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1. Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis

Author

Lattanzi, S, De Maria, G, Rosati, E, Didato, G, Chiesa, V, Ranzato, F, Canafoglia, L, Cesnik, E, Anzellotti, F, Meletti, S, Pauletto, G, Nilo, A, Bartolini, E, Marino, D, Tartara, E, Luisi, C, Bonanni, P, Marrelli, A, Stokelj, D, Dainese, F, Foschi, N, Cagnetti, C, Gazzina, S, Contento, M, Biggi, M, Magliani, M, Di Giacomo, R, Pastori, C, Canevini, M, Zambrelli, E, Billo, G, Casazza, M, Fallica, E, Rosa, G, Dono, F, Speranza, R, Cioclu, C, Vaudano, A, Kiferle, L, Galli, R, Guadagni, M, Galimberti, C, Kassabian, B, Ferreri, F, Osanni, E, Ciuffini, R, Badioni, V, Beretta, S, Lattanzi S., De Maria G., Rosati E., Didato G., Chiesa V., Ranzato F., Canafoglia L., Cesnik E., Anzellotti F., Meletti S., Pauletto G., Nilo A., Bartolini E., Marino D., Tartara E., Luisi C., Bonanni P., Marrelli A., Stokelj D., Dainese F., Foschi N., Cagnetti C., Gazzina S., Contento M., Biggi M., Magliani M., Di Giacomo R., Pastori C., Canevini M. P., Zambrelli E., Billo G., Casazza M., Fallica E., Rosa G., Dono F., Speranza R., Cioclu C., Vaudano A. E., Kiferle L., Galli R., Guadagni M., Galimberti C. A., Kassabian B., Ferreri F., Osanni E., Ciuffini R., Badioni V., Beretta S., Lattanzi, S, De Maria, G, Rosati, E, Didato, G, Chiesa, V, Ranzato, F, Canafoglia, L, Cesnik, E, Anzellotti, F, Meletti, S, Pauletto, G, Nilo, A, Bartolini, E, Marino, D, Tartara, E, Luisi, C, Bonanni, P, Marrelli, A, Stokelj, D, Dainese, F, Foschi, N, Cagnetti, C, Gazzina, S, Contento, M, Biggi, M, Magliani, M, Di Giacomo, R, Pastori, C, Canevini, M, Zambrelli, E, Billo, G, Casazza, M, Fallica, E, Rosa, G, Dono, F, Speranza, R, Cioclu, C, Vaudano, A, Kiferle, L, Galli, R, Guadagni, M, Galimberti, C, Kassabian, B, Ferreri, F, Osanni, E, Ciuffini, R, Badioni, V, Beretta, S, Lattanzi S., De Maria G., Rosati E., Didato G., Chiesa V., Ranzato F., Canafoglia L., Cesnik E., Anzellotti F., Meletti S., Pauletto G., Nilo A., Bartolini E., Marino D., Tartara E., Luisi C., Bonanni P., Marrelli A., Stokelj D., Dainese F., Foschi N., Cagnetti C., Gazzina S., Contento M., Biggi M., Magliani M., Di Giacomo R., Pastori C., Canevini M. P., Zambrelli E., Billo G., Casazza M., Fallica E., Rosa G., Dono F., Speranza R., Cioclu C., Vaudano A. E., Kiferle L., Galli R., Guadagni M., Galimberti C. A., Kassabian B., Ferreri F., Osanni E., Ciuffini R., Badioni V., and Beretta S.

Abstract

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P =.002). The number of prior antiseizure medications (adjusted hazard ratio [adjHR] = 1.07, 95% CI = 1.02-1.13, P =.009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001-1.008, P =.028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.

