Diffusion tensor imaging in photosensitive and nonphotosensitive juvenile myoclonic epilepsy.

INTRODUCTION/BACKGROUND: Juvenile myoclonic epilepsy (JME) syndrome is known to cause alterations in brain structure and white matter integrity. The study aimed to determine structural white matter changes in patients with JME and to reveal the differences between the photosensitive (PS) and nonphotosensitive (NPS) subgroups by diffusion tensor imaging (DTI) using the tract-based spatial statistics (TBSS) method. METHODS: This study included data from 16 PS, 15 NPS patients with JME, and 41 healthy participants. The mean fractional anisotropy (FA) values of these groups were calculated, and comparisons were made via the TBSS method over FA values in the whole-brain and 81 regions of interest (ROI) obtained from the John Hopkins University White Matter Atlas. RESULTS: In the whole-brain TBSS analysis, no significant differences in FA values were observed in pairwise comparisons of JME patient group and subgroups with healthy controls (HCs) and in comparison between JME subgroups. In ROI-based TBSS analysis, an increase in FA values of right anterior corona radiata and left corticospinal pathways was found in JME patient group compared with HC group. When comparing JME-PS patients with HCs, an FA increase was observed in the bilateral anterior corona radiata region, whereas when comparing JME-NPS patients with HCs, an FA increase was observed in bilateral corticospinal pathway. Moreover, in subgroup comparison, an increase in FA values was noted in corpus callosum genu region in JME-PS compared with JME-NPS. CONCLUSIONS: Our results support the disruption in thalamofrontal white matter integrity in JME, and subgroups and highlight the importance of using different analysis methods to show the underlying microstructural changes.

Evaluating the Potential of Light Exposure on Reducing the Frequency of Epileptic Seizures.

Epilepsy is one of the most common and devastating neurological disorders that causes unprovoked, recurrent seizures arising from excessive synchronized neuronal discharging. Although antiepileptic drugs (AEDs) reduce the frequency of epilepsy seizures, drug-refractory epileptic patients exert resistance to AEDs, resulting in treatment difficulty. Moreover, pharmacological treatments do not show satisfactory results in response to photosensitive epilepsy. In the recent era, light therapy emerged as a potential non-pharmacological approach for treating various diseases, including depression, seasonal affective disorders, migraine, pain, and others. Several studies have also shown the potential of light therapy in treating epilepsy. In addition, Red light evokes epilepsy seizures. Blue lenses filter the red light and significantly suppress the frequency of epilepsy seizures. However, the effects of green light on the frequency of epileptic seizures are not studied yet. In addition, light-activated gene therapy or optogenetics also emerged as a possible option for epilepsy treatment. Animal models have shown the therapeutic possibilities of optogenetics and light therapy; however, human studies addressing this possibility are still vague. This review provides the beneficial effects of light in reducing seizure frequency in epilepsy patients. A limited number of studies have been reported so far; therefore, light therapy for treating epilepsy requires more studies on animal models to provide precise results of light effects on seizures.

A comprehensive narrative review of epilepsy with eyelid myoclonia.

Epilepsy with eyelid myoclonia (EEM) is a generalized epilepsy syndrome with childhood-onset and 2:1 female predominance that consists of: 1. eyelid myoclonia with or without absence seizures, 2. eye closure induced seizures or EEG paroxysms, 3. clinical or EEG photosensitivity. While eyelid myoclonia is the disease hallmark, other seizure types, including absence seizures and generalized tonic-clonic seizures, may be present. It is thought to have a genetic etiology, and around one-third of patients may have a positive family history of epilepsy. Recently, specific genetic mutations have been recognized in a minority patients, including in SYNGAP1, NEXMIF, RORB, and CHD2 genes. There are no randomized controlled trials in EEM, and the management literature is largely restricted to small retrospective studies. Broad-spectrum antiseizure medications such as valproate, levetiracetam, lamotrigine, and benzodiazepines are typically used. Seizures typically persist into adulthood, and drug-resistant epilepsy is reported in over 50%.

