Prognostic value of transient pattern visual evoked potentials in children with cerebral visual impairment.

AIM: To investigate whether pattern reversal visual evoked potentials (PRVEPs) could predict future visual acuity in infants with cerebral visual impairment (CVI). METHOD: Fifty-five children (27 males, 28 females) with severe CVI seen in the ophthalmology department of a specialist children's hospital were identified retrospectively. Behavioural visual acuity and visual evoked potentials (VEPs) at presentation (time 1, T1) were compared with final visual acuity at late preschool/early school age (time 2, T2). Predictors of visual acuity at T2 were identified using univariate and multivariate logistic and linear regression analysis. RESULTS: Median age was 14 months at T1 (range: 6-44mo) and 63 months at T2 (range: 29-150mo). The presence of a PRVEP produced by a check width of 50' (minutes of arc) or smaller (T1) predicted (p=0.05) the presence of measurable preferential looking acuity at T2. The presence of PRVEP to check widths of 25' or smaller (T1) predicted (p=0.02) better preferential looking acuity (logMAR-equivalent) scores at T2. The latter association was independent of presenting acuity at T1. INTERPRETATION: The presence of PRVEPs to check widths of 50' and 25' in infancy provided useful information. VEPs in young children with CVI may have prognostic value regarding future acuity.

Clinical use of the Insight Inventory in cerebral visual impairment and the effectiveness of tailored habilitational strategies.

AIM: To investigate the utility of the Insight Inventory (a structured clinical inventory completed by caregivers) for assessment of children with cerebral visual impairment; and to investigate effectiveness of tailored habilitational strategies derived from the responses to the Insight Inventory. METHOD: Fifty-one eligible children (26 males, 25 females; mean age 9y 5mo, SD 3y, range 5-16y) were recruited from Great Ormond Street Hospital, London. They underwent baseline assessment including neuro-ophthalmological and neuropsychological evaluations, and parent- and child-reported ratings on a questionnaire-based measure of quality of life. Parents also completed the Insight Inventory. On the basis of responses to the Inventory, families received individualized habilitational strategies. Follow-up assessments 6 months later included repeating the Insight Inventory and quality of life questionnaires. RESULTS: Correlations were found between the Insight Inventory and the Wechsler Intelligence Scale for Children, Fourth Edition, the Beery-Buktenica Test of Visual-Motor Integration, and the Benton Facial Recognition Test, suggesting that the Insight Inventory is an effective tool to estimate visual-perceptual difficulties. At 6 months follow-up, caregiver reports indicated significant improvements in the quality of life of children below the age of 12 years. INTERPRETATION: The Insight Inventory is a simple questionnaire which covers practical aspects of cognitive visual function in everyday life. It provides in-depth information about the aspects that children struggle with. It can also guide programmes of individualized habilitation strategies, which may enhance the quality of life of younger children. WHAT THIS PAPER ADDS: Questionnaire scores demonstrate biologically plausible correlations with formal neuropsychological tests of visual function. After administration of matched practical habilitational strategies, younger children showed improvement in quality of life and functional vision scores.

Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies.

PURPOSE: To investigate and describe in detail the demographics, functional and anatomic characteristics, and clinical course of Leber congenital amaurosis (LCA) associated with mutations in the CEP290 gene (LCA-CEP290) in a large cohort of adults and children. DESIGN: Retrospective case series. PARTICIPANTS: Patients with mutations in CEP290 identified at a single UK referral center. METHODS: Review of case notes and results of retinal imaging (color fundus photography, fundus autofluorescence [FAF] imaging, OCT), electrophysiologic assessment, and molecular genetic testing. MAIN OUTCOME MEASURES: Molecular genetic testing, clinical findings including visual acuity and retinal imaging, and electrophysiologic assessment. RESULTS: Forty patients with LCA-CEP290 were identified. The deep intronic mutation c.2991+1655 A>G was the most common disease-causing variant (23/40 patients) identified in the compound heterozygous state in 20 patients (50%) and homozygous in 2 patients (5%). Visual acuity (VA) varied from 6/9 to no perception of light, and only 2 of 12 patients with longitudinal VA data showed deterioration in VA in their better-seeing eye over time. A normal fundus was found at diagnosis in younger patients (mean age, 1.9 years), with older patients showing white flecks (mean age, 5.9 years) or pigmentary retinopathy (mean age, 21.7 years). Eleven of 12 patients (92%) with OCT imaging had preservation of foveal architecture. Ten of 12 patients (83%) with FAF imaging had a perifoveal hyperautofluorescent ring. Having 2 nonsense CEP290 mutations was associated with worse final VA and the presence of nonocular features. CONCLUSIONS: Detailed analysis of the clinical phenotype of LCA-CEP290 in a large cohort confirms that there is a window of opportunity in childhood for therapeutic intervention based on relative structural preservation in the central cone-rich retina in a significant proportion of patients, with the majority harboring the deep intronic variant potentially tractable to several planned gene editing approaches.

