Varicella zoster immunity loss in multiple sclerosis patient treated with ocrelizumab.

Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.

Assessing conformal thin film growth under nonstochastic deposition conditions: application of a phenomenological model of roughness replication to synthetic topographic images.

In this work, a simple method to follow the evolution of the surface of thin films during growth on substrates characterised by high roughness is detailed. To account for real cases as much as possible, the approach presented is based on the hypothesis that deposition takes place under nonstochastic conditions, such as those typical of many thin film processes in industry and technology. In this context, previous models for roughness replication, which are mainly based on idealised deposition conditions, cannot be applied and thus ad hoc approaches are required for achieving quantitative predictions. Here it is suggested that under nonstochastic conditions a phenomenological relation can be proposed, mainly based on local roughening of surface, to monitor the statistical similarity between the film and the substrate during growth or, in other words, to detect changes of the bare substrate morphological profile occurring during the film growth on top. Such approximation is based on surface representation in terms of power spectral density of surface heights, derived from topographic images; in this work, such method will be tested on two separate batches of synthetic images which simulate thin films growth onto a real rough substrate. In particular, two growth models will be implemented: the first reproduces the surface profile obtained during an atomic force microscopy measurement by using a simple geometrical envelope of surface, regardless the thin film growth mechanism; the second reproduces the columnar growth expected under nonstochastic deposition conditions. It will be shown that the approach introduced is capable to highlight differences between the two batches and, in the second case, to quantitatively account for the replication of the substrate roughness during growth. The results obtained here are potentially interesting in that they account essentially for the geometrical features of the surfaces, and as such they can be applied to synthetic depositions that reproduce different thin film depositions and experimental contexts.

Thin film deposition onto rough surfaces is widespread among many industrial and technological applications such as photovoltaics, microelectronics, optics and biomedicine just to mention a few. In such cases, compared to substrate morphology, film deposition may be required to improve certain surface functionalities through roughening or smoothing of the pristine substrate morphology to accomplish different needs or applications. This raises a simple and legitimate question: how could the degree of replication of the substrate morphology after film deposition be determined? Quantitative approaches to this issue involve statistical descriptions of the two interfaces in terms of power spectral densities retrieved from scanning probe microscopy images of the surface. However, this requires an in-depth knowledge of the physics behind the process of film formation, leading to a complication in that models providing quantitative predictions for film conformality are based on ideal deposition conditions; thus, numerical results remained so far restricted to the case of atomically flat, and mostly unrealistic, surfaces. To tackle into this subject, an approximation is suggested that is based on phenomenological considerations and on the hypothesis that deposition is nonideal. On these premises, a simple conformality factor derived from a linear relation is introduced to relate the substrate and the evolving film morphology. Such approach is then applied to simulated atomic force microscopy images which describe the film growth onto a real substrate. Two models will be implemented: the first uses a simple geometrical envelope of the surface that uniquely matches with experiments without keeping into account the mechanism of growth, while the second reproduces the columnar growth expected under real deposition conditions. The application of conformality factors to the images so obtained shows that the second model accomplishes well to the final goal of obtaining quantitative results and enables to retrieve quantitative information especially in case of micro or nanometrically structured surfaces.

Management of psychogenic non-epileptic seizures: a multidisciplinary approach.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

Insight into epileptic and physiological déjà vu: from a multicentric cohort study.

BACKGROUND AND PURPOSE: The presence of a continuum between physiological déjà vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non-epileptic DV. METHODS: In all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Déjà Vu Experiences Assessment (I-IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview. RESULTS: Of E, 69% stated that they experienced 'recognition' and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures. CONCLUSION: Only E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I-IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual-memory network might be involved in epileptic DV.

Lacosamide monotherapy in clinical practice: A retrospective chart review.

OBJECTIVE: To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. MATERIALS AND METHODS: Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). RESULTS: A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. At OP2, 66.3% of first-line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first-line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first-line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). CONCLUSIONS: Lacosamide was effective and well tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizures.

Value of clinical features to differentiate refractory epilepsy from mimics: a prospective longitudinal cohort study.

BACKGROUND AND PURPOSE: Misdiagnosis of refractory epilepsy (rE) is common and such patients experience a long diagnostic delay. Our aim was to identify key clinical/laboratory factors in order to obtain an alternative diagnosis in patients referred for rE. METHODS: Between January 2010 and December 2015, 125 consecutive patients with a diagnosis of rE were prospectively enrolled. All patients underwent a comprehensive neurological, neuropsychiatric and cardiological evaluation, and had an observation time of at least 1 year after the study entry. RESULTS: Diagnosis of rE was confirmed in 104/125 (83.2%) patients (55 women, mean age 38.8 ± 14.3 years). Thirteen/125 patients (10.4%, seven women, mean age 50.8 ± 20.9) were diagnosed with syncope, which was cardiac/cardio inhibitory in 9/13 (69%). The remaining 8/125 patients (6.4%, six women, mean age 41.2 ± 14.6 years) were diagnosed with psychogenic non-epileptic seizures. Age at onset had a high accuracy in differentiating patients with syncope from others, with the best cut-off age at 35 years and above. Abnormal brain magnetic resonance imaging (MRI) had a significant yield of about 70% in rE. A diagnostic model including age at onset and brain MRI was highly accurate in differentiating patients with syncope from others. In patients with cardiac/cardio inhibitory syncope, the point score of historical features was ≥1 and falsely favoured the diagnosis of epileptic seizures. CONCLUSIONS: This prospective cohort study identifies rE mimics who are at high risk of morbidity and mortality. rE starting in adulthood should raise a high suspicion of cardiac syncope. Brain MRI is accurate in differentiating rE from other conditions.

