Chapter 34 - Visually evoked potentials

Due to the proximity of craniopharyngioma to the optic apparatus, one of the most common complications after surgery is visual deterioration. Intraoperative visual evoked potential (VEP), as a means of real-time visual function monitoring, has been integrated into transsphenoidal surgery for pituitary adenoma to predict postoperative visual outcome. Compared with pituitary tumor, craniopharyngioma often adheres to optic nerves, with increased risk of postoperative visual impairment. Furthermore, extended endoscopic endonasal surgery (EEES) can provide direct visualization of the surgical plane between the craniopharyngioma and the optic nerves, which contributes to analysis of the mechanism of real-time VEP changes during surgery. Therefore, VEP monitoring applied during EEES for craniopharyngioma may have more clinical value. However, only 9 patients who underwent EEES with VEP monitoring for craniopharyngioma have been sporadically reported to date. In this paper, the authors present the largest series to date analyzing the clinical value of VEP to predict postoperative visual outcome in adult patients with craniopharyngioma. Sixty-five adult patients who underwent EEES with intraoperative VEP monitoring for primary craniopharyngioma were retrospectively reviewed. The association between changes in VEP amplitude and postoperative visual outcome was determined. In addition, other potential prognostic factors with regard to postoperative visual outcomes were included in the analysis. Gross-total resection was achieved in 59 patients (90.8%). Reproducible and stable VEP was recorded in 128 of 130 eyes (98.5%). During surgery, VEP remained stable in 108 eyes, 10 (9.3%) of which had new visual acuity (VA) and/or visual field (VF) defects after surgery. Transient VEP decrease was recorded in 15 eyes, 4 (26.7%) of which had visual deterioration. Of the 5 eyes with permanent VEP decrease, 3 (60%) experienced postoperative visual impairment. Permanent VEP decrease (OR 19.868, p = 0.007) and tight adhesion (OR 6.104, p = 0.040) were independent adverse factors for postoperative VA deterioration. Tight adhesion (OR 7.150, p = 0.002) and larger tumor volume (OR 1.066, p = 0.001) were significant risk factors for postoperative VF defects. Intraoperative VEP monitoring can serve as a real-time warning to guide surgeons to avoid postoperative visual impairment. It effectively predicted VA changes in adult patients with craniopharyngioma after EEES. Tight adhesion and larger tumor volume were also strong predictors of postoperative visual impairment.

Visual evoked potentials (VEP) are visually evoked signals that extract electroencephalographic activity in the visual cortex that can detect retinal ganglion cells, optic nerves, chiasmal and retrochiasmal dysfunction, including optic radiations, and the occipital cortex. Because diabetes causes diabetic retinopathy due to microangiopathy and neuropathy due to metabolic abnormalities and intraneural blood flow disorders, assessment of diabetic visual pathway impairment using VEP has been attempted. In this review, evidence on the attempts to assess the visual pathway dysfunction due to abnormal blood glucose levels using VEP is presented. Previous studies have provided significant evidence that VEP can functionally detect antecedent neuropathy before fundus examination. The detailed correlations between VEP waveforms and disease duration, HbA1c, glycemic control, and short-term increases and decreases in blood glucose levels are evaluated. VEP may be useful for predicting postoperative prognosis and evaluating visual function before surgery for diabetic retinopathy. Further controlled studies with larger cohorts are needed to establish a more detailed relationship between diabetes mellitus and VEP.

The diagnostic application of averaged visual evoked potentials (VEPs) is illustrated in the investigation of hysterical amblyopia and multiple sclerosis. Averaged VEPs elicited either by a flash of light or a presentation of a grating lasting 100 ms were recorded from the occiput of patients. All the VEPs in hysterical amblyopia were normal. In multiple sclerosis the flash VEPs looked normal for both eyes, whereas the VEPs elicited by grating (2 and 5 c/deg) showed an increase in the latency of the first positive wave, again for both eyes. After physical exercise the VEPs from the right eye were dramatically reduced in amplitude (Uhthoff's sign).

