Summary
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.
The objective of this study was to determine areas of consensus among an international panel of experts for the clinical presentation and diagnosis of epilepsy with eyelid myoclonia (EEM; formerly ...known as Jeavons syndrome) to improve a timely diagnosis.
An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and five patients/caregivers). This international expert panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the diagnosis of EEM.
There was a strong consensus that EEM is a female predominant generalized epilepsy syndrome with onset between 3 and 12 years of age and that eyelid myoclonia must be present to make the diagnosis. There was a strong consensus that eyelid myoclonia may go unrecognized for years prior to an epilepsy diagnosis. There was consensus that generalized tonic-clonic and absence seizures are typically or occasionally seen in patients. There was a consensus that atonic or focal seizures should lead to the consideration of reclassification or alternate diagnoses. There was a strong consensus that electroencephalography is required, whereas magnetic resonance imaging is not required for diagnosis. There was a strong consensus to perform genetic testing (either epilepsy gene panel or whole exome sequencing) when one or a combination of factors was present: family history of epilepsy, intellectual disability, or drug-resistant epilepsy.
This international expert panel identified multiple areas of consensus regarding the presentation and evaluation of EEM. These areas of consensus may be used to inform clinical practice to shorten the time to the appropriate diagnosis.
Gamma oscillations and photosensitive epilepsy Hermes, Dora; Kasteleijn-Nolst Trenité, Dorothée G.A.; Winawer, Jonathan
Current biology,
05/2017, Letnik:
27, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Certain visual images, even in the absence of motion or flicker, can trigger seizures in patients with photosensitive epilepsy. As of yet, there is no systematic explanation as to why some static ...images are likely to provoke seizures, while others pose little or no risk. Here, we examined the neurophysiology literature to assess whether the pattern of neural responses in healthy visual cortex is predictive of the pathological responses in photosensitive epilepsy. Previous studies have suggested that gamma oscillations (30–80 Hz) measured in human visual cortex may play a role in seizure generation 1,2. Recently, we and others have shown that increases in gamma band power can come from two very different cortical signals, one that is oscillatory (with a narrow peak between 30 Hz and 80 Hz), and another that is broadband3. The oscillatory signal arises from neuronal synchrony in the local population, while the broadband signal reflects the level of asynchronous neuronal activity, and is correlated with multiunit spiking 4. These two responses have different biological origins and different selectivity for image properties. Here, we followed up on the previous proposals 1,2 to ask whether the image features that increase seizure likelihood in photosensitive epilepsy are linked to narrowband gamma oscillations specifically, or are associated with any kind of increase in visual activity. Based on published work, we compared pairs of image classes on a number of dimensions, and show that the type of image that elicits larger narrowband gamma oscillations in healthy visual cortex is also more likely to provoke seizures or pre-seizure activity in patients with photosensitive epilepsy. In contrast, images that elicit larger broadband, multiunit, or fMRI responses are much less predictive of seizure activity. We propose that a risk factor for seizures in patients with photosensitive epilepsy is engagement of the circuitry that produces gamma oscillations.
Hermes et al. show that the same visual stimuli that induce photosensitive epilepsy also elicit gamma oscillations in the visual cortex, suggesting a possible functional connection.
There are limited data about the treatment and management of epilepsy with eyelid myoclonia (EEM). The objective of this study was to determine areas of consensus among an international panel of ...experts for the management of EEM (formerly known as Jeavons syndrome).
An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and five patients/caregivers). This panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the treatment, other areas of management, and prognosis for EEM.
There was a strong consensus for valproic acid as the first-line treatment, with levetiracetam or lamotrigine as preferable alternatives for women of childbearing age. There was a moderate consensus that ethosuximide and clobazam are also efficacious. There was a strong consensus to avoid sodium channel-blocking medications, except for lamotrigine, as they may worsen seizure control. There was consensus that seizures typically persist into adulthood, with remission occurring in <50% of patients. There was less agreement about other areas of management, including dietary therapy, lens therapy, candidacy for driving, and outcome.
This international expert panel identified multiple areas of consensus regarding the optimal management of EEM. These areas of consensus may inform clinical practice to improve the management of EEM. In addition, multiple areas with less agreement were identified, which highlight topics for further research.
To evaluate the effect of cenobamate in patients with photoparoxysmal-EEG response (PPR) to intermittent photic stimulation (IPS) as proof of principle of efficacy in patients with epilepsy.
In this ...multicenter, single-blind study, adults with photosensitive epilepsy, with/without concomitant antiepileptic drug therapy, underwent IPS under 3 eye conditions after a single dose of placebo (day -1, day 2) or cenobamate (day 1; 100, 250, or 400 mg). Complete suppression was a standardized photosensitivity range reduction to 0 over ≥1 time points for all eye conditions. Partial suppression was a ≥3-point reduction over ≥3 testing times vs the same time points on day -1 in ≥1 eye condition. Pharmacokinetics and safety were assessed.
Of 6 evaluable patients, 5 reentered to receive higher doses. Cenobamate 100 mg produced partial suppression in 1 of 3 patients; 250 mg produced complete suppression in 1 of 4 and partial suppression in 4 of 4 patients; and 400 mg produced complete suppression in 1 of 4 and partial suppression in 2 of 4 patients. PPR was consistently reduced on days 1 and 2 (>24 hours after cenobamate) vs day -1 (placebo) with the 250- and 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 μg/h/mL resulted in partial suppression in 4 of 6 (66%) patients. Most common adverse events were dizziness and somnolence.
This proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy.
NCT00616148.
This study provides Class III evidence that, for patients with photosensitive epilepsy, cenobamate suppresses IPS-induced PPR.
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
Epileptic seizures can be provoked by several factors. Better understanding of these factors may improve a patient's sense of control and could reduce seizures. In daily practice, the recognition of ...seizure precipitants relies heavily on clinical or video-EEG evidence, which can be difficult to obtain. Studies of seizure provocation are largely based on selected hospital-based patient populations, which may lead to biased occurrence estimates. Self-reported seizure precipitants are rarely studied, yet are necessary to understand the experiences of patients and improve epilepsy management. We performed a cross-sectional community-based study of 248 epilepsy patients, selected by pharmacy records of anti-epileptic drug use. Self-reported seizure precipitants and potential associated characteristics were assessed using questionnaires. Almost half of all patients (47 %) reported one or more seizure precipitants, of which stress, sleep deprivation, and flickering lights were the most common. In this community-based setting, light-provoked seizures were especially frequent compared to the literature. Idiopathic generalized epilepsy (IGE), a lower age at seizure onset, and having auras or prodromes were found to be important independent prognostic factors associated with provoked seizures. IGE and a younger age at seizure onset have been linked to provoked seizures in earlier reports. The finding of auras or prodromes as a prognostic factor was unexpected, though case reports have described provoked seizures in patients having auras. Assessment of these factors may facilitate the early recognition of seizure precipitants in daily clinical practice. This is important for the optimization of epilepsy management for a large group of patients, as provoked seizures are expected to occur frequently.
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.
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.
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