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Our goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases.We retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution. We collected clinical, neurophysiological and neuroimaging data from patients who met defined inclusion and exclusion criteria.Study involved 61 patients (65.5% female) with mean age at study of 37.6 years, and mean age at its outset of 14.8 years. Median follow-up was 31.0 years (mean 28.9, range 15-53). They presented more frequently with a combination of myoclonic and generalized tonic-clonic seizures (GTCS) (65.6%). Sixty-five percent of patients (n = 40) had a 5-year terminal remission with a mean age at last seizure of 27.4 years. Thirty-two percent of seizure-free patients (n = 13) withdrew ASMs: 6 out of 13 had a recurrence of the seizures while 7 remained seizure-free (mean age at ASMs withdrawal 21.0 versus 35.7 years, p 0.05). In the multivariate model, a high GTCS frequency at onset (p = 0.026) was a prognostic factor of drug resistance.JME is often regarded as a benign epileptic syndrome, although a quarter of the individuals have refractory epilepsy. The possibility of withdrawing ASMs in patients who have been free of seizures over an extended time seems feasible.

Eyelid myoclonia with absences is recently included in the category of childhood epileptic syndromes. It is clinically characterized by brief seizures of eyelid myoclonia, sometimes followed by absences, and it is associated to EEG generalized discharges of polyspikes or polyspike-waves, which are triggered by eyes closure in a well-lit room. This epileptic syndrome probably has a genetic origin, as well as other genetic generalized epilepsies, in particular photosensitive epilepsies. We describe the case of a patient affected by eyelid myoclonia with absences, intellectual disability, and attention deficit hyperactivity disorder (ADHD), with a de novo mutation of the RORB gene (retinoid-related orphan receptor β); this gene is involved in vivo in different neuronal processes among which are migration and differentiation. We suggest that its mutation in our patient can be considered the cause of the aberrant functioning of the cerebral cortex, which is clinically expressed by epilepsy and neurodevelopment disorders.

Highlights • Data about only 96 cases of pregnancies exposed to PER are available to date. • Few information are available about perinatal metrics. • We report perinatal metrics and newborn vital signs of 4 pregnancies exposed to PER., Perampanel (PER) is approved in Italy as an adjunctive treatment for focal-onset seizures (FOS) and generalized tonic-clonic seizures (GTCs), and it could be an alternative to valproate in young women diagnosed with idiopathic generalized epilepsy. Nevertheless, clinical data about the outcome of pregnancies in women exposed to PER are lacking. Here, we report retrospectively collected data from four women suffering from FOS who were exposed to PER during pregnancy. Three pregnancies were carried out with PER as add-on therapy during the entire gestation (8 mg/day in two patients and 6 mg/day in one), without seizure frequency variations. The fourth patient started PER 2 mg/day as monotherapy during the 13th week of pregnancy due to seizure relapse and continued it until delivery with complete seizure control. All pregnancies showed good outcomes, and their newborns did not possess major congenital malformations. Apgar scores and auxological parameters at birth were normal. Fetal pathology in follow-up during pregnancies was absent in all cases. In our patients PER was well tolerated and appeared safe for the fetuses and did not result in major malformations or adverse events at birth. Nevertheless, this is a report involving a small number of patients and it does not suggest the general use of PER is safe during pregnancy.

Objective This research was focused on expert professionals in epilepsy care to understand their points of view on the care pathway and their living relationships with patients. Methods Researchers prepared a semi-structured parallel chart and distributed it online among 21 Italian centres of care. Each health professional was prompted to write five narratives on cases of patients with epilepsy, subsequently analysed through narrative medicine methods. Next, a consensus meeting was held, to individualise an action plan based on the narratives. Results Ninety-one parallel charts were collected from 25 epileptologists, who had a mean age of 50 years; their narratives concerned patients with a mean age of 37 years, with different types of epilepsy (53 % drug-resistant; 31 % unemployed). The limitations in the daily life of people with epilepsy (57 %), employment (42 %), caregiver burden (51 %), and the universal prevalence of fear were the primary topics that emerged. Attentive and reassuring care relationships were found to be the main element of coping (21 %). A new multi-factorial classification of epilepsies, integrating clinical with social and legal risk factors, was the main agreed action to face the issues identified. Conclusions The narrative medicine approach supplied a broader scenario of living with epilepsy, including the family and social impact and possible effects on the choices for care pathways. The epileptologists showed a strong motivation to care for patients with epilepsy and deep involvement in the care relationships; the use of parallel chart demonstrated to be an effective tool to preserve their wellbeing.

