Lacosamide during pregnancy and breastfeeding

Background The epilepsy treatment during pregnancy represents a balance between teratogenic hazard and seizure control. The aim of the study was to evaluate the safety and efficacy of lacosamide (LCS) during pregnancy and breastfeeding. Methods Patients referred to our Epilepsy Center for pregnancy planning who became pregnant while taking LCS were prospectively followed-up. Data on seizure frequency, side effects, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation and development of newborns were collected. Results Three cases of maternal exposure to LCS were reported. Treatment with LCS was continued throughout pregnancy and breastfeeding at a median daily dose of 400mg. Lacosamide was used as monotherapy in two patients and as add-on treatment in one woman. Seizure frequency did not change throughout pregnancy and two subjects remained seizure free. The median gestational age at delivery was 39 weeks. The median Apgar scores at 1 and 5min were 9 and 10, respectively; no major or minor congenital malformations were observed in the offspring. Normal developmental milestone were reached by all new-borns. Conclusions Worldwide pregnancy registries have provided consistent and increasing information about the efficacy and safety of the older antiepileptic drugs during gestation, while data are lacking for many of the newer generations. These cases could suggest a good level of efficacy and safety for LCS throughout pregnancy and breastfeeding and argue against teratogenic or toxic potentialities

Lacosamide monotherapy for partial onset seizures

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Cortical Activation in Mental Rotation and the Role of the Corpus Callosum: Observations in Healthy Subjects and Split-Brain Patients

none6The mental rotation (MR) is an abstract mental operation thanks to which a person imagines rotating an object or a body part to place it in an other position. The ability to perform MR was belived to belong to the right hemisphere for objects, and to the left for one’s ownbody images. Mental rotation is considered to be basic for imitation with the anatomical perspective, which in turn is needed for social interactions and learning. Altered imitative performances have been reported in patients with resections or microstructure alterations of the corpus callosum (CC). These patients also display a reduced MR ability compared to control subjects, as shown in a recent behavioral study. The difference was statistically significant, leading us to hypothesize a role of the CC to integrate the two hemispheres’ asymmetric functions. The present study was designed to detect, by means of a functional MRI, the cortical activation evoked during an MR task in healthy control subjects and callosotomized patients. The results suggest that performing MR requires activation of opercular cortex and inferior parietal lobule in either hemispheres, and likely the integrity of the CC, thus confirming that the main brain commissure is involved in cognitive functions.openPierpaoli, Chiara; Ghoushi, Mojgan; Foschi, Nicoletta; Lattanzi, Simona; Fabri, Mara; Polonara, GabrielePierpaoli, Chiara; Ghoushi, Mojgan; Foschi, Nicoletta; Lattanzi, Simona; Fabri, Mara; Polonara, Gabriel

Adjunctive Perampanel in Older Patients With Epilepsy: A Multicenter Study of Clinical Practice

Background Clinical data regarding use of newer antiseizure medications (ASMs) in an older population are limited. In randomized-controlled, placebo-controlled trials, older patients are under-represented, and protocols deviate markedly from routine clinical practice, limiting the external validity of results. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Perampanel is a third-generation ASM and the first and only non-competitive alfa-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist.Objective The aim of this study was to assess the effectiveness and tolerability of adjunctive perampanel over a 1-year period in a population of older patients with epilepsy treated in a real-world setting.Methods Older (>= 65 years of age) patients prescribed add-on perampanel at 12 Italian epilepsy centers were retrospectively identified. Seizure occurrence, adverse events (AEs), and drug withdrawal were analyzed. Effectiveness outcomes included the rates of seizure response (>= 50% reduction in baseline monthly seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes were the rate of treatment discontinuation due to AEs and the incidence of AEs.Results A total of 92 patients with a median age of 69 (range 65-88) years were included. The median daily dose of perampanel at 12 months was 6 mg (interquartile range 4-6 mg). At 12 months, 53 (57.6%) patients were seizure responders, and 22 (23.9%) patients were seizure free. Twenty (21.7%) patients discontinued perampanel; the reasons for treatment withdrawal were insufficient efficacy (n = 6/20; 30.0%), AEs (n = 12/20; 60.0%), and a combination of both (n = 2/20; 10%). The most common AEs included irritability (8.7%), somnolence (4.3%), and dizziness/vertigo (4.3%). The rate of behavioral and psychiatric AEs was higher in patients with history of psychiatric comorbidities (p = 0.044). There were no differences in the occurrence of behavioral and psychiatric AEs according to the concomitant use of levetiracetam (p = 0.776) and history of cognitive decline (p = 0.332).Conclusions Adjunctive perampanel was associated with improvement in seizure control and good tolerability in a real-life setting and can represent a viable therapeutic option in older patients with epilepsy

