ISCEV Standard for full-field clinical electroretinography (2008 update).

This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical electroretinography (ERG). The parameters for flash stimulation and background adaptation have been tightened, and responses renamed to indicate the flash strength (in cd x s x m(-2)). The ISCEV Standard specifies five responses: (1) Dark-adapted 0.01 ERG (rod response); (2) Dark-adapted 3.0 ERG (combined rod-cone response); (3) Dark-adapted 3.0 oscillatory potentials; (4) Light-adapted 3.0 ERG (cone response); (5) Light-adapted 3.0 flicker (30 Hz flicker). An additional Dark-adapted 10.0 ERG or Dark-adapted 30.0 ERG response is recommended.

The potential for vigabatrin-induced intramyelinic edema in humans.

PURPOSE: Vigabatrin (Sabril, Hoechst Marion Roussel) is an antiepilepsy drug (AED) presently marketed in 64 countries for the treatment of partial and secondarily generalized seizures. Vigabatrin (VGB) is marketed in a subset of these countries for the treatment of infantile spasms. Clinical experience in humans has shown that VGB provides effective seizure control with a wide margin of safety. However, animal toxicity studies raised concern when prolonged administration of VGB was shown to induce intramyelinic edema (IME) in some laboratory animal species. METHODS: Animal and human data were reviewed with respect to the potential for VGB-induced IME. Surveillance of patients receiving VGB in clinical trials or by prescription has been conducted for >15 years to identify patients developing clinical abnormalities that might be IME related. RESULTS: The histologic lesions of VGB-induced IME in animals are reliably reproduced and correlate with changes in multimodality evoked potentials (EPs) and magnetic resonance imaging (MRI). Numerous studies of the effects of VGB on EP and MRI in epilepsy patients have demonstrated no clear-cut IME-related changes in these modalities. Additionally, autopsy and surgical brain samples from VGB-treated patients have been scrutinized for potential IME histopathology. In an estimated 350,000 patient-years of VGB exposure (approximately 175,000 patients exposed for 2 years at an average dose of 2 g/day), no definite case of VGB-induced IME has been identified. CONCLUSIONS: Comprehensive review of a variety of sources of data failed to identify any definite case of IME in humans treated with VGB.

ON-pathway dysfunction in a patient with acquired unilateral night blindness.

PURPOSE: To investigate possible functional correlates of an apparent ON-pathway defect observed in the cone electroretinogram of a patient with acquired unilateral night blindness. METHOD: Visual evoked potentials were recorded to the onset of a grid pattern consisting of either incremental or decremental squares. Saccadic eye movements were measured to luminance increments and decrements presented 5 degrees from fixation. The patient's results were compared with normative data. RESULTS: Visual evoked potential latencies were prolonged to incremental stimulation of the patient's affected left eye but were within normal limits for the other three conditions (increments and decrements, right eye; decrements, left eye). A similar pattern of asymmetry between latencies to incremental and decremental stimulation of the affected eye was observed for saccadic eye movements. CONCLUSIONS: The observed predominant delay in response to luminance increments supports the hypothesis of an ON-pathway dysfunction in this patient with acquired unilateral night blindness.

Guidelines for calibration of stimulus and recording parameters used in clinical electrophysiology of vision. Calibration Standard Committee of the International Society for Clinical Electrophysiology of Vision (ISCEV).

In order to perform a technically adequate clinical electrophysiological procedure it is necessary to calibrate the stimulating and recording equipment. Published standards for the electroretinogram (ERG), electro-oculogram (EOG), visual evoked potential (VEP), and guidelines for the Pattern ERG (PERG) specify stimulus and recording parameters. Yet, most commercial instruments do not provide the means for calibration of these parameters. The goal of this document is to provide guidelines for proper calibration of stimulus and recording equipment. The need for such guidelines is clear on both clinical and scientific grounds. Stimulus and amplifier characteristics have substantial effects on the peak latency and amplitude measurements that are commonly used in clinical electrophysiology. Many review articles on clinical electrophysiology emphasize the need for establishing norms for each laboratory as a function of age and gender rather than relying on published norms. However, if stimulus and recording parameters are not calibrated periodically, then these norms may actually be misleading due to changes in stimulus or recording conditions induced by aging of equipment or inadvertent change in settings. This document is divided into two major sections. The first is concerned with calibration of the visual stimulus. It begins with background technical information on the physics of light and its measurement. This is followed by protocols for measurement of the luminous intensity of flash stimuli and the mean luminance, contrast, and visual angle of pattern stimuli. The second section is concerned with calibration of electrophysiologic recording systems. It begins with a description of the characteristics of bioelectrical signals and their measurement. This is followed by protocols for measurement of electrode impedance and amplifier calibration. Although this document was prepared as guidelines for clinical electrophysiological testing, it should be noted that the techniques described are more generally applicable to studies which are dependent upon accurate measurement of luminance or electrophysiological signals.

