VEP asymmetry with ophthalmological and MRI findings in two achiasmatic children

Achiasmia is a rarely diagnosed visual pathway maldevelopment where all or the majority of nasal retinal fibres fail to decussate at the optic chiasm. It has been identified by neuroimaging and also by visual evoked potential (VEP) asymmetry. VEP asymmetry has not been defined consistently in previous studies. The aim was to study VEP asymmetry to flash stimulation in two children with maldevelopment of the optic chiasm in comparison to control children. Both children had congenital nystagmus, optic nerve hypoplasia with a bilateral small double ring, bitemporal visual field defect and normal colour vision. In child 1 visual acuity in both eyes was 0.1, in child 2 it was 0.2. MRI showed reduced chiasmal size in child 1, while in child 2 it was combined with other midline abnormalities. VEP to monocular flash stimulation showed in both children distinctive occipital distribution, which was not observed in control children. The N2 wave was distributed asymmetrically over the ipsilateral hemisphere to the stimulated eye, while the P2 wave was distributed over both hemispheres. The P2 wave was however better defined over the ipsilateral hemisphere. Flash VEP occipital distribution remained similar in child 1, who was followed from 10 months to 9 years. These cases of achiasmia demonstrate a distinctive VEP asymmetry in the distribution of the flash VEP N2 wave, as well as the expected structural defect determined by neuroimaging.     

Achiasmia and unilateral optic nerve hypoplasia in an otherwise healthy infant

An 18-month-old white boy, observed by his parents at 1-2 months age to have poor visual attentiveness and nystagmus, underwent an ophthalmological evaluation. The patient also underwent unsedated 5-channel flash visual evoked potentials (VEP) and sedated electroretinogram (ERG) testing as well as magnetic resonance imaging (MRI) of the brain and orbits. The VEP in response to monocular stimulation demonstrated occipital asymmetry and was clearly suggestive of crossed asymmetry and also showed right optic nerve hypoplasia. The MRI and fundoscopic examinations supported the findings of achiasmia and probable optic nerve hypoplasia. The patient also had decreased Teller card visual acuity, nystagmus and a variable right esotropia. Neurological examination was normal. The ophthalmological and MRI findings in this 18-month-old male patient support the diagnosis of isolated non-decussating retinal-fugal fibre syndrome as well as hypoplasia of the optic nerve.     

The achiasmia spectrum: congenitally reduced chiasmal decussation

AIM: To describe the clinical spectrum of achiasmia, a congenital disorder of reduced relative decussation at the optic chiasm. METHODS: A retrospective case note and patient review of nine children (four boys). Achiasmia was defined by the combination of a characteristic asymmetry of the monocular visual evoked potential (VEP) response to flash and neuroimaging showing reduced chiasmal size. RESULTS: Three of the children had an associated skull base encephalocele with agenesis of the corpus callosum. In two patients achiasmia was associated with septo-optic dysplasia. Three patients had no neuroimaging abnormalities other than reduced chiasmal size and have no known pituitary dysfunction. One child had multiple physical deformities but the only brain imaging abnormality was reduced chiasmal size. CONCLUSIONS: Some children with disorders of midline central nervous system development, including septo-optic dysplasia and skull base encephaloceles, have congenitally reduced chiasmal decussation. Reduced relative decussation may co-exist with overall chiasmal hypoplasia. Children with an apparently isolated chiasmal decussation deficit may have other subtle neurological findings, but our clinical impression is that most of these children function well.     

VEP characteristics in children with achiasmia,in comparison to albino and healthy children

