Bernhard J Steinhoff

Diakonie Kork · Adults

Zusammenfassung Erfreulicherweise wurden im vergangenen Jahr nach langer Wartezeit die Leitlinien der Deutschen Gesellschaften für Neurologie und Epileptologie „Erster epileptischer Anfall und Epilepsien im Erwachsenenalter“ publiziert. Diese sorgfältig im Konsensverfahren erarbeiteten Ratschläge decken überwiegend die aktuelle Literatur und Praxis...

Zusammenfassung Pharmakotherapie und Kinderwunsch sind ein anspruchsvolles Thema, das hauptsächlich, aber nicht ausschließlich Frauen im gebärfähigen Alter betrifft, die ein Drittel aller Patientinnen mit Epilepsie ausmachen. Im folgenden Beitrag werden aktuelle Studiendaten dargestellt, daraus resultierende Empfehlungen bei Menschen mit Epilepsie...

Zusammenfassung Anfallssupprimierende Medikamente (ASM) werden bei erwachsenen Patientinnen und Patienten in der Regel über lange Zeit eingesetzt. Je nach pharmakokinetischem Profil sind dabei als Begleiterscheinung mannigfaltige Auswirkungen auf den Organismus und die Wirksamkeit und Verträglichkeit anderer Medikamente denkbar, die auch zu typisch...

Objective To assess antiseizure effects of cenobamate, a new antiseizure medication with at least two mechanisms of action, in the rare, highly pharmacoresistant and progressive epilepsy syndrome related to Rasmussen's encephalitis. Methods Three patients from the epilepsy centers in Freiburg, Kork, and Valencia are reported with focal epilepsy wh...

The goal of epilepsy treatment is seizure freedom, typically with antiseizure medication (ASM). If patients fail to attain seizure control despite two trials of appropriately chosen ASMs at adequate doses, they are classified as having drug-resistant epilepsy (DRE). Adverse events (AEs) commonly occur in people with DRE because they are typically o...

Objective In Europe, cenobamate has been approved for use as an adjunctive therapy in adult patients with epilepsy (PWE) with focal‐onset seizures (FOS) who have not responded satisfactorily to treatment with at least two antiseizure medications (ASMs). Pivotal trials and real‐world observational studies have demonstrated a high efficacy of cenobam...

While significant strides have been made in comprehending the pathophysiology and treatment of epilepsy, further investigation is warranted to elucidate the factors impacting its development and transmission, particularly within familial contexts. This study sought to explore the prevalence and risk factors associated with epilepsy in the offspring...

Objective: Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high...

Purpose This study is to report some preliminary surgical considerations and outcomes after the first implantations of a new and commercially available implantable epicranial stimulation device for focal epilepsy. Methods We retrospectively analyzed data from clinical notes. Outcome parameters were as follows: wound healing, surgery time, and adve...

Objective To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies. Methods EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes include...

Zusammenfassung Psychogene nicht-epileptische Anfälle (PNEA) (synonym: funktionelle/dissoziative Anfälle) sind eine wichtige Differenzialdiagnose zu epileptischen Anfällen und keine seltene Erkrankung. Die Versorgung von Patientinnen und Patienten mit PNEA erfolgt in spezialisierten Epilepsiezentren, die jederzeit Anfälle der Betroffenen überwachen...

Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) who suffer from ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies have suggested a high efficacy with unusu...

Objective Critical flicker frequency (CFF) and flicker frequency (FF) are used as indicators for the neurotoxic adverse events of drugs in pharmacology. In this pilot study, we investigated whether patients with epilepsy (PWE) treated with various antiseizure medications (ASM) had significantly different CFFs compared to healthy controls. In additi...

Purpose Photosensitivity is a phenomenon that may be elicited by standardized intermittent photic stimulation during EEG recording and is detected more frequently in children and adolescents. Nevertheless, at our Epilepsy Center, we routinely assess photosensitivity in all newly referred adult patients. In this investigation, we sought to address t...

Background and objective: Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population. Methods: EXPERIENCE/EPD332 was a pooled analysi...

This symposium took place during the 2023 Congress of the European Academy of Neurology (EAN). Mar Carreño, Director, Epilepsy Unit, Hospital Clínic and Instituto Clavel, Barcelona, Spain, presented the definition of drug-resistant epilepsy (DRE), and stressed that uncontrolled epilepsy does not necessarily indicate DRE. Before a diagnosis of DRE i...

