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

Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy

Introduction: Up to 30% of the patients diagnosed with epilepsy will continue suffering from seizures despite treatment with antiepileptic drugs, either in monotherapy or polytherapy. Hence, there remains the need to develop new effective and well-tolerated therapies. Aim: The objective of this article was to review the evidence for the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive treatment in adult patients with focal onset seizures. Evidence review: ESL is the newest, third-generation, single enantiomer member of the dibenzazepine family. Following oral administration, ESL is rapidly and extensively metabolized by hepatic first-pass hydrolysis to the active metabolite eslicarbazepine, which has linear, dose-proportional pharmacokinetics and low potential for drug-drug interactions. Eslicarbazepine works as a competitive blocker of the voltage gated sodium channels; unlike carbamazepine (CBZ) and oxcarbazepine (OXC), it has a lower affinity for the resting state of the channels, and reduces their availability by selectively enhancing slow inactivation. Efficacy and safety of ESL have been assessed in four randomized, Phase III clinical trials: the median relative reduction in standardized seizure frequency was 33.4% and 37.8% in the ESL 800 and 1,200 mg daily dose groups, and the responder rates were 33.8% and 43.1%, respectively. The incidence of treatment-emergent adverse events (TEAEs) increased with raising the dosage (ESL 400 mg: 63.8%, ESL 800 mg: 67.0%, ESL 1,200 mg: 73.1%). The TEAEs were generally mild to moderate in intensity, and the most common were dizziness, somnolence, headache and nausea. Open-label studies confirmed the findings from the pivotal trials and demonstrated sustained therapeutic effect of ESL over time and improvement of tolerability profile in patients switching from OXC/CBZ. No unexpected safety signals emerged over >5 years of follow-up. Conclusion: Once-daily adjunctive ESL at the doses of 800 and 1,200 mg was effective to reduce the seizure frequency and was fairly well tolerated in adults with focal onset epilepsy. Starting treatment at 400 mg/day, followed by 400 mg increments every 7-14 days, could provide the optimal balance of efficacy and tolerability

Myotonic dystrophy type 1 (Steinert's disease) and sleep disorders: prevalence and severity of respiratory disorders during sleep at diagnosis and lack of awareness by the patient

