Long-term clinical course and prognosis of hot water epilepsy: 15-Year follow-up.

OBJECTIVE: Hot water epilepsy (HWE) is a type of reflex epilepsy triggered by bathing with hot water. Hot water epilepsy is generally considered as a self-limiting benign disease although its long-term course and prognosis remains unknown. In this study, we aimed to determine the long-term clinical course and prognosis of hot water epilepsy and possible factors affecting them. METHODS: The diagnosis of HWE was made based on the clinical history obtained from patients and their first degree relatives witnessing to the seizures and video recordings of seizures if available; then, the type of seizure was identified. Good prognosis was defined as patients whose seizures were controlled with or without preventive measures and who did not require antiepileptic treatment. The poor prognosis was defined as patients whose seizures continued despite preventive measures and required antiepileptic treatment. RESULTS: The study included 50 (31 male and 19 female) patients with a mean follow-up of 17.63 ±â€¯10.46 (median, 15.0) years. The age at onset of seizure was 14.52 ±â€¯12.71 (median: 10.0) years. There were 38 (76%) patients in the good prognosis group. 18 (36%) of them achieved complete remission, who did not require preventive measures. In the remaining 20 (40%) patients, seizures could be controlled with only preventive measures. Seizures could be controlled with antiepileptic treatment in only 1 (2%) of 12 (24%) patients in the poor prognosis group. A significant relationship was found between the frequency of hot water seizures (HWSs) and poor prognosis (p = 0.019), as well as the presence of spontaneous seizures outside of bathing and poor prognosis (p = 0.000). SIGNIFICANCE: Hot water epilepsy, as previously known, is not a self-limiting benign disease. Approximately ¾ of the cases have a good prognosis, but the rest are in the case of chronic epilepsy. The low response rate to antiepileptics' treatment suggests that the pathogenesis of the HWE may differ from other epilepsies.

Characterizing Sunflower syndrome: a clinical series.

To characterize the clinical phenotype of Sunflower syndrome. Sunflower syndrome is a rare photosensitive epilepsy syndrome characterized by highly stereotyped seizures, photosensitivity, and heliotropism. We retrospectively reviewed the medical records of patients seen in the Massachusetts General Hospital for Children (MGHfC) pediatric epilepsy program with a history of Sunflower syndrome. Twenty-four patients were identified; 18 were female. At the time of initial MGHfC evaluation, patients' ages ranged from 6.4 to 25 years, with a median age of 11.5 years. All patients presented with hand-waving episodes (HWEs), although one patient no longer demonstrates this, but now has eye blinking episodes on exposure to light. Four have associated eye fluttering as a component of their most prevalent light-induced seizures. The average age at onset of HWEs was six years. Seventeen developed other symptoms prior to the onset of HWEs. The most prevalent symptom was an attraction to light and possible absence seizures. Light-induced seizures were generally refractory to broad-spectrum antiepileptic drugs (AEDs). Only three patients had a reduction of HWEs with the use of AEDs. Several non-pharmacological strategies reduced seizure frequency, however, efficacy varied. These non-pharmacological strategies included avoiding stimulus, focusing on other tasks, and occupying or restraining the hand that was involved in hand-waving. The use of tinted glasses reduced seizure frequency in 17 patients, however, no patient achieved seizure freedom. Twenty-two patients had available EEGs, 20 of which showed interictal epileptiform discharges. Additionally, many of the patients experienced a negative impact on their self-concept due to anxiety, depression, or negative interactions with peers. Sunflower syndrome is a generalized, pharmacoresistant epilepsy with childhood onset and remains poorly understood. To improve clinical care and scientific understanding, long-term prospective research exploring the natural history, etiology, and effective treatments for Sunflower syndrome should be conducted. [Published with video sequence].

Clinical advances in photosensitive epilepsy.

Photosensitive epilepsy is the most common subset of reflex epilepsy in humans. It is characterized by an abnormal electroencephalogram trait known as photoparoxysmal response (PPR) corresponding to ictal symptomology in response to intermittent photic stimulation. Increased exposure to photic stimulation through technological and societal advance has had a significant impact on the incidence and interest in photosensitive epilepsy. Paralleled scientific developments have deepened our understanding of the neurophysiology underlying photosensitivity, especially in the context of deep genomic sequencing and neuroimaging. Furthermore, given the relatively predictable nature of photosensitive epilepsy, there is substantial interest in translating advancements in this field to epilepsy as a whole. Herein, we comprehensively review the epidemiology, clinical features and novel insights into the mechanism behind photosensitive epilepsy with a focus on the clinical implications of new advancements.