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.

Visual mismatch negativity to masked stimuli presented at very brief presentation rates.

Mismatch negativity (MMN) has been characterised as a 'pre-attentive' component of an event-related potential (ERP) that is related to discrimination and error prediction processes. The aim of the current experiment was to establish whether visual MMN could be recorded to briefly presented, backward and forward masked visual stimuli, given both below and above levels of subjective experience. Evidence of visual MMN elicitation in the absence of the ability to consciously report stimuli would provide strong evidence for the automaticity of the visual MMN mechanism. Using an oddball paradigm, two stimuli that differed in orientation from each other, a + and an ×, were presented on a computer screen. Electroencephalogram (EEG) was recorded from nine participants (six females), mean age 21.4 years. Results showed that for stimuli that were effectively masked at 7 ms presentation, there was little variation in the ERPs evoked to standard and deviant stimuli or in the subtraction waveform employed to delineate the visual MMN. At 14 ms stimulus presentation, when participants were able to report stimulus presence, an enhanced negativity at around 175 and 305 ms was observed to the deviant and was evident in the subtraction waveform. However, some of the difference observed in the ERPs can be attributed to stimulus characteristics, as the use of a 'lonely' deviant protocol revealed attenuated visual MMN components at 14 ms stimulus presentation. Overall, results suggest that some degree of conscious attention is required before visual MMN components emerge, suggesting visual MMN is not an entirely pre-attentive process.

Trans-synaptic Retrograde Degeneration Following Hemispherectomy in Childhood.

Trans-synaptic retrograde degeneration (TRD) in the human visual system has been established. However there are few studies demonstrating macular thinning of the Retinal Ganglion cell Layer and/or Inner Plexiform layer (RGCL-IPL), corresponding to an acquired homonymous hemianopia. We report a 17 year old with a homonymous hemianopia, secondary to a hemispherectomy for intractable epilepsy. Three years following hemispherectomy, Optical Coherence Tomography (OCT) revealed evidence of TRD, corresponding to his complete homonymous hemianopia. Macular maps of the RGCL-IPL thickness provides useful additional information to measurements of optic nerve Retinal Nerve Fibre Layer Thickness (RNFL) in identifying TRD in acquired homonymous hemianopia.

Mutation of SALL2 causes recessive ocular coloboma in humans and mice.

Ocular coloboma is a congenital defect resulting from failure of normal closure of the optic fissure during embryonic eye development. This birth defect causes childhood blindness worldwide, yet the genetic etiology is poorly understood. Here, we identified a novel homozygous mutation in the SALL2 gene in members of a consanguineous family affected with non-syndromic ocular coloboma variably affecting the iris and retina. This mutation, c.85G>T, introduces a premature termination codon (p.Glu29*) predicted to truncate the SALL2 protein so that it lacks three clusters of zinc-finger motifs that are essential for DNA-binding activity. This discovery identifies SALL2 as the third member of the Drosophila homeotic Spalt-like family of developmental transcription factor genes implicated in human disease. SALL2 is expressed in the developing human retina at the time of, and subsequent to, optic fissure closure. Analysis of Sall2-deficient mouse embryos revealed delayed apposition of the optic fissure margins and the persistence of an anterior retinal coloboma phenotype after birth. Sall2-deficient embryos displayed correct posterior closure toward the optic nerve head, and upon contact of the fissure margins, dissolution of the basal lamina occurred and PAX2, known to be critical for this process, was expressed normally. Anterior closure was disrupted with the fissure margins failing to meet, or in some cases misaligning leading to a retinal lesion. These observations demonstrate, for the first time, a role for SALL2 in eye morphogenesis and that loss of function of the gene causes ocular coloboma in humans and mice.