The peripheral flicker effect: desensitization of the luminance pathway by static and modulated light.

Previous studies have shown that luminance flicker, presented peripheral to a foveal test target, increases thresholds for target detection: the peripheral flicker (PF) effect. These studies have also shown that thresholds are elevated more for luminance targets, relative to chromatic targets. In the present study we examined the specificity of the PF effect on the luminance mechanism and assessed the contribution of modulated stray-light to the test field, as well as longer range spatial interactions. We found that the presence of a foveal luminance pedestal, as well as PF, caused a notch to appear in the spectral sensitivity function around 570 nm. This result confirms the hypothesis that the PF effect decreases the sensitivity of the luminance pathway. To assess the contribution of stray-light to the PF effect, we modulated a luminance pedestal without the presence of PF in order to simulate the stray-light effect in isolation. A decrease in sensitivity for wavelengths around 570 nm occurred with modulated stray-light, suggesting that modulated stray-light contributes substantially to this effect. We then minimized the modulated stray-light by phase-reversing a checkerboard pattern in the periphery. A significant, though smaller, threshold elevation to mid-spectrum stimuli was obtained, suggesting that long range spatial effects are also active in the PF effect. We conclude that the PF effect causes a desensitization of foveal luminance pathways via local and more long range spatial interactions. Our results are consistent with previous data which suggest that the PF effect is due to selective adaptation of cells in the magnocellular pathway (M-cells). Our data imply that local network adaptation may be a property of the magnocellular pathway.

Hemianopic anosognosia.

In a prospective study of 32 consecutive patients with homonymous visual field defects due to ischemic infarcts we found hemianopic anosognosia (HAN), defined as the unawareness of visual loss in the homonymous hemifield (or hemiquadrant), in 20 patients (62%). HAN, although occurring predominantly in right-side lesions in 16 of 26 patients (62%) was also present in four of six patients (or 67%) with left-side lesions. This group of patients has been presented in a prior report on positive spontaneous visual phenomena. HAN was associated with somatic anosognosia in nine patients and hemineglect in 17 patients. Dissociation between somatic and hemianopic anosognosia, as well as between hemineglect and HAN, was present in several patients, indicating that these phenomena may be independent of each other. Eight patients had pure homonymous hemianopia; that is, hemianopia without cognitive, motor, or somatosensory deficits. Four of these patients (Group A) had awareness of the visual deficit, whereas three patients (Group B) had HAN. Patients in these two groups had similar anatomic lesions. Patients with phosphenes, photopsias, or visual hallucinations were usually aware of their visual field loss. We suggest that HAN is most often related to failure of discovery of the deficits, occasionally to severe visual hemineglect, sometimes to generalized cognitive impairment, or to a combination of these factors. We further conclude (1) there is no specific cortical area for conscious visual perception; (2) visual awareness is processed by a distributed network including multiple visual cortices, parietal and frontal lobes, the pulvinar, and lateral geniculate bodies (lesions localized at various nodes or centers in the network may produce similar phenomena); and (3) both hemispheres are involved in visual processing and conscious awareness.

Positive spontaneous visual phenomena limited to the hemianopic field in lesions of central visual pathways.

We prospectively studied 32 patients with ischemic infarction of the retrochiasmal visual pathways. Positive spontaneous visual phenomena (PSVP) in the blind hemifield were present in 13 patients (41%). The PSVP were subdivided into phosphenes, photopsias, visual hallucinations, palinopsia, and agitated delirium with hemianopia. PSVP were never associated with auditory or other sensory positive phenomena, except in patients with agitated delirium. Patients with photopsias, phosphenes, palinopsia, and visual hallucinations had similar lesions in MRI/CT, suggesting no anatomic area unique for these four phenomena. However, there was a significant difference in the severity of associated neurologic deficits between hemianopic patients with and without PSVP. Larger lesions destroying anteriorly located visual association areas precluded the development of PSVP, which may be related to release from inhibitory input of visual regions bordering the damaged area. Patients with the syndrome of agitated delirium and hemianopia had specific lesions involving the mesial aspect of the occipital lobe, the parahippocampal gyrus, and hippocampus.