Achiasmia is a rare disorder of visual pathway maldevelopment that can show diverse clinical and magnetic resonance imaging spectra. The aim of this study was to define the characteristics of visual evoked potentials (VEPs) that differentiate abnormal optic-nerve-fibre decussation in children with achiasmia versus children with albinism and healthy children. In four children with achiasmia, the following VEP characteristics were studied and compared to children with ocular albinism and with healthy control children: (a) flash and pattern onset VEP interhemispheric asymmetry; (b) flash N2, P2 and onset C1 amplitudes and latencies; (c) interocular polarity differences in interhemisphere potentials; and (d) chiasm coefficients (CCs). In the children with achiasmia, VEPs were related to an absence of or reduced optic-nerve-fibre decussation at the chiasm and showed: ipsilateral asymmetry, significantly higher VEP amplitudes over the ipsilateral hemisphere (p < 0.05), interocular inverse polarity and negative CC. Other VEP features (uncrossed asymmetry and positive CC) were also seen if additional visual pathway maldevelopment (such as severe optic nerve hypoplasia and/or absence of the optic tractus on one side) were associated with achiasmia. In the children with albinism, the VEPs were related to excess optic-nerve-fibre decussation at the chiasm and showed: contralateral asymmetry, significantly higher VEP amplitudes over the contralateral hemisphere (p < 0.001), interocular inverse polarity and negative CC. In achiasmia and albinism, the VEPs to flash stimulation were more robust and more clearly distinguished between the conditions compared with the VEPs to pattern onset stimulation. VEPs in achiasmia are associated with absent or reduced optic-nerve-fibre decussation, where ipsilateral interhemispheric asymmetry is associated with interocular inverse polarity and a negative CC.     

The clinical features of albinism and their correlation with visual evoked potentials

AIM: To investigate the relation between the clinical and electrophysiological abnormalities of patients undergoing visual evoked potential investigation for albinism. METHODS: 40 subjects with a probable or possible clinical diagnosis of albinism underwent pattern appearance and/or flash visual evoked potential (VEP) examination. The VEP findings are correlated with the clinical features of albinism determined by clinical examination and orthoptic assessment. RESULTS: The majority of patients with clinical evidence of albinism showed a contralateral predominance in the VEPs. There was close correlation between the clinical signs of albinism and the degree of contralateral VEP predominance. This manifested as an interhemispheric latency asymmetry to monocular pattern appearance stimulation but amplitude asymmetry to flash stimulation. The strongest correlation for pattern appearance interhemispheric latency difference was with foveal hypoplasia (rho = 0.58; p = 0.0003) followed by nystagmus (rho = 0.48; p = 0.0027) and iris transillumination (rho = 0.33; p = 0.039). The VEP abnormalities were of greater magnitude in those patients with most features of albinism. Several patients with apparently mild disorders of ocular pigmentation had small but significantly abnormal VEP latency asymmetries. CONCLUSION: There is a strong association between the magnitude of the interhemispheric latency asymmetry of the pattern appearance VEP, and of amplitude asymmetry of the flash VEP, with the clinical signs of albinism. The data are consistent with a spectrum of abnormalities in albinism involving both clinical expression and electrophysiological misrouting, which is wider than previously recognised.     

Exploration of retro-chiasmatic visual pathways in human albinism

PURPOSE: Several research studies have explored the abnormal crossing of the retinogeniculate and geniculocortical optic pathways in human albinos. This prospective study has dealt with visual evoked potentials (VEPs) of human subjects to identify the percentage of albinos with asymmetric VEPs. PATIENTS AND METHODS: A series of 16 albino patients ranging in age from 6 to 37 years were examined. They had measurable visual acuity, with or without nystagmus. Diffusion of flash stimuli not allowing selective study of the two visual pathways (direct and crossed), two stimulation patterns were used for VEP recordings: monocular full open field then hemi-field stimulation to isolate the activity of each visual pathway. ANALYSIS: In the normally pigmented subject, fibers derived from the nasal half of the retina of each eye decussate at the chiasma, while temporal retinal fibers are uncrossed and project to the ipsilateral hemisphere. In albinos, the majority of temporal retinal fibers subserving the nasal field (from fixation to an eccentricity of about 20 degrees ) anomalously cross with the nasal retinal fibers. Therefore with monocular stimulation, the evoked visual response should be obtained only in the contralateral hemisphere. The asymmetry, morphology and latency for the first major positive peak and the amplitude of the VEP were examined and compared with the normal population. CONCLUSION: We managed to demonstrate the characteristic VEP asymmetry only in 3 out of the 16 patients. The results presented herein lead to question the absolute validity of VEP abnormality in diagnosis of albinism for clinical purposes.     