THE PHYSIOLOGY OF THE RETINAL PIGMENT EPITHELIUM IN DANON DISEASE.

PURPOSE: Danon disease is caused by mutations in the lysosome-associated membrane protein-2 gene (LAMP2). In the eye, LAMP2 is expressed only in the retinal pigment epithelium. This study aimed to investigate the previously unreported impact of LAMP2 mutations on the electrooculogram generated by the retinal pigment epithelium. METHODS: Four members of a family with Danon disease were examined. All have mutations in c294G > A, of the LAMP2 gene on Xq24, by which no, or aberrant, protein will be formed. Electrooculograms to International Society for the Clinical Electrophysiology of Vision (ISCEV) standards were recorded with full-field electroretinography, Goldmann kinetic visual fields, and spectral optical coherence tomography with fundus autofluorescence imaging. RESULTS: Electrooculogram amplitude ratios of light rise:dark trough, the Arden index, fell at low-normal limits (range: 1.68-3.94) but misrepresent retinal pigment epithelium health, because the absolute dark trough voltages were abnormally low (median: 140 µV, range: 72-192 µV) as were the light rise amplitudes (median: 297 µV, range: 198-366 µV), and full-field electroretinograms were normal. Hyperfundus autofluorescence and hypofundus autofluorescence changes became more confluent and florid with increasing age of female patients. Goldmann visual field testing showed constriction of the central field. CONCLUSION: Low electrooculogram voltages indicate that the retinal pigment epithelium is unable to maintain its tight junctions in Danon disease.

Retinal characteristics of the congenital disorder of glycosylation PMM2-CDG.

The congenital disorder of glycosylation, PMM2-CDG, is associated with progressive photoreceptor degeneration, which causes a pigmentary retinopathy. We identified a sibling pair, mildly affected with PMM2-CDG, who showed preserved photoreceptor function, but profound deficits of the 'on-pathway' in the retina. This localises the site of early, or initial, retinal dysfunction in PMM2-CDG to the synapse in the outer plexiform layer between bipolar cells, photoreceptors and horizontal cells. We sought wider evidence to support this novel finding by reviewing retrospectively the case notes of eight patients, diagnosed with PMM2-CDG between the ages of 7 months to 16 years. We compared the clinical presentation and electroretinograms, (ERGs), of these patients with the sibling pair. We found that five of eight patients showed characteristic ERG features of on-pathway dysfunction in the form of reduced ERG b-wave amplitude. The remaining three patients had significant photoreceptor dysfunction by the time of ERG recording, and both a- and b-wave amplitudes were markedly attenuated. We conclude that ERG signs of on-pathway dysfunction can be detected in the early stages of PMM2-CDG. Referral for electroretinography evidence of this specific on-pathway deficit, with preservation of oscillatory potentials, can help establish the diagnosis of infants with developmental delay or failure to thrive in whom a glycosylation defect is suspected. Also by increasing our understanding of the interaction of N-glycoproteins at this synapse we may be able to design future therapeutic intervention to prevent or ameliorate the progressive visual loss associated with PMM2-CDG.

Pediatric oral fluorescein angiography: a retrospective review from a single institution.

PURPOSE: To describe our experience with locally developed evidence-based guidelines for oral fluorescein angiography (FA) for retinal imaging in children. METHODS: The medical records of consecutive pediatric patients (≤18 years of age) at University of Pittsburgh Medical Center Children's Hospital Eye Center who underwent oral FA between November 1, 2018, and April 1, 2022, were reviewed retrospectively. Adherence to or deviation from the guidelines was noted at the time of testing. RESULTS: A total of 55 patients aged 3-18 with 79 examinations were included. No patient was excluded from the retrospective case review because of lack of recorded data. The main indications for oral FA included uveitis, retinal vasculopathy, disk pathology, and retinal lesions. Three children had transient side effects, and 1 had delayed urticaria 4 hours after examination. No child had anaphylaxis. One patient had suboptimal imaging due to nonadherence to the guidelines-recommended fasting protocol. All other examinations (78/79), where guidelines were followed, provided images adequate for clinical decision making. CONCLUSIONS: Based on our experience, we recommend that oral FA be considered, especially in children where intravenous access is less well tolerated while awake. Informed consent that includes the possibility of delayed side effects is advisable.