POSSIBLE IMPLEMENTATION OF GABAERGIC AND GLUTAMATERGIC SYSTEMS IN REALIZATION OF ANTIEPILEPTIC EFFECTS OF ACOUSTIC RANGE ELECTRO - MAGNETIC FIELDS.

Seizure is a clinical manifestation of a hyperexcitable neuronal network, in which, the electrical balance underlying the normal neuronal activity is altered pathologically-excitation (Glutamatergic activity) predominates over inhibition (GABAergic activity). Arresting of seizure activity is carried out by restoration of neurotransmitter balance. This process has a direct relation with ion channel permeability in cell and ion transmembrane movement. Low frequency EMS may have a neurostimulating and neuromodulating effect that is based on electromagnetic induction of electric field in the brain. Under the conditions of certain amplitude, frequency and relaxation time low-frequency electromagnetic field (EMF) induces depolarization of separate neurons, and changes the total cortical excitability in case of repeatedly carried out procedures. It was shown that the exposure of acoustic range EMS in GEPRs treated with GABA-A or GABA-B receptors antagonists decreased behavior seizure activity in response to audiogenic stimuli. Injection of Glutamate receptor agonist on background EMS causes seizure activity, but seizure manifestations have less degree compared to non-stimulated rats. Thus, in response to electromagnetic stimulation, the reduction or complete cramping of seizures can be explained by a change in the activity of the neurotransmitter systems.

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.

Tap seizures in infancy: A critical review.

Tap seizure is a type of reflex myoclonic epilepsy in which seizures are evoked mainly by unexpected tactile stimuli and which is classified among the electroclinical syndromes of infancy. This condition, whose onset is in the first two years of life, is characterized by excellent prognosis and is extremely rare. We reviewed all published articles and case reports on Reflex Myoclonic Epilepsies focusing on touch-induced seizures in order to clarify clinical and electroencephalographic findings. Our aim is to increase knowledge about this specific disorder in order to help pediatricians avoid extensive investigations when making their diagnosis and reassure parents regarding absence of long-term complications.

Clinical and electrographic features of sunflower syndrome.

BACKGROUND: Sunflower Syndrome describes reflex seizures - typically eyelid myoclonia with or without absence seizures - triggered when patients wave their hands in front of the sun. While valproate has been recognized as the best treatment for photosensitive epilepsy, many clinicians now initially treat with newer medications; the efficacy of these medications in Sunflower Syndrome has not been investigated. We reviewed all cases of Sunflower Syndrome seen at our institution over 15 years to describe the clinical course, electroencephalogram (EEG), and treatment response in these patients. METHODS: Search of the electronic medical record and EEG database, as well as survey of epilepsy providers at our institution, yielded 13 cases of Sunflower Syndrome between 2002 and 2017. We reviewed the records and EEG tracings. RESULTS: Patients were mostly young females, with an average age of onset of 5.5 years. Seven had intellectual, attentional or academic problems. Self-induced seizures were predominantly eyelid myoclonia ±â€¯absences and 6 subjects also had spontaneous seizures. EEG demonstrated a normal background with 3-4 Hz spike waves ±â€¯polyspike waves as well as a photoparoxysmal response. Based on both clinical and EEG response, valproate was the most effective treatment for reducing or eliminating seizures and improving the EEG; 9 patients tried valproate and 66% had significant improvement or resolution of seizures. None of the nine patients on levetiracetam or seven patients on lamotrigine monotherapy achieved seizure control, though three patients had improvement with polypharmacy. CONCLUSIONS: Valproate monotherapy continues to be the most effective treatment for Sunflower Syndrome and should be considered early. For patients who cannot tolerate valproate, higher doses of lamotrigine or polypharmacy should be considered. Levetiracetam monotherapy, even at high doses, is unlikely to be effective.

Electroclinical and prognostic characteristics of epilepsy patients with photosensitivity.