Albinism: diagnosis by visual evoked potentials]

BACKGROUND: In albinism the majority of the nerve fibers of the optic nerve originating from an eye are innervating the contralateral hemisphere. As a result of the predominantly monocular innervation of the left and right hemispheres, the unilateral activation of the visual cortex (lateralization) can be detected with visual evoked potentials (VEP). PATIENTS AND METHODS: The VEPs were elicited with pattern onset stimulation. Five channels were recorded (2 channels over the left and right occipital lobe and 1 in the midline). 22 Patients with pendular nystagmus and 15 normal volunteers were examined. 5 of the normal volunteers were also examined with simulated pendular nystagmus (5-10 degrees, 1 Hz). The nystagmus was simulated by a simple galvanometer scanner based optical system. RESULTS: Unilateral activation of the hemispheres (lateralisation) was never detectable by normal volunteers. The lateralization of the VEP was detectable in all patients with oculocutaneous albinism with pattern onset stimulation. CONCLUSION: The pathological crossing of the nerve fibres in the optic chiasm is always detectable in oculocutaneous and ocular albinism with multichannel pattern onset VEP. The lateralization of the VEP is a more sensitive indicator of ocular albinism than other symptoms like macular hypoplasia, hypopigmentation, iris transillumination, nystagmus, reduced visual acuity et cetera.     

Chiasmal coefficient of flash and pattern visual evoked potentials for detection of chiasmal misrouting in albinism

The diagnosis of albinism can be confirmed by electrophysiological examination, when chiasmal misrouting can be demonstrated. The present study describes a quantitative analysis method for this purpose. A chiasmal coefficient (CC) was calculated by correlating the differential potential over left and right hemisphere, when stimulating left versus right eye. This CC will be negative in albinism and positive in normal individuals. VEPs were recorded in 20 control subjects, four children with congenital motor nystagmus and six children with albinism. In up to 25% of the controls the CC was negative, when using flash VEP. However, with pattern VEP all had a positive CC. All children with albinism had a negative CC. Three of the four patients with congenital motor nystagmus had a positive CC, and one child had a small negative value with flash stimulation. In conclusion, determination of CC is a valuable and objective analysis method for electrophysiological determination of chiasmal misrouting. The method is relatively simple and only needs two electrode tracings. One should be aware of false-positive results when using flash stimulation. Whenever possible pattern stimulation should be used.     

ISCEV standard for clinical visual evoked potentials (2009 update)

Visual evoked potentials (VEPs) can provide important diagnostic information regarding the functional integrity of the visual system. This document updates the ISCEV standard for clinical VEP testing and supersedes the 2004 standard. The major change in this revision is that test parameters have been made more precise to achieve better consistency of results within and between test centers. The ISCEV standard VEP protocols are defined for a single recording channel with a midline occipital active electrode. These protocols are intended for assessment of prechiasmal function; additional electrode sites are recommended for evaluation of chiasmal and postchiasmal function. ISCEV has selected a subset of stimulus and recording conditions that provide core clinical information and can be performed by most clinical electrophysiology laboratories throughout the world. These are: 1. Pattern-reversal VEPs elicited by checkerboard stimuli with large 1° (i.e., 60 min of arc; min) and small 0.25° (15 min) checks. 2. Pattern onset/offset VEPs elicited by checkerboard stimuli with large 1° (60 min) and small 0.25° (15 min) checks. 3. Flash VEP elicited by a brief luminance increment, a flash, which subtends a visual field of at least 20°.     

Anatomical differences in optic nerve,chiasma and tractus opticus in human albinism as demonstrated by standardised clinical and MRI evaluation

BACKGROUND: There has been long-standing clinical and electrophysiological evidence that in patients with albinism the visual pathways cross atypically: most fibres from one eye cross to the contralateral visual cortex. Purpose of the study: to determine whether the size and configuration of the optic chiasm in human albinos is different from normally pigmented controls. PATIENTS AND METHODS: 17 patients (11 female, mean age 35.8 years) with oculocutaneous albinism underwent a standardised graded morphological and functional evaluation. Magnetic resonance images were reformatted to the region of the optic chiasm and analysed using observer-independent morphometry. In addition, fMRI of the visual cortex was performed during VEP analysis (1.5 Tesla Siemens Vision). Morphological and fMRT results were compared to an age-correlated group of n = 16 normally pigmented healthy volunteers with normal visual acuity and stereopsis. RESULTS: 65 % of the patients (n = 10) showed signs of dysplasia of the optic nerve head. Statistical morphometry showed distinct differences in chiasmal morphology between albinos and normally pigmented probands (smaller optic nerves, different angles of optical entry into the chiasm and of the beginning of the Tractus optici leaving the chiasm, overall chiasmal width and height). CONCLUSIONS: Optic nerve head anomalies are frequent in albinism and influence visual outcome. Size and configuration of the optic chiasm in human albinos is distinctly different from normally pigmented control persons and reflects the atypical crossing of optic fibres.     