Introduction To evaluate the knowledge of healthcare workers about first-aid measures to be performed during and after a tonic–clonic seizure. Methods One hundred and fifty-four healthcare workers (86 physicians) working at 8 tertiary hospitals in the Apulia region, Italy, responded to a questionnaire comprising of 28 questions based on available Italian and international recommendations about what to do during a tonic–clonic seizure. Results One hundred and fifty-four healthcare workers completed and returned surveys with a response rate of 96.25%. There were 55 nurses (35.7%), 86 physicians (55.8%), and 13 healthcare workers with different roles (Electroencephalograph technicians, psychologists, social workers). Among physicians, there were 7 cardiologists, 3 surgeons, 12 infectious-disease specialists, 11 internal medicine specialists, 2 psychiatrists, 2 gynecologists, 27 specialists working in the emergency department, and 22 physicians with different specializations. Nearly 90% of the respondents identified head protection as important first aid, while 100% responded to not keep the legs elevated. To avoid tongue bite, both physicians and other healthcare workers would put something in the mouth (54.0%), like a Guedel cannula (71.0%) fingers (29.5%). Grabbing arms and legs, trying to stop the seizure, would be potentially performed by 11.6% of our sample. Physicians would administer a benzodiazepine during the seizure (65.7%) and during the postictal phase (29.2%), even if the patient is known to have epilepsy (23.7%), and in this case, 11.3% of respondents would administer the usual antiepileptic medications. More than half of respondents would call the emergency telephone number, because of necessary hospitalization in case of tonic–clonic seizure, even if it is experienced by a patient known to have epilepsy. Conclusion Our survey suggests the need for epilepsy educational programs on first-aid management of seizures among healthcare workers.

Aim: To provide field-practice information on the safety and efficacy of eslicarbazepine. Patients & methods: Patients who switched from carbamazepine or oxcarbazepine to eslicarbazepine were consecutively and retrospectively identified in two Italian reference centers for the treatment of epilepsy. Results: Eighteen patients with a mean age of 39 ± 16 years were recruited. Mean monthly seizure frequency was 18 ± 22 (range: 2–59) before switching to eslicarbazepine, and decreased to 11 ± 18 (0–56) after switching (p = 0.03). The monthly number of seizures decreased in 16/18 patients (89%) and it remained unchanged in one. Six patients became seizure-free after switching, five of whom had underwent overnight switch. The mean score of the adverse event profile questionnaire before switching was 42.5 ± 9.5 and it decreased to 35.0 ± 6.4 with eslicarbazepine therapy; 8/11 patients (73%) reported improved scores. Conclusion: Although the limited number of patients should be taken into account, switching to eslicarbazepine allowed a reduction of monthly number of seizures in about 55% of patients. Furthermore, eslicarbazepine showed a good safety profile with a potential lower impact on quality of life of patients.

Purpose Patients with juvenile myoclonic epilepsy (JME) may be resistant or show adverse effects to valproate. We present a multicenter, prospective, long-term, open-label study evaluating the efficacy and safety of levetiracetam in JME. Methods Patients with newly diagnosed (10) or resistant/intolerant to previous AEDs JME (38) were enrolled. After a 8 week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased up to 3000 mg/day according to the patient's response. Efficacy parameters were: number of seizure-free patients, number of days with myoclonus (DWM), and monthly frequency of generalised tonic-clonic (GTC) seizures. Adverse events were recorded. Results The overall mean dose of levetiracetam was 2208 mg/day. The mean study period was 19 (range 0.3–38) months. Five patients dropped out. 11/38 (28.9%) patients with add-on treatment and 5/10 (50%) newly diagnosed patients were seizure-free for a mean period of 17.2 (±8.8) months. Eighteen patients (37.5%) were without myoclonia, and 35 (72.9%) had no GTC seizures over the study period. The mean monthly frequency of DWM and of GTC seizures in the entire group was significantly reduced after levetiracetam. Five patients complained of side effects. Conclusions This open-label study suggests levetiracetam may be effective and well tolerated in resistant cases of JME or may become a reasonable alternative to valproate in newly diagnosed patients.

