[Self-induced epileptic seizures: Prevalence, Causes and Treatment]. / Selbstinduzierte epileptische Anfälle Prävalenz, Ursachen und Behandlung.

Self-induced seizures were first described in 1827. A majority of authors found that in unselected patients with epilepsy, the prevalence rate of these seizures was 1%. In patients with photosensitive epilepsy, there was roughly a 25% prevalence. Apart from visual stimulation, many other mechanisms of self-induction have been described. A feeling of pleasure or relaxation during seizures may be a reason for self-inductive behaviour. But often the procedure of self-induction is experienced as involuntary. Treatment is always difficult. Behavioral therapy has been proven effective in some patients. In patients with photosensitive epilepsy, sunglasses are recommended. Fenfluramine, clonazepam and valproate seem to be a bit more effective than other drugs. After all, the treatment effect depends on the motivation of the patient to change the condition.

Musicogenic reflex seizures in epilepsy with glutamic acid decarbocylase antibodies.

BACKGROUND: Musicogenic reflex seizures (MRS) are a rare form of seizures described in patients with temporal lobe epilepsy (TLE), mainly of unknown etiology. Epilepsy with antibodies against glutamic acid decarboxylase (GAD-ab) is a form of autoimmune epilepsy for which no specific semiology has been described. AIM OF THE STUDY: To retrospectively review the incidence of MRS in the general epileptic population and in the series of patients with epilepsy and GAD-ab and to describe its clinical and paraclinical characteristics. METHODS: Patients recorded between January 2010 and January 2016 in the Database of Bellvitge Hospital Epilepsy Unit were reviewed. RESULTS: From a group of 1510 epileptic patients, three reported MRS (0.0019%) (two patients with epilepsy and GAD-ab and one patient with cryptogenic TLE). The incidence of MRS in patients with epilepsy and GAD-ab was 2 of 22 (9%). Both patients had a normal magnetic resonance Imaging (MRI), but FDG-PET showed medial temporal lobe hypometabolism (unilateral or bilateral) in both and also in the insula in one of them. MRS (recorded via video-EEG[electroencephalography] in one patient) arose from the right temporal lobe. CONCLUSIONS: MRS may be a distinctive seizure type in patients with epilepsy and antiGADab. Determination of GAD-ab should be carried out in all cases of MRS, even those with normal structural MRI.

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.

Provoked and reflex seizures: surprising or common?

Most patients with epilepsy report that seizures are sometimes, or exclusively, provoked by general internal precipitants (such as stress, fatigue, fever, sleep, and menstrual cycle) and by external precipitants (such as excess alcohol, heat, bathing, eating, reading, and flashing lights). Some patients describe very exotic and precise triggers, like tooth brushing or listening to a particular melody. Nevertheless, the most commonly noticed seizure increasers by far are stress, lack of sleep, and fatigue. Recognized reflex seizure triggers are usually sensory and visual, such as television, discotheques, and video games. Visually evoked seizures comprise 5% of the total of 6% reflex seizures. The distinction between provocative and reflex factors and seizures seems artificial, and in many patients, maybe all, there is a combination of these. It seems plausible that all of the above-mentioned factors can misbalance the actual brain network; at times, accumulation of factors leads then to primary generalized, partial, or secondarily generalized seizures. If the provoking factors are too exotic, patients may be sent to the psychiatrist. Conversely, if the seizure-provoking fluctuating mechanisms include common habits and environmental factors, these may hardly be considered as provocative factors. Awareness of precipitating factors and its possible interactions might help us to unravel the pathophysiology of epilepsy and to change the notion that seizure occurrence is unpredictable. This article provides an overview of the epidemiology, classification, diagnosis, treatment, and especially similarities in the variety of provocative and reflex factors with resulting general hypotheses.

Photosensitivity: epidemiology, genetics, clinical manifestations, assessment, and management.

Photosensitivity is a genetically determined trait that may be asymptomatic throughout life or manifest with epileptic seizures. Photosensitivity usually begins before the age of 20 years with a peak age at onset at around 12. Both natural and artificial light may trigger seizures. Precise investigation must be carried out by intermittent photic stimulation that can elicit a clearly defined EEG response; video-EEG samples are reported to illustrate the various determinants of response and the main factors altering the effectiveness of intermittent photic stimulation. Management of photosensitive epilepsy includes non-pharmacological (e.g. avoidance of the provocative stimuli and wearing appropriate tinted glass) and pharmacological treatment. This review focuses on the emerging aspects of photosensitivity, in particular, the new guidelines for intermittent photic stimulation and briefly addresses epidemiological (in non-epileptic and epileptic subjects), genetic, diagnostic, and therapeutic issues. [Published with video sequences].