Published
2021

2. Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, RealWorld Study

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Cerulli Irelli, E., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Di Gennaro, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Gangitano, M., La Neve, A., Mecarelli, O., Montalenti, E., Morano, A., Piazza, F., Pizzanelli, C., Pulitano, P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Giacomo, R., Di Liberto, A., Domina, E., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fisco, G., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giallonardo, A. T., Giorgi, F. S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Milano, C., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quarato, P. P., Quintas, R., Renna, R., Rizzo, G. R., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Vaudano, A. E., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi, Simona, Canafoglia, Laura, Canevini, Maria Paola, Casciato, Sara, Cerulli Irelli, Emanuele, Chiesa, Valentina, Dainese, Filippo, De Maria, Giovanni, Didato, Giuseppe, Di Gennaro, Giancarlo, Falcicchio, Giovanni, Fanella, Martina, Ferlazzo, Edoardo, Gangitano, Massimo, La Neve, Angela, Mecarelli, Oriano, Montalenti, Elisa, Morano, Alessandra, Piazza, Federico, Pizzanelli, Chiara, Pulitano, Patrizia, Ranzato, Federica, Rosati, Eleonora, Tassi, Laura, and Di Bonaventura, Carlo

Subjects
Antiseizure medication, Focal seizures, Brivaracetam, Epilepsy, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), Settore MED/26, Settore MED/39 - Neuropsichiatria Infantile
Abstract

Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications. Results: A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p

Published
2022

4. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 35, 12, (1289-1301), 10.1007/s40263-021-00856-3)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.

Published
2021

5. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 10.1007/s40263-021-00856-3)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.

Published
2021

6. Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Author

Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi S., Canafoglia L., Canevini M.P., Casciato S., Chiesa V., Dainese F., De Maria G., Didato G., Falcicchio G., Fanella M., Ferlazzo E., Fisco G., Gangitano M., Giallonardo A.T., Giorgi F.S., La Neve A., Mecarelli O., Montalenti E., Piazza F., Pulitano P., Quarato P.P., Ranzato F., Rosati E., Tassi L., and Di Bonaventura C.

Subjects
medicine.medical_specialty, business.industry, Context (language use), Brivaracetam, medicine.disease, Discontinuation, law.invention, Psychiatry and Mental health, Epilepsy, Randomized controlled trial, Tolerability, focal epilepsy, add-on therapy, seizure, law, Concomitant, Internal medicine, Medicine, Pharmacology (medical), Neurology (clinical), Levetiracetam, Original Research Article, business, medicine.drug
Abstract

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp

Published
2021

23. Gender differences in health-related quality of life in multiple sclerosis

Author

Casetta, I. Riise, T. Wamme Nortvedt, M. Economou, N.T. De Gennaro, R. Fazio, P. Cesnik, E. Govoni, V. Granieri, E.

Abstract

Women have about twice the risk of developing multiple sclerosis (MS) compared with men, a ratio that seems to be increasing. Most studies show that female patients seem to have a more favourable outcome of the disease. We studied the gender-specific impact of MS on health-related quality of life. We surveyed the population prevalence of MS patients in Ferrara, Italy. Data were extracted from the MS registry of the study area. Health-related quality of life was assessed using the MSQOL54 questionnaire. We analysed 370 patients (105 men and 265 women). They had worse scores than the general population in all health-related quality of life dimensions, ranging from 2.5 standard deviations (SD) lower for physical functioning to less than 0.5 standard deviations for mental health. Health-related quality of life scores were inversely correlated with disability scores. The impact of disability on health-related quality of life was higher for men than women regarding physical functioning (p < 0.01), vitality (p < 0.001), social functioning (p < 0.001), emotional wellbeing (p < 0.05) and mental health (p < 0.01). For scales reflecting mental health, a marked reduction with increasing disability was seen for men, while a linear reduction in the range of Expanded Disability Status Scale score 0-5 was reported for women, followed by no clear decrease for higher scores. We conclude that MS affects health-related quality of life in all of its dimensions. The impact of disability seems to be stronger among men, in particular for scales related to mental well-being. This could indicate that interventions should to be gender specific in order to better meet patients' needs. © The Author(s) 2009.