To evaluate if pregnancy induces a change in seizure frequency and in percentage of subjects remaining seizure-free. This is a prospective case–control study conducted in our tertiary epilepsy centre. Controls were matched 2:1 with the cases for relevant clinical parameters. Cases had to be referred to our centre for at least 9 months before-pregnancy, during pregnancy and the-9-months-after-birth. Controls were followed for the correspondent periods of time: named respectively control period 1–2–3. Seizure frequency was defined as “improved” if there was a 50 % of reduction, “worsened” if there was a 50 % of increase, and “unchanged” in the rest of cases. We recruited 36 cases and 72 controls [in both group mean age was 28 years, partial epilepsy (80.6 %), generalized epilepsy (19.4 %)]; 30 cases and 60 controls were seizure-free before pregnancy and in period 1, respectively. During pregnancy 72 % of cases remained “unchanged” while 8 and 19 % respectively “improved” and “worsened”; moreover, there was no statistical difference in the number of seizure-free patients and in the monthly seizure frequencies. No differences were found in controls. In this prospective case–control study, pregnancy does not affect seizure frequency in women with epilepsy.

Summary Purpose: To count patients with newly diagnosed epilepsy entering early and late remission and to identify prognostic predictors of late remission. Methods: Children and adults with previously untreated epilepsy from two Italian tertiary centers (Monza, Bari) were the study population. All patients received monotherapy at treatment start; drug choice and schedule were left to the physician’s judgment. A retrospective audit was performed and the following prognostic predictors were identified: age, gender, putative etiology, first electroencephalography (EEG) record, neurologic and psychiatric examination, disease duration at diagnosis, seizure type(s) and number prior to starting treatment, epilepsy syndrome, and first antiepileptic drug. Early remission was defined by 2-year seizure control immediately after treatment start. Late remission was defined by 2-year seizure control achieved at least 24 months after treatment start. Prognostic predictors were assessed by logistic regression analysis, adjusting for age, gender, and center. Results: One hundred seventy-four women and 178 men (mean age 31.5 years) were included and followed for 2399.6 person-years. The cumulative time-dependent probability of 2-year remission was 56.3% at 2 years after treatment start, and 62.6, 69.4, and 79.5% at 3, 5, and 10 years. One hundred fifteen patients (23.0%) achieved early remission and 38 patients (10.8%) achieved late remission. The interaction between partial seizures and number of seizures prior to treatment was the only independent predictor of late remission. Discussion: The course of epilepsy and the chance of remission are together a complex and dynamic process, possibly explained by the diversity of the mechanisms underlying drug response and the use of an increasing number of drugs.

Summary Purpose: A multicenter, prospective, long-term, open-label study to evaluate the effects of levetiracetam on electroencephalogram (EEG) abnormalities and photoparoxysmal response (PPR) of patients affected by juvenile myoclonic epilepsy (JME). Methods: Forty-eight patients with newly diagnosed JME (10) or resistant/intolerant (38) to previous antiepileptic drugs (AEDs) were enrolled. After an 8-week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased to up to 3,000 mg/day. Efficacy parameters were based on the comparison and analysis of EEG interictal abnormalities classified as spikes-and-waves, polyspikes-and-waves, and presence of PPR. Secondary end point was evaluation of EEG and PPR changes as predictive factors of 12-month seizure freedom. Results: Overall, mean dose of levetiracetam was 2,208 mg/day. Mean study period was 19.3 ± 11.5 months (range 0.3–38). During the baseline period, interictal EEG abnormalities were detected in 44/48 patients (91.6%) and PPR was determined in 17/48 (35.4%) of patients. After levetiracetam treatment, 27/48 (56.2%) of patients compared to 4/48 (8.3%) in the baseline period (p < 0.0001) had a normal EEG. Thirteen of 17 (76.4%) (p < 0.0003) patients showed suppression of PPR. Cumulative probability of days with myoclonia (DWM) 12-month remission was significantly higher (p < 0.05) in patients with a normal (normalized) EEG after levetiracetam treatment compared to those with an unchanged EEG. Conclusions: Levetiracetam appeared to be effective in decreasing epileptiform EEG abnormalities, and suppressing the PPR in JME patients. This effect, along with a good efficacy and tolerability profile in this population further supports a first-line role for levetiracetam in the treatment of JME