Introduzione ed obiettivi dello studio: La distrofia miotonica (DM), la distrofia più comune nell'adulto, è una malattia autosomica dominante caratterizzata da una ampia varietà di manifestazioni multisistemiche. La distrofia miotonica di tipo 1 (DM1) è causata da espansione della tripletta CTG all’estremità 3’ del gene della DM proteina chinasi. Tra le caratteristiche cliniche multisistemiche della DM1 vi è la compromissione respiratoria. Gli obiettivi di questo studio consistevano nel valutare la prevalenza e la gravità dei disturbi respiratori nei pazienti con DM1 al momento della diagnosi e nell'indagare sulla consapevolezza di malattia e di compromissione respiratoria da parte dei pazienti. Pazienti e Metodi: Tra i pazienti ricoverati presso la Clinica Neurologica di Ancona tra settembre 2007 e ottobre 2010 sono stati arruolati tutti i soggetti a cui veniva formulata la diagnosi genetica di DM1 confermata geneticamente. I pazienti sono stati sottoposti ad esame obiettivo generale e neurologico, visita oculistica, radiografia del torace e elettromiografia (EMG). Abbiamo analizzato le caratteristiche cliniche dei pazienti, il motivo che ha portato alla diagnosi, la presenza di sintomi suggestivi di un disturbo respiratorio (come affaticamento, dispnea, cefalea mattutina, ecc.). Tutti i pazienti venivano sottoposti a monitoraggio cardiorespiratorio notturno, spirometria ed emogasanalisi. Miotonia ed ipostenia sono state valutate utilizzando la scala per la disabilità (MDRS) e l'eccessiva sonnolenza diurna è stata determinata mediante la scala di sonnolenza di Epworth (ESS). Sono stati considerati come affetti da alterata funzione polmonare, i pazienti che avevano almeno uno dei seguenti reperti: PaCO2 diurna ≥ 45 mm Hg, capacità vitale forzata (FVC) <80% del predetto, AHI> 10 eventi per ora di sonno, SaO2 <90% per ≥ 5% della notte. L'indicazione alla ventilazione a pressione positiva non invasiva (NIV) veniva posta in presenza di uno tra PaCO2 ≥ 45 mm Hg, saturazione di ossigeno notturna ≤ 88% per 5 minuti consecutivi, FVC <50% del predetto. Risultati: I dati sono stati raccolti su 21 pazienti (11 femmine/10 maschi), età media 39,7 anni (range 19-61 anni). L'EMG mostrava un quadro di distrofia miotonica in tutti i pazienti. Nessuno dei pazienti aveva deformità della gabbia toracica. Il motivo che ha portato alla diagnosi di DM1 è stata la presenza di un parente affetto in 7 casi (33,35%), il fenomeno miotonico in tre (14,3%), il rilievo di iperCKemia agli esami ematici in 2 (9, 5%), ipostenia in 7 (33,35%) e altri motivi (mal di testa e vertigini) in 2 (9,5%). Il 33% dei pazienti risultava avere emogasanalisi, spirometria e monitoraggio cardiorespiratorio notturno nella norma mentre il restante 67% presentava un’alterazione di almeno uno di tali esami. L’indagine che evidenziava compromissione della funzionalità respiratoria era il solo esame notturno in un paziente (5%), la sola spirometria in due pazienti (10%), emogasanalisi ed esame notturno in un paziente (5%), emogasanalisi e spirometria in tre pazienti (15%), spirometria ed esame notturno in tre pazienti (15%), tutti e tre gli esami in 4 pazienti (20%). Dei 14 soggetti con compromissione della funzione respiratoria 9 avevano una situazione così severa da soddisfare i criteri per NIV. Soltanto quattro dei 21 pazienti esaminati, adeguatamente interrogati, riportavano sintomi indicativi di alterazione della funzionalità respiratoria.Uno di questi pazienti non aveva compromissione della funzione respiratoria. Conclusioni: In tre anni, sono stati arruolati 21 pazienti con DM1. E' probabile che l'incidenza di DM1 nella nostra regione sia significativamente più elevata rispetto a quanto ci si possa aspettare in relazione ai dati epidemiologici della letteratura. La maggior parte dei pazienti arruolati aveva prove di funzionalità respiratoria alterate. Non è stata trovata nessuna relazione significativa tra sintomi soggettivi, caratteristiche clinico-demografiche dei pazienti e compromissione respiratoria (p> 0,005). Un tempestivo riconoscimento di una compromissione respiratoria può portare ad un miglioramento della sopravvivenza e della qualità della vita mediante l'applicazione di NIV. L'importanza del monitoraggio della funzione respiratoria nei pazienti affetti da DM1 ha lo scopo di evitare procedure d’urgenza come l’intubazione. In relazione alla disomogeneità del quadro strumentale respiratorio, i tre esami che indagano la funzionalità respiratoria nei pazienti con DM1 andrebbero eseguiti tutti sin dal momento della diagnosi. Le linee guida relative alla indicazione alla NIV non tengono inoltre conto delle differenze che esistono tra le diverse patologie neuromuscolari, sarebbe pertanto necessaria la stesura di linee guida specifiche per ciascuna patologia neuromuscolare ed in particolare per la DM1

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

How Should We Lower Blood Pressure after Cerebral Hemorrhage? A Systematic Review and Meta-Analysis

SUMMARY: The aim of the study was to evaluate the safety and efficacy of early intensive vs. conservative BP lowering treatment in patients with ICH. Randomized controlled trials with active and control groups receiving intensive and conservative BP lowering treatments were identified. The following outcomes were assessed: 3-month mortality and combined death or major disability, 24-h hematoma growth, early neurological deterioration, occurrence of hypotension, severe hypotension, and serious treatment-emergent adverse events. Five trials were included involving 4,350 participants, 2,162 and 2,188 for intensive and conservative treatment groups, respectively. The pooled risk ratio of 3-month death or major disability was 0.96 (0.91-1.01) and the weighted mean difference in absolute hematoma growth was -1.53 (95% CI -2.94 to -0.12) mL in the intensive compared to conservative BP-lowering. There were no differences across the treatments in the incidence rates of 3-month mortality, early neurological deterioration, hypotension, and treatment-related adverse effects other than renal events. Key Messages: The early intensive anti-hypertensive treatment was overall safe and reduced the hematoma expansion in patients presenting with acute-onset spontaneous ICH and high BP levels

