Predictors of functional outcome after symptomatic intracranial hemorrhage complicating intravenous thrombolysis: results from the SITS-ISTR.

BACKGROUND AND PURPOSE: Several risk factors of symptomatic intracerebral hemorrhage (SICH) following intravenous thrombolysis for acute ischaemic stroke have been established. However, potential predictors of good functional outcome post-SICH have been less studied. METHODS: Patient data registered in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) from 2005 to 2021 were used. Acute ischaemic stroke patients who developed post intravenous thrombolysis SICH according to the SITS Monitoring Study definition were analyzed to identify predictors of functional outcomes. RESULTS: A total of 1679 patients with reported SICH were included, out of which only 2.8% achieved good functional outcome (modified Rankin Scale scores of 0-2), whilst 80.9% died at 3 months. Higher baseline National Institutes of Health Stroke Scale (NIHSS) score and 24-h ΔNIHSS score were independently associated with a lower likelihood of achieving both good and excellent functional outcomes at 3 months. Baseline NIHSS and hematoma location (presence of both SICHs, defined as remote and local SICH concurrently; n = 478) were predictors of early mortality within 24 h. Independent predictors of 3-month mortality were age, baseline NIHSS, 24-h ΔNIHSS, admission serum glucose values and hematoma location (both SICHs). Age, baseline NIHSS score, 24-h ΔNIHSS, hyperlipidemia, prior stroke/transient ischaemic attack, antiplatelet treatment, diastolic blood pressure at admission, glucose values on admission and SICH location (both SICHs) were associated with reduced disability at 3 months (≥1-point reduction across all modified Rankin Scale scores). Patients with remote SICH (n = 219) and local SICH (n = 964) had comparable clinical outcomes, both before and after propensity score matching. CONCLUSIONS: Symptomatic intracerebral hemorrhage presents an alarmingly high prevalence of adverse clinical outcomes, with no difference in clinical outcomes between remote and local SICH.

Predictors of cognitive functioning after carotid revascularization.

PURPOSE: High-grade carotid stenosis can affect cognition, but the relationship between stenosis correction and cognitive outcome is not fully understood, yet. The aim of this study was to evaluate the predictors of post-operative neurocognitive functioning in patients with symptomatic severe internal carotid artery (ICA) stenosis undergoing carotid endarterectomy (CEA). MATERIALS AND METHODS: Patients with history of transient ischemic attack within the past 6 months and ipsilateral high-grade stenosis of ICA undergoing CEA were prospectively enrolled. Cerebral hemodynamics was assessed by means of the cerebral vasomotor reactivity (CVR) to hypercapnia measured through transcranial Doppler ultrasonography. Coloured Progressive Matrices plus Complex Figure Copy Test, and phonemic plus categorical (ca) Verbal Fluency tests were performed to assess right and left hemisphere cognitive functions, respectively. Cerebral hemodynamics and cognitive functions were assessed before and 6 months after CEA. RESULTS: One hundred and eighty-one patients were included. The mean age was 73.2 (6.9) years and 121 (66.9%) were males. At 6 months from CEA, the scores obtained in the cognitive tests exploring the re-vascularized hemisphere's functions and ipsilateral cerebral hemodynamics were improved. At multivariate linear regression analysis, the 6-month change in cognitive performance was inversely associated with age [ß = -0.17, 95% confidence interval (CI) -0.22 to -0.12; p < .001] and CVR value obtained before CEA on the side of ICA stenosis (ß = -6.25, 95% CI -7.40 to -5.10; p < .001). CONCLUSIONS: In patients with symptomatic high-grade ICA stenosis, age and cerebral hemodynamic status before CEA predicted the neurocognitive performance changes after surgical stenosis correction.

Longitudinal Study on Low-Dose Aspirin versus Placebo Administration in Silent Brain Infarcts: The Silence Study.

BACKGROUND: We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment. METHODS: We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment. RESULTS: Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-a [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence. CONCLUSIONS: These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis. EU Clinical trial is registered with EudraCT Number: 2005-000996-16; Sponsor Protocol Number: 694/30.06.04.

