Photosensitivity and self-induction in patients aged 50 and older.

OBJECTIVE: Photosensitivity is known to occur predominantly in children and adolescents and with a clear female predominance. Little is known on the prevalence of photosensitivity in older patients (50+) and its phenotypical appearance. METHODS: A retrospective observational study was performed investigating the prevalence of a photoparoxysmal EEG response (PPR) on at least one EEG during the period 2015-2021. Data were gathered from patients aged 50 years and older by retrieving clinical and EEG characteristics from existing medical records. Data on photosensitivity-related symptoms in daily life were gathered with telephone interviewing. RESULTS: In 248 patients a PPR had been elicited, of whom 16 patients (6.5%) were 50 years or older. In older patients, photosensitivity was a persistent feature of childhood-onset epilepsy (n = 8), of adult-onset epilepsy (n = 7), or an incidental finding (n = 1). In the 50+ group, 56% of photosensitive patients was female, whereas 72% in the total PPR-group. In six of 16 older patients, eye closure sensitivity was observed; two of these patients reported self-induction. Symptoms of photosensitivity in daily life were present in eight out of nine patients who consented in a telephone interview. For seven of these patients, wearing sunglasses was helpful. SIGNIFICANCE: Female preponderance for photosensitivity was not found in epilepsy patients of 50 years and older. In 44% of the older photosensitive patients in this series, the PPR was a feature of adult-onset epilepsy. Symptoms of photosensitivity in daily life in older patients with epilepsy seem comparable to those in younger patients, and thus worthwhile to diagnose and treat them equally.

Efficacy of color lenses in abolishing photosensitivity: Beyond the one-type-fits-all approach?

OBJECTIVE: Red-light filtering lenses represent an additional option to medication in photosensitive epilepsy. Blue lenses (Clarlet Z1 F133) can dramatically reduce seizure frequency, with a substantial restriction in luminance that can limit their applicability in daily life. We investigated the efficacy of 4 blue lenses with higher transmittance and reduced chromatic distortion in abolishing the photoparoxysmal EEG response (PPR) compared to the gold-standard Z1 lenses. METHODS: We reviewed EEG data during photic-and pattern stimulation in 19 consecutive patients (6-39 years) with photosensitivity (PS). Stimulation was performed at baseline and while wearing Z1 and the four new lenses. Lenses were tested in the same session by asking the patient to wear them in a sequentially randomized fashion while stimulating again with the most provocative photic/pattern stimuli. The primary outcome was the change in the initial PPR observed for each lens, categorized as no change, reduction, and abolition. RESULTS: Photosensitivity was detected in 17 subjects (89.5%); pattern sensitivity (PtS) was identified in 14 patients (73.7%). The highest percentages of PPR abolition/reduction were observed with Z1, for both PS and PtS. Regarding the new lenses, B1 + G1 offered the best rates, followed by B1 + G2. B1 + G3 and B1 showed lower efficacy rates, particularly for PtS. In the comparative analysis, no significant differences in PPR suppression were detected between the five lenses for PS. For PtS, the capacity of Z1 for PPR abolition was significantly higher compared with B1 + G3 and B1. CONCLUSIONS: This preliminary study suggests efficacy of the new group of blue lenses with potentially greater tolerability, particularly in regions with fewer sunlight hours during winter. In line with the current trend for personalized approach to treatment, this study suggests that in some patients there might be scope in extending the testing to offer the lens with the higher transmittance effective in abolishing the PPR.

Clinical utility of EEG in diagnosing and monitoring epilepsy in adults.

Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.

"Headache and epilepsy"--how are they connected?

