Chronic Refractory Epilepsy Research Articles

Long-term epilepsy associated-tumors (LEATs): what is new?

Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.

Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy

Background and aimsRefractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa mesenchymal stem cells (OM-MSCs) are considered a preferable MSC source for clinical application. This study aims to investigate whether OM-MSCs are a promising alternative source for treating refractory epilepsy clinically and uncover the mechanism by OM-MSCs administration on an epileptic mouse model.MethodsOM-MSCs were isolated from turbinal and characterized by flow cytometry. Autologous human OM-MSCs treatment on a patient was carried out using intrathecal administration. Epileptic mouse model was established by 1 mg/kg scopolamine and 300 mg/kg pilocarpine treatment (intraperitoneal). Stereotaxic microinjection was employed to deliver the mouse OM-MSCs. Mouse electroencephalograph recording was used to investigate the seizures. Brain structure was evaluated by magnetic resonance imaging (MRI). Immunohistochemical and immunofluorescent staining of GFAP, IBA1, MAP2, TUBB3, OLIG2, CD4, CD25, and FOXP3 was carried out to investigate the neural cells and Treg cells. QRT-PCR and ELISA were performed to determine the cytokines (Il1b, Il6, Tnf, Il10) on mRNA and protein level. Y-maze, the object location test, and novel object recognition test were performed to measure the cognitive function. Footprint test, rotarod test, balance beam test, and grip strength test were conducted to evaluate the locomotive function. Von Frey testing was carried out to assess the mechanical allodynia.ResultsMany beneficial effects of the OM-MSC treatment on disease status, including seizure type, frequency, severity, duration, and cognitive function, and no apparent adverse effects were observed at the 8-year follow-up case. Brain MRI indicated that autologous OM-MSC treatment alleviated brain atrophy in epilepsy patients. A study in an epileptic mouse model revealed that OM-MSC treatment recruited Treg cells to the brain, inhibited inflammation, rebuilt the neural network, and improved the cognitive, locomotive, and perceptive functions of epileptic mice.ConclusionsAutologous OM-MSC treatment is efficacious for improving chronic refractory epilepsy, suggesting a future therapeutic candidate for epilepsy.Trial registration: The study was registered with Chinese Clinical Trial Registry (ChiCTR2200055357).

Pharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs.

In the last few years, different formulations containing cannabidiol (CBD) were tested with regard to its efficacy on chronic pain, refractory epilepsy, anxiety, aggressive behavior and atopic dermatitis in dogs. CBD is generally administered orally, but its low bioavailability, probably due to a first-pass metabolism, represents a great limitation. The aim of this study was to evaluate if CBD bioavailability increases after oral transmucosal administration (OTM) compared to oral treatment. Twelve dogs diagnosed with mild chronic pain were enrolled in the study and treated once orally or OTM (6 dogs/group) with a pure CBD in oil formulation at a dosing rate of 1 mg/kg b.w. At prefixed time points, blood samples were collected to define CBD plasma concentrations vs. time profiles, and the main pharmacokinetics parameters were obtained by non-compartmental model. CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively. No significant difference in pharmacokinetic parameters were observed between treatments. The OTM administration did not increase cannabidiol bioavailability compared to oral treatment. The almost perfectly superimposable mean plasma concentrations of cannabidiol following the two treatments suggests that CBD is not able to be adsorbed by the oral mucosa or that its absorption is very scarce, and that CBD is swallowed and absorbed in the gastrointestinal tract.

Проблемы диагностики аутоиммунной эпилепсии

Objective of the Review: To analyse and systematise knowledge in the problems with autoimmune epilepsy diagnostics. Main part. Clinical phenotypes of immune-mediated epilepsy depend on various types of antibodies. However, autoimmune epilepsy is diagnosed also in patients who are followed up for chronic refractory unexplained epilepsy, especially in initial epileptic status and late onset epilepsy without structural changes on brain imaging. Brain imaging changes may not be observed, especially in early disease. Very often a diagnostic challenge in autoimmune epilepsy is the difference between epileptic seizures and behavioural symptoms and the mental changes caused by involvement of limbic brain structures. An important role in detection of seizures and differential diagnosis is played by video-EEG-monitoring, which allows identifying the true number of seizures, epileptiform activity between seizures, behavioural changes not related to paroxysmal activity of cortical neurons. Any specific EEG signs for differentiation between various types of autoimmune epilepsy have not been found yet. Still, EEG can provide patterns that are unique for certain forms of autoimmune encephalitis. Conclusion. Video-EEG-monitoring significantly contributes to autoimmune epilepsy diagnostics, and some changes can be used as markers of disease severity. It is very important, especially in patients with impairment of consciousness, where identification of the clinical status and response to therapy is challenging. Keywords: autoimmune epilepsy, video-EEG-monitoring, epilepsy diagnostics