Clinical Spectrum of Biopsy Proven Mitochondrial Myopathy.

Objectives: Clinical spectrum of mitochondrial myopathy extends beyond chronic progressive external ophthalmoplegia (CPEO). While information on encephalomyopathies is abundant, clinical data on predominant myopathic presentation of mitochondrial disorders are lacking. Materials and Methods: Clinical, electrophysiological, biochemical, and follow-up data of patients with predominant myopathic presentation and muscle biopsy confirmed primary mitochondrial myopathy was obtained. We excluded known syndromes of mitochondrial cytopathies and encephalomyopathies. Results: Among 16 patients, 7 had CPEO, 4 had CPEO with limb-girdle muscle weakness (LGMW), and 5 had isolated LGMW. Systemic features included seizures with photosensitivity (n = 3), diabetes (n = 1), cardiomyopathy (n = 1), and sensorineural hearing loss (n = 1) and were more common in isolated LGMW. Elevated serum creatine kinase (CK) and lactate levels and electromyography (EMG) myopathic potentials were more frequent with LGMW. During follow-up, LGMW had more severe progression of weakness. Conclusion: We identified three subsets of mitochondrial myopathy with distinct clinical features and evolutionary patterns. Isolated LGMW was seen in 30% of patients and would represent severe end of the spectrum.

Genetic and phenotypic spectrum of Chinese patients with epilepsy and photosensitivity.

Objective: To determine the contribution of genetic etiologies in epilepsy with photosensitivity. Methods: A total of 35 epileptic patients with genetic photosensitivity from January 2019 to May 2021 were analyzed. Results: Pathogenic variants were identified in 35 patients, including SCN1A(7) CHD2(6), TPP1(3), SYNGAP1(3), GABRA1(2), GABRG2(1), KCTD7(1), MFSD8(1), KCNC1(1) GBA(1), CACNA1A(1), KCNMA1(1), FLNA(1), SZT2(1), SLC2A1(1), 5q33.2-34del(1), and mitochondrial variants(3). The predominant epileptic syndrome was progressive myoclonus epilepsy (PME) and Dravet syndrome, while the most common seizure type in both spontaneous seizures and photoconvulsive response (PCR) was myoclonic seizures. The abnormal EEG background and brain MRI were mainly seen in the PME patients. In PME, initial low-frequencies (1-6 Hz) photosensitivity was observed in 70% (7/10) of patients. Among the other patients, 12 patients (48.0%, 12/25) had photosensitivity at initial low -frequencies and 12 patients (48.0%, 12/25) had photosensitivity at initial middle frequencies (6-20 Hz). At the 1-year follow-up, 77.7% (21/27) still remained photosensitive. Conclusion: The most common genes for epilepsy with genetic photosensitivity are SCN1A and CHD2, and the most common syndromes are PME and Dravet syndrome. MFSD8, KCNMA1, SZT2, FLNA, and SLC2A1 variants might be candidate genes for photosensitivity. PPRs at initial low-frequencies may be a marker of PME, and the most typical feature of genetic photosensitivity may be low- or middle- frequencies induced PPRs. Photosensitivity in epilepsy with genetic photosensitivity may be difficult to disappear in a short period of time.

A Computational Biomarker of Photosensitive Epilepsy from Interictal EEG.

People with photosensitive epilepsy (PSE) are prone to seizures elicited by visual stimuli. The possibility of inducing epileptiform activity in a reliable way makes PSE a useful model to understand epilepsy, with potential applications for the development of new diagnostic methods and new treatments for epilepsy. A relationship has been demonstrated between PSE and both occipital and more widespread cortical hyperexcitability using various types of stimulation. Here we aimed to test whether hyperexcitability could be inferred from resting interictal electroencephalographic (EEG) data without stimulation. We considered a cohort of 46 individuals with idiopathic generalized epilepsy who underwent EEG during intermittent photic stimulation: 26 had a photoparoxysmal response (PPR), the PPR group, and 20 did not, the non-PPR group. For each individual, we computed functional networks from the resting EEG data before stimulation. We then placed a computer model of ictogenicity into the networks and simulated the propensity of the network to generate seizures in silico [the brain network ictogenicity (BNI)]. Furthermore, we computed the node ictogenicity (NI), a measure of how much each brain region contributes to the overall ictogenic propensity. We used the BNI and NI as proxies for testing widespread and occipital hyperexcitability, respectively. We found that the BNI was not higher in the PPR group relative to the non-PPR group. However, we observed that the (right) occipital NI was significantly higher in the PPR group relative to the non-PPR group. Other regions did not have significant differences in NI values between groups.