A real‐world comparison among third‐generation antiseizure medications: Results from the COMPARE study

Objective: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives.Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models.Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-na & iuml;ve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-na & iuml;ve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-na & iuml;ve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM.Significance: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics

Visual integration across fixation: automatic processes are split but conscious processes remain unified in the split-brain

The classic view holds that when “split-brain” patients are presented with an object in the right visual field, they will correctly identify it verbally and with the right hand. However, when the object is presented in the left visual field, the patient verbally states that he saw nothing but nevertheless identifies it accurately with the left hand. This interaction suggests that perception, recognition and responding are separated in the two isolated hemispheres. However, there is now accumulating evidence that this interaction is not absolute; for instance, split-brain patients are able to detect and localise stimuli anywhere in the visual field verbally and with either hand. In this study we set out to explore this cross-hemifield interaction in more detail with the split-brain patient DDC and carried out two experiments. The aim of these experiments is to unveil the unity of deliberate and automatic processing in the context of visual integration across hemispheres. Experiment 1 suggests that automatic processing is split in this context. In contrast, when the patient is forced to adopt a conscious, deliberate, approach, processing seemed to be unified across visual fields (and thus across hemispheres). First, we looked at the confidence that DDC has in his responses. The experiment involved a simultaneous “same” versus “different” matching task with two shapes presented either within one hemifield or across fixation. The results showed that we replicated the observation that split brain patients cannot match across fixation, but more interesting, that DDC was very confident in the across-fixation condition while performing at chance-level. On the basis of this result, we hypothesised a two-route explanation. In healthy subjects, the visual information from the two hemifields is integrated in an automatic, unconscious fashion via the intact splenium, and this route has been severed in DDC. However, we know from previous experiments that some transfer of information remains possible. We proposed that this second route (perhaps less visual; more symbolic) may become apparent when he is forced to use a deliberate, consciously controlled approach. In an experiment where he is informed, by a second stimulus presented in one hemifield, what to do with the first stimulus that was presented in the same or the opposite hemifield, we showed that there was indeed interhemispheric transfer of information. We suggest that this two-route model may help in clarifying some of the controversial issues in split-brain research

Is the Imitative Competence an Asymmetrically Distributed Function?

This study reconsiders behavioral and functional data from studies investigating the anatomical imitation (AI) and the related mental rotation (MR) competence, carried out by our group in healthy subjects, with intact interhemispheric connections, and in split-brain patients, completely or partially lacking callosal connections. The results strongly point to the conclusion that AI and MR competence requires interhemispheric communication, mainly occurring through the corpus callosum, which is the largest white matter structure in the human brain. The results are discussed in light of previous studies and of future implications

Asymmetry for Symmetry: Right-Hemispheric Superiority in Bi-Dimensional Symmetry Perception

A right-hemispheric superiority has been shown for spatial symmetry perception with mono-dimensional stimuli (e.g., bisected lines). Nevertheless, the cerebral imbalance for bi-dimensional stimuli is still controversial, and the aim of the present study is to investigate this issue. Healthy participants and a split-brain patient (D.D.C.) were tested in a divided visual field paradigm, in which a square shape was presented either in the left or right visual field and they were asked to judge whether a dot was placed exactly in the center of the square or off-center, by using the left/right hand in two separate sessions. The performance of healthy participants was better when the stimuli presented in the left visual field (LVF) were on-center rather than off-center. The performance of D.D.C. was higher than chance only when on-center stimuli were presented in the LVF in the left hand session. Only in this condition did his accuracy not differ with respect to that of the control group, whereas in all of the other conditions, it was lower than the controls’ accuracy. We conclude that the right-hemispheric advantage already shown for mono-dimensional stimuli can be extended also to bi-dimensional configurations, confirming the right-hemispheric superiority for spatial symmetry perception