Published
2009

31. Restless legs syndrome and pregnancy.

Author

Manconi M, Govoni V, De Vito A, Economou NT, Cesnik E, Casetta I, Mollica G, Ferini-Strambi L, Granieri E, Manconi, M, Govoni, V, De Vito, A, Economou, N T, Cesnik, E, Casetta, I, Mollica, G, Ferini-Strambi, L, and Granieri, E

Published
2004
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32. Trajectory Control for Very Flexible Aircraft

Author

MICHIGAN UNIV ANN ARBOR, Shearer, Christopher M., Carlos, Cesnik E., MICHIGAN UNIV ANN ARBOR, Shearer, Christopher M., and Carlos, Cesnik E.

Abstract

This paper focuses on trajectory control of the 6-DOF body fixed reference frame located on a very flexible aircraft. The 6-DOF equations of motion of a reference point on the aircraft are coupled with the aeroelastic equations that govern the geometrically nonlinear structural response of the vehicle. A low-order strain-based nonlinear structural analysis coupled with unsteady finitestate potential flow aerodynamics form the basis for the aeroelastic model. The nonlinear beam finite element structural model assumes constant strain over an element in extension, twist, and in/out of plane bending. The geometrically nonlinear structural formulation, the finite state aerodynamic model, and the nonlinear rigid body equations together provide a low-order complete nonlinear aircraft analysis tool. Due to the inherent flexibility of the aircraft modeling, the low order structural fre quencies are of the same order as the rigid body modes. This creates a coupling which cannot be separated by previous control schemes. The flexibility must be accounted for directly in the controller development. To accomplish this a heuristic approach based upon pilot behavior is developed. This approach separates the problem into two parts: a fast inner-loop and a slower outer-loop. Dominant kinematic nonlinearities are handled in the outer-loop while the inner-loop is further separated into a lateral and longitudinal motion. Control of the inner-loop lateral motion is accomplished using a standard Linear Quadratic Regulator. For the longitudinal motion Dynamic Inversion is utilized. Differences between the desired and actual trajectories are handled in the nonlinear outer-loop using traditional proportional-integral-derivative design guidelines. The closed loop time integration is accomplished using an implicit modified Newmark method. Numerical simulations are presented highlighting the strengths and weaknesses of the method.

Published
2006

35. Multicenter case-control study on restless legs syndrome in multiple sclerosis: The REMS Study

Author

Rems, Italian Study Group, Manconi M, Ferini-Strambi L, Filippi M, Bonanni E, Iudice A, Murri L, Gl, Gigli, Fratticci L, Merlino G, Terzano G, Granella F, Parrino L, Silvestri R, Aricò I, Dattola V, Russo G, Luongo C, Cicolin A, Tribolo A, Cavalla P, Savarese M, Trojano M, Ottaviano S, Cirignotta F, Simioni V, Salvi F, Mondino F, Perla F, Chinaglia G, Zuliani C, Cesnik E, Enrico Granieri, Placidi F, Mg, Palmieri, Manni R, Terzaghi M, Bergamaschi R, Rocchi R, Ulivelli M, Bartalini S, Ferri R, Lo Fermo S, Ubiali E, Viscardi M, Rottoli M, Nobili L, Protti A, Ferrillo F, Allena M, Mancardi G, Guarnieri B, Londrillo F, Manconi, M, FERINI STRAMBI, Luigi, Filippi, Massimo, Bonanni, E, Iudice, A, Murri, L, Gigli, Gl, Fratticci, L, Merlino, G, Terzano, G, Granella, F, Parrino, L, Silvestri, R, Arico, I, Dattola, V, Russo, G, Luongo, C, Cicolin, A, Tribolo, A, Cavalla, P, Savarese, M, Trojano, M, Ottaviano, S, Cirignotta, F, Simioni, V, Salvi, F, Mondino, F, Perla, F, Chinaglia, G, Zuliani, C, Cesnik, E, Granieri, E, Placidi, F, Palmieri, Mg, Manni, R, Terzaghi, M, Bergamaschi, R, Rocchi, R, Ulivelli, M, Bartalini, S, Ferri, R, Lo Fermo, S, Ubiali, E, Viscardi, M, Rottoli, M, Nobili, L, Protti, A, Ferrillo, F, Allena, M, Mancardi, G, Guarnieri, B, and Londrillo, F.