The quantitative effect of blue lenses on pediatric photoparoxysmal response - An electroencephalographic cohort study.

PURPOSE: To determine and quantify the effect of blue lenses (Z1) on photosensitivity (PS) suppression in patients aged 5-18 years with and without epilepsy. METHODS: The retrospective cohort study was carried out in 100 pediatric patients aged 5-18 years with grade 4 PS assessed with EEG for medical indications. All EEG procedures were carried out and recordings assessed by two independent researchers. The study cohort was divided into groups with and without the diagnosis of epilepsy. The overall effect of the Z1 lenses on photoparoxysmal response (PPR) was determined by directly comparing the maximum discharge values in each patient without and with Z1 lenses in a within-subject design yielding the index of overall improvement (IOI). The differences in PS suppression by brain region and side were assessed by an additional between-subject comparison of age groups (below and above 14 years). Then, overall findings were compared with the PPR change criteria developed in 2006 by Capovilla (PPR disappearance, persistence, or attenuation) which warranted another subset analysis. Finally, in a between-subject design, we assessed whether the presence of epilepsy affects the intensity of PPR in children with PS, compared to non-epilepsy children. RESULTS: The IOI in the entire cohort was 66.1±2.5% (P<0.001). There were no significant differences in IOI between the left and right hemispheres, between the age groups, and between the epilepsy and non-epilepsy groups, despite some qualitative variation. With reference to literature findings, whereas median IOI were comparable in PPR disappearance and attenuation subsets, they differed significantly from the median IOI in the PPR persistence subset. CONCLUSION: Using Z1 lenses results in neither a complete PPR disappearance, nor a complete lack of effect. However, the correlation between the quantified PS suppression and the Z1 filter may be expected to become a valuable piece of information for both clinicians and manufacturers.

Temporal Onset Focal Seizures Induced by Intermittent Photic Stimulation.

The study aimed to review the clinical, radiological, and pathological findings and electroencephalogram (EEG) of pediatric epilepsy patients with temporal onset focal seizures induced by intermittent photic stimulation (IPS). Four patients with temporal onset photosensitivity focal seizures were analyzed. Three (75%) of the four patients were female. The average age of seizure-onset was 4.4 years. The interictal EEG showed both generalized and focal spike and waves in one patient and focal or multifocal spike and waves alone in three patients. Photoparoxysmal response (PPR) was evoked in all patients and showed generalized discharges (patients 2-4), both generalized and posterior discharges (patient 1). Both generalized and focal discharges could coexist in interictal discharges and PPR. The sensitive frequencies of PPR and photoconvulsive response (PCR) were 12-30 and 10-16 Hz, respectively, which were close to the occipital rhythm. In all patients, the onset of PCR was recorded, namely, the left anterior and mesial temporal lobe (TL), the left posterior TL, and the whole left TL, which showed two forms: the seizure of two patients was the onset of slow waves in the temporal area without spreading generalized discharges (patients 1 and 4), and the other one was fast rhythmic activities in the temporal area, spreading to the occipital area or gradually evolving into the generalized discharges (patients 2 and 3). During follow-up, except for patient 3 who had occasional seizures, the seizures of the remaining patients were under control. Temporal onset focal seizures could be induced by IPS. Temporal onset photosensitivity seizures were mostly easy to control with antiseizure drugs.

Understanding Sunflower syndrome: Results of an online questionnaire.