When do asymmetrical full-field pattern reversal visual evoked potentials indicate visual pathway dysfunction in children?

Our study aimed to find out the association between full-field pattern reversal visual evoked potential (pVEP) transoccipital asymmetries and half-field pVEP transoccipital distributions in children. Over a six-month period, 46 patients (mean age: 9 years 9 months) had both monocular full-field and half-field pVEPs to test checks subtending 50 min of arc in a 35 degree full-field and 0-17.5 degree lateral half-field. Silver-silver chloride electrodes placed at Oz, O1 and O2 were referred to Fz. Monocular full-field data were categorised according to the degree of transoccipital asymmetry. Half-field data were measured and summated to see whether they explained any full-field asymmetry. In this cohort of 46 patients, eight (17%) patients had symmetrically distributed monocular full-field pVEPs for each eye. Four of these patients had normal half-field pVEP distributions for each eye, but the other four showed a half-field deficit in one or both eyes. Of the 38 patients with asymmetrically distributed full-field pVEPs in at least one eye, 17 (44%) patients showed a half-field deficit, 20 (53%) showed responsive, but symmetrically distributed half-field responses, and one patient (3%) showed typical half-field distributions. Half-field pVEPs can help explain full-field asymmetries and should be attempted in any child able to co-operate with testing and in whom visual pathway dysfunction is suspected.

The reproducibility of binocular pattern reversal visual evoked potentials: a single subject design.

This study aimed to investigate the within-participant variability over time of both amplitude and peak latency measures of pattern reversal visual evoked potentials (pVEPs). As a large number of factors are known to contribute to the variability of the pVEPs (such as fixation instability and drowsiness), testing was conducted in controlled conditions with two co-operative participants. PVEPs were recorded during 24 sessions, over an eight-week period using the same equipment and recording settings. The participants viewed a plasma monitor binocularly from a distance of 1 meter. High contrast (97%), black and white checks of side subtense 50', 25', and 12.5' pattern reversed 3/s in a 28 degree test field. The different sized checks were presented in a pseudo-random order. Three runs, each of 100 trials, were acquired to each stimulus from an active electrode placed at Oz referred to aFz. The amplitude of N80-P100 and the latency of P100 were measured. P100 amplitude and latency were stable across sessions and did not depend upon the order of check size presentation. As expected, variation in amplitude was greater than peak latency. The coefficients of variation for different check sizes and participants were 9-14% for pVEP amplitude, but only 1-2% for P100 latency.

Visual field loss in children with craniosynostosis.

AIMS: To identify visual field deficits in a group of children with syndromic craniosynostosis. METHODS: Kinetic visual field examination and visual evoked potentials (VEPs) were recorded in 16 children with syndromic craniosynostosis as part of their ophthalmic evaluation. VEPs were analyzed for inter-hemispheric asymmetries and component amplitude and latency, while visual fields were analyzed both qualitatively and quantitatively. RESULTS: All children with craniosynostosis were found to have visual field deficits compared to controls. In the Crouzon group, deficits tended to involve the nasal field, while infero-nasal field deficits were the most consistent finding in children with Apert syndrome. Children with Pfeiffer's demonstrated the greatest deficits, with severe constrictions affecting the whole visual field. VEPs were asymmetrical in four cases while the P100 component was subnormal in ten of the 16 patients for either amplitude and/or latency. CONCLUSION: Although we may speculate about the mechanisms that cause visual field deficits, we currently are unable to explain the reason for the differing types and extent of visual field loss in the different syndromic groups. We can conclude that the visual field deficits do indicate previous or ongoing visual dysfunction that cannot be monitored employing central vision tests alone.

Mapping degeneration of the visual system in long-term follow-up after childhood hemispherectomy - A series of four cases.

