedema. Eight years previously he had suffered a penetrating injury to the affected eye and 6 months prior to presentation a blunt contusive injury. Examination revealed a post-traumatic cystic bleb and signs of hypotonic papilloedema and maculopathy. Filtering blebs may therefore occur as a complication of trauma and be symptomatic over long periods of time. [ABSTRACT FROM AUTHOR]

Purpose: To report abnormalities of retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT) in patients with trans-synaptic degeneration. Design: Observational case reports. Methods: Two patients with congenital/long standing occipital lobe lesions who had asymptomatic homonymous hemianopic field defects were examined using OCT. Results: In case 1, there was loss of RNFL in the projection of the nasal hemifovea temporally and the horizontal projection nasally in the right eye and thinning in the superior and inferior temporal arcades in the left eye corresponding to visual field abnormalities. In case 2, abnormalities in the RNFL pattern corresponded to the visual defects even though the field defect was incomplete. Conclusion: OCT measurements of the RNFL provide useful information in the diagnosis of congenital/long standing occipital lobe lesions. [Copyright &y& Elsevier]

Purpose: To describe 2 adult patients who presented with papilledema after band atrophy (i.e., twin and triple peaks papilledema). Design: Retrospective small case series. Participants: Two outpatients. Methods: Observations made on 2 patients whose cases were reviewed in the neuro-ophthalmology clinic. Results: The first patient had a pituitary tumor presenting with papilledema, causing a triple peaks clinical sign. Color photographs, optical coherence tomograms, and magnetic resonance images are shown. The second patient developed twin peaks papilledema due to a chiasmal glioma causing secondary raised intracranial pressure. Conclusion: Twin peaks papilledema is a rare clinical sign that may develop in adults as well as in children. The first report and optical coherence tomography features of triple peaks papilledema illustrate a new clinical sign. [Copyright &y& Elsevier]

The article presents an obituary for neuro-ophthalmologist Doctor James Arthur Sharpe.

A letter to the editor is presented in response to the article related to electrophysiology assessment and neuroimaging in previous issue.

Leber hereditary optic neuropathy (LHON) is a maternally inherited, bilateral, sequential optic neuropathy that usually affects young males. LHON arises from a defect in complex I of the oxidative phosphorylation chain that generates increased reactive oxygen species and causes a decline in cellular ATP production. There exists no cure at present for LHON. Asymptomatic LHON mutation carriers show signs of increased mitochondrial biogenesis that may compensate for the compromise in complex I activity. Partial recovery in LHON is associated with a wider optic disc diameter and a younger age at disease onset, which may allow for greater mitochondrial bioenergetic capacity. Rescuing a mitochondrial bioenergetic deficit soon after disease onset may improve the chances of recovery and reduce visual loss in the second eye. We here propose that a calorie-restricted ketogenic diet has the potential to enhance mitochondrial bioenergetic capacity and should be explored as a potential therapeutic option for treating LHON. [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.

Challenges the belief that contour interaction is the degradation of visual performance when additional contours flank visual stimuli. Report of two patients that showed abnormal foveal interactions under binocular viewing conditions; Conclusion.

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]

The Optic Neuritis Treatment Trial previously reported that corticosteroids accelerated visual recovery in optic neuritis (ON) without improving outcome. This finding related largely to multiple sclerosis (MS), and subsequently neurologists tended to await spontaneous recovery in ON. Since then, non-MS cases of ON have been identified with antibodies to aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG). These disorders can closely mimic multiple sclerosis-associated or idiopathic demyelinating optic neuritis (MS/IDON) initially but risk a worse visual outcome. Scrutinising the clinical features and neuroimaging often enables differentiation between MS/IDON and other causes of ON. Early treatment with high-dose corticosteroids is an important determinant of visual outcome in non-MS/IDON. Prompt use of plasma exchange may also save sight. In this review, we contrast the presentations of myelin oligodendrocyte glycoprotein associated optic neuritis (MOG-ON) and aquaporin 4 associated optic neuritis (AQP4-ON) with MS/IDON and provide an approach to acute management while awaiting results of antibody testing. [ABSTRACT FROM AUTHOR]