The relationship between headache and seizures is a complicated one, since these two conditions are related in numerous ways. Although the nature of this association is unclear, several plausible explanations exist: the two disorders coexist by chance; headache is part (or even the sole ictal phenomenon) of seizures or the post-ictal state; both disorders share a common underlying etiology; and epilepsy mimics the symptoms of migraine (as in benign childhood epilepsy). Seizures and headaches as well as their respective primary syndromes (epilepsy and headache/migraine) share several pathophysiological mechanisms. These mechanisms especially involve neurotransmitter and ion channel dysfunctions. Also, photosensitivity seems to play a role in the connection. In order to improve the care for patients with a clinical connection between migraine and epilepsy, it is necessary to try to understand more accurately the exact pathophysiological point of connection between these two conditions. Both experimental and clinical measures are required to better understand this relationship. The development of animal models, molecular studies defining more precise genotype/phenotype correlations, and multicenter clinical studies with revision of clinical criteria for headache/epilepsy-related disorders represent the start for planning future translational research. In this paper, we review the relationship between migraine and epilepsy in terms of epidemiology and pathophysiology with regard to translational research and clinical correlations and classification.

Whole-genome linkage scan for epilepsy-related photosensitivity: a mega-analysis.

Photoparoxysmal response (PPR) is considered to be a risk factor for idiopathic generalised epilepsy (IGE) and it has a strong genetic basis. Two genome-wide linkage studies have been published before and they identified loci for PPR at 6p21, 7q32, 13q13, 13q31 and 16p13. Here we combine these studies, augmented with additional families, in a mega-analysis of 100 families. Non-parametric linkage analysis identified three suggestive peaks for photosensitivity, two of which are novel (5q35.3 and 8q21.13) and one has been found before (16p13.3). We found no evidence for linkage at four previously detected loci (6p21, 7q32, 13q13 and 13q31). Our results suggest that the different family data sets are not linked to a shared locus. Detailed analysis showed that the peak at 16p13 was mainly supported by a single subset of families, while the peaks at 5q35 and 8q21 had weak support from multiple subsets. Family studies clearly support the role of PPR as a risk factor for IGE. This mega-analysis shows that distinct loci seem to be linked to subsets of PPR-positive families that may differ in subtle clinical phenotypes or geographic origin. Further linkage studies of PPR should therefore include in-depth phenotyping to make appropriate subsets and increase genetic homogeneity.

Ictal headache and visual sensitivity.

Migrainous headache is reported by patients with photosensitive epilepsy, whereas their relatives complain more often about headache than the relatives of patients with other types of epilepsy. We therefore investigated whether headache itself could be an epileptic symptom related to photosensitivity. Four probands with headache and photosensitive epilepsy were selected. Their first-degree family members were studied using video-EEG with extensive intermittent photic stimulation and pattern stimulation. Nine of the 12 subjects (10 female and two male, mean age 30 years, range 14-46 years) proved to be photosensitive with either focal (n = 5) or generalized (n = 4) epileptiform discharges. In two subjects an ictal recording of headache occurred after visual stimulation. We found evidence that, in specific patients, headache could be an ictal sign of epilepsy. Photic stimulation during EEG recording can contribute to correct diagnosis and lead to the best care and management of the patient.

Evaluation of brivaracetam, a novel SV2A ligand, in the photosensitivity model.

OBJECTIVE: To assess the activity of brivaracetam, a novel SV2A ligand, in the photosensitivity model as a proof-of-principle of efficacy in patients with epilepsy. METHODS: A subject-blind placebo-controlled study in patients with photosensitive epilepsy was performed to investigate the effect of single-dose brivaracetam (10, 20, 40, or 80 mg) on photosensitive responses. Each patient was exposed to intermittent photic stimulation that evoked a generalized photoparoxysmal EEG response. Individual standard photosensitivity ranges (SPRs) were recorded post-placebo (day -1) and post-brivaracetam until return to baseline (day 1 to 3). Plasma concentrations of brivaracetam and any concomitant antiepileptic drugs were determined. RESULTS: Of the 18 evaluable patients, none achieved SPR abolishment post-placebo, whereas 14 (78%) achieved complete abolishment post-brivaracetam. Decrease in SPR was seen in 8 patients (44%) post-placebo compared to 17 (94%) post-brivaracetam. Duration of response was twice as long post-brivaracetam 80 mg (59.5 hours) compared with lower doses, although the overall effect was not dose-dependent. Time to maximal photosensitive response was dose-related with the shortest time interval observed at the highest dose (0.5 hours post-brivaracetam 80 mg). The area under the effect curve (SPR change from pre-dose vs time) appeared linearly correlated with the area under the plasma concentration curve. Brivaracetam was well tolerated. The most common adverse events were dizziness and somnolence. CONCLUSIONS: Our findings show that brivaracetam clearly suppresses generalized photoparoxysmal EEG response. As such, investigations of the antiepileptic properties and tolerability of brivaracetam are warranted in further clinical studies of patients with epilepsy.

