Nicoletta Foschi

Brivaracetam add-on for refractory focal epilepsy A systematic review and meta-analysis

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.

Clinical effectiveness of osteopathic treatment in chronic migraine: 3-Armed randomized controlled trial

OBJECTIVE To assess the effectiveness of OMT on chronic migraineurs using HIT-6 questionnaire, drug consumption, days of migraine, pain intensity and functional disability. DESIGN 3-Armed randomized controlled trial setting: all patients admitted in the Department of Neurology of Anconas United Hospitals, Italy, with a diagnosis of migraine and without chronic illness, were considered eligible for the study. INTERVENTIONS Patients were randomly divided into three groups: (1) OMT+medication therapy, (2) sham+medication therapy and (3) medication therapy only. Patients received 8 treatments in a study period of 6 months. MAIN OUTCOME MEASURES Changing from baseline HIT-6 score. RESULTS 105 subjects were included. At the end of the study, ANOVA showed that OMT significantly reduced HIT-6 score (mean change scores OMT-conventional care: -8.74; 95% confidence interval (CI) -12.96 to -4.52; p<0.001 and OMT-sham: -6.62; 95% CI -10.85 to -2.41; p<0.001), drug consumption (OMT-sham: RR=0.22, 95% CI 0.11-0.40; OMT-control: RR=0.20, 95% CI 0.10-0.36), days of migraine (OMT-conventional care: M=-21.06; 95% CI -23.19 to -18.92; p<0.001 and OMT-sham: -17.43; 95% CI -19.57 to -15.29; p<0.001), pain intensity (OMT-sham: RR=0.42, 95% CI 0.24-0.69; OMT-control: RR=0.31, 95% CI 0.19-0.49) and functional disability (p<0.001). CONCLUSIONS These findings suggest that OMT may be considered a valid procedure for the management of migraineurs. The present trial was registered on www.ClinicalTrials.gov (identifier: NCT01851148).

Lacosamide monotherapy for partial onset seizures

PURPOSE To evaluate the 1-year efficacy and safety of oral lacosamide as conversion monotherapy in adult patients with partial onset seizures with or without generalization. METHOD We prospectively followed-up consecutive patients converted to lacosamide monotherapy after 1-year seizure freedom on lacosamide add-on therapy and withdrawal of the concurrent antiepileptic drug (AED). Seizure occurrence, treatment compliance and drug toxicity were assessed every 3 months up to 1 year. The study outcomes were the retention rate of lacosamide as single AED and the seizure freedom under lacosamide monotherapy at 1 year from withdrawal of background AED. The safety variable was the prevalence of lacosamide related adverse events (AEs). RESULTS Among the 58 included patients, at 1 year from withdrawal of background medication, 37 (63.8%) retained lacosamide as single AED and 32 (55.2%) were free from seizure occurrence under lacosamide monotherapy throughout the entire follow-up. The history of less than three lifetime AEDs turned out to be significant predictor of seizure freedom (adjusted OR = 6.38, 95% CI 1.85-21.98, p = 0.003). Twelve (20.8%) subjects reported mild to moderate AEs, with the commonest being drowsiness, dizziness, and headache. CONCLUSION Conversion to lacosamide monotherapy could be effective and well tolerated in selected adults patients with partial onset seizures who had achieved seizure freedom during lacosamide add-on therapy.