We highlight an under-recognised cause of acquired esotropia with this prospective observational case series of adults with diplopia secondary to cerebellar dysfunction. We also show deterioration of cerebellar esotropia over time, which has not been previously described. Seven adults (four women) developed diplopia at a median age of 63 years (range: 31-75 years), as the initial manifestation of the underlying cerebellar disorder. Causes of cerebellar dysfunction were familial cerebellar ataxia of unknown mutation (two patients), idiopathic cerebellar ataxia (four patients), and spinocerebellar ataxia 3 (one patient). At onset, three patients had unilateral and four had bilateral lateral rectus under-action. These were initially diagnosed as lateral rectus paresis, but the diagnosis was revised, as our examination showed no slowing of abducting saccades assessed clinically and full abduction with gaze-evoked nystagmus. Esotropia was concomitant and worse for distance, although at onset one patient's esotropia was equal for near and distance. There was a trend of worsening esotropia over time, following a median interval follow-up of 4 years (range: 1-18). All patients were first observed to have cerebellar eye signs after a median interval of 5 years (range: 1-30) from presentation, i.e., impaired pursuit (7/7 patients), gaze-evoked nystagmus (7/7), hypometric saccades (3/7), downbeat nystagmus (2/7), and skew deviation (4/7). Only two patients have not developed non-ocular cerebellar eye signs, after 5 and 8 years from diplopia onset, respectively; the other five patients had gait ataxia, which could be mild. The patients were successfully treated with prisms (7/7), botulinum toxin injections (1/7), and strabismus surgery (1/7). [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) may affect the nervous system in many ways. We describe an immunocompetent teenage girl with lymph node TB who had first presented with bilateral optic neuritis. Detailed history identified features inconsistent with immune-mediated optic neuritis. Several unusual features prompted further investigation, including transient visual obscurations without raised intracranial pressure, prominent disc swelling and absence of laboratory findings to support an immune- mediated cause. Whole body PET/ MR imaging identified widespread mediastinal and supraclavicular lymphadenopathy. Despite no known TB contacts, a negative interferon gamma release assay and a normal chest X-ray, a targeted lymph node biopsy confirmed TB. [ABSTRACT FROM AUTHOR]

The timing of imaging in neuro-ophthalmology is critical. There are few published studies, however, that address the question of how urgently to request imaging for neuro-ophthalmic clinical scenarios. We therefore conducted a national survey of expert opinion on the urgency of neuroimaging in neuro-ophthalmology. We devised a list of 40 clinical scenarios, reflecting a wide range of neuro-ophthalmic presentations. For each scenario, respondents were asked to state how urgently they would obtain neuroimaging in day-to-day NHS (National Health Service) practice. There were five response options: 'Emergency' (i.e., within 1 d), 'Urgent' (i.e., within 1 week), 'Semi-urgent' (i.e., within 1 month), 'Observation' (only if not resolving after a period of observation [greater than 1 month]), and 'Not normally scanned unless new features appear.' Respondents were recruited by e-mailing individuals who were on the UKNOSIG (UK Neuro-Ophthalmology Special Interest Group) mailing list. All were Consultant Ophthalmologists or Neurologists specialising in neuro-ophthalmology. Consensus was set at an a priori level of 80% agreement. Only 17 out of 40 scenarios met the criterion for consensus. Nine of these were for emergency/urgent imaging, three were for not imaging, and five were for semi-urgent imaging. For the remaining 23 scenarios, consensus was not reached. Unanimity (100% agreement) was not reached for any scenario. Agreement between neuro-ophthalmologists on the urgency of neuroimaging is patchy, with consensus for some clinical scenarios and disagreement for many. There is a need for a prospective study of neuroimaging in neuro-ophthalmology to determine whether timing of imaging influences outcomes. [ABSTRACT FROM AUTHOR]

Photophobia is one of the most common symptoms in migraine, and the underlying mechanism is uncertain. The discovery of the intrinsically-photosensitive retinal ganglion cells which signal the intensity of light on the retina has led to discussion of their role in the pathogenesis of photophobia. In the current review, we discuss the relationship between pain and discomfort leading to light aversion (traditional photophobia) and discomfort from flicker, patterns, and colour that are also common in migraine and cannot be explained solely by the activity of intrinsically-photosensitive retinal ganglion cells. We argue that, at least in migraine, a cortical mechanism provides a parsimonious explanation for discomfort from all forms of visual stimulation, and that the traditional definition of photophobia as pain in response to light may be too restrictive. Future investigation that directly compares the retinal and cortical contributions to photophobia in migraine with that in other conditions may offer better specificity in identifying biomarkers and possible mechanisms to target for treatment. [ABSTRACT FROM AUTHOR]

