Photosensitive epilepsy and image safety.

Photosensitive epilepsy came to prominence in the 1950s with the advent of television. Photosensitive epilepsy occurs in 1 in 4000 of the population. The incidence is 1.1 per 100,000 per annum, however amongst 7-19 year-olds the incidence is more than five times as common. Photosensitive epilepsy is twice as common in females as in males. The onset is around puberty, but less than 25 per cent of patients lose their photosensitivity in their twenties. Patients are investigated in the EEG laboratory using intermittent photic stimulation. Peak sensitivity is between 16 and 20 flashes/s but 49 per cent of patients are sensitive to 50 flashes/s, explaining the sensitivity to PAL television systems. From 1993 the development of broadcast guidelines was developed restricting both flash rates and the areas of screen involved, as well as the use of long-wavelength red. Automatic analysis systems can now test material for compliance with guidelines in real time.

Examining visual field defects in the paediatric population exposed to vigabatrin.

The antiepileptic drug, vigabatrin, has been linked to a specific pattern of visual field loss. The majority of studies have not included the paediatric population due to difficulties assessing visual field function. This is a particular problem as vigabatrin is effective against infantile spasms. A field-specific visual evoked potential was developed which consisted of a central stimulus (0-5 degrees radius) and a peripheral stimulus (30-60 degrees radius). Both stimuli consist of black and white checks which increase in size with eccentricity. Responses are recorded from occipital electrodes O2 and O1 referred to frontal electrode Fz. Electroretinograms and perimetry was performed were possible as a comparison. Thirty-nine children with epilepsy treated with vigabatrin aged from 3 to 15 years were included in the study; 35/39 children complied with the field-specific VEP, 26/39 complied with the ERG and 11/39 performed perimetry. Of these results, 18 children had normal ERG responses and eight had abnormal response. Visual field testing revealed four children had abnormal and seven had abnormal visual field results. The Field-specific VEP identified three of four abnormal perimetry results and six of seven normal perimetry results, giving a sensitivity of 75% and a specificity of 85.7%. When comparing perimetry results with the ERG parameters only the 30-Hz flicker amplitude, with a cut-off amplitude below 70 microV, gave a useful sensitivity of 75% and a specificity of 71%. The field-specific VEP is a useful alternative method that is both well tolerated by young children and gives a reliable indication of likely peripheral visual field loss associated with vigabatrin. The defect appears to have a similar prevalence in children as it does in adults.

Vigabatrin; its effect on the electrophysiology of vision.

Vigabatrin is known to induce visual field defects in approximately one third of patients treated with the drug. It is apparent from electrophysiological studies that the cause of this defect is at retinal level probably as a result of the build up of GABA. Studies of electrophysiological retinal parameters such as the EOG and photopic, scotopic and 30-Hz flicker ERG have revealed changes in Arden Index, photopic a and b wave latency and amplitude, changes in oscillatory potentials, and changes in latency and amplitude of the 30Hz response. However, many of these changes such as the Arden Index, oscillatory potentials, latency and amplitude of photopic b wave appear to be related to current anti-epileptic drug treatment rather than visual field defects. Certain parameters, particularly the amplitude of the 30-Hz flicker response, do appear to correlate with the severity of the field defect. Paediatric patients treated with the drug at age 9 years or below cannot reliably perform visual field perimetry. To identify these patients a special VEP H-Stimulus has been developed to produce separate responses from central and peripheral field stimulation by alternating at slightly separate rates. Forty-five healthy children between ages 3 and 10 years have been used to develop a normal database. This technique has a sensitivity of 75% and a specificity of 87.5% in identifying the field defect and may be used in children with epilepsy from age 3 upwards.

Field-specific visual-evoked potentials: identifying field defects in vigabatrin-treated children.