Objective To observe the clinical features and visual function of recurrent neuromyelitis optica (NMO).Methods Thirty-four patients with NMO were enrolled in this retrospective case series study.The patients included two males and 32 females.The average first onset age was (35.03± 14.56) years old and the average recurrent rate were (4.24±2.45) times.The recurrent rate of optic neuritis (ON) ranged from two to 12 times.The recurrent rate of ON was two times in 15 eyes of 10 patients,≥three times in 37 eyes of 24 patients.Vision acuity,direct ophthalmoscope,fundus pre-set lens examination,visual field and visual evoked potential (VEP) were evaluated.Clinical features were observed.The abnormal rate of optic nerve including optic edema and atrophy; abnormal rate of visual field including decreasing retinal sensitivity,central and paracentral scotoma,ring scotoma,half field defects,tunnel visual field,visual field centrality constriction; abnormal rate of VEP including Prolonged latent phase and/or decreasing amplitude of P100 wave from patients of first episode or recurrence was analyzed.Serum NMO-IgG was detected from 28 patients hy indirect immunofluorescence technique to observe its positive rate.Results All patients were characterized by repeated episodes of ON and myelitis.The main clinical feature of ON was visual loss,and the main clinical features of myelitis included sensory disability,dyskinesia and vesicorectal disorder.Blindness rate was 41.67％ after the first attack of ON,33.33％ after two relapses,and 64.86％ after ≥ three relapses.The difference of blindness rate between first attack and two episodes was not significant (x2=0.270,P=0.603).However,the blindness rate in patients having ≥ three episodes was significantly higher than those having two episodes (x2=4.300,P=0.038).With recurrence rate increasing,the abnormal rate of the optic nerve (x2 =6.750,P =0.034) and VEP(x2 =6.990,P =0.030)increased.But the abnormal rate of visual field did not increase along with recurrent rate (x2 =0.660,P=0.718).Seropositive rate of NMO-IgG did not differ significantly between patients with first attack ON and that with recurrent ON (x2 =1.510,P =0.470).But the seropositive patients had significantly higher bilateral blindness rate than seronegative patients (x2=5.063,P=0.027).Conclusions NMO are characterized by recurrent ON and myelitis.Visual loss,sensory disability,dyskinesia and vesicorectal disorder are the main clinical features.With recurrence rate increasing,the blindness rate,abnormalities the optic nerve and the abnormity rate of VEP increase.Seropositive recurrent NMO patients have higher bilateral blindness rate than seronegative patients. Key words: Neuromyelitis optica/diagnosis; Optic neuritis/diagnosis; Vision, binocular; Vision,low; Visual fields

BackgroundMigraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers.MethodsTwenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups.ResultsThe mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann’s areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers.ConclusionThis study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology.This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata.

Visual evoked potentials (VEPs) are widely used to objectively assess visual system function in animal models of ophthalmological diseases. Although use of chronically implanted electrodes is common in longitudinal VEP studies using rodent models, reliability of recordings over time has not been assessed. We compared VEPs 1 and 7 days after electrode implantation in the adult mouse. We also examined stimulus-independent changes over time, by assessing electroencephalogram (EEG) power and approximate entropy of the EEG signal. Stainless steel screws (600-μm diameter) were implanted into the skull overlying the right visual cortex and the orbitofrontal cortex of adult mice (C57Bl/6J, n = 7). Animals were reanesthetized 1 and 7 days after implantation to record VEP responses (flashed gratings) and EEG activity. Brain sections were stained for glial activation (GFAP) and cell death (TUNEL). Reliability analysis, using intraclass correlation coefficients, showed VEP recordings had high reliability within the same session, regardless of time after electrode implantation and peak latencies and approximate entropy of the EEG did not change significantly with time. However, there was poorer reliability between recordings obtained on different days, and a significant decrease in VEP amplitudes and EEG power. This amplitude decrease could be normalized by scaling to EEG power (within-subjects). Furthermore, glial activation was present at both time points but there was no evidence of cell death. These results indicate that VEP responses can be reliably recorded even after a relatively short recovery period but decrease response peak amplitude over time. Although scaling the VEP trace to EEG power normalized this decrease, our results highlight that time-dependent cortical excitability changes are an important consideration in longitudinal VEP studies. This study shows changes in VEP characteristics over time in chronically implanted mice. Thus, future preclinical longitudinal studies should consider time in addition to amplitude and latency when designing and interpreting research.