This investigation is a cross-sectional study of peripapillary retinal nerve fibre layer (RNFL) thickness in a cohort of homonymous quadrantanopia (HQ) patients with evidence of post-geniculate pathology. Forty-four cases were recruited and divided into three groups; 14 acquired HQ cases; 7 congenital HQ cases; and lastly 23 control individuals. Compared with the controls, RNFL thinning was most obvious at the superior sector in inferior quadrantanopia and at the inferior sector in superior quadrantanopia as would be expected from the known fibre trajectories. The findings are likely to reflect retrograde trans-synaptic degeneration in cases of post-geniculate damage lesser in extent than those previously studied. A further analysis was carried out comparing RNFL thickness (overall, mean of the two eyes) with the Humphrey mean deviation score (mean of the two eyes). For this analysis, data of an additional 28 patients with dense homonymous hemianopia and three cases with sub-quadrantic homonymous scotoma were also included. A statistically significant straight line relationship was found ( r = 0.5, p < 0.001), indicating a strong correlation between the RNFL thinning and the visual deficit. [ABSTRACT FROM AUTHOR]

Following damage to the human post-geniculate visual pathway retrograde trans-synaptic degeneration of the optic nerve fibres occurs. It has been known for some time from investigations carried out in primates that a decline in the number of retinal ganglion cells follows occipital lobectomy. However, this is not detectable in all species studied and whether this occurs in humans was controversial until recent studies that have shown that following lesions of the occipital lobe, the retinal nerve fibre layer thickness measured by optical coherence tomography is reduced and corresponding shrinkage of the optic tract can be demonstrated by magnetic resonance imaging. The time course of the degeneration in humans is, however, unknown. In the present study, we have used optical coherence tomography to demonstrate for the first time progressive thinning of the retinal nerve fibre layer following occipital lobe/optic radiation damage due to stroke. First, in a group of 38 patients the measurement was taken on a single occasion at a known time interval since the stroke, ranging from 6 days to 67 years. Here, a negative straight line relationship (linear regression r = 0.54, P < 0.001) was found between nerve fibre layer thickness and elapsed time since injury in log years, giving a rate of decline of 9.08 µm per log year after adjusting for age. This indicates a decelerating rate of loss that differs from the rate of decline found with chronological age in this same group, which shows a steady rate of thinning by 0.4 µm per year (P = 0.006) after adjusting for duration of the disease. In a second study serial measurements were taken following the acute event in a group of seven patients with homonymous hemianopia; here a negative straight line relationship was found between time and nerve fibre layer thickness in micrometres over a period of data collection beginning at a mean of 36.9 days post-stroke (range 5–112) and ending at a mean of 426.6 days post-stroke (range 170–917). Evidence from clinical observation (funduscopy) suggested that retrograde trans-synaptic degeneration occurred in humans only where the damage to the post-geniculate pathway occurred prenatally. The results reported herein add weight to the previous demonstration that this type of degeneration does indeed occur in the human visual system by showing that it can be monitored over time and hence may provide a model for trans-synaptic degeneration in the human central nervous system. [ABSTRACT FROM PUBLISHER]

Background: Glial fibrillary acidic protein (GFAP) is a specific intermediate filament of the cytoskeleton of the astrocyte and may be used as a specific marker for astrocytic damage. It is detectable in the cerebrospinal fluid following a relapse caused by Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) spectrum disease. Higher levels are found following an NMO-related relapse. It is not known if GFAP is also detectable in the serum following such relapses. In particular, it is not known if lesions limited to the optic nerve release GFAP in sufficient quantities to be detectable within the serum. The aim of this study was to ascertain the extent to which serum GFAP levels can distinguish between an episode of optic neuritis (ON) related to NMO spectrum disease and ON from other causes. Methodology/Principal Findings: Out of 150 patients consecutively presenting to our eye hospital over the period March 2009 until July 2010, we were able to collect a serum sample from 12 patients who had presented with MS-related ON and from 10 patients who had presented with NMO spectrum disease-related ON. We also identified 8 patients with recurrent isolated ON and 8 patients with a corticosteroid-dependent optic neuropathy in the absence of any identified aetiology. GFAP was detectable in the serum of all but three patients (two patients with MS-related ON and one with recurrent optic neuritis). The median serum GFAP level in the patient group with NMO spectrum disease was 4.63 pg/mL whereas in all other cases combined together, this was 2.14 pg/mL. The difference was statistically significant (P = 0.01). A similar statistically significant difference was found when cases with pathology limited to the optic nerve were compared (P = 0.03). Conclusions: Glial pathology in NMO related optic neuritis is reflected in elevated serum GFAP levels independently of whether or not there is extra-optic nerve disease. [ABSTRACT FROM AUTHOR]