Visual electrophysiology in the clinical evaluation of optic neuritis,chiasmal tumours,achiasmia, and ocular albinism: an overview

Background and Methods In routine clinical evaluation of optic neuritis and chiasmal tumours, pattern electroretinography and visual evoked potentials (VEPs) to pattern-reversal stimulation are useful examinations. Similarly, in achiasmia and ocular albinism, VEPs to flash and pattern-onset stimulation provide relevant information. Results The role of visual electrophysiology in these diseases is to assess potential dysfunction of the visual pathway: (a) at the acute stage of optic neuritis, to determine the magnitude of conduction block of the optic nerve fibres; (b) at the clinical recovery stage of optic neuritis, to determine optic nerve conduction delay due to demyelination, and to follow possible remyelination; (c) at the recovery of optic neuritis when visual acuity does not normalise, to define loss of optic nerve fibres and retrograde degeneration of retinal ganglion cells; (d) in tumours at the chiasm, to detect abnormal conduction along the crossed and/or uncrossed fibres; and (e) in achiasmia or albinism, which are both congenital disorders associated with nystagmus, to detect achiasmia and absence of or reduced optic nerve fibre decussation at the chiasm, or to detect ocular albinism and excess of optic nerve fibre decussation at the chiasm. In optic neuritis, two recent examinations have been used to detect retrograde axonal degeneration: photopic negative response of the electroretinogram, to assess dysfunction of ganglion cell axons; and optic coherence tomography, to measure thinning of the retinal nerve fibre layer. In optic neuritis, multifocal VEPs provide a promising clinical examination, because this can show areas that are associated with normal or abnormal optic nerve fibre function. Conclusions Visual electrophysiology defines function of the visual pathway and is relevant: (1) in optic neuritis, when visual acuity does not recover well; (2) in tumours of the chiasm with normal visual fields, as in paediatric patients who cannot adequately perform perimetry; and (3) in children with congenital nystagmus and suspected achiasmia or ocular albinism.     

Visual evoked potentials in children with neurofibromatosis type 1

The purposes of this investigation were to determine: (a) if visual evoked potential (VEP) abnormalities could be identified in children with neurofibromatosis type 1 (NF1) with no evidence of optic pathway or brain neoplasias on MRI; and (b) if VEP abnormalities could be explained by the presence of hyperintense T2-weighted foci on MRI testing, known as unidentified bright objects (UBOs). To answer these questions, VEPs were recorded from 16 children with NF1 and compared to 13 normal subjects in the same age range tested with the same protocol. Pattern-reversal VEPs were recorded at four stimulus sizes both monocularly and binocularly, the latter to hemi-field stimuli. Flash VEPs were recorded in dark- and light-adapted conditions. VEP measurements and MRI readings for UBOs were conducted in a masked fashion. Ten of the 16 children with NF1 had abnormal VEPs to at least one of the four types of stimuli. Abnormalities included delayed responses (n=6), absent flash VEP P2 component (n=3), or both (n=1). Abnormalities of the P2 component of the dark-adapted flash VEP were the most common finding (n=7), although no single testing strategy was able to identify all children with abnormal VEPs. UBOs were present in all children, demonstrating that their presence does not fully account for VEP abnormalities in children with NF1. This study also demonstrates that VEP abnormalities are present also in the absence of neoplasias of the optic pathways or of the brain. Our results are suggestive of a primary abnormality of visual processing in children with NF1.     