OBJECTIVE: To characterize the clinical phenotype, treatments, and impact on quality of life of Sunflower syndrome. METHODS: A 138-question survey was created focusing on seizure description, disease course, treatment history, medical history, family history, and aspects of quality of life of individuals with Sunflower syndrome. The survey was administered to individuals with Sunflower syndrome who experience hand waving episodes (HWE) and/or their caregivers via Research Electronic Data Capture (REDCap). RESULTS: Sixty-eight responses were included in analysis. Seventy-one% of respondents were female. The mean age of participants was 13.6 years, with 84% of respondents under the age of 18. The average age of onset of HWE was 6.7 years. HWE frequency varied from a few episodes per week to multiple episodes per hour. Sixty-two% of participants experienced other seizure types. Participants had been on an average of 1.9 anti-seizure medications with varying efficacy. Other methods to reduce HWE included wearing a hat or sunglasses, hand holding, using special tinted lenses, and avoiding the sun and bright lights. Sixty-nine% of participants reported anxiety or depression related to their epilepsy, and 65% said their HWE affected their social life. SIGNIFICANCE: Sunflower syndrome is a highly stereotyped, refractory epilepsy which significantly impacts the lives of affected individuals. It remains underrecognized and poorly understood. These results characterize Sunflower syndrome in a large population of affected individuals and provides a basis for future research to better understand the epilepsy and improve clinical care.

Prevalence of photoparoxysmal response in patients with epilepsy: Effect of the underlying syndrome and treatment status.

OBJECTIVE: To prospectively study the prevalence of photoparoxysmal response (PPR) and its determinants in epilepsy patients. METHODS: Consecutive patients, older than 2 years, undergoing EEG from January 2016 to December 2019 were prospectively studied for the presence of PPR. Patients with emergent EEG and those with only sleep record were excluded. Intermittent photic stimulation was performed as per standard techniques with frequencies from 1-30 Hz. RESULTS: Of the 1893 subjects included, 1492 (78%) patients had epilepsy while 401 (22%) had other diagnoses. In epilepsy group, 1028 (68.7%) had focal epilepsy, 343 (21.6%) had generalized epilepsy, while (9.7%) patients had unclassified epilepsy. Overall, 36 (2.2%) patients with epilepsy had PPR. The mean age of these patients was 19.5 ± 9.4 years and 75% were females. PPR was noted in 5 (0.5%) patients with focal epilepsy and 31 (9%) patients with generalized epilepsies [p < 0.0001; Odds ratio: 20.3 (95% CI, 7.8 - 52.7)]. PPR was noted in 1.5% of treated and 18% of untreated patients with genetic generalized epilepsy (n = 145) and 22% of untreated patients with juvenile myoclonic epilepsy (n = 86). Patients with untreated epilepsy had 17 times higher odds of having PPR [p < 0.0001; Odds ratio: 17.6 (95% CI, 4.1 - 75.6)]. CONCLUSION: Underlying epilepsy syndrome and treatment status are the two most important determinants of PPR. Variability in these two factors is largely responsible for the variable reported prevalence of PPR.

Understanding seizure risk with wide field fundus photography: Implications for screening guidelines in the era of COVID-19 and telemedicine.

PURPOSE: To report two cases of photosensitive seizures due to fundus photography flash. OBSERVATIONS: Two patients with seizure history present to a retina clinic for routine follow up. While obtaining imaging, these patients experienced a seizure triggered by fundus camera flash. CONCLUSIONS: Fundus photography is essential and ubiquitous amongst optometry and ophthalmology practices, especially in the rising era of telemedicine in the setting of the recent COVID-19 pandemic. To our knowledge, there are no other reports in the literature of seizures triggered by fundus photography flash. However, we believe this to be an under-reported phenomenon and suggest that all eye care providers screen patients for a history of seizures or epilepsy prior to fundus photography.

Light-emitting-diode and Grass PS 33 xenon lamp photic stimulators are equivalent in the assessment of photosensitivity: Clinical and research implications.