Subjects
Male, demography, trazodone, insomnia, amitriptyline, Comorbidity, Relapsing-Remitting, Sleep medicine, Hypnotic, alprazolam, Restless legs syndrome, multiple sclerosis, sleep, Sleep Initiation and Maintenance Disorders, Insomnia, citalopram, Prospective Studies, Prospective cohort study, diazepam, lorazepam, prazepam, zolpidem, adult, article, blood examination, clinical trial, controlled study, disease course, disease duration, disease severity, female, health survey, human, major clinical study, male, multicenter study, priority journal, restless legs syndrome, risk factor, Adult, Case-Control Studies, Cross-Sectional Studies, Female, Health Surveys, Humans, Italy, Middle Aged, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting, Restless Legs Syndrome, Chronic Progressive, Settore MED/26 - Neurologia, Sleep onset, medicine.symptom, medicine.medical_specialty, Multiple Sclerosis, medicine.drug_class, Multiple sclerosis, Sleep, NO, Physiology (medical), Internal medicine, mental disorders, medicine, Multiple Sclerosis and Restless Legs Syndrome, diagnosis/epidemiology, business.industry, medicine.disease, Adult, Case-Control Studies, Comorbidity, Cross-Sectional Studies, Female, Health Surveys, Humans, Italy, Male, Middle Aged, Multiple Sclerosis, diagnosis/epidemiology, Multiple Sclerosis, diagnosis/epidemiology, Prospective Studies, Restless Legs Syndrome, diagnosis/epidemiology, Sleep Initiation and Maintenance Disorders, Physical therapy, Neurology (clinical), business
Abstract

Study objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. Design: Prospective, multicenter, case-control epidemiologic survey. Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine. Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects. Interventions: N/A. Measures and results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.

36. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomized, double blind, placebo controlled, phase III study

Author

Lauria, G, Dalla Bella, E, Antonini, G, Borghero, G, Capasso, M, Caponnetto, C, Chiò, A, Corbo, M, Eleopra, R, Fazio, R, Filosto, M, Giannini, F, Granieri, E, La Bella, V, Logroscino, G, Mandrioli, J, Mazzini, L, Monsurrò, Mr, Mora, G, Pietrini, V, Quatrale, R, Rizzi, R, Salvi, F, Siciliano, G, Sorarù, G, Volanti, P, Tramacere, I, Filippini, G, Cazzato, D, Cesnik, E, Groppo, E, Sette, E, Pani, C, Costantino, E, Orlandini, F, Boi, D, Querin, G, D'Ascenzo, C, Sagnelli, A, Piccirillo, G, Aiello, M, Chetta, A, Grassi, A, Lunetta, C, Maestri, E, Padovani, A, Cotelli, M, Todeschini, A, Morino, S, Di Pasquale, A, Latino, P, Casali, S, Battistini, S, Pirrelli, M, Cantello, R, Nasuelli, N, Servo, S, De Gennaro, R, Gastaldo, E, Georgoulopoulou, E, Fini, N, Taiello, Ac, Colletti, T, Calvo, A, Moglia, C, Fuda, G, Marinou, K, Riva, N, Cerri, F, Lopez, Id, De Cicco, D, Battaglia, G, Marcello, N, Rinaldi, M, Scialò, C, Mantero, V, Mascolo, M, Carlesi, C, Caldarazzo Ienco, E, Di Muzio, A, Verriello, L, D'Amico, D, Simone, Il, Tortelli, R, Cortese, R, Bartolomei, I, G., Lauria, E., Dalla Bella, G., Antonini, G., Borghero, M., Capasso, C., Caponnetto, A., Chiò, M., Corbo, R., Eleopra, R., Fazio, M., Filosto, F., Giannini, E., Granieri, V., La Bella, G., Logroscino, J., Mandrioli, L., Mazzini, Monsurro', Maria Rosaria, G., Mora, V., Pietrini, R, Quatrale, R., Rizzi, F., Salvi, G., Siciliano, G., Sorarù, P., Volanti, I., Tramacere, G., Filippini, on behalf of the EPOS Trial Study, Group, Lauria, G., Bella, E. D., Antonini, G., Borghero, G., Capasso, M., Caponnetto, C., Chio, A., Corbo, M., Eleopra, R., Fazio, R., Filosto, M., Giannini, F., Granieri, E., Bella, V. L., Logroscino, G., Mandrioli, J., Mazzini, L., Mora, G., Pietrini, V., Quatrale, R., Rizzi, R., Salvi, F., Siciliano, G., Soraru, G., Volanti, P., Tramacere, I., Filippini, G., Lauria, G, Dalla Bella, Eleonora, Antonini, G, Borghero, G, Capasso, M, Caponnetto, C, Chiò, A, Corbo, M, Eleopra, R, Fazio, R, Filosto, M, Giannini, F, Granieri, E, LA BELLA, V, Logroscino, G, Mandrioli, J, Mazzini, L, Monsurrò, Maria Rosaria, Mora, G, Pietrini, V, Quatrale, R, Rizzi, R, Salvi, F, Siciliano, G, Sorarù, G, Volanti, P, and Tramacere Irene, Filippini, G.