Objectives Assess effectiveness/tolerability of brivaracetam (BRV) in routine practice in a large international population (Spain/Germany/Australia/United States) and Australian patients only. Method EXPERIENCE/EPD332 was a pooled analysis of patient-level data from patients with epilepsy initiating BRV in clinical practice. Effectiveness/tolerabi...

Objectives Assess effectiveness and tolerability of brivaracetam (BRV) in patients switching from levetiracetam (LEV) and from other antiseizure medications (ASMs). Method Subgroup analysis of EXPERIENCE/EPD332, a pooled analysis of patient-level data from patients with epilepsy initiating BRV in clinical practice. ≥50% seizure reduction from base...

Despite the approval of ~20 additional antiseizure medications (ASMs) since the 1980s, one‐third of epilepsy patients experience seizures despite therapy. Drug‐resistant epilepsy (DRE) is associated with cognitive and psychiatric comorbidities, socioeconomic impairment, injuries, and a 9.3–13.4 times higher mortality rate than in seizure‐free patie...

Objective To assess the course of COVID-19 infections and the tolerability of the mRNA vaccines of Moderna and Pfizer/BioNTech and the viral vector vaccines from Astra Zeneca and Johnson & Johnson in adult patients with epilepsy (PWE).Methods From July 2020 to July 2021, we consecutively included adult outpatients with confirmed epilepsy. These PWE...

Objective Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC). Several studies suggest antiseizure effects also beyond these three epilepsy syndromes. Methods In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with e...

Levetiracetam (LEV) and brivaracetam (BRV) are pyrrolidone derivate compounds binding at the presynaptic SV2A receptor site and thus representing antiepileptic drugs (AEDs) with a unique mode of action. LEV was extensively investigated in randomized controlled trials and has a very favorable efficacy in both focal and generalized epilepsies. Its ph...

Cenobamate (CNB) is a tetrazole alkyl carbamate derivative that was recently labeled in the USA and in Europe. CNB has a dual mode of action by the inhibition of voltage-dependent sodium channels and the positive allosteric modulation of high-affinity GABAA receptors. Once daily dosing is possible. CNB undergoes a complex metabolism mainly by glucu...

Potassium bromide (KBr) is the oldest anti-convulsant agent, and its efficacy had already been discovered in the nineteenth century. Today, it is available in only a few countries. When used in humans, KBr is mainly applied in severe childhood epilepsies with generalized tonic-clonic seizures like Dravet syndrome. Positive effects in children with...

Background De novo missense variants in KCNQ5, encoding the voltage-gated K⁺ channel KV7.5, have been described to cause developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. Methods 1292 families...

Objective Evaluate long-term efficacy (percent seizure frequency reduction and responder rates), safety, and tolerability of adjunctive cenobamate in an open-label extension (OLE) of the randomized, double-blind, placebo-controlled study. Methods Patients (aged 18-70 years) with uncontrolled focal seizures despite treatment with 1-3 antiseizure me...

Purpose The results of the double-blind (DB), placebo-controlled trial C017 demonstrated that ceno- bamate achieved highly significant rates of seizure freedom vs placebo in patients with uncontrolled FOS. Here we assess the long-term efficacy of cenobamate during the open-label extension (OLE) of the 017 study. Methods Subjects who completed the...

Purpose Results from two double-blind, placebo-controlled studies demonstrated that adjunctive ceno- bamate significantly reduced the frequency of seizures vs placebo. Cenobamate 200mg/day achieved seizure freedom in 28.3% vs 8.8% placebo (P<0.0003; 013 study maintenance phase) and 21.1%, 11.2% for cenobamate 400mg/d and 200mg/d, respectively, vs 1...

Purpose There has been little success with polytherapy for patients with drug-resistant epilepsy. The need for optimizing AED combinations is high. Cenobamate is a novel AED with a unique, dual, complementary mechanism of action (MoA) combining GABA-A positive allosteric modulation (via a binding site different from benzodiazepines) together with b...

Photosensitivity is a phenomenon which is defined more precisely by intermittent photic stimulation that elicits a photoparoxysmal response (PPR). Data about the prognosis of people with PPR are scarce. Pure PPR mostly appears in later childhood and adolescence, has a female preponderance and disappears in many people during the third decade. Howev...

The PER a M panel pooled analys I s of effec T iveness and tolerability (PERMIT) study was a pooled analysis of data from 44 real-world studies from 17 countries, in which people with epilepsy (PWE; focal and generalized) were treated with perampanel (PER). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (...

Purpose To assess how efficacy and safety outcomes were affected when cenobamate was co-administered with antiseizure medications (ASMs) that use either sodium channel blocker (SCB) or non-sodium channel blocker (non-SCB) mechanisms of action (MoAs) in patients with uncontrolled focal seizures. Methods An exploratory post-hoc analysis of a randomi...