Objective: To identify novel genes implicated in epilepsy with auditory features (EAF) in phenotypically heterogeneous families with unknown molecular basis. Methods: We identified 15 probands with EAF in whom an LGI1 mutation had been excluded. We performed electroclinical phenotyping on all probands and available affected relatives. We used whole-exome sequencing (WES) in 20 individuals with EAF (including all the probands and 5 relatives) to identify single nucleotide variants, small insertions/deletions, and copy number variants. Results: WES revealed likely pathogenic variants in genes that had not been previously associated with EAF: a CNTNAP2 intragenic deletion, 2 truncating mutations of DEPDC5, and a missense SCN1A change. Conclusions: EAF is a clinically and molecularly heterogeneous disease. The association of EAF with CNTNAP2, DEPDC5 ,a ndSCN1A mutations widens the phenotypic spectrum related to these genes. CNTNAP2 encodes CASPR2, a member of the voltage-gated potassium channel complex in which LGI1 plays a role. The finding of a CNTNAP2 deletion emphasizes the importance of this complex in EAF and shows biological convergence. Neurol Genet 2015;1:e5; doi

The objective of this observational study was to compare the efficacy of levetiracetam and topiramate during the first 15 days of add-on treatment in adults with refractory partial epilepsy. Two cohorts of patients with > or =3 simple or complex partial seizures with or without secondary generalisation per month over an 8-week baseline period received levetiracetam or topiramate in two distinct phases, in addition to standard antiepileptic treatment. During the first 15 days of the therapy, levetiracetam was added at the dosage of 250 mg b.i.d. or topiramate at 25mg o.i.d. Efficacy parameters included number of seizure-free days (SFDs), mean and percent reduction in seizure frequency (in general and by type), and number of seizure-free patients in the first 15 days of treatment compared to last 15 days of the baseline period. Sixty-one patients received levetiracetam and 61 topiramate. The general characteristics of the two treatment groups were similar. The total number of SFDs during 15 days before treatment was 637 with levetiracetam and 621 with topiramate; in the 15-day evaluation period the SFDs increased to 748 (17.4%) and 668 (7.6%), respectively (ANOVA, p

Peri-ictal water drinking (PIWD) has been reported as the action of drinking during or within two minutes of an electroclinical seizure. It is considered a peri-ictal vegetative symptom, evident both during childhood and adulthood epilepsy. The aim of this paper was to describe the clinical and electroencephalographic features of two new adult subjects suffering from symptomatic temporal lobe epilepsy with episodes of PIWD recorded by VIDEO-EEG and to review literature data in order to better define this peculiar event during seizures, a rare and probably underestimated semiological sign. To date, 51 cases with focal epilepsy and seizures associated with PIWD have been reported. All patients presented with temporal lobe epilepsy. All cases but one had symptomatic epilepsy. Most of the patients had an involvement of the right hemisphere. Water drinking was reported as an ictal sign in the majority of patients, and less frequently was reported as postictal. We believe that PIWD might be considered a rare automatic behaviour, like other automatisms. Automatisms are more frequently described in patients with temporal lobe epilepsy. PIWD was reported also to have lateralizing significance in the non-dominant temporal lobe, however, because of its rarity, this finding remains unclear.