Subjects
Male, Gastroenterology, law.invention, Randomized controlled trial, law, Amyotrophic lateral sclerosis, MOTOR NEURON DISEASE, education.field_of_study, Recombinant Protein, Middle Aged, Recombinant Proteins, Treatment Outcome, Psychiatry and Mental Health, Neuromuscular, Settore MED/26 - Neurologia, Female, erythropoietyn, clinical trial, medicine.drug, Human, ALS, Adult, Aged, Amyotrophic Lateral Sclerosis, Double-Blind Method, Erythropoietin, Humans, medicine.medical_specialty, Population, Socio-culturale, Placebo, Double blind, Arts and Humanities (miscellaneous), Epoetin Alfa, Neurology (clinical), Surgery, Internal medicine, medicine, education, business.industry, Epoetin alfa, medicine.disease, Clinical trial, business, Amyotrophic Lateral Sclerosi
Abstract

Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intentionto-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. Results We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 ( placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. Conclusions RhEPO 40 000 IU fortnightly did not change the course of ALS.

39. Brivaracetam as add-on treatment in patients with post-stroke epilepsy: real-world data from the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST)

Author

Simona Lattanzi, Laura Canafoglia, Maria Paola Canevini, Sara Casciato, Emanuele Cerulli Irelli, Valentina Chiesa, Filippo Dainese, Giovanni De Maria, Giuseppe Didato, Giancarlo Di Gennaro, Giovanni Falcicchio, Martina Fanella, Edoardo Ferlazzo, Massimo Gangitano, Angela La Neve, Oriano Mecarelli, Elisa Montalenti, Alessandra Morano, Federico Piazza, Chiara Pizzanelli, Patrizia Pulitano, Federica Ranzato, Eleonora Rosati, Laura Tassi, Carlo Di Bonaventura, Angela Alicino, Michele Ascoli, Giovanni Assenza, Federica Avorio, Valeria Badioni, Paola Banfi, Emanuele Bartolini, Luca Manfredi Basili, Vincenzo Belcastro, Simone Beretta, Irene Berto, Martina Biggi, Giuseppe Billo, Giovanni Boero, Paolo Bonanni, Jole Bongorno, Francesco Brigo, Emanuele Caggia, Claudia Cagnetti, Carmen Calvello, Edward Cesnik, Gigliola Chianale, Domenico Ciampanelli, Roberta Ciuffini, Dario Cocito, Donato Colella, Margerita Contento, Cinzia Costa, Eduardo Cumbo, Alfredo D'Aniello, Francesco Deleo, Jacopo C DiFrancesco, Roberta Di Giacomo, Alessandra Di Liberto, Elisabetta Domina, Fedele Dono, Vania Durante, Maurizio Elia, Anna Estraneo, Giacomo Evangelista, Maria Teresa Faedda, Ylenia Failli, Elisa Fallica, Jinane Fattouch, Alessandra Ferrari, Florinda Ferreri, Giacomo Fisco, Davide Fonti, Francesco Fortunato, Nicoletta Foschi, Teresa Francavilla, Rosita Galli, Stefano Gazzina, Anna