Objective We determined retention on open‐label cenobamate therapy in the clinical development program to assess the long‐term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures. Methods Data from two randomized, controlled cenobamate studies and one open‐label safety and pharmacokinetic study were p...

Cenobamate (CNB) is a tetrazole alkyl carbamate derivative that was recently labeled in the USA and in Europe. CNB has a dual mode of action by the inhibition of voltage-dependent sodium channels and the positive allosteric modulation of high-affinity GABAA receptors. Once daily dosing is possible. CNB undergoes a complex metabolism mainly by glucu...

Clinical trial results have demonstrated that adjunctive cenobamate (CNB) substantially decreases seizure frequency in adults with uncontrolled focal onset seizures with an acceptable and well-identified safety profile. This manuscript summarizes an expert panel’s recommendations regarding optimized CNB treatment of epilepsies with focal onset seiz...

Purpose To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as b...

Objective: De novo missense variants in KCNQ5, encoding the voltage–gated K+ channel KV7.5, have been described as a cause of developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease–related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. Methods: 1292 fam...

With an elimination half‐life of 105 hours, perampanel (PER) allows a once‐daily dosing regimen. In pivotal trials, when PER was tapered, it was therefore usually discontinued abruptly. Thus, in our hospital we have always practiced abrupt cessation. In this case series, we investigated how long PER serum concentrations still remain measurable afte...

Objective This study was undertaken to improve understanding of late relapse following epilepsy surgery in pharmacoresistant epilepsy. Methods Retrospective comparison was made of 99 of 1278 patients undergoing surgery during 1999–2015 with seizure relapses after at least 2 years of complete seizure freedom with matched controls experiencing conti...

Zusammenfassung „Sudden unexpected death in epilepsy“ (SUDEP) ist der plötzliche, unerwartete Tod eines Epilepsiepatienten, der unter „gutartigen“ Umständen und ohne typische Todesursachen auftritt. SUDEP betrifft alle Epilepsiepatienten. Das individuelle Risiko hängt vor allem von Merkmalen der Epilepsie und Anfälle sowie von Lebensumständen ab. F...

National and international guidelines inevitably require the proof of antiseizure drug resistance prior to presurgical diagnostics and especially prior to epilepsy surgery; however, there are individual constellations where epilepsy surgery is not an alternative but the first-line treatment if one considers the risk-benefit ratio. By means of a cas...

Objective There is evidence that everolimus (EVE) significantly reduces seizure frequency in epilepsy patients with tuberous sclerosis complex (TSC). Given that TSC‐related proliferative processes are more dynamic during brain development, seizure outcomes of patients treated with EVE may be age‐related and may be less convincing in adult patients....

Photosensitivity is a phenomenon which is defined more precisely by intermittent photic stimulation that elicits a photoparoxysmal response (PPR). Data about the prognosis of people with PPR are scarce. Pure PPR mostly appears in later childhood and adolescence, has a female preponderance and disappears in many people during the third decade. Howev...

„Sudden unexpected death in epilepsy“ (SUDEP) ist der plötzliche, unerwartete Tod eines Epilepsiepatienten, der unter „gutartigen“ Umständen und ohne typische Todesursachen auftritt. SUDEP betrifft alle Epilepsiepatienten. Das individuelle Risiko hängt vor allem von Merkmalen der Epilepsie und Anfälle sowie von Lebensumständen ab. Fokale zu bilater...

Purpose Although levetiracetam (LEV) is globally established as a leading antiseizure medication (ASM) it is still a controversial matter whether dose increases correspond with an increased efficacy if LEV in the recommended dose range did not show satisfying efficacy. In our clinical perception we questioned the value of dose increases in such non...

We present the case of a young male patient who suffered from a rare type of progressive myoclonic epilepsy. The long diagnostic pathway including the results of somatosensory evoked potentials (SEP), which finally enabled the precise diagnosis to be found and the individual course of treatment are described. We briefly review the underlying Lafora...

Seizure manifestations may be difficult to describe in words alone. Thus, initially, 24 seizure images were developed to support communication and gain assistance during obtaining the patient's history. Before being used in clinical practice, these seizure images must be investigated for validity and reliability. We tested the images with untrained...

Therapeutic options for patients with treatment-resistant epilepsy represent an important unmet need. Addressing this unmet need was the main factor driving the drug discovery program that led to the synthesis of padsevonil, a first-in-class antiepileptic drug candidate that interacts with two therapeutic targets: synaptic vesicle protein 2 and GAB...