The assessment of the effect of photic stimulation is an integral component of an EEG exam and is especially important in patients referred for ascertained or suspected photosensitivity with or without a diagnosis of epilepsy. A positive test result relies on eliciting a specific abnormality defined as the "photoparoxysmal response". Reliability of this assessment is strongly influenced by technical and procedural variables, a critical one represented by the physical properties of the stimulators used. Established clinical norms are based on data acquired with the "gold-standard" Grass PS stimulators. These are no longer commercially available and have been replaced by stimulators using light emitting diode (LED) technology. To our knowledge no comparative study on their efficacy has been conducted. To address this gap, we recruited 39 patients aged 5-54 years, referred to two specialized centers with confirmed of suspected diagnosis of photosensitive epilepsy or generalized epilepsy with photosensitivity in a prospective randomized single-blind cross-over study to compare two commercially available LED-bases stimulation systems (FSA 10® and Lifeline® stimulators) against the Grass PS 33 xenon lamp device. Our findings indicate that the LED systems tested are equivalent to the Grass stimulator both in identifying the PPR in affected individuals.

Dynamic origin of spike and wave discharges in the brain.

Spike and wave discharges are the main electrographic characteristic of a number of epileptic brain disorders including childhood absence epilepsy and photosensitive epilepsy. The basic dynamic mechanism that underlies the occurrence of these abnormal electrical patterns in the brain is not well understood. The current paper aims to provide a dynamic explanation for features and generation mechanism of spike and wave discharges in the brain. The main proposition of this study is that epileptic seizures could be interpreted as a resonance phenomenon rather than a limit cycle behavior. To shows this, a revised version of Jansen-Rit neural mass model is employed. The system can switch between monostable and bistable regimes, which are considered in this paper as wake and sleep states of the brain, respectively. In particular, it is shown that, in monostable region, the model can depict the alpha rhythm and alpha rhythm suppression due to mental activity. Frequency responses of the model near the bistable regime demonstrate that high amplitude harmonic excitation may lead to spike and wave like oscillations. Based on the computational results and the concept of stochastic resonance, a model for absence epilepsy is presented which can simulate spontaneous transitions between ictal and interictal states. Finally, it is shown that spike and wave discharges during epileptic seizures can be explained as a resonance phenomenon in a nonlinear system.

Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants.

Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and PSE, underscoring the evolutionarily conserved role of these lipids in glial membranes. Further, we show the compromise in plasma membrane structure that underlies the glial cell membrane collapse in cpes mutants and leads to the PSE phenotype.

Parallel scheme for real-time detection of photosensitive seizures.

The production and distribution of videos and animations on gaming and self-authoring websites are booming. However, given this rise in self-authoring, there is increased concern for the health and safety of people who suffer from a neurological disorder called photosensitivity or photosensitive epilepsy. These people can suffer seizures from viewing video with hazardous content. This paper presents a spatiotemporal pattern detection algorithm that can detect hazardous content in streaming video in real time. A tool is developed for producing test videos with hazardous content, and then those test videos are used to evaluate the proposed algorithm, as well as an existing post-processing tool that is currently being used for detecting such patterns. To perform the detection in real time, the proposed algorithm was implemented on a dual core processor, using a pipelined/parallel software architecture. Results indicate that the proposed method provides better detection performance, allowing for the masking of seizure inducing patterns in real time.

Epileptic spasms and early-onset photosensitive epilepsy in Patau syndrome: An EEG study.