Teresa Giallonardo, Filippo Sean Giorgi, Loretta Giuliano, Francesco Habetswallner, Francesca Izzi, Benedetta Kassabian, Angelo Labate, Concetta Luisi, Matteo Magliani, Giulia Maira, Luisa Mari, Daniela Marino, Addolorata Mascia, Alessandra Mazzeo, Chiara Milano, Stefano Meletti, Annacarmen Nilo, Biagio Orlando, Francesco Paladin, Maria Grazia Pascarella, Chiara Pastori, Giada Pauletto, Alessia Peretti, Gabriella Perri, Marianna Pezzella, Marta Piccioli, Pietro Pignatta, Nicola Pilolli, Francesco Pisani, Laura Rosa Pisani, Fabio Placidi, Patrizia Pollicino, Vittoria Porcella, Silvia Pradella, Monica Puligheddu, Stefano Quadri, Pier Paolo Quarato, Rui Quintas, Rosaria Renna, Giada Ricciardo Rizzo, Adriana Rum, Enrico Michele Salamone, Ersilia Savastano, Maria Sessa, David Stokelj, Elena Tartara, Mario Tombini, Gemma Tumminelli, Anna Elisabetta Vaudano, Maria Ventura, Ilaria Viganò, Emanuela Viglietta, Aglaia Vignoli, Flavio Villani, Elena Zambrelli, Lelia Zummo, Lattanzi S., Canafoglia L., Canevini M.P., Casciato S., Cerulli Irelli E., Chiesa V., Dainese F., De Maria G., Didato G., Di Gennaro G., Falcicchio G., Fanella M., Ferlazzo E., Gangitano M., La Neve A., Mecarelli O., Montalenti E., Morano A., Piazza F., Pizzanelli C., Pulitano P., Ranzato F., Rosati E., Tassi L., Di Bonaventura C., Alicino A., Ascoli M., Assenza G., Avorio F., Badioni V., Banfi P., Bartolini E., Basili L.M., Belcastro V., Beretta S., Berto I., Biggi M., Billo G., Boero G., Bonanni P., Bongiorno J., Brigo F., Caggia E., Cagnetti C., Calvello C., Cesnik E., Chianale G., Ciampanelli D., Ciuffini R., Cocito D., Colella D., Contento M., Costa C., Cumbo E., D'Aniello A., Deleo F., DiFrancesco J.C., Di Giacomo R., Di Liberto A., Domina E., Dono F., Durante V., Elia M., Estraneo A., Evangelista G., Faedda M.T., Failli Y., Fallica E., Fattouch J., Ferrari A., Ferreri F., Fisco G., Fonti D., Fortunato F., Foschi N., Francavilla T., Galli R., Gazzina S., Giallonardo A.T., Giorgi F.S., Giuliano L., Habetswallner F., Izzi F., Kassabian B., Labate A., Luisi C., Magliani M., Maira G., Mari L., Marino D., Mascia A., Mazzeo A., Milano C., Meletti S., Nilo A., Orlando B., Paladin F., Pascarella M.G., Pastori C., Pauletto G., Peretti A., Perri G., Pezzella M., Piccioli M., Pignatta P., Pilolli N., Pisani F., Pisani L.R., Placidi F., Pollicino P., Porcella V., Pradella S., Puligheddu M., Quadri S., Quarato P.P., Quintas R., Renna R., Rizzo G.R., Rum A., Salamone E.M., Savastano E., Sessa M., Stokelj D., Tartara E., Tombini M., Tumminelli G., Vaudano A.E., Ventura M., Vigano I., Viglietta E., Vignoli A., Villani F., Zambrelli E., and Zummo L.

