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

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

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

Oxcarbazepine and adverse events: impact of age, dosage, metabolite serum concentrations and concomitant antiepileptic therapy

The aim of this study was to investigate the relationships between oxcarbazepine (OXC) dosage, metabolite mono-hydroxy-derivative (MHD) serum concentrations, number of concomitant antiepileptic drugs, age and incidence of adverse events (AEs) in epileptic patients. A retrospective analysis was conducted of 414 consecutive epileptic patients on OXC alone or added-on to previous therapy. The sample was collected from the period 2001 to 2006. Statistical analysis was performed in two groups: with and without AEs. Eighty-seven patients (21%) experienced at least one AE. The most frequent was hyponatremia, reported in 9.2%. OXC was discontinued because of AEs in 27 cases. There were no important differences between patients with and without AEs, except for age (p=0.04). The categorization of patients into three different age ranges, <20, 20-59 and Ž60 years, disclosed that the risk of AEs is notably lower in young (<20 years) and adult (20-59 years) patients (OR 0.46 and 0.51, respectively). In particular, the patients who experienced hyponatremia were significantly older than those who did not (p=0.0045). The other variables showed no major changes according to age. The incidence of major AEs during OXC treatment, leading to withdrawal, was found to be low and influenced by age, but not by OXC dosage, MHD concentrations or number of concomitant antiepileptic drug

Conscious and unconscious processing of facial expressions: Evidence from two split-brain patients

We investigated how the brain's hemispheres process explicit and implicit facial expressions in two 'split-brain' patients (one with a complete and one with a partial anterior resection). Photographs of faces expressing positive, negative or neutral emotions were shown either centrally or bilaterally. The task consisted in judging the friendliness of each person in the photographs. Half of the photograph stimuli were 'hybrid faces', that is an amalgamation of filtered images which contained emotional information only in the low range of spatial frequency, blended to a neutral expression of the same individual in the rest of the spatial frequencies. The other half of the images contained unfiltered faces. With the hybrid faces the patients and a matched control group were more influenced in their social judgements by the emotional expression of the face shown in the left visual field (LVF). When the expressions were shown explicitly, that is without filtering, the control group and the partially callosotomized patient based their judgement on the face shown in the LVF, whereas the complete split-brain patient based his ratings mainly on the face presented in the right visual field. We conclude that the processing of implicit emotions does not require the integrity of callosal fibres and can take place within subcortical routes lateralized in the right hemisphere

Brivaracetam add-on for refractory focal epilepsy

OBJECTIVE: To evaluate the efficacy and safety of the new antiepileptic drug brivaracetam (BRV) as add-on treatment for drug-resistant partial epilepsy using meta-analytical techniques. METHODS: Randomized, placebo-controlled, single- or double-blind, add-on trials of BRV in adult patients with drug-resistant partial epilepsy were identified through a systematic literature search. The following outcomes were assessed: 50% or greater reduction in seizure frequency, seizure freedom, incidence of treatment-emergent adverse events (TEAEs), and treatment withdrawal. Risk ratio (RR) with 95% confidence interval was estimated for each outcome. RESULTS: Six trials were included involving 2,399 participants according to the intent-to-treat, 1,715 for BRV, and 684 for placebo groups, respectively. The pooled RRs for the 50% responders and seizure freedom were 1.79 (1.51-2.12) and 4.74 (2.00-11.25), respectively. The subanalysis by levetiracetam (LEV) status did not show a statistically significant difference in the 50% responder rate when comparing BRV with placebo in patients with concomitant assumption of LEV. The TEAEs significantly associated with BRV were irritability (2.99 [1.28-6.97]), fatigue (2.19 [1.44-3.33]), somnolence (1.97 [1.45-2.68]), and dizziness (1.66 [1.19-2.31]). The overall RRs for treatment withdrawal due to TEAEs or any reason were 1.58 (1.04-2.40) and 1.27 (0.93-1.73), respectively. CONCLUSIONS: In adults with drug-refractory focal epilepsy, add-on BRV was effective to reduce seizure frequency and fairly well-tolerated. Further studies are needed to draw definitive conclusions about its efficacy in non-LEV-naive participants and evaluate its long-term safety profile