OBJECTIVE: To derive a visual-evoked potential (VEP) technique for identifying visual field defects in children with epilepsy treated with vigabatrin and unable to perform perimetry. BACKGROUND: Studies have linked vigabatrin to a specific pattern of visual field loss. Few studies have included the pediatric population because of difficulties in assessing the visual field by perimetry below a developmental age of 9 years. METHODS: A field-specific VEP was developed with a central (0 degrees to 5 degrees radius) and peripheral stimulus (30 degrees to 60 degrees radius). Stimuli consisted of black and white checks that increased in size with eccentricity. Checks reversed at different rates, allowing separate central and peripheral responses to be recorded. Five vigabatrin-treated young adults with field defects were identified using this stimulus. Electroretinograms (ERG) were recorded to examine the effects of vigabatrin on retinal function. Thirty-nine children aged 3 to 15 years were included in the study. Twelve patients were examined by both the field-specific stimulus test and perimetry. The diagnostic performance of the field-specific stimulus test was compared with that of perimetry. RESULTS: Thirty-five of 39 children complied with the field-specific stimulus, 26 of 39 complied with the ERG, and 12 of 39 complied with perimetry. Using the summed amplitude of the peripheral response from O(2) and O(1), responses below 10 microV were deemed abnormal. The field-specific stimulus identified 3 of 4 abnormal perimetry results and 7 of 8 normal perimetry results, giving a sensitivity of 75% and a specificity of 87.5%. When comparing perimetry results with the ERG parameters, only the 30-Hz flicker amplitude, with a cutoff below 70 microV, gave a useful indication of visual field loss. CONCLUSION: Field-specific VEP are well tolerated by children older than 2 years of age and are sensitive and specific in identifying vigabatrin-associated peripheral field defects.

Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms.

Previous work has indicated recreational use of methylenedioxymethamphetamine (MDMA or ecstasy) is associated with elevated scores on self-report measures of depression. We sought to examine the long-term effects of consumption on depression in a group of individuals who had consumed large quantities of the drug in the past, but were now leading relatively drug free lives. Respondents to this study (n = 29) had consumed an average of 1.5 ecstasy tablets in the last month, 8.4 in the last 6 months and 23.3 in the last 12 months. The estimated total consumed was 527 tablets, indicating that these respondents were indeed former chronic users of the drug. None of the respondents had consumed ecstasy in the last 14 days. Levels of depression (Beck's Depression Inventory) were significantly (p < 0.01) elevated compared to a matched non-drug using control group. Within the group of former chronic users, these levels of depression were not significantly affected by current use of alcohol, cannabis or amphetamine, but were positively correlated with an external locus of control (p < 0.05), infrequent but severe- (p < 0.05) and frequent but mild- (p < 0.005) self-report measures of life stress. Multiple regression indicated that levels of frequent but mild life stress (p < 0.005) and the quantity of ecstasy tablets respondents consumed over a 12-h period (p < 0.05) were the only variables that were significant predictors of self-reported levels of depression. The results of this study indicate that former chronic ecstasy users report higher levels of depression than their matched controls.

Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction.

PURPOSE: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin-attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin. METHODS: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro-oculography, and flash and pattern visual evoked potentials, was undertaken. RESULTS: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro-oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30-Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level. CONCLUSION: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.

Separating the retinal electrophysiologic effects of vigabatrin: treatment versus field loss.

OBJECTIVE: To separate the retinal electrophysiologic markers associated with vigabatrin-attributed visual field loss (VGB-VFL) from those associated with current vigabatrin therapy. METHODS: A nonrandomly selected cohort of 8 previous and 18 current vigabatrin users and a reference cohort of 8 never vigabatrin-treated patients with epilepsy receiving other antiepilepsy drugs (AED) underwent electro-oculography (EOG), electroretinography (ERG), and automated static threshold perimetry. A cohort of 22 normal subjects underwent ERG. The validity of the retinal electrophysiologic variables to detect the presence and severity of VGB-VFL was assessed using receiver operator characteristic curves. RESULTS: Of 26 patients exposed to vigabatrin, 18 exhibited VGB-VFL. No patients receiving alternative AED showed this type of visual field abnormality. The presence and severity of VGB-VFL was significantly associated with the latency (implicit time) and amplitude of the ERG cone function. The amplitude of the cone flicker response was the strongest predictor of VGB-VFL and revealed a sensitivity of 100% at a specificity of 75%. The EOG, the photopic and scotopic ERG, and the latency of the ERG second oscillatory potential (OP2) were not significantly related to the presence of VGB-VFL. Vigabatrin therapy was significantly associated with the photopic amplitude, the scotopic a-wave latency, and the latency of OP2. CONCLUSION: In patients who cannot perform reliable perimetry, the cone-specific ERG flicker amplitude provides the best screening method for detecting VGB-VFL.