QT INTERVAL IN TEMPORAL LOBE EPILEPSY VERSUS NON TEMPORAL LOBE EPILEPSY

Abstract Introduction Background SUDEP is leading cause of mortality in patients with chronic refractory epilepsy. Despite several epidemiological studies, case series , monitored and witnessed SUDEP the exact mechanism is not proposed Objective This work was carried out to assess QT interval prolongation in epilepsy and whether there’s a difference in QT interval prolongation between temporal epilepsy and non-temporal epilepsy. Patients and methods This study was conducted on 100 patients, 50 aged and sex matched healthy controls who underwent a prolonged (6 to 24 hours) 22 channel computerized EEG monitor with 10-20 system electrode placement and 12 lead electrocardiogram (25 millisecond speed). QT, QTd and QTc using Bazzet’s formulae were calculated. Results The results showed statistically significant difference prolongation of QT interval in epilepsy particularly temporal lobe epilepsy. Conclusion Significant prolongation of QT interval in epilepsy patients (11% suffered pathological prolonged QT). Marked prolongation of QTc and QTd in temporal lobe epilepsy over non temporal group.

Vagus nerve stimulation in chronic refractory epilepsy: chasing the cardiologist

Epilepsy the second most common chronic neurological disorder after stroke affect 0.5-2% population worldwide. Antiepileptic drugs though remain the corner stone in management of epilepsy in majority of patients but still 30% of patients continues to have seizure or experience unacceptable pharmacological side effect. Electrical stimulation of vagus nerve is an effective and promising neurophysiological treatment for patients with refractory epilepsy who are either unsuitable candidate of surgery or falls in category of surgically refractory epilepsy.

Intraperitoneal injection of lipopolysaccharide prevents seizure-induced respiratory arrest in a DBA/1 mouse model of SUDEP.

ObjectiveSudden unexpected death in epilepsy (SUDEP) is the cause of premature death of 50% patients with chronic refractory epilepsy. Respiratory failure during seizures is regarded as an important mechanism of SUDEP. Previous studies have shown that abnormal serotonergic neurotransmission is involved in the pathogenesis of seizure‐induced respiratory failure, while enhancing serotonergic neurotransmission in the brainstem suppresses it. Because peripheral inflammation is known to enhance serotonergic neuron activation and 5‐HT synthesis and release, we investigated the effect of intraperitoneal lipopolysaccharide (LPS)‐induced inflammation on the S‐IRA susceptibility during audiogenic seizures in DBA/1 mice.MethodsAfter DBA/1 mice were primed by exposing to sound stimulation for three consecutive days, they were tested for seizure severity and seizure‐induced respiratory arrest (S‐IRA) induced by sound stimulation under different conditions. We determined the dose and time course of the effects of intraperitoneal administration of LPS on audiogenic seizures and S‐IRA. The effects of blocking TLR4 or RAGE receptors and blocking 5‐HT receptors on the LPS‐induced effect on S‐IRA were investigated. Statistical significance was evaluated using the Kruskal‐Wallis test.ResultsIntraperitoneal injection of LPS significantly had dose‐dependent effects in reducing the incidence of S‐IRA as well as seizure severity in DBA/1 mice. The protective effect of LPS on S‐IRA peaked at 8‐12 hours after LPS injection and was related to both reducing seizure severity and enhancing autoresuscitation. Blocking TLR4 or RAGE receptor with TAK‐242 or FPS‐ZM1, respectively, prior to LPS injection attenuated its effects on S‐IRA and seizure severity. Injection of a nonselective 5‐HT receptor antagonist, cyproheptadine, or a 5‐HT3 receptor antagonist, ondansetron, was effective in blocking LPS‐induced effect on S‐IRA. Immunostaining results showed a significant increase in c‐Fos‐positive serotonergic neurons in the dorsal raphe.SignificanceThis is the first study that demonstrates the effect of intraperitoneal LPS injection‐induced inflammation on reducing S‐IRA susceptibility and provides additional evidence supporting the serotonin hypothesis on SUDEP. Our study suggests that inflammation may enhance brainstem 5‐HT neurotransmission to promote autoresuscitation during seizure and prevent SUDEP.