Efficacy and safety of adjunctive cannabidiol in patients with Lennox-Gastaut Syndrome: a systematic review and meta-analysis

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of marijuana, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs). OBJECTIVE: The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques. METHODS: Randomized, placebo-controlled, single- or double-blinded trials were identified. Main outcomes included the\u2009 65\u200950% reduction in baseline drop and non-drop seizure frequency, and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated through the inverse variance method. RESULTS: Two trials were included involving 396 participants. Patients presenting\u2009 65\u200950% reduction in drop seizure frequency during the treatment were 40.0% with CBD and 19.3% with placebo [RR 2.12 (95% CI 1.48-3.03); p\u2009<\u20090.001]. The rate of non-drop seizure frequency was reduced by 50% or more in 49.4% of patients in the CBD and 30.4% in the placebo arms [RR 1.62 (95% CI 1.09-2.43); p\u2009=\u20090.018]. The RR for CBD withdrawal was 4.93 (95% CI 1.50-16.22; p\u2009=\u20090.009). The RR to develop any AE during CBD treatment was 1.24 (95% CI 1.11-1.38; p\u2009<\u20090.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea and increased serum aminotransferases. CONCLUSIONS: Adjunctive CBD resulted in a greater reduction in seizure frequency and a higher rate of AEs than placebo in patients with LGS presenting seizures uncontrolled by concomitant AEDs

Blood pressure variability and clinical outcome in patients with acute intracerebral hemorrhage

BACKGROUND: The aim of this study was to evaluate whether fluctuations of blood pressure (BP) levels occurring in the acute stage of spontaneous intracerebral hemorrhage (ICH) affect the 3-month clinical outcome. METHODS: We retrospectively identified consecutive patients hospitalized for acute spontaneous ICH. BP measurements over the first 72 hours from the onset of symptoms were recorded, and standard deviation (SD), coefficient of variation (CV), and maximum-minimum difference (max-min) were determined to characterize both systolic and diastolic BP variability (BPV). The measure of outcome was the 3-month functional status assessed by the modified Rankin Scale following a baseline severity-adjusted analysis. RESULTS: Among the 138 enrolled patients with ICH, 67 (48.6%) were classified as having a poor 3-month functional recovery. A dose-response relationship with poor outcome was found for each measure of systolic BPV--adjusted odds ratios (ORs) for the highest thirds of SD 7.95 (95% confidence interval [CI], 2.88-21.90), CV 7.74 (95% CI, 2.88-20.80), and max-min 8.36 (95% CI, 2.72-25.62; P < .001). The strength of association with diastolic BPV turned out to be weaker and significant only for the higher values (adjusted ORs for the highest thirds of SD 6.74 [95% CI, 2.52-18.04], CV 4.57 [95% CI, 1.77-11.81], and max-min 4.34 [95% CI, 1.72-10.93]). CONCLUSIONS: In patients with acute ICH, BPV was a strong predictor of the 3-month clinical outcome and may represent a still neglected potential therapeutic target

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

Neutrophil-to-Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage

BACKGROUND AND PURPOSE: Increasing evidence suggests that inflammatory mechanisms are involved in the intracerebral hemorrhage-induced brain injury. We evaluated the prognostic role of the peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) in patients with intracerebral hemorrhage. METHODS: Patients with acute spontaneous intracerebral hemorrhage were retrospectively identified. Total white blood cells, absolute neutrophil count, and absolute lymphocyte count were obtained and the NLR computed from the admission blood work. The study end point was the occurrence of death or major disability at 3 months. RESULTS: One hundred seventy-seven subjects were enrolled. Ninety-four (53.1%) had unfavorable outcome. The absolute neutrophil count, absolute lymphocyte count, and NLR were independently associated with the 3-month status. The NLR resulted the best discriminating variable and the best predictive cut-off value was 4.58. CONCLUSIONS: In patients with acute intracerebral hemorrhage, higher neutrophils, lower lymphocytes, and higher NLRs predicted worse 3-month outcome