Bitemporal form of partial reading epilepsy: further evidence for an idiopathic localization-related syndrome.

Idiopathic partial reading epilepsy (RE) is a rare syndrome. We report the clinical and electroencephalographic characteristics of two right-handed patients with the following: reading-induced independent bilateral temporal lobe seizures, accompanied by alexia in left (dominant) sided seizures recorded on video-EEG (electroencephalography); subclinical activation over left posterior temporal and occipital electrodes during reading; no spontaneous seizure and no other trigger than reading; onset in adolescence; and history of varying resistance to treatment. Bilateral independent temporal lobe reflex seizures are part of the clinical spectrum of RE. It may result from hyperexcitability of bilateral cortical networks involved in the early steps of the reading process.

Stimulus-induced seizure in sick neonates--novel observations with potential clinical implications.

Stimulus-induced seizure is a well-described entity in children and adults and is often associated with severe epilepsy and neurologic impairment. The occurrence and clinical expression of stimulus-induced seizure in three sick neonates is described. The cohort comprised 26 neonates undergoing continuous video-electroencephalography (vEEG) monitoring between July and December 2007. Three cases (11.5%) of stimulus-induced seizure were identified. The underlying injury included stroke (n = 2) and intraventricular hemorrhage (n = 1). Seizures were induced by physical stimuli such as stroking the forehead, movements, (i.e., starting to feed), and one during endotracheal suctioning. Stimulus-evoked electrographic patterns have been reported in neonates with brain injury; however, these events appear to be more common than previously thought, especially with the abundance of subclinical seizures observed in these patients. These observations stress the usefulness of vEEG monitoring and importance of care to avoid unnecessary stimuli in at-risk neonates.

Headache, epilepsy and photosensitivity: how are they connected?

Although headache and epilepsy have often been associated, the precise electroclinical and pathophysiological interaction between these disorders and in particular its relations with photosensitivity is as yet to be fully understood in adults or children. The association between headache and epilepsy commonly occurs in all types of epilepsy and not only in occipital epilepsy. Generally, peri-ictal headache is often neglected, regardless of its severity, because patients are more concerned about their seizures. Altered cerebral cortex excitability may be the link between these two conditions and photosensitivity shows this. The physician should bear this association in mind when dealing with epileptic and migraine patients so as to be able to offer such patients an accurate diagnosis and appropriate treatment; this should be borne in mind when declaring epileptic patients 'seizure free'. To date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may, on occasion, be the sole ictal epileptic manifestation. Lastly, studies designed to investigate the triggering role of photosensitivity in both headache and epilepsy are warranted.

Comorbidity between headache and epilepsy in a pediatric headache center.

The purpose of this study was to analyse the comorbidity between headache and epilepsy in a large series of children with headache (1,795). Fifty-six cases (3.1%) suffered from idiopathic headache and idiopathic or cryptogenic epilepsy or unprovoked seizures. There was a strong association between migraine and epilepsy: in migraineurs (46/56) the risk of epilepsy was 3.2 times higher when compared with tension-type headache, without significant difference between migraine with and without aura (P = 0.89); children with epilepsy had a 4.5-fold increased risk of developing migraine than tension-type headache. In cases with comorbidity, focal epilepsies prevailed (43/56, 76.8%). Migraineurs affected by focal epilepsies (36/56) had a three times higher risk of having a cryptogenic epilepsy (27/36, 75%) than an idiopathic epilepsy (9/36, 25%) (P = 0.003). In migraine with aura, epilepsy preceded migraine in 71% of cases. Photosensitivity (7/56, 12.5%) and positive family history for epilepsy (22/56, 39%) were frequent in cases with comorbidity.

Reflex epileptic features in patients with focal epilepsy of unknown cause.