The visual physiology of the wild type mouse determined with pattern VEPs

Chapter 6 Visual evoked potentials

Optic neuritis (ON) is linked to multiple sclerosis (MS). The presence of white matter lesions on cerebral magnetic resonance imaging (MRI) predicts the risk of MS after ON with considerable accuracy. Oligoclonal bands (OCB) are present in 95 % of MS patients, and a lumbar puncture can also be valuable in the evaluation of patients with ON. We analyzed CSF findings in patients referred with ON in the context of MRI and visual evoked potential (VEP) pathology. We assessed the possible contributory role of a lumbar puncture and weigh this against disadvantages of the procedure. Between February 2003 and November 2011, 505 patients were referred by ophthalmologists to the Clinic of Optic Neuritis, Glostrup Hospital, University of Copenhagen. None had MS prior to referral. A total of 437 were included in the study, and all underwent MRI, a lumbar puncture and VEP. Patients with other organic causes of their symptoms and patients with >3 months between onset and tests were excluded. All files were reviewed retrospectively. CSF leukocytes and the IgG index were elevated in 33 and 41 %, respectively, and OCBs were detected in 61 % of patients. CSF abnormalities correlated strongly with VEP and MRI (p < 0.0001). Patients with normal VEP and MRI had a 96 % probability of a normal lumbar puncture. The contributory role of a lumbar puncture in the evaluation of ON seems negligible when patients have a normal VEP and MRI. We suggest that all patients should be evaluated with VEP and MRI before deciding on a lumbar puncture.

The purpose of the present study is to investigate longitudinal changes in Visual evoked potential (VEP) parameters as an objective test after transsphenoidal surgery, its correlation with subjective tests and clinical value of VEP in the prediction of visual outcome. Fifty patients with pituitary macroadenoma who underwent surgical removal of the tumor recruited in this study. All the patients underwent ophthalmic examination, static automated perimetry (SAP), VEP and magnetic resonance imaging (MRI) preoperatively and 3months after surgery. Fifty patients with pituitary macroadenoma (size: 25.1 ± 9.9mm) were recruited in the study. Before surgery, the pattern of VEP showed a prolonged latency with reduced amplitude in eyes with abnormal visual acuity or abnormal visual field. The P100 wave latencies and amplitudes showed significant correlation with visual acuity and SAP scores. After surgery, visual acuity and visual field improvements were seen in 51% and 65.6% of eyes, respectively. Mean SAP and visual acuity scores increased significantly (p < 0.01), P100 wave latency declined and amplitude improved after surgery but not significantly. The mean age of patients, size of tumors and preoperative P100 wave latency were significantly lower in eyes with visual field and acuity improvement. VEP is a helpful quantitative and objective complementary test to visual acuity and SAP exams for assessing pre-operative visual abnormalities and post-operative visual outcome in patients with pituitary macroadenoma.

The primate visual system is composed by two color-opponent pathways--red-green (R-G) and blue-yellow (B-Y)--subserved by the so-called parvo- and koniocellular streams respectively. The authors' aim was to compare the relative involvement of chromatic visual subsystems in multiple sclerosis (MS). In 30 MS patients with different forms of MS they recorded visual evoked potentials (VEPs) to onset (300 msec) and offset (700 msec) of equiluminant R-G and B-Y sinusoidal gratings of different contrast (90% and 25%). Equiluminance was established psychophysically by establishing the R-G and the B-Y color ratio at which chromatic gratings alternating at 15 and 10 Hz respectively had minimum visibility. The negative wave at stimulus onset with a peak latency of 120 to 160 msec was evaluated. Ordinary VEPs to luminance (LUM) contrast (black-white reversing checkerboards of 15' check size and 50% contrast) were also recorded for comparison. Latencies of R-G VEPs were abnormal in 53.3% and 58.3% of patients at 90% and 25% contrast respectively, whereas abnormal B-Y VEPs were 56.6% and 48.3%. Latencies of LUM VEPs were abnormal in 45% of patients. Interocular latency asymmetries were abnormal in 59.2% and 33.3% of patients for R-G, and 51.8% and 62.9% for B-Y. Latency asymmetries for LUM VEP were abnormal in 46.4% of patients. The higher rate of VEP abnormalities found with equiluminant chromatic stimuli compared with achromatic stimuli confirms the general vulnerability of color-opponent visual pathways in MS, even if the number of patients with abnormal findings was not significantly different when both test conditions were compared. VEPs to R-G and B-Y equiluminant stimuli appear to be involved approximately to the same extent.