Migraine: incorrect self-management for a disabling disease.

Migraine is an economically and socially relevant pathology but patients' consciousness and consequently a proper management is often unsatisfactory. In this study, we aimed to evaluate the disease awareness, the general approach and the impact on working activity in a population of headache-affected hospital workers. During an 18-month period, hospital workers responded to a questionnaire investigating headache presence, characteristics and awareness. Specific attention was paid to define headache impact on working activities. 1774 consecutive subjects were enrolled. Headache was documented in 45.7% of the sample, migraine in 16.6%. 40.6% of the patients with headache and 50.7% of the migraneous subjects had a specialist medical evaluation. Triptans use was significantly lower than non-steroidal anti-inflammatory drugs use. 39.5% of migraneous complained of attacks during working time, 60.2% acknowledged a negative influence on work quality. 25.5% of migraneous patients reported a loss of working days attributable to the disease. Migraine is disabling for workers with negative consequences on job capacity and quality. Efforts should be made to improve disease awareness to stimulate a better diagnostic and therapeutic approach.

Neutrophil-to-lymphocyte ratio improves outcome prediction of acute intracerebral hemorrhage.

BACKGROUND: The inflammatory response plays a role in determining the course of intra-cerebral hemorrhage (ICH) and immune parameters may have prognostic value. The aim of the study was to determine whether the peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) were associated to 30-day functional status after ICH, and improved the accuracy of outcome prediction when added to the Modified ICH score. METHODS: We retrospectively identified consecutive patients with spontaneous ICH who underwent blood sampling and cranial CT neuroimaging within 24 h from onset. Total white blood cells (WBC), absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected, and the NLR computed as the ANC to ALC ratio. The study endpoint was 30-day functional status; poor outcome was defined as death or major disability (modified Rankin Scale score ≥ 3). RESULTS: Two hundred and eight patients were enrolled, of which 111 (53.4%) had a modified Rankin Scale score ≥ 3 at 30 days from ICH. At multivariate analysis, the WBC (adjusted odd ratio [adjOR] for 1000 leukocytes increase 1.20, 95% confidence interval [CI] 1.05-1.38), ANC (adjOR for 1000 neutrophils increase 1.34, 95% CI 1.14-1.57), ALC (adjOR for 1000 lymphocytes increase 0.34, 95% CI 0.20-0.59) and NLR (adjOR for 1-point increase 1.49, 95% CI 1.24-1.79) were independently associated with 30-day poor outcome. Predictive accuracy of the Modified ICH score was enhanced by adding the NLR. CONCLUSIONS: The NLR was associated with 30-day mortality and morbidity after ICH, and improved the accuracy of outcome prediction when added to the Modified ICH score.

Swallowing impairments in Amyotrophic Lateral Sclerosis and Myotonic Dystrophy type 1: Looking for the portrait of dysphagic patient in neuromuscular diseases.

BACKGROUND: Dysphagia is a critical symptom of Neuromuscular Diseases and is often associated with considerable morbidity and mortality. OBJECTIVE: This study is designed to investigate the prevalence of dysphagia and to identify different clinical profiles of swallowing disorders in Myotonic Dystrophy type 1 (DM1) and Amyotrophic Lateral Sclerosis (ALS), the most common Neuromuscular Diseases in the adult age. METHODS: Consecutive DM1 and ALS patients from 2013 to 2015 referred to a Centre for Neuromuscular Disease were enrolled. A comprehensive assessment of swallowing function with a Clinical Swallowing Examination and Fluid and Food Trials was performed. RESULTS: 157 patients were included: 86 ALS, 71 DM1. The dysphagic patients affected by ALS and DM1 (79% and 86% of the respective samples) showed two different profiles. ALS patients with dysphagia were older and underweight. They experienced a global dysfunction of the oral and pharyngeal phases with more difficulty in swallowing thin liquids. Conversely, DM1 patients with dysphagia were younger and tended to obesity. Most of them showed impairment of oral phase and had more frequently difficulty in swallowing solid bolus. CONCLUSION: The recognition of specific clinical profiles supports and guides the detection of swallowing disorders in patients with neuromuscular diseases.