Therapeutic hypothermia for pediatric refractory status epilepticus May Ameliorate post-status epilepticus epilepsy

BackgroundTo compare the clinical characteristics and outcomes of pediatric patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) who received therapeutic hypothermia (TH) plus anticonvulsants or anticonvulsants alone. MethodsTwo-medical referral centers, retrospective cohort study. Pediatric Intensive Care Unit (PICU) at Taoyuan Chang Gung Children's hospital and Kaohsiung Chang Gung Memorial Hospital. We reviewed the medical records of 23 patients with RSE/SRSE who were admitted to PICU from January 2014 to December 2017. Of these, 11 patients received TH (TH group) and 12 patients did not (control group). ResultsThe selective endpoints were RSE/SRSE duration, length of PICU stay, and Glasgow Outcome Scale (GOS) score. We applied TH using the Artic Sun® temperature management system (target temperature, 34–35 °C; duration, 48–72 h). Of the 11 patients who received TH, 7 had febrile infection-related epilepsy syndrome (FIRSE), one had Dravet syndrome, and three had traumatic brain injury. The TH group had significantly shortern seizure durations than did the control group (hrs; median (IQR) 24(40) vs. 96(90), p < 0.05). Two patients in the TH group died of pulmonary embolism and extreme brain edema. The length of PICU stay was similar between the groups (days; median (IQR) 30(42) v.s 30.5(30.25)). The TH group had significantly better long-term outcomes than did the control group (GOS score, median (IQR) 4(2) v.s 3 (0.75), p = 0.01∗). The TH group had a significantly lower incidence of later chronic refractory epilepsy than did the control group (TH v.s non-TH, 5/11 (45%) v.s. 12/12(100%), p < 0.01). ConclusionsTH effectively reduced the seizure burden in patients with RSE/SRSE. Our findings support that for patients with RSE/SRSE, TH shortens the seizure duration, ultimately reducing the occurrence of post-status epilepticus epilepsy and improving patients’ long-term survival.

Hospital service utilization trajectories of individuals living with epilepsy in New South Wales, Australia, 2012–2016: A population-based study

ObjectivesThis study aimed to examine five-year trajectories of hospital service utilization among individuals living with epilepsy in New South Wales (NSW), Australia, and to identify factors predictive of trajectory group membership. MethodsThis study used group-based trajectory modeling of hospital admissions over a five-year period for individuals living with epilepsy who had an epilepsy-related hospitalization during 1 January 2012 and 31 December 2012 in NSW, Australia (n = 5762). ResultsThe analysis revealed the following five distinct hospital service utilization trajectory groups: “one-off users” (Group 1; 22.9%), “low-chronic users” (Group 2; 47.1%), “moderate-declining users” (Group 3; 10.3%), “moderate-chronic users” (Group 4; 18.3%), and “high-chronic users” (Group 5; 1.5%). There were key features that defined trajectory group membership, in particular the relative proportions of group members with chronic health conditions, other comorbid conditions, refractory epilepsy, and status epilepticus. For instance, “high-chronic users” (Group 5) had higher proportions of individuals with chronic health conditions (34.8%) and refractory epilepsy (19.1%); “moderate-declining users” (Group 3) had higher proportions of individuals with chronic health conditions (35.1%) and status epilepticus (9.8%); and “low-chronic users” (Group 2) had the lowest proportion of individuals with chronic health conditions. ConclusionIt is important to gain a better understanding of hospital service utilization among individuals living with epilepsy. This research has identified trajectory groups of hospital service utilization profiles of individuals living with epilepsy. Identification of predictors of trajectory group membership allows targeting of strategies to reduce hospital admissions, inform healthcare service delivery, and improve the health and wellbeing of individuals living with epilepsy.

Development of a genomics module within an epilepsy-specific electronic health record: Toward genomic medicine in epilepsy care.

Both clinical genomics and e-Health technology are changing the way medicine is being practiced. Although the basic clinical methodology of good medical care will remain unchanged, the combined power of genomics and electronic health records has the capability of enhancing, and in some cases transforming, the practice of medicine. This is particularly true in the care of patients with complex long-term medical conditions such as chronic refractory epilepsy, especially in those with related complex comorbidities including intellectual disability and psychiatric disease. Herein we outline the development and integration of an epilepsy genomics module into a preexisting epilepsy electronic patient record (EPR) system. We describe how this EPR infrastructure is used to facilitate discussion at multidisciplinary clinical meetings around molecular diagnosis and resulting changes in management. This work illustrates the role of eHealth technology in embedding genomics into the clinical pathway.

