Search

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.

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.

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.

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

As in much of Europe, and in the particular context of the Bologna Convention on tertiary education, the Italian university system has experienced substantial reform in recent years, the major aims of which include increasing the participation, progression and retention rates of students in higher education. Reform has reduced the length of undergraduate degree programmes to three years with the intention that students should be able to graduate at an earlier age than in the past, in line with graduates from other European countries. This paper offers a first econometric analysis of student withdrawal and progression three years after the introduction of major reform. We use administrative data on students of two Italian universities in a probit model of the probability that the student drops out, and an OLS model of student progression. Our analyses suggest that, notwithstanding the reforms, the drop-out (withdrawal) rate is still very high and only a small proportion of students are likely to complete their studies within the institutional time. In particular, we find that differences in students' prior educational background and performance have remarkably large effects on their withdrawal and progression probabilities. We infer from our results that poor retention and completion rates of Italian university students are unlikely to improve without further significant institutional change.

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

A field monitoring system for the 2 Tesla solenoid of the D0 detector is described. It is comprised of a very small NMR probe cabled to a DSP based signal processing board. The design magnetic field range is from 1.0 to 2.2 Tesla, corresponding to an RF frequency range of 42.57 to 93.67 MHz. The desired accuracy is one part in 10/sup 5/. To minimize material in the interaction region of the D0 detector, the overall thickness of the NMR probe is 4 mm, including its mounting plate, and its width is 10 mm. To minimize cable mass, 4 mm diameter IMR-100A cables are used for transmitting the RF signals from a nearby patch panel 25 meters to each of four probes mounted within the bore of the solenoid. RG213U cables 45 meters long are used to send the RF from the D0 movable counting house to the patch panel. With this setup, the detector signal voltage at the movable counting house is in the range of 250-400 mV.

The aim of this paper is to analyse the out-of-sample performance of SETAR models relative to a linear AR and a GARCH model using daily data for the Euro effective exchange rate. The evaluation is conducted on point, interval and density forecasts, unconditionally, over the whole forecast period, and conditional on specific regimes. The results show that overall the GARCH model is better able to capture the distributional features of the series and to predict higher-order moments than the SETAR models. However, from the results there is also a clear indication that the performance of the SETAR models improves significantly conditional on being on specific regimes.

The properties of Pearson's goodness-of-fit test, as used in density forecast evaluation, income distribution analysis and elsewhere, are analysed. The components-of-chi-squared or "Pearson analog" tests of Anderson (1994) are shown to be less generally applicable than was originally claimed. For the case of equiprobable classes, where the general components tests remain valid, a Monte Carlo study shows that tests directed towards skewness and kurtosis may have low power, due to differences between the class boundaries and the intersection points of the distributions being compared. The power of individual component tests can be increased by the use of nonequiprobable classes.

In the context of policy reforms in Higher Education in both the UK and Italy, we review recent evidence on student outcomes in higher education and subsequent transitions into the labour market for both these countries. We also provide the results of some new analysis for each of the two and, among other things, show that pre-university qualifications are strong influences on degree performance in both countries but that, unlike the UK, Italian university graduate earnings are largely insensitive to measured educational performance. Length of time taken to graduate in Italy exerts a significant negative effect both on degree performance and on graduate earnings. Similarly, being over-qualified for one's job is associated with a 5% pay penalty. Finally, we make recommendations regarding possible data improvements to enhance the policy usefulness of the analyses for each of the two countries.

The aim of this paper is to compare the forecasting performance of SETAR and GARCH models against a linear benchmark using historical data for the returns of the Japanese yen/US dollar exchange rate. The relative performance of the models is evaluated on point forecasts and on interval forecasts. Point forecasts evaluation over the whole forecast period indicates that the performance of the models, when distinguishable, tends to favour the linear models. However, we show that if the evaluation of point forecasts is conducted over distinct subsamples or specific regimes there is more evidence of forecasting gains, especially from the SETAR models. Moreover, when we evaluate the validity of interval forecasts, the results produce clear evidence of the superiority of the non-linear models, and tend to favour especially the GARCH models.

In recent years there has been a considerable development in modelling nonlinearities and asymmetries in economic and financial variables. The aim of this work is to compare the forecasting performance of different models for the returns of some of the most traded exchange rates in terms of the US dollar, namely the French Franc (FF/$), the German Mark (DM/$) and the Japanese Yen (Y/$). We compare the relative performance of some nonlinear models and contrast them with their linear counterparts. Although we find evidence of some forecasting gains from nonlinear models, the results are sensitive to the forecast horizon and to the metric adopted to measure the forecasting accuracy. The use of data at different frequencies allows us to evaluate the possible effects of temporal aggregation.

In recent years there has been a considerable development in time seriesanalysis, represented mainly by alternative linear models able to describe more adequately the short and long term dynamics and by the renewed interest in modelling nonlinearities and asymmetries in economic and financial variables. Given the relevance of such variables in devising economic and monetary policy, it is of theoretical, as well as practical, importance to propose statistical methods appropriate to represent their dynamic behaviour. The aim of this work is to compare the forecasting performance of different models for the returns of some of the most traded exchange rates, namely the French Franc (FF/$), the German Mark (DM/$) and the Japanese Yen (Y/$). We compare the relative performance of some nonlinear models and contrast them with their simpler linear counterparts. Although we find evidence of noticeable forecasting gains from nonlinear models, the results are sensitive to the metric adopted to measure the forecasting accuracy.e.