INTRODUCTION: Patau syndrome, trisomy 13, is the third commonest autosomal trisomy. It is associated with a 25-50% prevalence of epilepsy, but detailed electroclinical descriptions are rare. The occurrence of early-onset photosensitivity has recently been reported in single patients. MATERIALS/PATIENTS: We collected electroclinical data on 8 infants (age range from 2 months to 3 years and 9 months, median: 17 months) with Patau syndrome referred for an EEG in our Clinical Neurophysiology Department between 1991 and 2011. METHODS: All EEGs, case-notes, cytogenetic diagnosis and neuroimaging when available were reviewed; data on the occurrence of seizures, epileptiform discharges, photoparoxysmal response and their characteristics in terms of positive frequencies, latencies, grade and duration were noted and analysed. RESULTS: Two patients had been previously diagnosed with epilepsy (one with tonic spasms and one with multiple seizure types). We found 3 patients with photosensitive myoclonic epilepsy (37.5%), and one with non-photosensitive myoclonic epilepsy. We also recorded non-epileptic myoclonic jerks in one patient known to suffer from epileptic spasms. Among photosensitive patients we found self-limited, Waltz's grade 2-4, spike-wave/polyspike-wave discharges in low, medium and high frequency ranges in two patients and in the high frequency range in the third patient, with latencies and duration from less than 1s to a maximum of 9s. CONCLUSIONS: In our cohort of Patau syndrome patients, we found a high prevalence of spasms and photic-induced myoclonic jerks. Photosensitivity shows an unusual early age of onset.

A case of temporal onset partial seizure induced by photic stimuli.

There are only a few case reports of photic stimulation induced partial seizures arising from the temporal lobe. A 12-year-old female with a history of three convulsions was admitted for a diagnostic evaluation. During continuous video-electroencephalogram monitoring, a complex partial seizure with secondary generalization was induced immediately after a photoparoxysmal response with a 15-Hz photic stimulation. This is a rare case of photosensitive temporal lobe seizure.

Evidence for increased visual gamma responses in photosensitive epilepsy.

BACKGROUND: A sustained gamma (30-70 Hz) oscillation induced in occipital cortex by high-contrast visual stimulation has been well characterised in animal local field potential recordings and in healthy human participants using magnetoencephalography (MEG). The spatial frequency of a static grating stimulus that gives maximal gamma is also that most likely to provoke seizures in photosensitive epilepsy. METHODS: We used MEG to study visual responses induced by grating stimuli of varying contrast and size in twelve patients with photosensitive epilepsy and two matched control groups, one with epilepsy but no photosensitivity, the other healthy controls. We used a beamformer approach to localise cortical responses and to characterise the time-frequency dynamics of evoked and induced oscillatory responses. RESULTS: A greater number of patients with photosensitivity had particularly amplitude gamma responses compared to controls. Formal statistical testing failed to find a group difference. One photosensitive patient, tested before and after sodium valproate, had a peak gamma amplitude when drug naive over four times larger than the group mean for controls; this high amplitude was substantially decreased after treatment with sodium valproate. We found no difference in the frequency of the sustained gamma response between the three groups. DISCUSSION: Altered power, but not frequency, in induced cortical responses to a static grating stimulus may be a characteristic of photosensitive epilepsy. Our failure to find a group difference on statistical testing may have been due to a wide intersubject variability and heterogeneity of the photosensitive group. A high amplitude response would be in keeping with previous evidence of altered contrast gain and increased spatial recruitment in photosensitive epilepsy.

Impaired white-matter integrity in photosensitive epilepsy: a DTI study using tract-based spatial statistics.

BACKGROUND AND PURPOSE: The present study was designed to map alterations in brain white-matter in photosensitive epilepsy (PSE) by applying tract-based spatial statistics (TBSS) analysis. METHODS: Diffusion tensor-imaging (DTI) data from MRI brain scans were collected from eight PSE patients and 16 gender- and age-matched non-epileptic controls using a SIEMENS Trio 3.0-Tesla scanner. For the white-matter analysis, DTI scans were processed using FSL software (http://www.fmrib.ox.ac.uk/fsl/index.html). Fractional anisotropy (FA) values in the PSE and control groups were compared using TBSS analysis corrected for multiple comparisons using threshold-free cluster enhancement. RESULTS: Compared with the control subjects, the corpus callosum of PSE patients had significantly lower FA values. CONCLUSION: Our DTI study indicates that white-matter in the corpus callosum was abnormal in PSE patients, and that DTI methods can serve as useful non-invasive tools to evaluate white-matter changes in PSE patients.