Seizure course during pregnancy in catamenial epilepsy

Objective: Our aim was to evaluate seizure course in catamenial epilepsy (CE) and noncatamenial epilepsy (NCE) during pregnancy. Methods: We prospectively followed women referred to our Epilepsy Center for pregnancy planning to the end of the pregnancy. According to their seizure frequency variations across the menstrual cycle, all patients were divided into either the CE or the NCE group. Data on seizure frequency during pregnancy were collected for each patient and compared with seizure frequency during the pregestational 9 months. Results: Fifty-nine women with CE and 215 with NCE were included. Forty-seven subjects (79.7%) with CE and 48 subjects (22.3%) with NCE remained seizure-free throughout pregnancy (odds ratio [OR] = 2.612, 95% confidence interval [CI] 1.901–3.323, p < 0.001), whereas 30 (50.8%) in the CE group and 18 (8.4%) in the NCE group had reduced seizure frequency during pregnancy (OR = 2.427, 95% CI 1.724–3.129, p < 0.001). Decreases in seizures ≥50% occurred in 26 women (44.1%) with CE and 14 women (6.5%) with NCE (OR = 2.426, 95% CI 1.679–3.173, p < 0.001). Multiple logistic regression models confirmed the significant role of catamenial pattern as predictor for better outcomes. Conclusions: Better seizure control during pregnancy in the catamenial group may be attributable to the absence of cyclical hormone variations and the increase in circulating progesterone levels. These data may have practical implications for therapeutic management of patients with CE during pregnancy.

A novel inherited SCN1A mutation associated with different neuropsychological phenotypes: Is there a common core deficit?

We report a three-generation, clinically heterogeneous family in which we identify a novel inherited splicing mutation of the SCN1A gene. Thirteen subjects were submitted to genetic analysis, clinical and instrumental examination, and neuropsychological assessment. In eight subjects, a heterozygous c.2946+5G>A donor splice site alteration in the SCN1A gene was found. Half of them had never had a seizure and showed normal EEG and cognitive profile, whereas the other half had a history of seizures and variable neuropsychological impairments ranging from moderate cognitive disabilities to mild visual-motor impairments. Different clinical phenotypes were identified, including generalized epilepsy with febrile seizure plus (GEFS+), Dravet syndrome, and partial epilepsy with febrile seizure plus (PEFS+). Remarkable clinical heterogeneity can be found among family members carrying the same SCN1A gene mutation. Variable involvement of visual-motor abilities might represent a neuropsychological feature which needs to be further explored in other familial cases.

Eslicarbazepine acetate as adjunctive treatment in partial‐onset epilepsy

The aim of the study was to assess the clinical response to eslicarbazepine acetate (ESL) as add‐on therapy in adult patients with partial‐onset epilepsy by means of the time‐to‐baseline seizure count method.

Emergency room access for recurring seizures: when and why

To develop a hypothetical model identifying potentially modifiable predictive factors of Emergency Room (ER) visits by patients suffering from drug resistant epilepsy.

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.

Klinische Effektivität einer osteopathischen Behandlung bei Migräne

Zusammenfassung Zielsetzung Beurteilung der Effektivitat einer osteopathischen Behandlung (OMT) bei Patienten mit chronischer Migrane anhand von HIT-6-Fragebogen, Medikamenteneinnahme, Anzahl Migranetagen, Schmerzintensitat und funktioneller Beeintrachtigung. Studiendesign 3-armige randomisierte, kontrollierte Studie. Alle in der Abteilung fur Neurologie der Ospedali Riuniti di Ancona, Italien, aufgenommene Patienten mit diagnostizierter Migrane ohne weitere chronische Erkrankung galten als studiengeeignet. Interventionen Die Patienten wurden nach dem Zufallsprinzip 3 Gruppen zugeteilt: 1) OMT plus Medikamententherapie, 2) Scheinbehandlung plus Medikamententherapie und 3) nur Medikamententherapie. Die Patienten erhielten im Studienzeitraum von 6 Monaten 8 Behandlungen. Wichtigste Ergebnisparameter Abweichung vom HIT-6-Ausgangswert. Ergebnisse 105 Patienten wurden in die Studie einbezogen. Nach Abschluss der Studie zeigte die ANOVA eine erhebliche Reduktion der HIT-6-Werte durch die OMT (mittlere Anderung der Werte fur OMT vs. konventionelle Versorgung: −8,74; 95% Konfidenzintervall (KI) −12,96 bis −4,52; p Fazit Diese Ergebnisse legen nahe, OMT als ein valides Verfahren fur die Behandlung von Migranepatienten einzustufen.