The effect of miR-146a gene silencing on drug-resistance and expression of protein of P-gp and MRP1 in epilepsy.

To investigate the effect of miR-146a gene silencing on brain tissue and related drug-resistance proteins in rats and explore its resistance mechanism. A rat model of chronic refractory epilepsy was established. The rats were divided into four groups: Normal group, Model group, Negative control group and AntagomiR-146a group. Hematoxylin and eosin (HE) stain was used to detect brain histopathological changes. We examined the expression of mRNA of miR-146a, multidrug resistance (MDR1) and multidrug-resistant associated protein (MRP1) by RT-PCR. The expressions of protein of High motility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) pathway and P-glycoprotein (P-gp), MRP1 were detected by Western-blotting. We demonstrated that the pathological lesion was lighter in antagomiR-146a group compared with the model group. The mRNA expression of miR-146a in AntagomiR-146a group was significantly decreased compared to the model group. Furthermore, the mRNA expression of MDR1 and MRP1 in AntagomiR-146a group was lower than that in the model group. In addition, the protein expression of HMGB1, TLR4, NF-κB and P-gp, MRP1 in AntagomiR-146a group was lower than that in model group. These results demonstrated that miR-146a gene silencing can attenuate pathological changes and improve drug resistance in refractory epilepsy. Also, it is closely related to the HMGB1/TLR4/NF-κB signaling pathway regulation.

Conscious control of breathing: A key to prevention of sudden unexpected death in epilepsy?

Conscious control of breathing: A key to prevention of sudden unexpected death in epilepsy?

Elevated Expression of TRPC4 in Cortical Lesions of Focal Cortical Dysplasia II and Tuberous Sclerosis Complex.

Focal cortical dysplasia type II (FCD II) and tuberous sclerosis complex (TSC) are well-known causes of chronic refractory epilepsy in children. Canonical transient receptor potential channels (TRPCs) are non-selective cation channels that are commonly activated by phospholipase C (PLC) stimulation. Previous studies found that TRPC4 may participate in the process of epileptogenesis. This study aimed to examine the expression and distribution of TRPC4 in FCD II (n=24) and TSC (n=11) surgical specimens compared with that in age-matched autopsy control samples (n=12). We found that the protein levels of TRPC4 and its upstream factor, PLC delta 1 (PLCD1), were elevated in FCD II and TSC samples compared to those of control samples. Immunohistochemistry assays revealed that TRPC4 staining was stronger in malformed cells, such as dysmorphic neurons, balloon cells and giant cells. Moderate-to-strong staining of the upstream factor PLCD1 was also identified in abnormal neurons. Moreover, double immunofluorescence staining revealed that TRPC4 was colocalised with glutamatergic and GABAergic neuron markers. Taken together, our results indicate that overexpression of TRPC4 protein may be involved in the epileptogenesis of FCD II and TSC.

Developing from child to adult: Risk factors for poor psychosocial outcome in adolescents and young adults with epilepsy.

Childhood-onset epilepsy during the years of transition to adulthood may affect normal social, physical, and mental development, frequently leading to psychosocial and health-related problems in the long term. This study aimed to describe the main characteristics of patients in transition and to identify risk factors for poor psychosocial outcome in adolescents and young adults with epilepsy. Patients with epilepsy, 15-25years of age, who visited the Kempenhaeghe Epilepsy Transition Clinic from March 2012 to December 2014 were included (n=138). Predefined risk scores for medical, educational/occupational status, and independence/separation/identity were obtained, along with individual risk profile scores for poor psychosocial outcome. Multivariate linear regression analysis and discriminant analysis were used to identify variables associated with an increased risk of poor long-term psychosocial outcome. Demographic, epilepsy-related, and psychosocial variables associated with a high risk of poor long-term outcome were lower intelligence, higher seizure frequency, ongoing seizures, and an unsupportive and unstable family environment. Using the aforementioned factors in combination, we were able to correctly classify the majority (55.1%) of the patients regarding their risk of poor psychosocial outcome. Our analysis may allow early identification of patients at high risk of prevention, preferably at pretransition age. The combination of a chronic refractory epilepsy and an unstable family environment constitutes a higher risk of transition problems and poor outcome in adulthood. As a consequence, early interventions should be put into place to protect youth at risk of poor transition outcome.