Hereditary foveal hypoplasia - clinical differentiation

BACKGROUND: In a family cataract, esotropia and foveal hypoplasia is dominantly transmitted. PATIENTS AND METHOD: Besides the physical examination visual evoked potentials and PAX6 mutation analysis were performed on five of six affected persons and on two who were not. RESULTS: A man of the first generation, deceased before this study, was known to have low vision. His two daughters and their children and grandchildren suffer from cataract, esotropia and foveal hypoplasia. In two cases accompanied by aniridia and atypical iris coloboma respectively. The best visual acuity is 0.5. The VEPs taken of three of the affected people were normal. The PAX6 mutation analysis demonstrated a T to A translocation in the Intron 8 at the position + 2 (= IVS8 + 2T --> A). CONCLUSION: 1) This study confirms that foveal hypoplasia in the so-called isolated form have a similar origin as in aniridia namely PAX6 mutation and that it is a symptom in all cases while the iris anomaly may be variable. 2) In contrast to this foveal hypoplasia in albinism may occur variably in a family while the asymmetry of VEP is a constant finding. 3) Therefore the VEP alone is helpful to differentiate clinically wether a foveal hypoplasia belongs to the albino or to the aniridia group.     

Chiasmal misrouting and foveal hypoplasia without albinism

BACKGROUND/AIMS: To present the ophthalmological and electrophysiological characteristics of three darkly pigmented, female patients with misrouting and foveal hypoplasia. One of the patients had primary ciliary dyskinesia and situs inversus totalis (Kartagener syndrome). METHODS: Fundus photographs were taken and the angles at which the main temporal arterial branches leave the optic nerve head (ONH) were analysed. Optical coherence tomography (OCT) was performed through the presumed foveal region. Pattern onset visually evoked potentials (VEPs) (check sizes 60', 40/400 ms) were recorded and the chiasmal coefficient was calculated to detect misrouting. RESULTS: Fundus photography showed normally pigmented fundi with absence of the usual foveal hyperpigmentation, foveal avascular zone, and macular and foveal reflexes. On OCT no foveal pit was found. The VEP recordings showed the largest positive CI component over the right hemisphere for the left eye, and over the left hemisphere for the right eye, with the CI almost absent over the ipsilateral hemispheres. The differential derivations showed opposite polarity for the recordings of the two eyes. The chiasmal coefficients of all three patients were significantly indicative of misrouting (-0.99, -0.91, and -0.99, respectively). CONCLUSION: Based on the investigations in these patients the authors propose the hypothesis that foveal hypoplasia and misrouting exist as a distinct entity, and do not comprise the exclusive hallmark of albinism. The findings suggest that misrouting may exert a retrograde influence on foveal development.     

Radiation optic neuropathy

Following surgery for pituitary adenoma, radiation therapy is an accepted treatment in reducing tumor recurrence. However, a potential therapeutic complication is delayed radionecrosis of perisellar neural structures, including the optic nerves and chiasm. This particular cause of visual loss, radiation optic neuropathy (RON), has not been emphasized in the ophthalmologic literature. Four cases of RON seen in the past five years are reported. Diagnostic criteria include: (1) acute visual loss (monocular or binocular), (2) visual field defects indicating optic nerve or chiasmal dysfunction, (3) absence of optic disc edema, (4) onset usually within three years of therapy (peak: 1-1 1/2 years), and (5) no computed tomographic evidence of visual pathway compression. Pathologic findings, differential diagnosis and therapy will be discussed in outlining the clinical profile of RON.     

Maturational topography of the visual evoked potential in fetal lambs

The normal maturational course of the visual evoked potential (VEP) in human newborns and infants is well documented. Unfortunately, there is a paucity of data about VEP maturation in the normal preterm infant. Since this population is at risk to develop many abnormalities affecting the VEP (intraventricular hemorrhage, hydrocephalus, and retinopathy of prematurity), one must question whether such VEP data collected from this group is representative of normal maturation. To provide normative parametric developmental data we have been studying VEP development in fetal lambs. Six fetal lambs between 105 and 120 days gestational age were externalized and surgically instrumented with subcutaneous recording electrodes placed over the occipital and parietal regions. High-intensity light-emitting diodes (LEDs) externalized fiberoptic cables were secured adjacent to the orbit. from 108 to 141 days gestation, fetal VEPs were recorded in response to bright flash stimulation and the maturational topography was investigated.Over the occipital regions, the emergence of major positivities at P400 and P650 were observed beginning around 120 days gestation. Over the parietal area, the emergence of P200 and P500 components was observed by 128 days gestation. The latency-maturation functions revealed that the slope of the parietal function was steeper than the occipital counterpart, suggesting that the maturation of parietal neurons occurs at a faster rate than neuronal development in the occipital regions.     