Impact of sleep disorders on the risk of seizure recurrence in juvenile myoclonic epilepsy.

OBJECTIVE: The aim of this study was to investigate the presence of sleep disturbances in patients with juvenile myoclonic epilepsy (JME) using sleep questionnaires. Further, we tried to evaluate whether alterations in sleep quality may influence the clinical expression of JME. METHODS: Sixty-two patients with JME treated with levetiracetam were included. Demographic and clinical variables were collected. Moreover, all patients submitted the Pittsburgh Sleep Quality index (PSQI) and the Epworth Sleepiness Scale (ESS) in order to respectively assess sleep quality during the last month and daytime sleepiness. All patients were followed up for a 6-month period and divided in two groups: seizure-free (Group 1) and seizure recurrence (Group 2). The PSQI and ESS scores were synthesized as binary variables <5/≥5 and <10/≥10, respectively. A comprehensive analysis was performed to evaluate the independent effect of the sleep quality and daytime sleepiness on the risk of having seizures during the follow-up. RESULTS: Both reduced sleep quality during the last month and daytime sleepiness were associated with an increased risk of suffering from seizures during the follow-up period. In fact, a PSQI score<5 or an ESS score<10 resulted significantly associated with the absence of seizure recurrence (p<0.004 and p<0.001, respectively). Increasing age had a significantly protective effect in the risk of seizure relapse. CONCLUSIONS: Our findings show that reduced sleep quality and daytime sleepiness in patients with JME increase the risk of seizure occurrence in spite of an appropriate pharmacological treatment. This negative effect seems to be more relevant in younger patients. Sleep disorders and their specific correction should be taken into consideration for the management of patients with JME.

Neurocognitive functioning and cerebrovascular reactivity after carotid endarterectomy.

OBJECTIVE: To evaluate in patients with TIA and ipsilateral high-grade internal carotid artery (ICA) stenosis whether changes in cognitive performance and cerebral hemodynamics occurred after carotid endarterectomy (CEA) and to explore their relationship. METHODS: Participants were patients who underwent CEA, had TIA within the last 6 months, and had an ipsilateral severe ICA stenosis. Coloured Progressive Matrices (CPM) plus Complex Figure Copy Test (CFCT) and phonemic (ph) plus categorical (ca) Verbal Fluency (VF) tests were performed to assess right and left hemisphere cognitive functions, respectively. Hemodynamics was assessed with transcranial Doppler ultrasonography by means of the cerebral vasomotor reactivity (CVR) to hypercapnia. RESULTS: A total of 137 patients were included. Before CEA, patients with right ICA obtained lower scores on the CPM and CFCT; patients with left ICA stenosis performed worse on the phonemic and categorical VF tests. The CVR was decreased on the side of the stenosis. At 6 months from CEA, CVR and cognitive performance were significantly improved. The performance change in cognitive tests exploring the revascularized hemisphere was positively associated with the ipsilateral CVR variation (CPM: R2 for linear regression = 0.759, adjR2 = 0.737; CFCT: R2 = 0.734, adjR2 = 0.710; (ph)VF: R2 = 0.774, adjR2 = 0.749; (ca)VF: R2 = 0.732, adjR2 = 0.703). CONCLUSION: Cognitive performance was enhanced at 6 months since CEA, and the improvement was related to the CVR increase. Cerebral hemodynamics may be an independent and potentially reversible determinant of cognitive dysfunction in severe carotid artery disease.

Correction to: Management of pregnancy-related issues in multiple sclerosis patients: the need for an interdisciplinary approach.

The original version contained a mistake. The authors have specified only in a few paragraphs that all the contents of the paper are meant for Copaxone but not for unbranded glatiramer acetate, Authors ask to add the specification of Copaxone or branded glatiramer acetate everytime.