Levetiracetam: a long-term follow-up study of efficacy and safety.

OBJECTIVES: To evaluate the efficacy and safety of long-term add-on treatment with levetiracetam 1,000-4,000 mg/day. PATIENTS AND METHODS: In this multicenter, open-label follow-up study, 505 patients, from 10 European countries, who had benefited from previous add-on treatment with levetiracetam in a clinical trial or compassionate-use program were enrolled; 274 (54.3%) stayed to the end. Most then continued levetiracetam by prescription or in a named patient program, where it was not yet commercially available. Mean treatment duration was 1,045 days (range: 24 days to >7 years). Median daily dosage was 3,000 mg/day (range: 250-6,000 mg/day), with 250 (49.5%) patients receiving levetiracetam for >3 years. RESULTS: Median total and partial seizure frequency per week over the evaluation period were 0.8 and 0.7; seizure frequency per week was generally stable over time and remained low. There was a probability of 6.6% of remaining seizure-free for the first 3 years, and of 18.9% of having a seizure-free period of at least 3 years at any time. Most adverse events were mild or moderate and unrelated to study drug. Levetiracetam was well tolerated, and provided stable seizure control during long-term treatment.

Living with epilepsy: long-term prognosis and psychosocial outcomes.

OBJECTIVE: To analyze the impact of seizures on everyday life and the long-term effects of epilepsy on health status and psychosocial outcomes. METHODS: Follow-up study was conducted of a cohort of consecutive patients newly diagnosed with epilepsy between 1953 and 1967. In 1995 (mean follow-up 34 years), a random sample of 333 patients received a questionnaire asking clinical and demographic information and validated measures for psychosocial outcomes. Comparisons were made with the general Dutch population. RESULTS: The response rate was 73% (116 men and 127 women); mean age was 49.9 years (SD 11.2 years). Mean age at epilepsy onset was 15 years (SD 11 years); mean duration was 24.4 years (SD 13.1 years). In total, 134 (55%; 72 men and 62 women) patients were seizure-free for the previous 5 years, and 81 patients still had seizures in the last year. One hundred twenty-seven patients were taking antiepileptic drugs, of which 51 were on monotherapy. Epilepsy patients have a positive health evaluation, comparable with the general Dutch population. Fewer epilepsy patients married or had children than the general Dutch population; more patients live at home with their parents or in foster homes or institutions (p < 0.001). Having epilepsy at school age has a significant negative effect on learning achievement (p < 0.01). Employment status is affected less, though more epilepsy patients are unfit to work than individuals from the general population (p < 0.05). CONCLUSIONS: Epilepsy has a marked negative impact on education and achievement in later life. Despite worse psychosocial outcomes than the Dutch population, patients with epilepsy cope well with their epilepsy, regardless of their handicaps.

Video games are exciting: a European study of video game-induced seizures and epilepsy.