ERGs on the brain: the benefits of simultaneous flash retinal and cortical responses in paediatric cerebral visual impairment

Purpose

To highlight the importance of simultaneous flash electroretinogram (ERG) and visual evoked potential (VEP) recording to differentiate a true flash VEP response from an artefact caused by the intrusion of the ERG on a mid-frontal reference electrode in cases of severe cerebral visual impairment (CVI).

Methods

We report an observational case series of four children with severe CVI who underwent simultaneous flash ERG and VEP recordings. Flash VEPs from Oz–Fz and lower lid skin ERGs referred to Fz were recorded simultaneously to Grass intensity setting 4 flash stimulation.

Results

In all cases, atypical, but reproducible VEPs were evident. Comparison of the timing and waveform of the VEPs and ERGs showed the occipital responses were inverted ERGs and no true flash VEP was evident.

Conclusions

While ISCEV and neurophysiology standards do not require the simultaneous recording of the flash ERG with the VEP, these cases highlight the usefulness of this non-invasive technique particularly in suspected paediatric cerebral visual impairment to differentiate a true VEP from an artefact caused by ERG contamination.

     

Clinical and Imaging Findings One Year Following Traumatic Chiasm Transection

Traumatic chiasm transection is a rare condition characterized by bitemporal hemianopsia following head trauma. In a study of visual complications following head trauma, only 4.4% of patients suffered from chiasmal injuries. Complete transection of the chiasm is even more rare and best visualized using magnetic resonance imaging (MRI). We report the one-year follow-up of clinical, visual field, and MRI findings of a patient with complete transection of the optic chiasm following head trauma.     

VEP projections in congenital nystagmus; VEP asymmetry in albinism: a comparison study.

Visual evoked potential (VEP) asymmetry in which a preponderance of nasal and temporal retina afferents project to the contralateral hemisphere after full-field monocular stimulation is considered specific to albinism. Some reports, however, suggest that patients with congenital nystagmus (CN) share the albino-like visual pathway anomaly. To examine the clinical specificity of albino misrouting, VEP topography was assessed in ten patients with congenital nystagmus and in ten age-matched albino patients. As an additional control, the VEP response profiles from eight albino patients with no nystagmus were also evaluated. The results are definitive; VEP contralateral asymmetry reflecting temporal retinal misprojection is evinced only in albino patients. Furthermore, ocular-motor instabilities in CN cannot be readily attributed to albino-type misrouted retinal-cortical projections.     

Mechanism of binocular interaction in refraction errors: study using pattern-reversal visual evoked potentials

In this study we sought to determine whether a natural condition involving fine discrimination, for example moderately severe myopia, might yield interesting information regarding the binocular interaction expressed by visual evoked potentials (VEPs). We studied ten normal subjects with a mild refraction deficits. Transient VEPs were elicited by monocular and binocular stimulation under conditions of natural and lens-corrected vision. The visual stimulus was a pattern-reversal checkerboard consisting of 15' and 40' checks. VEPs in response to binocular stimulation were compared with monocular VEPs. We plotted the monocular `better-VEP' and `worse-VEP' response, since significant differences between individual eye stimulations were present. We found no significant difference between the mean N75 and P100 latencies of the binocular VEP and the better monocular VEP, regardless of the check size used and of natural or corrected vision. Under all stimulus conditions, the mean amplitude of the N75-P100 of the binocular VEPs was also larger than the better monocular VEP response. The difference proved more significant when we stimulated our subjects with smaller squares and left vision uncorrected. The mean P100-N145 amplitude obtained with binocular stimulation was larger than the better monocular VEP response only when using small checks (15') and uncorrected vision. Overlapping latencies are consistent with an earlier hypothesis that monocular and binocular VEPs originate postsynaptically from the binocular neurons in the primary visual cortex. The gain in amplitude achieved by binocular stimulation may depend upon the removal of `tonic interocular inhibition' and/or on a cortical modulatory mechanism. This revised version was published online in July 2006 with corrections to the Cover Date.