Magnetic source imaging in fixation-off sensitivity: relationship with alpha rhythm.

A patient in whom a variety of abnormal EEG findings can be elicited by elimination of central vision and fixation demonstrates fixation-off sensitivity. The underlying mechanisms of fixation-off sensitivity and its relationship with alpha rhythm remain unclear. To obtain a better understanding of this issue, we used a whole-head magnetoencephalograph to study an epileptic child with fixation-off sensitivity resulting in a 3-Hz, large-amplitude oscillation (300 microV) over the occipital regions on the EEG. Magnetic source localization revealed alpha activity around the calcarine fissure and surrounding parieto-occipital areas. Magnetic sources of abnormalities relating to fixation-off sensitivity, however, usually were located deeper in the brain, suggesting more extensively distributed sources, with involvement of the cingulate gyrus and the basomesial occipitotemporal region. Distributions of the sources of both types of activities show independent clusters but also an appreciable domain of overlap. Our findings indicate that abnormalities related to fixation-off sensitivity can emerge in thalamocortical networks, with larger and more anterior cortical distribution than those that generate alpha rhythm. Transition in the type of oscillation appears not only to depend on a change in cellular dynamics but also to be reflected in a different spatial distribution of the underlying neuronal networks.

Characteristics of a unique visual field defect attributed to vigabatrin.

PURPOSE: Vigabatrin (VGB) therapy is associated with a loss of peripheral vision. The characteristics and prevalence of VGB-attributed visual field loss (V-AVFL) and associated risk factors were evaluated in patients with epilepsy. METHODS: The material comprised the visual fields and case notes of 88 patients with suspected V-AVFL (25 spontaneous reports and 63 cases from an open-label extension trial) and of 42 patients receiving alternative antiepileptic drugs (AEDs) from a cross-sectional study. RESULTS: Forty-two reliable cases of visual field loss could not be assigned to an alternative known cause and were therefore attributed to VGB (13 spontaneous reports and 29 from the open-label study). All cases except one were asymptomatic. Seven cases of field loss were present in the reference cohort of 42 patients; all cases could be attributed to a known aetiology. Thirty-six of the 42 confirmed cases of V-AVFL exhibited a bilateral defect that was most profound nasally, and three, a concentric constriction. The prevalence of V-AVFL was 29% (95% confidence interval, 21-39%). Male gender was associated with a 2.1-fold increased relative risk of V-AVFL (95% confidence interval, 1.20-4.6%). Age, body weight, duration of epilepsy, and daily dose of VGB, and concomitant AEDs did not predict the occurrence of V-AVFL. CONCLUSIONS: The unique visual field defect attributed to VGB is profound in terms of the frequency of occurrence and the location and severity of loss. The asymptomatic nature of the field loss indicates that V-AVFL can be elicited only by visual field examination.

Visual field defects associated with vigabatrin therapy.

OBJECTIVE: To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug vigabatrin and to characterise the features of visual dysfunction found. METHODS: Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16 patients with epilepsy unexposed to vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. RESULTS: Of 31 assessable patients treated with vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12 patients (39%) in whom a definite bilateral field defect was found, possibly caused by vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking vigabatrin, although this returned towards normal when vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. CONCLUSIONS: Treatment with vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of vigabatrin on the retina and seemed to persist if the drug was withdrawn.

