Introduction
Both levetiracetam (LEV) and brivaracetam (BRV) eliminate the electroencephalogram photoparoxysmal response (PPR) in the human phase IIa photosensitivity model of epilepsy. The ...physiochemical properties of BRV differ from those of LEV, having higher potency and lipophilicity plus 10- to 15-fold greater affinity for synaptic vesicle glycoprotein 2A.
Objective
We compared the rapidity of the effects of both drugs in the central nervous system (CNS) of patients with photosensitive epilepsy using time to PPR elimination post-intravenous infusion as a pharmacodynamic endpoint.
Methods
Using a randomized, double-blind, two-period, balanced, crossover design, we tested patients with photosensitive epilepsy with equipotent milligram doses of intravenous LEV 1500 mg versus BRV 100 mg post-15-min intravenous infusion (part 1) and post-5-min intravenous infusion (part 2, same doses). Eight patients per part were deemed sufficient with 80% power to determine a 70% reduction for intravenous BRV:LEV intrapatient time ratio to PPR elimination, with a 0.05 two-sided significance level. Plasma antiseizure medicine concentrations were measured using liquid chromatography/mass spectrometry.
Results
Nine patients six women; mean age 27.8 years (range 18–42) completed the study; seven of these participated in both parts 1 and 2. In 31 of 32 instances, patients experienced PPR elimination. In mixed-effects model time analysis, BRV eliminated PPRs more quickly than did LEV (median 2 vs. 7.5 min, respectively). However, no statistically significant difference in BRV:LEV time ratio to PPR elimination was observed for two of our multiple primary outcomes: for the 15-min infusion alone (
p
= 0.22) or the 5-min infusion alone (
p
= 0.11). However, BRV was faster when we excluded an outlier patient in part 1 (
p
= 0.0016). For our remaining primary outcome, parts 1 and 2 data combined, the median intrapatient BRV:LEV time ratio was 0.39 95% confidence interval (CI) 0.16–0.91, i.e., PPR elimination was 61% faster with BRV,
p
= 0.039. PPR was completely eliminated in ≤ 2 min in 11 patients with BRV and in four patients with LEV. No period or carryover effects were seen. No serious or severe adverse effects occurred. At PPR elimination (n = 16), median plasma BRV was 250 ng/mL (range 30–4100) and median plasma LEV was 28.35 μg/mL (range 1–86.7).
Conclusion
Outcome studies directly comparing LEV and BRV are needed to define the clinical utility of the response with BRV, which was several minutes faster than that with LEV.
Clinical trials
ClinTrials.gov Identifier = NCT03580707; registered 07-09-18
Abstract In juvenile myoclonic epilepsy (JME), occurrence of seizures and epileptiform EEG discharges is influenced by internal and external factors. The most important internal factor is the ...chronodependency: the occurrence of myoclonic jerks in the early morning is one of the hallmarks of JME. Approximately two-thirds of the patients with JME report that seizures are provoked by a variety of general factors like stress, fatigue, fever, and sleep and more specific precipitants like flashing sunlight, music, reading, thinking, and excess alcohol. The prevalence rate of photosensitivity (photoparoxysmal EEG response) in patients with JME ranges from 8 to 90%; it is seen more often in females and adolescents and depends on drug use. Since both JME and photosensitivity are connected with generalized types of epilepsy and myoclonus, the two traits are comorbid for that reason. Epileptiform EEG discharges can be provoked by other activation methods: sleep, hyperventilation, and specific cognitive tasks. Attention seems to have a non-specific, inhibitory effect of the epileptiform discharges. Hyperventilation can induce absence seizures in patients with JME, while cognitive tasks are efficient in precipitating myoclonic seizures. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?
Despite the fact that migraine and epilepsy are among the commoner brain diseases and that comorbidity of these conditions is well known, only few reports of migralepsy and hemicrania epileptica (HE) ...have been published according to the current ICHD-II criteria. Particularly, ICHD-II describes “migraine-triggered seizure” (i.e., migralepsy) among complications of migraine at “1.5.5” (as a rare event in which a seizure happens during migrainous aura), while hemicrania epileptica (coded at “7.6.1”) and post-ictal headache (coded at “7.6.2”) are described among headaches attributed to epileptic seizure. However, to date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may be the sole ictal epileptic manifestation. Based on the current knowledge, migralepsy is highly unlikely to exist as such. We, therefore, propose to delete this term until clear evidence its existence is provided. Moreover, we herein propose a revision of terminology and classification criteria to properly represent the migraine/headache relationships. We suggest the term “ictal epileptic headache” in cases in which headache/migraine is the sole ictal epileptic manifestation.