OBJECTIVES: There is a gap of knowledge regarding reflex seizures in patients with focal epilepsy of unknown cause (FEUC). We aimed to evaluate the prevalence, demographic and clinical characteristics of reflex seizures in patients with FEUC to provide an insight to the underlying ictogenic mechanisms and to draw attention to this important but under-investigated topic. PATIENTS AND METHODS: After carefully questioning for reflex triggers, 186 patients diagnosed according to ILAE criteria and followed-up for a minimum of 5 years were included. The demographic and clinical properties as well as electrophysiological and neuroimaging data of these patients were reevaluated and compared to the patients without reflex seizures. RESULTS: The reflex seizure rate was 6.5 % in patients with FEUC. Patients with reflex features had lower monotherapy rates (p = 0.005) and higher major depression rates (p = 0.001) than patients without reflex features. The distribution of the patients according to their reflex triggers were as follows: hot-water induced (n = 3, 25 %), photosensitive (n = 2, 16.7 %), eating- induced (n = 2, 16.7 %), musicogenic (n = 2, 16.7 %), startle induced (n = 2, 16.7 %) and both musicogenic and startle type (n = 1, 8.3 %) respectively. The drug resistance rate of patients with reflex seizures was 25 % (n = 3). One patient with drug resistant reflex seizures showed benefit from epilepsy surgery and became seizure-free during last 3 years of follow-up. CONCLUSION: A careful and thoroughly history taking specifically questioning and focusing on seizure inducing factors in patients with FEUC is needed to confirm the presence of reflex seizures in patients with FEUC, who had higher rates of polytherapy and major depression. Elaborative evaluation of reflex features in FEUC might contribute to effective seizure control, ensure new therapeutic approaches, enlighten the obscurity and the resulting anxiety of having a diagnosis of FEUC in epilepsy patients.

Analysis of gene variants in the GASH/Sal model of epilepsy.

Epilepsy is a complex neurological disorder characterized by sudden and recurrent seizures, which are caused by various factors, including genetic abnormalities. Several animal models of epilepsy mimic the different symptoms of this disorder. In particular, the genetic audiogenic seizure hamster from Salamanca (GASH/Sal) animals exhibit sound-induced seizures similar to the generalized tonic seizures observed in epileptic patients. However, the genetic alterations underlying the audiogenic seizure susceptibility of the GASH/Sal model remain unknown. In addition, gene variations in the GASH/Sal might have a close resemblance with those described in humans with epilepsy, which is a prerequisite for any new preclinical studies that target genetic abnormalities. Here, we performed whole exome sequencing (WES) in GASH/Sal animals and their corresponding controls to identify and characterize the mutational landscape of the GASH/Sal strain. After filtering the results, moderate- and high-impact variants were validated by Sanger sequencing, assessing the possible impact of the mutations by "in silico" reconstruction of the encoded proteins and analyzing their corresponding biological pathways. Lastly, we quantified gene expression levels by RT-qPCR. In the GASH/Sal model, WES showed the presence of 342 variations, in which 21 were classified as high-impact mutations. After a full bioinformatics analysis to highlight the high quality and reliable variants, the presence of 3 high-impact and 15 moderate-impact variants were identified. Gene expression analysis of the high-impact variants of Asb14 (ankyrin repeat and SOCS Box Containing 14), Msh3 (MutS Homolog 3) and Arhgef38 (Rho Guanine Nucleotide Exchange Factor 38) genes showed a higher expression in the GASH/Sal than in control hamsters. In silico analysis of the functional consequences indicated that those mutations in the three encoded proteins would have severe functional alterations. By functional analysis of the variants, we detected 44 significantly enriched pathways, including the glutamatergic synapse pathway. The data show three high-impact mutations with a major impact on the function of the proteins encoded by these genes, although no mutation in these three genes has been associated with some type of epilepsy until now. Furthermore, GASH/Sal animals also showed gene variants associated with different types of epilepsy that has been extensively documented, as well as mutations in other genes that encode proteins with functions related to neuronal excitability, which could be implied in the phenotype of the GASH/Sal. Our findings provide valuable genetic and biological pathway data associated to the genetic burden of the audiogenic seizure susceptibility and reinforce the need to validate the role of each key mutation in the phenotype of the GASH/Sal model.

A locus for autosomal dominant reflex epilepsy precipitated by hot water maps at chromosome 10q21.3-q22.3.