To evaluate correlations between longitudinal changes in neuro-ophthalmologic measures and quality of life (QOL) and disability in patients with multiple sclerosis (MS), using optical coherence tomography (OCT), visual evoked potentials (VEP), and visual field examination. Fifty-four patients with relapsing-remitting MS were enrolled in this study and underwent Multiple Sclerosis Quality of Life questionnaire (54 items) (MSQOL-54) and Expanded Disability Status Scale (EDSS) evaluation, as well as complete neuro-ophthalmologic examination including visual field testing and retinal nerve fiber layer (RNFL) measurements using Cirrus and Spectralis OCT and VEP. All patients were re-evaluated at 12, 24, and 36 months. Logistical regression was performed to analyze which measures, if any, could predict QOL. Overall, RNFL thickness results at the baseline evaluation were significantly different from those at 3 years (p ≤ 0.05), but there were no differences in functional measures (visual acuity, contrast sensitivity, color vision, visual field, and VEP). A reduced MSQOL-54 score was associated with an increase in EDSS score and a decrease in both functional and structural parameters. Patients with longer MS duration presented with a lower MSQOL-54 score (reduction in QOL). Patients with progressive axonal loss as seen in RNFL results had a lower QOL and more functional disability.

To investigate the response properties of the electrically evoked potentials (EEPs) elicited by intraorbital optic nerve stimulation with penetrating electrodes using different stimulus parameters. Visually evoked potentials (VEPs) were recorded as a control and for comparative purposes. Teflon-coated tungsten wire electrodes (100 microm core-diameter, 300 microm exposed tip) were inserted intraorbitally into the optic nerve. A charge-balanced biphasic current was delivered to the optic nerve via inserted wire electrodes in 26 anaesthetized rabbits. EEPs were recorded by epidural electrodes placed over the visual cortex. The charge density threshold for eliciting EEPs was determined. Stimulus pulse amplitude, duration, frequency and waveform were varied to study their effects on EEPs. After the experiments, the stimulated optic nerves were examined histologically for examination of implantation position of the stimulating electrode into the optic nerve tissue. EEPs were successfully elicited by intraorbital optic nerve stimulation with penetrating electrodes. The measured amplitude of the first large positive peak (P1) was smaller and the latency of P1 was shorter compared with VEPs. The measured charge density threshold to elicit EEPs was 21.36 +/- 5.64 microC/cm(2). The amplitude of P1 increased and the latency of P1 decreased with increasing pulse amplitude of fixed duration stimuli. The amplitude of P1 increased with increasing pulse duration of fixed amplitude stimuli. For fixed charge stimuli, the amplitude of P1 decreased and the latency of P1 increased as the pulse duration increased. As frequency of stimuli varied from 1 to 10 Hz, the amplitude of P1 decreased monotonically. Among the different charge-balanced biphasic pulse stimulating waveforms, the symmetrical cathode-first biphasic pulse elicited the largest amplitude of P1. Our study demonstrates that intraorbital optic nerve stimulation with different stimulus parameters by penetrating electrodes can evoke cortical responses with different properties. The short-duration symmetrical cathode-first biphasic pulses of current with low frequencies are more efficacious in eliciting electrophysiological responses in the visual cortex than other stimulating waveforms.

Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Fort Lauderdale, Florida, May 5-10, 2002.

P-EV002. Visual evoked potentials in neuromyelitis optica spectrum disorders