OBJECTIVE: Although hemidisconnection surgery may eliminate or reduce seizure activity in patients with epilepsy, there are visual, cognitive and motor deficits which affect patients' function post-operatively, with varying severity and according to pathology. Consequently, there is a need to map microstructural changes over long time periods and develop/apply methods that work with legacy data. METHODS: In this study, we applied the novel single shell 3-Tissue method to data from a cohort of 4 patients who were scanned 20-years following childhood hemidisconnection surgery and presented with variable clinical outcomes. We have successfully reconstructed tractography of the whole visual pathway from single shell diffusion data with reduced number of gradient directions. RESULTS: All patients presented with degeneration of the visual system characterised by low fractional anisotropy and high mean diffusivity. There were no apparent microstructural differences between both optic nerves that could explain the different level of visual function across patients. However, we provide evidence suggesting an association between the level of visual function and DTI metrics within the remaining components of the visual system, particularly the optic tract, of the contralateral hemisphere post-surgery. SIGNIFICANCE: We believe this study suggests that diffusion MRI can be used to monitor the integrity of the visual system following hemispherectomy and if extended to larger cohorts and a greater number of time-points, including pre-surgically, can provide a clearer picture of the natural history of visual system degeneration. This knowledge may in turn help to identify patients at greatest risk of poor visual outcomes that might benefit from rehabilitation therapies.

Altered visual population receptive fields in human albinism.

Albinism is a congenital disorder where misrouting of the optic nerves at the chiasm gives rise to abnormal visual field representations in occipital cortex. In typical human development, the left occipital cortex receives retinal input predominantly from the right visual field, and vice-versa. In albinism, there is a more complete decussation of optic nerve fibers at the chiasm, resulting in partial representation of the temporal hemiretina (ipsilateral visual field) in the contralateral hemisphere. In this study, we characterize the receptive field properties for these abnormal representations by conducting detailed fMRI population receptive field mapping in a rare subset of participants with albinism and no ocular nystagmus. We find a nasal bias for receptive field positions in the abnormal temporal hemiretina representation. In addition, by modelling responses to bilateral visual field stimulation in the overlap zone, we found evidence in favor of discrete unilateral receptive fields, suggesting a conservative pattern of spatial selectivity in the presence of abnormal retinal input.

Quantitative MRI demonstrates abnormalities of the third ventricle subventricular zone in neurofibromatosis type-1 and sporadic paediatric optic pathway glioma.

BACKGROUND: The subventricular zone of the third ventricle (TVZ) is a germinal stem cell niche, identified as the possible location of optic pathway glioma (OPG) cell origin. Paediatric OPGs are predominantly diagnosed as low-grade astrocytomas, which are either sporadic or are associated with neurofibromatosis type-1 (NF1). These tumours often cause a significant impairment to visual acuity (VA). Infiltrative/invasive tumour activity is associated with increased apparent diffusion coefficient (ADC) and cerebral blood flow (CBF). This study aimed to determine whether TVZ imaging features differed between sporadic-OPG, NF1-OPG and controls, and whether the ADC and CBF profile at the germinal stem cell niche (the TVZ) correlated with the primary outcome of VA. METHODS: ADC and CBF MRI data were acquired from 30 paediatric OPG patients (median age 6 years; range 8 months-17 years), along with VA measurements, during clinical surveillance of their tumour. Values for mean ADC and maximum CBF were measured at the TVZ, and normalized to normal-appearing grey matter. These values were compared between the two OPG groups and the healthy control subjects, and multivariate linear regression was used to test the linear association between these values and patient's VA. RESULTS: In the TVZ, normalized mean ADC was higher in NF1-associated OPG patients (N = 15), compared to both sporadic OPG patients (N = 15; p = 0.010) and healthy controls (N = 14; p < 0.001). In the same region, normalized maximum CBF was higher in sporadic OPG patients compared to both NF1-OPG patients (p = 0.016) and healthy controls (p < 0.001). In sporadic OPG patients only, normalized mean ADC in the TVZ was significantly correlated with visual acuity (R2 = 0.41, p = 0.019). No significant correlations were found between TVZ CBF and ADC values and visual acuity in the NF1-associated OPG patients. CONCLUSION: Quantitative MRI detects TVZ abnormalities in both sporadic and NF1-OPG patients, and identifies TVZ features that differentiate the two. TVZ features may be useful MRI markers of interest in future predictive studies involving sporadic OPG.