Subjects
Adult, Antiseizure medication, Brivaracetam, Cerebrovascular diseases, Focal seizures, Stroke, Settore MED/26, Antiseizure medication, Brivaracetam, Focal seizures, Stroke, Cerebrovascular diseases, Double-Blind Method, Drug Therapy, Seizures, Humans, Aged, Retrospective Studies, Epilepsy, General Medicine, Middle Aged, Pyrrolidinones, Treatment Outcome, Neurology, Italy, Combination, Anticonvulsants, Drug Therapy, Combination, Neurology (clinical)
Abstract

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.

Published
2022

40. Case Report: A Case of Creutzfeldt-Jakob Heidenhain Variant Simulating PRES.

Author

Antonioni A, Raho EM, Gozzi A, Cotta Ramusino N, Cesnik E, Padroni M, De Vito A, Pugliatti M, and Tugnoli V

Abstract

The Heidenhain Variant of Creutzfeldt-Jakob disease (CJD) is an uncommon early clinical syndrome of the otherwise regular sporadic CJD, which belongs to the group of prion diseases caused by a transmissible agent, the misfolded form of the prion protein. The most characteristic symptoms of CJD are rapidly progressive cognitive impairment, typical motor manifestations and mental and behavioural changes. Conversely, in the Heidenhain Variant, different kinds of visual disturbances are observed at onset due to microvacuolar spongiform degeneration or, less frequently, confluent spongiform changes in the parieto-occipital area, detectable through brain MRI with hyperintensity in T2-FLAIR or DWI in the same areas. Since this an extremely rare condition with a heterogeneous clinical presentation, it may easily be misdiagnosed with other diseases at the earlier stages. Here, we describe the case of a patient initially diagnosed with posterior reversible encephalopathy syndrome (PRES), presenting with visual disturbances and headache at onset in a context of poorly controlled arterial hypertension. Subsequently, a rapid worsening of cognitive decline, associated with myoclonus and startle reaction led to further investigations, shifting the diagnosis toward a rapidly evolving neurodegenerative form. This hypothesis was also supported by EEG traces, MRI and CSF analysis. Finally, the clinical-instrumental evolution confirmed the diagnosis of Heidenhain Variant of CJD.

Published
2022
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41. The distribution of the transient global amnesia in the province of Ferrara, Italy, a clue to the pathogenesis?

Author

Govoni V, Cesnik E, Ferri C, and Fallica E

Subjects
Amnesia, Female, Humans, Incidence, Italy epidemiology, Male, Retrospective Studies, Amnesia, Transient Global epidemiology
Abstract

The pathophysiology of transient global amnesia (TGA) is still uncertain. In the province of Ferrara (Fe-province), Italy, given the health organization and the alarming clinical features, the cases of TGA in the resident population virtually correspond to the resident outpatients diagnosed as TGA cases in the ER of the University Hospital of Ferrara. Thanks to this, a retrospective survey identified 35 (14 men, 21 women) first-ever TGA cases in the resident population in 2018 (346,975 inhabitants) giving a crude incidence rate of 10.10/100,000 (95% CI 7.00-14.00), 8.40/100,000 (95% CI 4.60-14.10) for men, and 11.60/100,000 (95% CI 7.20-17.80) for women, a non-significant gender difference. The incident cases of TGA were evenly distributed according to both season and month. The monthly cases of TGA followed the Poisson distribution (goodness-of-fit test: λ = 2.9, χ 2  = 2.557, 5 degrees of freedom, p > 0.70). The incidence of TGA in the Fe-province was higher in the highest level of urbanization (21.40/100,000 95% CI 13.10-33.00) than in the lowest one (4.20/100,000 95% CI 1.92-8.00). The incident cases of TGA increased with the level of urbanization (χ 2 trend test = 19.940, p < 0.001) and the population density (inhabitants/km 2 ) level (χ 2 trend test = 46.684, p < 0.001). Since urbanization is likely involved in stress-related disorders, these findings achieved in a well-defined homogeneous population seem to support the hypothesis of the involvement of stress, maybe in vulnerable individuals, in TGA.