Dipole-modeling of the visual evoked P300.

We collected visual event-related potentials (ERPs) from 6 normal subjects using an "oddball" paradigm. Subjects were required to count the occurrences of matching shapes presented in the left and right visual field. Shapes matched on 20% of trials. ERPs were recorded from 20 or 43 electrodes distributed over the scalp. A multiple spatio-temporal equivalent dipole (ED) model was used to fit the early sensory and P300 component. A latency window to analyze the P300 was determined using the global field power statistic. The spatial topography of the P300 over this window was characterized by a midline positivity that decreased in amplitude with spatial distance from the peak. After sensory components were fit, the source of P300 could be accounted for by 1 or 2 EDs, which were usually located near medial temporal areas. This result is at odds with evidence from depth recordings during the oddball paradigm, showing that multiple regions of the brain are active during this interval.

The effects of luminance and chromatic background flicker on the human visual evoked potential.

Previous studies report that background luminance flicker, which is asynchronous with signal averaging, reduces the amplitude and increases the latency of the pattern-onset visual evoked potential (VEP). This effect has been attributed to saturation of the magnocellular (m-) pathway by the flicker stimulus. In the current study, we evaluate this hypothesis and further characterize this effect. We found that flicker had similar effects on the pattern-onset and pattern-reversal VEP, suggesting that the reversal and onset responses have similar generators. Chromatic flicker decreased latency of the chromatic VEP whereas luminance flicker increased peak latency to luminance targets. This result indicates that luminance flicker saturates a rapidly conducting m-pathway whereas chromatic flicker saturates a more slowly conducting parvocellular (p-) pathway. Finally, evoked potentials to chromatic and luminance stimuli were recorded from 34 electrodes over the scalp in the presence of static and asynchronously modulated backgrounds. An equivalent dipole model was used to assess occipital, parietal, and temporal lobe components of the surface response topography. Results showed that chromatic flicker reduced activity to a greater extent in the ventral visual pathway whereas luminance flicker reduced activity to a greater extent in the dorsal visual pathway to parietal lobe. We conclude that the VEP to isoluminant color and luminance stimuli contains both m- and p-pathway components. Asynchronous flicker can be used to selectively reduce the contribution of these pathways to the surface recorded VEP. Our results provide evidence of parallel pathways in the human visual system, with a dorsal luminance channel projecting predominantly to the posterior parietal lobe and a ventral color channel projecting predominantly to inferior temporal lobe.

Supranuclear eye movement dysfunction in mitochondrial myopathy with tRNA(LEU) mutation.

A patient with multiple neurological deficits and biopsy-proven mitochondrial myopathy with mutation of tRNA(LEU) at nucleotide 3243 was referred for eye movement evaluation. He had restricted range of voluntary motions in all directions and full range of eye movements on passive rotation of head while fixating a visual target. Eye movement recordings revealed decreased horizontal and vertical saccadic velocities and markedly decreased smooth pursuit gain in both directions. The vestibulo-ocular reflex showed gain abnormalities with many saccadic intrusions on the smooth reflex response. His brother, with similar mutation, was clinically asymptomatic. However, his eye movement recordings revealed slow horizontal saccadic velocities leftward and normal saccadic velocities rightward in both eyes as well as in upward and downward direction. Smooth pursuit and vestibulo-ocular reflexes were within normal limits. Although eye movement abnormalities are seen commonly in mitochondrial myopathies, the exact mechanism is not known. Our cases suggest supranuclear dysfunction as one of the mechanisms for ophthalmoparesis.

Locating VEP equivalent dipoles in magnetic resonance images.

Pattern-reversal and diffuse flash visual evoked potentials (VEPs) were obtained from 4 normal adults. A spatiotemporal dipole model was used to determine the location of the hypothetical equivalent dipoles consistent with the scalp distribution of the VEPs. Equivalent dipoles representing ERG and VEP activity were placed within 3-D magnetic resonance images of the brain. Most of the localization error appeared to be due to inadequate sampling of the potential field in frontal and occipital areas by the 10-20 system of electrode placement. Locating electrophysiologic dipoles within magnetic resonance images of brain structure allows evaluation of dipole localization techniques.