Brand-to-generic levetiracetam switching: a 4-year prospective observational real-life study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether switching from branded levetiracetam (Keppra® ) to a levetiracetam generic equivalent product (Matever® ) in an epilepsy cohort could provide adequate results in terms of seizure control and tolerability. METHODS: To be eligible for the study, patients had to have been taking Keppra® as monotherapy or polytherapy for at least 6 months. Between March 2013 and April 2017, patients were invited to switch to Matever® as part of their follow-up. We evaluated the number of seizures per month, drug-related adverse events and electroencephalography before the switch (T0, baseline) and 6 months after switching (T1). Furthermore, we reported the long-term follow-up of patients who continued to use Matever® after the end of the study, considering the most recent visit for each patient (T2). RESULTS: A total of 55 patients refused the switch. Among the remaining 125 patients, 59 (47%) were treated using Keppra® as monotherapy and 66 (53%) were on Keppra® as polytherapy. All 125 patients were subjected to switching from Keppra® to Matever® . Comparing patients before (T0) and after (T1) switching, we found no statistically significant differences in terms of seizure frequency and occurrence of adverse effects. There were no significant differences (number of seizures/month and drug-related adverse events) between patients treated with Matever® as monotherapy and patients who refused the switch and continued to use Keppra® as monotherapy for a long-term follow-up of 48 months. Electroencephalography findings were also unchanged. CONCLUSION: In our sample, brand-to-generic levetiracetam switching was effective and safe in both monotherapy and polytherapy regardless of the epilepsy syndrome.

Effects of working gas pressure on zirconium dioxide thin film prepared by pulsed plasma deposition: roughness, wettability, friction and wear characteristics.

In joint arthroplasty one of the main issues related to the failure of prosthetic implants is due to the wear of the ultra-high molecular weight polyethylene (UHMWPE) component. Surface treatments and coatings have been recognized as enhancing methods, able to improve the tribological properties of the implants. Therefore, the main objective of this work was to investigate the possibility to fabricate yttria-stabilized zirconia (YSZ) coatings on a metal (AISI 316-L) substrate by means of Pulsed Electron Deposition, in order to improve the tribological behavior of the polymer-metal coupling, by reducing the initial wear of the UHMWPE component. In order to optimize the coating characteristics, the effects of working gas pressure on both its morphological and tribological properties were analyzed. Morphological characterization of the films was evaluated by Atomic Force Microscopy (AFM). Coating wettability was also estimated by contact angle (CA) measurement. Tribological performance (coupling friction and wear of UHMWPE) was evaluated by using a ball-on-disc tribometer during highly-stressing tests in dry and lubricated (i.e. NaCl and serum) conditions; friction and wear were specifically evaluated at the initial sliding distances - to highlight the main effect of coating morphology - and after 100m - where the influence of the intrinsic materials properties prevails. AFM analysis highlighted that the working pressure heavily affected the morphological characteristics of the realized films. The wettability of the coating at the highest and lowest deposition pressures (CA ~ 60°, closed to substrate value) decreased for intermediate pressures, reaching a maximum CA of ~ 90°. Regarding tribological tests, a strong correlation was found in the initial steps between friction coefficient and wettability, which decreased as the distance increased. Concerning UHMWPE wear associated to coated counterpart, at 100m a reduction rate of about 7% in dry, 12% in NaCl and 5% in presence of serum was obtained compared to the uncoated counterpart. Differently from what highlighted for friction, no correlation was found between wear rate and morphological parameters. These findings, in agreement with literature, underlined the effect of the deposition pressure on the morphological properties, but suggested that physical characteristics are influenced too. Further research on the deposition process will be required in order to improve the tribological performance of the coating at long distances, addressing - above all - orthopedic applications.

Seed layer technique for high quality epitaxial manganite films.

We introduce an innovative approach to the simultaneous control of growth mode and magnetotransport properties of manganite thin films, based on an easy-to-implement film/substrate interface engineering. The deposition of a manganite seed layer and the optimization of the substrate temperature allows a persistent bi-dimensional epitaxy and robust ferromagnetic properties at the same time. Structural measurements confirm that in such interface-engineered films, the optimal properties are related to improved epitaxy. A new growth scenario is envisaged, compatible with a shift from heteroepitaxy towards pseudo-homoepitaxy. Relevant growth parameters such as formation energy, roughening temperature, strain profile and chemical states are derived.