Selective associative phonagnosia after right anterior temporal stroke.

We report the case of a 48 year old men who developed a selective impairment in famous voice recognition after ischemic stroke in right subcortical structures (lenticular nucleus and head of the caudate) and right anterior temporal lobe. He underwent fibrinolytic treatment. During the following days he progressively recovered and was discharged without neurological focal sign. Patent foramen ovale was found. When he got back to his house he noticed that he was unable to recognize the voice of his favoured singers and needed to ask who was the singer to his relatives. Neuropsychological examination revealed a selective impairment in famous voice recognition in the absence of alteration of voice perception, face perception and famous face recognition. All other neuropsychological domains were spared. In particular language, memory and executive functions were intact. Neuroimaging carried out by means of PET and MRI revealed two small ischemic lesions in the right subcortical region, involving lenticular and caudate nuclei and in the right temporal pole. To our knowledge, this is the first case described in literature of a patient showing a selective associative phonagnosia after right anterior temporal stroke. The present case helps to clarify the brain circuits underlying famous voice recognition and adds evidence in favour of a right hemisphere involvement in processing knowledge of familiar voices. These findings are discussed in relation to current models of brain organization of person-specific and general semantic knowledge.

Sleep Apnea, Cognitive Profile, and Vascular Changes: An Intriguing Relationship.

BACKGROUND: Sleep breathing disorders can affect cognitive performances through complex brain anatomical and functional changes. OBJECTIVE: Our aim was to evaluate the correlations between cognitive performances and obstructive sleep apnea syndrome (OSAS), as well as the possible influence of vascular factors. METHODS: Thirty-four non-demented OSAS patients and 34 controls were submitted to a neuropsychological evaluation and to a vascular screening including the study of cerebrovascular reactivity by means of the breath-holding index (BHI) calculation. After 6 months, polisomnographic, neuropsychologic, and hemodynamics assessment was repeated in patients. RESULTS: At baseline, some cognitive performances involved in executive and memory functions were significantly lower in patients with respect to controls. Significantly lower values in mean BHI were also detected in patients with respect to controls (p < 0.0001). At the 6-month evaluation, 18 patients had a reduction in OSAS severity (group 1) and 16 remained stable (group 2). Group 1 patients had a significant improvement in left and mean BHI (p < 0.001) and in short-term (p = 0.02) and long-term Rey Auditory Verbal Learning Test (p < 0.001). No change in cerebrovascular reactivity and cognitive profile was detected in group 2 patients. CONCLUSIONS: Patients with OSAS may experience a reduced cognitive efficiency. Improvement of OSAS was associated to favorable hemodynamic changes and increased level of performances in verbal memory tasks so suggesting an involvement of vascular underlying mechanisms in sustaining cognitive dysfunctions in OSAS. Our preliminary data suggest the need for further studies to deepen the knowledge about the relationships between OSAS, cerebral hemodynamic compromise, and cognitive impairment risk.

Neutrophil-to-lymphocyte ratio and neurological deterioration following acute cerebral hemorrhage.

Immunity plays key roles in pathophysiology of intracerebral hemorrhage (ICH). The aim of the study was to determine whether the peripheral leukocyte count and neutrophil-to-lymphocyte ratio (NLR) predicted neurological deterioration (ND) after ICH. We identified consecutive patients with ICH who had blood sampling performed within 24 hours from symptom's onset. Total white blood cells (WBC), absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were retrieved, and the NLR computed as the ratio of the ANC to ALC values. The study endpoint was the occurrence of neurological deterioration (ND) within 7 days after ICH. One hundred ninety-two subjects were enrolled, whose 54 (28.1%) presented ND. At multivariate analysis, the WBC (adjusted odd ratio [adjOR] for 1,000 leukocytes increase 1.29, 95% confidence interval [CI] 1.11-1.50), ANC (adjOR for 1,000 neutrophils increase 1.61, 95% CI 1.30-1.99), ALC (adjOR for 1,000 lymphocytes increase 0.21, 95% CI 0.09-0.49) and NLR (adjOR for 1-point increase 1.65, 95% CI 1.36-2.00) were independently associated with ND (p≤0.001). The NLR resulted the best discriminating variable for the occurrence of the adverse outcome (area under the curve 0.888, 95% CI 0.832-0.945; p < 0.001). The NLR predicted ND after acute ICH and can aid in the risk stratification of patients.