BACKGROUND: Video game seizures have been reported in photosensitive and non-photosensitive patients with epilepsy. The game Super Mario World, has led to many cases of first seizures. We examined whether this game was indeed more provocative than other programs and whether playing the game added to this effect. METHODS: We prospectively investigated 352 patients in four European cities, using a standard protocol including testing of a variety of visual stimuli. We correlated historical data on provocative factors in daily life with electroencephalographic laboratory findings. RESULTS: The video game, Super Mario World proved more epileptogenic than standard TV programs and as provocative as programs with flashing lights and patterns. Most striking was the fact that video game-viewing and-playing on the 50 and 100 Hz TV was significantly more provocative than viewing the standard program (P < 0.001, P < 0.05 respectively). Playing the video game Mario World on a 50 Hz TV, appeared to be significantly more provocative than playing this game on the 100 Hz TV (P < 0.001). Of 163 patients with a history of TV-, VG- or CG-seizures, 85% of them showed epileptiform discharges in response to photic stimulation, 44% to patterns, 59% to 50 Hz TV and 29% to 100 Hz TV. CONCLUSIONS: Children and adolescents with a history of video game seizures are, in the vast majority, photosensitive and should be investigated with standardised photic stimulation. Games and programs with bright background or flashing images are specifically provocative. Playing a video game on a 100 Hz TV is less provocative [published with videosequences].

Reflex epilepsy and reflex seizures of the visual system: a clinical review.

Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.

Genome search for susceptibility loci of common idiopathic generalised epilepsies.

Genetic factors play a major role in the aetiology of idiopathic generalised epilepsies (IGEs). The present genome scan was designed to identify susceptibility loci that predispose to a spectrum of common IGE syndromes. Our collaborative study included 130 IGE-multiplex families ascertained through a proband with either an idiopathic absence epilepsy or juvenile myoclonic epilepsy, and one or more siblings affected by an IGE trait. In total, 413 microsatellite polymorphisms were genotyped in 617 family members. Non-parametric multipoint linkage analysis, using the GeneHunter program, provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkage findings provide suggestive evidence that at least three genetic factors confer susceptibility to generalised seizures in a broad spectrum of IGE syndromes. The chromosomal segments identified harbour several genes involved in the regulation of neuronal ion influx which are plausible candidates for mutation screening.

Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects.

OBJECTIVE: To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy. METHODS: A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased. RESULTS: Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences. CONCLUSION: For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.

Video-game epilepsy: a European study.

With the introduction of Nintendo video-games on a large scale, reports of children having seizures while playing suggested a possible specific, provocative factor. Although 50% of the photosensitive patients are also sensitive to a 50-Hz television, nonphotosensitive patients with a history of video-game seizures were described as well. The question arises whether this is a mere coincidence, provoked by fatigue and stress, is related to the reaction to the television screen itself, or depends on the movement and color of the pictures of this specific game. A European study was performed in four countries and five sites. All patients were selected because of a history of television, video- or computer-game seizures, with a history of sun-light-, discotheque-, or black and white pattern-evoked seizures, or were already known to be sensitive to intermittent photic stimulation. A total of 387 patients were investigated; 220 (75%) were female and 214 (55%) of those were < 18 years of age. After a routine examination, intermittent photic, pattern, and television stimulation were performed in a standardized way. The patients were investigated with Super Mario World and a standard relatively nonprovocative TV program, both on a 50- and 100-Hz television. Regardless of the distance, Super Mario World proved to be more provocative than the standard program (Wilcoxon, p < 0.05). Eighty-five percent showed epileptiform discharges evoked by intermittent photic stimulation. Forty-five percent of patients were 50-Hz television sensitive and 26% were 100-Hz television sensitive. Pattern sensitivity was found in 28% of patients. The patients, referred because of a television, video- or computer-game seizure, were significantly more sensitive to pattern and to the 50-Hz television (chi square, p < 0.001). More patients are sensitive when playing Super Mario, compared with the standard program (Wilcoxon, p = 0.001) and more sensitive with playing versus viewing (p = 0.016). Of the patients who were referred because of seizures in front of the television, or evoked by a video- or computer game, 14% proved not to be photosensitive. Although no difference in age or use of medication was found, twice as many men were found in this nonphotosensitive group.

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.