BACKGROUND AND PURPOSE: Epilepsy with photosensitivity (PSE) is one of the reflex epilepsy types with pathophysiology still unexplained. In our study we aimed to evaluate the clinical, electroencephalogram (EEG) and prognosis of patients with PSE diagnosis. METHODS: A total of 44 patients with PSE diagnosis according to international classification were included in this retrospective and cross-sectional study. The age, gender, syndrome, clinical and EEG characteristics of patients, and treatment response were investigated. RESULTS: The mean age was 22.09±6.49 years for 28 females and 16 males included in the study. Of patients, 17 had idiopathic photosensitive occipital lobe epilepsy (IPOLE), 11 had juvenile myoclonic epilepsy (JME), 11 had other PSE and 5 had juvenile absence epilepsy (JAE), with the most common visual trigger factors television and sunlight. In terms of seizure type, the most common was generalized tonic clonic seizure (GTCS), with myoclonus, absence and other seizure types observed. There was family history present in 17 patients and valproic acid was most commonly used for treatment. CONCLUSION: As noted in the literature, our data show that PSE has defined age group and clinical presentation, good prognosis but requires correct choice of medication for treatment. It is thought that good description of these epilepsy types will reduce misdiagnosis and mistreatment rates.

Remote effects of short-term neonatal hyperthermia in Krushinsky-Molodkina rats prone to audiogenic seizures strain.

Using the audiogenic seizure prone Krushinsky-Molodkina rat strain, it was demonstrated that short-term (5 min) exposure of 14-day-old pups to an elevated temperature (42°C) resulted in a significant decrease in audiogenic seizure severity at the age of 1 month. Presumably, this effect is determined by the activation of the heat-shock protein system (stress proteins).

Epilepsy and music: practical notes.

Music processing occurs via a complex network of activity far beyond the auditory cortices. This network may become sensitised to music or may be recruited as part of a temporal lobe seizure, manifesting as either musicogenic epilepsy or ictal musical phenomena. The idea that sound waves may directly affect brain waves has led researchers to explore music as therapy for epilepsy. There is limited and low quality evidence of an antiepileptic effect with the Mozart Sonata K.448. We do not have a pathophysiological explanation for the apparent dichotomous effect of music on seizures. However, clinicians should consider musicality when treating patients with antiepileptic medication or preparing patients for epilepsy surgery. Carbamazepine and oxcarbazepine each may cause a reversible altered appreciation of pitch. Surgical cohort studies suggest that musical memory and perception may be affected, particularly following right temporal lobe surgery, and discussion of this risk should form part of presurgical counselling.

Orofacial reflex myocloni. Definition, relation to epilepsy syndromes, nosological and prognosis significance. A focused review.

PURPOSE: There is increasing awareness that reflex epileptic mechanisms provide unique insight into ictogenesis in human epilepsies. Among the complex triggers of seizures, this review considers orofacial reflex myocloni (ORM) from the aspects of history and delineation, clinical and electroencephalographic presentation, syndromatic relations, prevalence, mechanisms of ictogenesis and nosological implications, treatment and prognosis. METHODS: We reviewed all published articles and case reports on ORM in order to clarify clinical and electroencephalographic findings, treatment and outcome. RESULTS: ORM, besides Reading Epilepsy (RE), is closely related to idiopathic generalized epilepsies especially Juvenile Myoclonic Epilepsy (JME) where hyperexcitability of the network supporting linguistic communication seems to provide the precondition for eliciting reflex myocloni in the perioral muscles active in the precipitating task. CONCLUSION: The conclusions on ictogenesis derived from ORM support the concept of both, RE and JME, as system disorders of the brain.

How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?

PURPOSE: Human photosensitive epilepsy models have been used as proof of principle (POP) trials for epilepsy. Photosensitive patients are exposed to intermittent photic stimulation and the reduction in sensitivity to the number of standard visual stimulation frequencies is used as an endpoint. The aim of this research was to quantify the predictive capabilities of photosensitive POP trials, through a survey of current literature. METHODS: A literature search was undertaken to identify articles describing photosensitive POP trials. Minimally efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials that produced 50-100% response (ED50-100). Ratios of these doses were calculated and summarised statistically. RESULTS: The search identified ten articles describing a total of 17 anti-epileptic drugs. Of these, data for both MED and ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios between partial epilepsy (0.82) was not significantly different from that of generalised epilepsy (1.08) (p=0.51). CONCLUSION: Photosensitive POP trials are a useful tool to quantitatively predict efficacy in epilepsy, and can be useful as early and informative indicators in anti-epileptic drug discovery and development.

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].

Reflex seizures in Rett syndrome.

Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.