Expression Patterns of TRPC1 in Cortical Lesions from Patients with Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is known as a common cause of chronic refractory epilepsy, but the underlying mechanisms of the factors that lead to FCD-related epilepsy are unclear. Previous studies have shown that canonical transient receptor potential channels (TRPCs) might be involved in the process of epileptogenesis. Canonical transient receptor potential channel 1 (TRPC1), which is ubiquitously expressed in the brain, has been shown to be involved in epileptiform bust firing in knockout mice. In this study, we examined the expression of TRPC1 in FCD type Ia (FCDIa), FCD type IIa (FCDIIa), and FCD type IIb (FCDIIb) surgical specimens from patients and age-matched autopsy control samples. Real-time quantitative PCR and western blotting indicated that TRPC1 mRNA and protein levels were increased in FCDIa, FCDIIa, and FCDIIb samples compared to control samples. Immunohistochemistry results revealed that TRPC1 was mainly distributed in microcolumns, dysmorphic neurons, and balloon cells. Further double immunofluorescent staining showed that TRPC1 was co-localized with glutamatergic and GABAergic markers. Taken together, our results demonstrate that the overexpression and specific cellular location of TRPC1 might be related to the epileptogenesis of FCD.

Breathing Inhibited When Seizures Spread to the Amygdala and upon Amygdala Stimulation.

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with chronic refractory epilepsy. Impaired breathing during and after seizures is common and suspected to play a role in SUDEP. Understanding the cause of this peri-ictal hypoventilation may lead to preventative strategies. In epilepsy patients, we found that seizure invasion of the amygdala co-occurred with apnea and oxygen desaturation, and electrical stimulation of the amygdala reproduced these respiratory findings. Strikingly, the subjects were unaware of the apnea. These findings indicate a functional connection between the amygdala and brainstem respiratory network in humans and suggest that amygdala seizures may cause loss of spontaneous breathing of which patients are unaware-a combination that could be deadly.

P97. The pathophysiology of sudden unexpected death in epilepsy (SUDEP)

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people suffering from chronic refractory epilepsy. The underlying pathophysiological mechanisms that are critically involved in SUDEP are still not well understood. Cardiac arrhythmia, depressed autonomic function after seizure activity and also seizure-related respiratory failure have been discussed to be part of the final cascade leading to SUDEP. This final cascade is thought to be triggered by the seizure activity resulting in dramatically elevated levels of epinephrine, norepinephrine as well as other regulatory hormones and neurotransmitters. However, not all cases of SUDEP are directly linked to a seizure suggesting that SUDEP is not an unitary event and most likely caused by multiple factors. We therefore analysed the respiratory patterns, heartbeat and arousals of patients in the epilepsy video-eeg monitoring unit (EMU), before and after the withdrawal of antiepileptic (AED). The frequency, variability of the breathing and heartbeat in correlation with the sleep-stages were analysed. Moreover, the respiratory pattern peri-ictal (before and following generalized tonic–clonic and complex partial seizures) were analyzed, since this period has been identified as the crucial time window for SUDEP.

Subjectively Perceived Side-Effects of Anti-Epileptic Drugs in Chronic Refractory Epilepsy

Purpose: Antiepileptic drugs (AEDs) can cause side-effects. Patient-reported side-effects due to this type of medication are very common, but thus far only investigated in community based populations. We investigated the subjectively perceived side-effects of anti-epileptic drug treatment in patients with refractory epilepsy. Methods: A non-selected group, of patients visiting the outpatient department between September 2011 and November 2011 was invited to complete a questionnaire only if they had experienced side-effects of their AED treatment during last year. The questionnaire, the SIDAED, assessed four different categories; cognition, mood, cosmetics and general health. Subgroup analyses were based on their medication use: mono- or polytherapy, older and newer AEDs and AEDs with a high or a low risk for cognitive and behavioral/mood side-effects. Results: In total, 203 patients or their relatives completed the questionnaire. Mean age of the patients was 37 years (2-81). Most reported complaints (85%) were about their general health followed by cognition, mood and cosmetics. Subgroup analyses showed no differences between patients using monotherapy or polytherapy. Also, no differences were found between patients using older AEDs or newer drugs. Patients using AEDs with a high risk for side-effects did complain more about their mood but not about their cognition. Regression analysis showed that using a high risk AED for behavioral side-effects contributed significantly to the total experienced side-effects. Conclusion: In conclusion, our study illustrates that patients are a reliable respondent to indicate side-effects despite of their refractory epilepsy. Particularly, mood complaints due to antiepileptic drugs (such as levetiracetam) are correctly noticed.

Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. Commission of European Affairs of the International League Against Epilepsy.

Jose Manuel Rodriguez Delgado

Jose Manuel Rodriguez Delgado