Hot water epilepsy (HWE) is a form of reflex or sensory epilepsy wherein seizures are precipitated by an unusual stimulus, the contact of hot water over the head and body. Genome-wide linkage analysis of a large family with ten affected members, provided evidence of linkage (Z (max) = 3.17 at theta = 0 for D10S412) to chromosome 10q21. Analysis of five additional HWE families, for markers on chromosome 10, further strengthened the evidence of linkage to the same chromosomal region with three out of five families showing concordance for the disease haplotype and providing a two-point LOD score of 4.86 at theta = 0 and 60% penetrance for D10S412. The centromere-proximal and -distal boundaries of the critical genetic interval of about 15 Mb at 10q21.3-q22.3 were defined by D10S581 and D10S201, respectively. Sequence analysis of a group of functional candidate genes, the ion channels KCNMA1, VDAC2 and solute carriers SLC25A16, SLC29A3 revealed no potentially pathogenic mutation. We propose to carry out further analysis of positional candidate genes from this region to identify the gene responsible for this unusual neurobehavioral phenotype.

Photosensitive epilepsy and photosensitivity of patients with possible epilepsy in Chinese Han race: A prospective multicenter study.

Photosensitive is probably caused by multiple factors including gender, familiar, etc. We aim to study the clinical and EEG features of Chinese Han patients with photosensitivity. A total of 5482 consecutive patients with possible epilepsy from 3 center in China. Of the 73 patients with PPR to IPS, 48 were female. 69.9% patients were evoked by frequency ranged 8 Hz-25 Hz, with accompanying seizures in 13 patients. 6 of 9 patients with eyes closure sensitivity experienced epileptic seizures during IPS. We found some new features: 1) The patients with eyes closure sensitivity apt to experience electro-clinical seizures provoked by IPS; 2) Female epilepsy patients with PPR and ECS maybe difficult to be seizure free. Preventive measures for related seizures should be performed to the patients with generalized PPR, upper threshold evoking frequency, and eyes closure sensitivity when they received the IPS.

Photosensitivity in epileptic syndromes of childhood and adolescence.

PURPOSE: Photosensitivity, a reaction of the brain to external photic stimulation, can be graded from 1 to 4, and is most frequently seen in the first decades of life. This study investigated photosensitivity in children with epilepsy. METHODS: A retrospective study performed in the neuropaediatric department of the largest paediatric hospital in Kiel, treating patients at all medical care levels. The clinical data and EEG records of 566 patients with the most common epileptic syndromes were analyzed, in particular regarding photosensitivity. Their EEGs included application of intermittent light stimulation using standard techniques at twice the minimum. RESULTS: The proportion of photosensitive patients was significantly higher in the paediatric cohort than in adult patients, as published in the literature: 46% of patients with generalized epilepsies showed photosensitivity as compared to 20% with focal epilepsies. Photosensitivity was more common in idiopathic generalized epilepsy (IGE), (epilepsy with grand mal on awakening, 74%; juvenile absence epilepsy, 56%; juvenile myoclonic epilepsy, 50%; childhood absence epilepsy, 44%) than in focal types (idiopathic partial - Rolandic epilepsy, 23%; symptomatic/cryptogenic type of epilepsy, 16%), while in patients who experienced occasional seizures (neonatal/febrile seizures), this ranged between 40% and 23%, respectively. The generalized photoparoxysmal response, (PPR), grades 3 and 4 were found significantly more often in patients with IGE (92%) than in patients with focal epilepsies. Finally, the female preponderance was confirmed (37% to 27% of all epilepsies). CONCLUSIONS: Photosensitivity can be detected both in patients with IGE, with idiopathic and symptomatic/cryptogenic types of focal epilepsies, and with epileptic (occasional) seizures. PPR grades 3 and 4 are the most common in IGE.

A descriptive analysis of seizure events among adults who participated in a computer-based assessment.

The purpose of this study was to document seizure events associated with the use of a computer-based assessment and to describe the contextual factors surrounding these seizure episodes. Study participants were adults with epilepsy who were enrolled at research sites in Atlanta and Boston. Subjects were asked to complete a computer-based assessment at 3 time points. Fourteen seizure events were documented; they occurred during 1.6% of all completed assessments (896) and affected 4.4% of the participants (320). The mean age of participants who experienced seizure events was 41.4 years; about 70% were female, and 70% were white. A variety of possible precipitating factors for seizure events included hunger, fatigue, stress, and medication changes. Participants indicated computer use could have triggered their seizures in 2 instances. These findings suggest use of computer-based assessments may pose minimal risks for adults with epilepsy, particularly those without a history of photosensitivity epilepsy.