This paper tests the Expectations Hypothesis (EH) of the term structure of interest rates using new data for Germany. The German term structure appears to forecast future short-term interest rates surprisingly well, compared with previous studies with US data, while it has lower predictive power for long-term interest rates. However, the direction suggested by the coefficient estimates is consistent with that implied by the EH, that is when the term spread widens, long rates increase. The use of instrumental variables to deal with possible measurement errors in the data significantly improves regressions for the long rates. Moreover, reestimation with proxy variables to account for the possibility of time-varying term premia confirms that the evolution of both short and long rates corresponds to the predictions of the EH and that most of the information is in the term spread. These results are important as they suggest that monetary policy in Germany could be guided by the slope of the term structure.

In this paper we examine the expectations hypothesis of the term structure (EHT) using a newly constructed monthly database of zero coupon bond yields from the German Government bond market. We use data at the short end of the maturity spectrum (maturities less than two years) and employ two approaches to predict future movements in shorter-term interest rates - one based on the yield spread, the other based on the forward-spot rate spread. We find that for the period considered, 1985 - 2-1994 - 12, both spreads contain substantial information for predicting future interest rate movements. Moreover, the results are, in general, consistent with the implications of the EHT, as far as the value of the coefficient of the spread is concerned. This means that in Germany the spread can be used as an important indicator for the conduct of monetary policy.

In this report we describe the measurements performed on the E760 hydrogen Jet Target in order to some of the basic parameters of the system. These measurements were performed in the context of the upgrade program of the target for the successor experiment E835. Fermilab experiment E760 studied charmonium states formed in antiproton-proton annihilations. The antiproton-proton interactions were produced in a jet of hydrogen gas which intersected the antiproton beam coasting in the Fermilab Antiproton Accumulator. The results from E760 have shown that an increase in integrated luminosity by a factor of more than 5 is needed to complete the study of the charmonium spectrum. The E835 experiment is designed to achieve this by increasing the intensity of the antiproton beam and the density of the hydrogen-cluster-jet. This report is concerned with preparations for the work needed to increase the density of the hydrogen-cluster-jet.

A case of sacral neurinoma diagnosed in a 67-year-old woman whose clinical symptomatology consisted for fully 54 years of faint but persistent episodes of lumbo- and sacralgia is reported. Only at the terminal moment of observation did the patient present motor and sensitivity disturbances in the lower extremities, paralysis of the sphincters and sacral decubitus. The mass was identified radiologically and submitted to biopsy. It was localized in the left wing of the sacrum and on the corresponding side of the iliac bone, and presented a diameter of 6 X 9 cm. The slow, practically asymptomatic course, the exclusively intra-osseous site, the histological report and late onset of a cauda syndrome, suggest that the origin of the neoplasia lies in the sacral nerves.

Summary The extent to which corn roots affect the availability of phosphorus by inducing changes in the rhizosphere was investigated. The entire root system of a corn plant was confined to a core, 2 cm in diameter, intended to simulate a macro-rhizosphere. Outside this core were four soil zones, each 5 mm thick and separated from each other by 43 μm mesh nylon fabric. After specified growing periods, the soil from the five areas was analyzed for phosphatase activity, pH, and available P content. Soil phosphatase was enriched up to 40% by corn roots in the central core and to a lesser extent 5 mm away. No decrease in organic P levels in these zones was observed suggesting that enzyme activity was not limiting the mineralization of phosphatase-hydrolyzable compounds. Available P tended to decrease in soil zones closest to the root core but these changes were not statistically significant. Root-induced pH changes of as much as 0.5 units were observed between the root core and the outer zones over the two-week growing period. Available P levels increased as the root-induced pH changes acidified the rhizosphere.

A case of periosteal ossification of the femur in a 14-yr-old boy is reported. The clinical, radiological and scintiscan pictures illustrated marked pseudotumoral lesions in a subject with a mild form of osteopsathyrosis.

After outlining the problem of pathological fractures in patients suffering from malignant tumours, a recent acrylic cement osteosynthesis technique is presented. This makes immediate immobilization of the fracture possible, alleviation of pain and so early use of the fractured extremity. The personal series is illustrated and it is concluded that the technique also offers suitable prophylaxis when radiography of the skeleton points to osteolytic areas in which pathological fracture can be foreseen.

The synovial membrane--the articular district of the s.i.--responds to pathogenic stimuli by cell hyperplasia, giving rise to the so-called pannus. This together with regression and haemorrhage, may lead to self-maintenance of the condition, over and above the persistence of the original insult, resulting in chronicity and degeneration. If performed when the disease is still limited to histiocyte hyperplasia, synovectomy is effective in both single-joint forms and systemic conditions, such as rheumatoid arthritis. These conclusions (already evident in the literature) emerged from a review of a series of 67 synovectomies and 29 tenosynovectomies performed between 1969 and 1978 for various joint and tendon afflictions (not including T.B.) marked by synovial hyperplasia.