Psychosomatic epileptology deals with a large number of different psychiatric and psychosomatic clinical pictures. Against the background of the increasing processing power of smartphones, computers and the Internet and a high level of acceptance of digital media, e‑mental health applications are being developed in large numbers. These applications...

Purpose This post hoc analysis assessed the effects of adjunctive perampanel on myoclonic and absence seizure outcomes in patients (aged ≥12 years) with idiopathic generalized epilepsy (IGE) and generalized tonic-clonic seizures during the double-blind (up to 8 mg/day) and open-label extension (OLEx; up to 12 mg/day) phases of Study 332. Methods P...

Introduction The aim of our study was to evaluate intracerebral network changes in epilepsy patients demonstrating secondary bilateral synchrony (SBS) in EEG by applying a new Diffusion Tensor Imaging (DTI) method using an energy-based global tracking algorithm. Materials and methods 10 MRI negative epilepsy patients demonstrating SBS in 10-20 sur...

Objective High‐frequency deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) reduces the frequency and intensity of focal and focal to bilateral tonic‐clonic epileptic seizures. We investigated the impact of high‐frequency ANT‐DBS on vigilance in epilepsy patients during relaxed and drowsy wakefulness, to better understand the effects an...

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s...

Background Bilateral cyclic high frequency deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) reduces the seizure count in a subset of patients with epilepsy. Detecting stimulation-induced alterations of pathological brain networks may help to unravel the underlying physiological mechanisms related to effective stimulation d...

Brivaracetam (BRV) is indicated for adjunctive treatment of focal (partial-onset) seizures with or without secondary generalisation in patients 4 years of age and older in the European Union (EU). An ongoing 12-month, prospective, non-interventional post-marketing study (EP0077; NCT02687711) is collecting real-world information on patients receivin...

Objective This post hoc analysis evaluated the efficacy and safety of adjunctive perampanel 4 mg/d received as modal dose, which may have differed from randomized dose, for treatment of focal seizures. Methods Data were pooled from four randomized, double‐blind, placebo‐controlled, phase III studies of adjunctive perampanel in patients (aged ≥12 y...

Brivaracetam (BRV) was recently introduced for the treatment of patients with focal epilepsy. BRV undergoes relatively few interactions, but one of them leads to the elevation of carbamazepine (CBZ)-10,11-CBZ-epoxide (CBZ-E) if BRV is co-administered with CBZ. This interaction has been considered to be clinically negligible. We present a case serie...

Background: More than a third of patients with epilepsy are treatment resistant, and thus new, more effective therapies to achieve seizure freedom are needed. Cenobamate (YKP3089), an investigational antiepileptic drug, has shown broad-spectrum anticonvulsant activity in preclinical studies and seizure models. We aimed to evaluate the safety, effi...

Until the early 1990s, a limited number of antiepileptic drugs (AEDs) were available. Since then, a large variety of new AEDs have been developed and introduced, several of them offering new modes of action. One of these new AED families is described and reviewed in this article. Levetiracetam (LEV) and brivaracetam (BRV) are pyrrolidone derivate c...

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilep...

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilep...

Purpose The de novo development of PNEA has been described after brain surgery [1]. De novo psychogenic non-epileptic attacks (PNEA) after epilepsy surgery has an estimated incidence of 1.8% to 8.8% [2,3] and is not well studied. This is a European multicenter retrospective cohort study to record patients with de novo psychogenic non-epileptic atta...

This article critiques the International League Against Epilepsy (ILAE) 2015‐2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been repl...

This educational review describes the classification of paroxysmal events and a four‐dimensional epilepsy classification system. Paroxysmal events are classified as epileptic and non‐epileptic paroxysmal events. Non‐epileptic events are, in turn, classified as psychogenic and organic paroxysmal events. The following four dimensions are used to clas...

Purpose To investigate the correlation between steady-state plasma concentrations of perampanel (PER) with efficacy and tolerability in adult patients with difficult-to-treat epilepsy. Methods PER plasma concentrations were assessed at steady-state conditions in 92 adult patients (57% female, 43% male, mean age 39,5 years, age range 20–73 years)....

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals...

Wir berichten den Fall einer inzwischen 71 Jahre alten Patientin mit einer idiopathisch generalisierten Epilepsie mit Myoklonien und generalisierten tonisch-klonischen Anfällen bei photoparoxysmaler Reaktion Grad 4 nach Waltz, die trotz der üblichen medikamentösen und expositionsreduzierenden prophylaktischen Maßnahmen über Jahre nicht anfallsfrei...