Cardiovascular implantable electronic devices represent important limitations to magnetic resonance imaging (MRI). Recently, MRI-conditional dual chamber pacemakers and leads have become available. We describe a case of a patient with neuro-sarcoidosis presenting with diplopia and hydrocephalus requiring an MRI-conditional programmable ventriculo-peritoneal shunt, who developed complete heart block. In view of the ongoing need for neuro-imaging, MRI-conditional dual chamber pacemaker and leads were implanted. Cardiac and brain MRI were requested to guide immunosupression. Overall the scans demonstrated stable neurological disease, but confirmed cardiac sarcoid, with oedema on T2 weighted images suggesting active disease and extensive sub-endocardial late gadolinium enhancement, including the basal septum. This case illustrates why sarcoid patients who develop bradyarrhythmias should ideally have an MRI-conditional pacing system. [ABSTRACT FROM AUTHOR]

Two patients presented with loss of vision after viewing a smartphone screen in bed in the dark. The cause appeared to be differential bleaching of photopigment, with one eye becoming light-adapted while the other eye (blocked by a pillow) became dark-adapted. [ABSTRACT FROM AUTHOR]

Abstract: Patients with homonymous hemianopia may report the completion of forms that overlap the vertical meridian of their field defects. While previous investigations of “hemianopic completion” have variously attributed to the disorder to inattention, residual vision or unstable fixation, we believe that our investigation has controlled for such potentially confounding factors. We report patient P.O.V. who experienced hemianopic completion in everyday life following a surgical lesion of his left occipital lobe. He showed normal spatial attention and normal spatial orienting: hemianopic completion can therefore occur in the absence of inattention. His completion was retinotopic and affected partial as well as complete forms: his hemianopic completion cannot be attributed to residual visual input or poor fixation. P.O.V.''s completion was also systematically affected by varying stimulus contrast and pattern masking. We argue that while other explanations may be appropriate for different cases, P.O.V.''s hemianopic completion reflects normal “constructive” visual processes and can be attributed to the unconstrained operation of visual routines that are normally involved in the perception of partially occluded forms. As such, this disorder has the potential to shed light on some of the most basic aspects of visual perception. [Copyright &y& Elsevier]

The article discusses the 'Act FAST' public education campaign launched in Great Britain in February 2009 with aim to reduce presentation time of patient with storke. Topics discussed include symptoms of sudden visual loss, occipital lobe and eye stoke, public awareness of visual manifestations of stroke and role of early diagnosis to minimize carotid endarterectomy. It also discusses the significance of improved opportunities for thrombolysis.

The article presents a case study of a 52-year-old man with a history of myocardial infarction presented with difficulty in focusing. Physical examination, magnetic resonance imaging (MRI), and positron emission tomography scan results led to the diagnosis of Parinaud's syndrome, which developed as part of paraneoplastic limbic encephalitis. High-dose methylprednisolone and intravenous immunoglobulin were administered, pharyngeal lesion was removed surgically after which the patient stabilised. INSET: Learning points.

A 19-year-old female presented with a 4-month history of bilateral, para-central flickering lights, stable over that time after a sudden onset. Examination revealed isolated, bilateral, reproducible and incongruent para-central scotomata. Conventional imaging of the retina and OCT of the macula were not conclusive. Infrared imaging of the fundi showed typical lesions of acute macular neuroretinopathy. The unique physical properties of the near infrared waves recently widened the field of retinal imaging and are of particular interest in the diagnosis of deep retinal layers. [ABSTRACT FROM AUTHOR]