Highlights • Photoparoxysmal EEG responses (PPR) are very common (42%) in patients with Dravet Syndrome (DS). • PPR in DS occurs at a strikingly young age and seems to be connected with a more severe ...course. • Repetitive intermittent photic stimulation with optimal protocol increases detection rate of PPR.
Low‐grade gliomas frequently are associated with epilepsy. The purpose of this study is to determine the impact of epilepsy and antiepileptic drug (AED) treatment on cognitive functioning and ...health‐related quality of life (HRQOL) in these patients. One hundred fifty‐six patients without clinical or radiological signs of tumor recurrence for at least 1 year after histological diagnosis and with an epilepsy burden (based on seizure frequency and AED use) ranging from none to severe were compared with healthy controls. The association between epilepsy burden and cognition/HRQOL was also investigated. Eighty‐six percent of the patients had epilepsy and 50% of those using AEDs actually were seizure‐free. Compared with healthy controls, glioma patients had significant reductions in information processing speed, psychomotor function, attentional functioning, verbal and working memory, executive functioning, and HRQOL. The increase in epilepsy burden that was associated with significant reductions in all cognitive domains except for attentional and memory functioning could primarily be attributed to the use of AEDs, whereas the decline in HRQOL could be ascribed to the lack of complete seizure control. In conclusion, low‐grade glioma patients suffer from a number of neuropsychological and psychological problems that are aggravated by the severity of epilepsy and by the intensity of the treatment.
Abstract Juvenile myoclonic epilepsy (JME) is a recognizable, frequent epileptic syndrome. The most typical ictal phenomenon is bilateral myoclonia without loss of consciousness (M), with most ...patients also presenting with generalized tonic-clonic seizures (GTCSs) and some with absence seizures (ASs). The most striking features of JME are its onset around the time of puberty and the fact that seizure episodes occur after awakening from a sleep period or in the evening relaxation period and are facilitated by sleep deprivation and sudden arousal. Photic sensitivity is common in the EEG laboratory but uncommon or unrecognized in daily life. The clinical features of JME make it easy to diagnose. In recent years, awareness of JME has increased, and patients are often accurately diagnosed clinically before confirmation by EEG. The typical circumstance at diagnosis is a first GTCS episode, and one learns during the interview that the patient has had M in the morning for some time before the GTCS episode. There are only few differential diagnoses: the adolescent-onset progressive myoclonus epilepsies, or other forms of idiopathic generalized epilepsies of adolescence. With JME being so common, we propose that a first GTCS episode in a teenager should be considered as revealing JME until proven otherwise. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?
Abstract Hardly anyone has been posthumously diagnosed as much as Vincent van Gogh. This article does not attempt to add yet another illness to the long list, nor indeed to make any definite ...statement about the ‘right diagnosis’. Rather, it attempts to place the diagnoses actually made during his lifetime into their historical and cultural context. It examines how these diagnoses were imbedded in the medical paradigms popular at the time, and how these paradigms in their turn relate to the general cultural context of the era. It also shows how the ‘patient’ reacted to the diagnoses presented to him and to the underlying medical paradigms. Those who give diagnoses and those who receive them are involved in the same cultural context, taking for granted the medical fashions of their times, including the biases incorporated in them.
Abstract Heritable EEG traits are often associated with epilepsy, and photoparoxysmal EEG response (PPR) is the most notable example of this observation in JME. Such EEG traits may be a subclinical ...expression of the defective mechanism that leads to epilepsy. Therefore, these traits can be used to map epilepsy genes by dissecting the complex epilepsy phenotype in endophenotypic sections that on their own have a presumed monogenic cause. Two characteristics make PPR particularly interesting as a useful endophenotype for epilepsy gene mapping. First, it shows an increased comorbidity with some but not all forms of epilepsy. Second, its mode of inheritance is compatible with a monogenic cause, which promises relative straightforward gene identification through positional cloning. Here, we summarize the current state of affairs. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?
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