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

Two visual mechanisms of photosensitivity.

PURPOSE: Photosensitive epilepsy is the most common of the "reflex" epilepsies. Precipitated by television viewing, flickering light, or specific visual patterns, it is the cause of seizures in 10% of young people with epilepsy. Photosensitivity is associated with two types of EEG abnormalities: photoparoxysmal responses (PPRs) and occipital spikes (OSs). It is unclear whether these abnormalities are mediated by different mechanisms, and furthermore, the clinical significance of OS is unknown. METHODS: By using our previously established population of patients with photosensitive epilepsy, all showing EEG abnormalities on intermittent photic stimulation or pattern stimulation, we examined the effects of pattern contrast, spatial and counterphase temporal frequency, and colour on these abnormalities. RESULTS: PPRs and not OSs show linear contrast dependency and are elicited by stationary stimuli and by non-colour-opponent isoluminant stimuli. CONCLUSIONS: PPRs and OSs are generated independently by the parvocellular and magnocellular visual systems, respectively. The results add support to the hypothesis that only PPRs and not OSs are clinically significant.

Mechanisms of video-game epilepsy.

PURPOSE: We aimed to elucidate the mechanisms underlying video-game epilepsy by comparing the flicker- and spatial-frequency ranges over which photic and pattern stimulation elicited photoparoxysmal responses in two different populations: (a) 25 patients with a history of seizures experienced while playing video games; and (b) 25 age- and medication-matched controls with a history of photosensitive epilepsy, but no history of video-game seizures. METHODS: Abnormality ranges were determined by measuring photoparoxysmal EEG abnormalities as a function of the flicker frequency of patterned and diffuse intermittent photic stimulation (IPS) and the spatial frequency of patterns on a raster display. RESULTS: There was no significant difference between the groups in respect of the abnormality ranges elicited by patterned or diffuse IPS or by spatial patterns. When the groups were compared at one specific IPS frequency (-50 Hz), however, the flicker frequency of European television displays, the video-game patients were significantly more likely to be sensitive. CONCLUSIONS: The results suggest that video-game seizures are a manifestation of photosensitive epilepsy. The increased sensitivity of video-game patients to IPS at 50 Hz indicates that display flicker may underlie video-game seizures. The similarity in photic- and pattern-stimulation ranges over which abnormalities are elicited in video-game patients and controls suggests that all patients with photosensitive epilepsy may be predisposed toward video-game-induced seizures. Photosensitivity screening should therefore include assessment by using both IPS at 50 Hz and patterns displayed on a television or monitor with a 50-Hz frame rate.

Photic stimulation: standardization of screening methods.

PURPOSE: Differences in methodology of intermittent photic stimulation within and between countries in Europe make collaborative research and interpretation of results difficult. METHOD: Experts in the field of photic stimulation from European countries have given an overview of methods used in routine photic stimulation. A consensus meeting was organized in May 1996 in the Netherlands. RESULTS: Methodology, including specification of a photo stimulator, procedure of photic stimulation, and interpretation of EEG results, has been defined according to available scientific and clinical knowledge. CONCLUSIONS: Consensus was reached in setting up a safe, quick, simple and reliable method to determine whether or not patients are photosensitive. A specification of an international standard for intermittent photic stimulation in the routine EEG examination is given with the purpose of improving patient care and facilitating collaborative research.

Morphology of transient VEPs to luminance and chromatic pattern onset and offset.

Characteristics of the visual evoked response to chromatic and luminance-modulated stimuli reflect the activity of underlying neural mechanisms, although selective neuronal activity depends upon stimulus parameters. In the present study, the behaviour of the transient visual evoked response to low spatial and temporal frequency chromatic stimuli is investigated at a range of colour luminance ratios. Our results show that the response to pattern-offset may be used in addition to the pattern-onset response as part of the signature of the evoked response to luminance-modulated or isoluminant chromatic stimuli.