Management of pregnancy-related issues in multiple sclerosis patients: the need for an interdisciplinary approach.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS), most probably autoimmune in origin, usually occurring in young adults with a female/male prevalence of approximately 3:1. Women with MS in the reproductive age may face challenging issues in reconciling the desire for parenthood with their condition, owing to the possible influence both on the ongoing or planned treatment with the possible consequences on the disease course and on the potential negative effects of treatments on foetal and pregnancy outcomes. At MS diagnosis, timely counselling should promote informed parenthood, while disease evolution should be assessed before making therapeutic decisions. Current guidelines advise the discontinuation of any treatment during pregnancy, with possible exceptions for some treatments in patients with very active disease. Relapses decline during pregnancy but are more frequent during puerperium, when MS therapy should be promptly resumed in most of the cases. First-line immunomodulatory agents, such as interferon-ß (IFN-ß) and glatiramer acetate (GA), significantly reduce the post-partum risk of relapse. Due to substantial evidence of safety with the use of GA during pregnancy, a recent change in European marketing authorization removed the pregnancy contraindication for GA. This paper reports a consensus of Italian experts involved in MS management, including neurologists, gynaecologists and psychologists. This consensus, based on a review of the available scientific evidence, promoted an interdisciplinary approach to the management of pregnancy in MS women.

Persistence to oral disease-modifying therapies in multiple sclerosis patients.

Dimethyl fumarate (DMF), fingolimod (FTY) and teriflunomide (TFN) are oral disease-modifying therapies (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS) whose efficacy and tolerability have been separately assessed in phase III trials. Conversely, little evidence exists about their head-to-head comparison. The aim of the study was to evaluate the 1-year persistence to DMF, FTY and TFN in patients with RRMS. Patients affected by RRMS who started treatment with DMF, FTY or TFN were identified. The study end-point was 12-month drug persistence as time to discontinuation and proportion of patients who discontinued medication within 1-year. A total of 307 patients were included (DMF = 114, FTY = 129, TFN = 64). The mean times to discontinuation were 144 (84), 189 (72) and 138 (120) days in the DMF, FTY and TFN cohorts (p = 0.036). At 12-month, the proportion of patients discontinuing medication was lower for subjects taking FTY (9.8%) compared with those starting DMF (21.9%) and TFN (23.6%) (p = 0.020). Compared to FTY cohort, DMF [adjOR = 3.26 (1.38-7.70); p = 0.007] and TFN [adjOR = 2.89 (1.10-7.63); p = 0.032] treated patients were more likely to have discontinued their drug at 1-year since initiation. In patients with RRMS, FTY was associated with a better persistence profile as compared to DMF and TFN.

Framingham Risk Score and the Risk of Progression from Mild Cognitive Impairment to Dementia.