Jeavons Syndrome: Clinical Features and Response to Treatment.

BACKGROUND: Jeavons syndrome is an underreported epileptic syndrome characterized by eyelid myoclonia, eyelid closure-induced seizures or electroencephalography paroxysms, and photosensitivity. Drug-resistant epilepsy is common, but the prognostic factors and clinical course leading to drug resistance have not been well characterized. METHODS: We identified 30 patients who met the diagnostic criteria of Jeavons syndrome at a single institution between January 1, 2000 and December 15, 2016. Criteria for Jeavons syndrome included all of the following: (1) eyelid myoclonia with or without absences, (2) eye-closure-induced seizures or electroencephalography paroxysms, and (3) seizure onset after 12 months of age. We reviewed and described the epilepsy history, antiepileptic drug trials, and response to treatments. RESULTS: Mean age at seizure onset was 7.3 years, and 80% were female. Absence seizures (63%) and generalized tonic-clonic seizures (23%) were most common at onset. Diagnosis was delayed by an average of 9.6 years. After a median follow-up of two years, 80% of patients had drug resistant epilepsy and 70% experienced generalized tonic-clonic seizures. Generalized tonic-clonic seizures and seizure types other than absence seizures increased the risk of drug-resistant epilepsy (P values 0.049 and 0.03, respectively). Valproic acid, lamotrigine, ethosuximide, and levetiracetam were the most effective in reducing seizures by more than 50%. CONCLUSIONS: The diagnosis of Jeavons syndrome is often delayed. Generalized tonic-clonic seizures and seizure types other than absence seizures may be predictors of drug-resistant epilepsy among patients with Jeavons syndrome.

Photosensitivity in Dravet syndrome is under-recognized and related to prognosis.

OBJECTIVE: To detect determinants for photoparoxysmal EEG response (PPR) in SCN1A-related Dravet syndrome (DS). METHODS: Data were studied from nationwide medical histories and EEGs of DS-patients (n=53; 31 males, age 2-19years). Detailed questionnaires on visual stimuli were completed by parents (n=49). RESULTS: PPR was found in 22 patients (42%; median age 1.25yr), and repeatedly in 17%. PPR (17% of 249 intermittent photic stimulation (IPS)-EEGs) occurred more often with optimal IPS protocols (OR 2.11 [95%CI 1.09-4.13]) and in EEGs showing spontaneous epileptiform abnormalities (OR 5.08 [95%CI 2.05-12.55]). PPR-positive patients tended to be younger at first (p=0.072) and second seizure (p=0.049), showed severe intellectual disability (p=0.042), and had more often spontaneous occipital epileptiform abnormalities (p<0.001). Clinical sensitivity was reported in medical files in 22% of patients and by parents in 43% (self-induction 24%). Clinical or EEG proven visual sensitivity was detected in 65% of cases. CONCLUSIONS: Sensitivity to visual stimuli is very common in DS and more often noticed by parents than confirmed by EEG. Detection of PPR improves with repetitive tests using accurate IPS protocols. SIGNIFICANCE: Photosensitivity is an important feature in DS and seems to be a marker of the severity of the disorder. Therefore repeated standardized IPS should be encouraged.

Reflex epilepsies; clinical and demographic characteristics in a tropical country.

BACKGROUND: This study is aimed at defining the clinical spectrum and demographic aspects of reflex epilepsy in a tropical country in Asia. METHODS: We studied 526 consecutive patients with epilepsy. Details of seizure provoking factors were obtained from direct interviews and medical records. RESULTS: Of the 526 patients, 47(8.9%) were found to be having reflex epilepsy. There were 25(53.2%) males and 22(46.8%) females. Family history of epilepsy and reflex epilepsy were found in 8(17%) and 3(6.4%) respectively. Provoking factors were, eating (34%), higher cerebral functions (17%), bathing (10.6%), photosensitivity (8.5%), startle induced (4.3%), and mixed (more than one of the above: 25.5%). Seizures were provoked by above factors, exclusively in 10 (21.3%), mostly (more than 50% occasions) in 10 (21.3%), and sometimes (less than 50% occasions) in 27 (57.4%) patients. The type of seizure was complex partial evolving to generalized in 23 (48.9%), complex partial in 10 (21.3%), and generalized in 14 (29.8%). CONCLUSION: Our study highlights geographical differences in the spectrum of reflex epilepsy.

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.