Microstructural Investigations of the Visual Pathways in Pediatric Epilepsy Neurosurgery: Insights From Multi-Shell Diffusion Magnetic Resonance Imaging.

BACKGROUND: Surgery is a key approach for achieving seizure freedom in children with focal onset epilepsy. However, the resection can affect or be in the vicinity of the optic radiations. Multi-shell diffusion MRI and tractography can better characterize tissue structure and provide guidance to help minimize surgical related deficits. Whilst in adults tractography has been used to demonstrate that damage to the optic radiations leads to postoperative visual field deficits, this approach has yet to be properly explored in children. OBJECTIVE: To demonstrate the capabilities of multi-shell diffusion MRI and tractography in characterizing microstructural changes in children with epilepsy pre- and post-surgery affecting the occipital, parietal or temporal lobes. METHODS: Diffusion Tensor Imaging and the Spherical Mean Technique were used to investigate the microstructure of the optic radiations. Furthermore, tractography was used to evaluate whether pre-surgical reconstructions of the optic radiations overlap with the resection margin as measured using anatomical post-surgical T1-weighted MRI. RESULTS: Increased diffusivity in patients compared to controls at baseline was observed with evidence of decreased diffusivity, anisotropy, and neurite orientation distribution in contralateral hemisphere after surgery. Pre-surgical optic radiation tractography overlapped with post-surgical resection margins in 20/43 (46%) children, and where visual data was available before and after surgery, the presence of overlap indicated a visual field deficit. CONCLUSION: This is the first report in a pediatric series which highlights the relevance of tractography for future pre-surgical evaluation in children undergoing epilepsy surgery and the usefulness of multi-shell diffusion MRI to characterize brain microstructure in these patients.

Can illusory deviant stimuli be used as attentional distractors to record vMMN in a passive three stimulus oddball paradigm?

A passive three stimulus oddball paradigm was used to investigate Visual Mismatch Negativity (vMMN) a component of the Event Related Potential (ERP) believed to represent a central pre-attentive change mechanism. Responses to a change in orientation were recorded to monochrome stimuli presented to subjects on a computer screen. One of the infrequent stimuli formed an illusory figure (Kanizsa Square) aimed to capture spatial attention in the absence of an active task. Nineteen electrodes (10-20 system) were used to record the electroencephalogram in fourteen subjects (ten females) mean age 34.5 years. ERPs to all stimuli consisted of a positive negative positive complex recorded maximally over lateral occipital areas. The negative component was greater for deviant and illusory deviant compared to standard stimuli in a time window of 170-190 ms. A P3a component over frontal/central electrodes to the illusory deviant but not to the deviant stimulus suggests the illusory figure was able to capture attention and orientate subjects to the recording. Subtraction waveforms revealed visual discrimination responses at occipital electrodes, which may represent vMMN. In a control study with 13 subjects (11 females; mean age 29.23 years), using an embedded active attention task, we confirmed the existence of an earlier (150-170 ms) and attenuated vMMN. Recordings from an intracranial case study confirmed separation of N1 and discrimination components to posterior and anterior occipital areas, respectively. We conclude that although the illusory figure captured spatial attention in its own right it did not draw sufficient attentional resources from the standard-deviant comparison as revealed when using a concurrent active task.

Sensory function in severe semilobar holoprosencephaly.

We report a 4-year-old child with severe semi-lobar holoprosencephaly (HPE) not expected to survive after birth. Magnetic resonance imaging (MRI) revealed agenesis of the corpus callosum, absence of the third ventricle, fused thalami and basal ganglia. To investigate sensory function, visual, auditory and somatosensory evoked potential and imaging studies were carried out. The visual response evoked by human face stimuli evoked larger responses over the left side of the holosphere as compared to responses evoked by checkerboard pattern, while auditory evoked potentials were evident over the frontal regions to both pure tones and speech stimuli. No consistent scalp somatosensory evoked potentials were evident. This case demonstrates that electrophysiological measures are able to identify and quantify sensory processing not expected to be present based on the anatomical presentation of the cortex in a child with severe HPE.