BACKGROUND: Mild cognitive impairment (MCI) often represents the clinical manifestation of cognitive deterioration preceding Alzheimer's disease (AD). Currently, there are no reliable approaches for an objective evaluation of the risk of developing AD in MCI patients. OBJECTIVE: The aim of this study was to verify whether the Framingham cardiovascular risk profile (FCRP) could be useful to identify patients at the highest risk of conversion from MCI to AD. METHODS: Patients with amnestic MCI (aMCI) were carefully investigated to assess their vascular risk profile. They were also submitted to a comprehensive neuropsychological evaluation. The FCRP was calculated for each patient and the apolipoprotein E (ApoE) genotype was determined from peripheral blood cells. The main outcome was defined as a conversion to AD within 24 months after inclusion. RESULTS: 385 consecutive aMCI subjects were included. Age, FCRP, and vascular age showed a fairly predictive value on conversion to AD. Selecting the subpopulation of ApoE ɛ4 carriers, we observed that FCRP had an increased performance in predicting the conversion. The rate of conversion increased from 12.5% in the FCRP low-risk group to 43.2% in the high-risk group (p < 0.0001). ApoE ɛ4 carriers had a 3.7-times increased probability of conversion with respect to the other subjects (p < 0.0001). CONCLUSIONS: FCRP assessment could be considered a reliable approach to predict conversion to AD in aMCI subjects. The presence of ApoE ɛ4 increases significantly the risk of conversion. These data confirm the narrow relationship between genetic and vascular risk factors in influencing the evolution of cognitive impairment.

Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis.

Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses, but the most desirable route of administration is still matter of debate. The aim of the study was to compare the efficacy and safety of oral versus intravenous steroids for treatment of acute relapses in patients with MS. Randomized or quasi-randomized, parallel group trials with direct comparison between oral and intravenous steroid treatment in MS patients with acute relapse were identified through a systematic literature search. Six trials were included involving 419 participants, 210 for oral, and 209 for intravenous groups, respectively. The weighted mean differences (WMDs) in the Kurtzke's Expanded Disability Status Scale (EDSS) score reduction between the oral and intravenous groups were 0.32 [(-0.09 to 0.73); p = 0.129] and 0.11 [(-0.12 to 0.33); p = 0.355] at 1 and 4 weeks after treatment, respectively. The risk ratios (RRs) for improvement by at least one EDSS point were 0.79 [(0.37-1.68); p = 0.539] at week 1 and 0.92 (0.76-1.12); p = 0.400] at week 4. There were no differences in the relapse rate and relapse freedom at 6 months between groups. The WMDs in the mean percentage reduction of Gadolinium-enhancing lesions between oral and intravenous arms were 0.14 (-0.02, 0.29); p = 0.083] and 0.04 (-0.19, 0.28); p = 0.705] at 1 and 4 weeks from treatment. Among the adverse events, insomnia was significantly associated with the oral route of steroid administration [RR 1.25 (1.07-1.46); p = 0.005]. In adult patients with acute MS relapse, there were no clear-cut differences in the efficacy and overall tolerability between oral and intravenous steroids.

Raven coloured progressive matrices in migraine without aura patients.

Conflicting results emerged from studies investigating cognitive performances in migraine patients. Based on clinical and neuroradiological aspects, the possible involvement of executive functions has been especially taken into consideration. The aim of this study was to evaluate, in a population of subjects affected by migraine without aura (MwoA), frontal lobe cognitive functions. We enrolled all the consecutive patients affected by MwoA referred to our headache centre for a first evaluation. Each patient underwent a neuropsychological evaluation including Raven coloured progressive matrices (CPM). We collected variables as age, education, years of migraine, frequency of attacks and CPM scores. Relationship between continuous variables was explored with multiple regression lines, selecting the best-fitting trendline for each relationship. We obtained a final sample of 36 subjects (females: 62.5%; mean age: 42.25 ± 10.21 years). Patients had mean length of migraine history of 12.25 ± 11.00 years and a mean frequency of attacks of 8.06 ± 7.15 per month. Linear regression underlines a progressive decrease of CPM score with the increase of the migraine history's length (R 2 = 0.8871; p < 0.001), and the frequency of migraine attacks (R 2 = 0.3122; p < 0.05). Our findings suggest that pathological CPM scores can be associated with the severity of migraine. These data seem to confirm the hypothesis of an impairment of executive functions in MwoA. Different hypotheses to explain cognitive impairment in migraine have been postulated including the impact of the typical white matter lesions and a long history of drug abuse. The possible relevant clinical consequence of a full comprehension of this particular aspect related to migraine deserves further attention and consideration.

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.