Published
2021
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42. Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis.

Author

Lattanzi S, De Maria G, Rosati E, Didato G, Chiesa V, Ranzato F, Canafoglia L, Cesnik E, Anzellotti F, Meletti S, Pauletto G, Nilo A, Bartolini E, Marino D, Tartara E, Luisi C, Bonanni P, Marrelli A, Stokelj D, and Dainese F

Subjects
Adult, Drug Therapy, Combination, Female, Humans, Levetiracetam therapeutic use, Male, Middle Aged, Proportional Hazards Models, Treatment Outcome, Anticonvulsants therapeutic use, Epilepsies, Partial drug therapy, Pyrrolidinones therapeutic use
Abstract

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [ adj HR] = 1.07, 95% CI = 1.02-1.13, P = .009) and baseline monthly seizure frequency ( adj HR = 1.004, 95% CI = 1.001-1.008, P = .028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs., (© 2020 International League Against Epilepsy.)

Published
2021
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43. Incidence study of Guillain-Barré syndrome in the province of Ferrara, Northern Italy, between 2003 and 2017. A 40-year follow-up.

Author

Granieri E, Andreasi NG, De Martin P, Govoni V, Castellazzi M, Cesnik E, Pugliatti M, and Casetta I

Subjects
Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Child, Child, Preschool, Cohort Studies, Female, Humans, Italy epidemiology, Longitudinal Studies, Male, Middle Aged, Sex Factors, Young Adult, Guillain-Barre Syndrome epidemiology
Abstract

Background: Guillain-Barré syndrome (GBS) is an acute/subacute autoimmune inflammatory polyradiculoneuropathy. Previous epidemiological studies carried out in the province of Ferrara, Italy, from 1981 to 2002 indicated that GBS incidence had tendency of increase in the period considered., Objectives: We aimed at updating the epidemiology of GBS in the years 2003-2017 and carrying on the work started in the 1980s., Methods: We conducted an incidence study, by adopting a complete enumeration approach. Cases were identified from administrative, medical records, and database of the Ferrara Hospital and other provincial structures of the study area. Case ascertainment and definition are analogous to those adopted in previous surveys., Results: In the period 1 January 2003 to 31 December 2017, 73 patients living in the province of Ferrara (mean population 353,142) were found to be new cases of GBS fulfilling the NINCDS criteria. Male/female ratio 1.15. The mean incidence rate was 1.38 per 100,000 (95% CI 1.08-1.74), 1.54 per 100,000 for men and 1.23 per 100,000 for women, a nonsignificant difference. During the period considered, the rates had slow increase or mild decrease, without nonsignificant difference. The highest rates were observed for the age groups 70-79 years for both sexes. A half of patients reported infectious events in the weeks before the onset of symptoms., Conclusion: In line with many epidemiological data, in the whole period 2003-2017, we observed a trend towards increase or decrease in incidence and periods of relative stability. Similar temporal heterogeneity with the comparison to our previous works was found.

Published
2019
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44. The urgent neurological consultation in the population of the province of Ferrara, Italy.

Author

Govoni V, Della Coletta E, Fallica E, and Cesnik E

Subjects
Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Female, Geography, Medical, Humans, Italy epidemiology, Male, Middle Aged, Nervous System Diseases epidemiology, Nervous System Diseases therapy, Neurology, Patient Admission, Prevalence, Retrospective Studies, Young Adult, Ambulatory Care, Nervous System Diseases diagnosis, Referral and Consultation
Abstract

In the province of Ferrara, Italy, the urgent neurological consultation (UNC) cases in the population correspond to the resident outpatients who undergo a UNC in the ER of the university hospital of Ferrara (UHFe). Thanks to this health organization a retrospective survey identified 612 UNC cases (range of age 7-102 years, median 67,5 years) in the study period giving a period prevalence rate of 173 per 100,000 (95% CI 159.3-187.3) which increased with age (χ 2 for trend = 178.4 p < 0.001). The daily UNC cases (range 0-14, mean = 7.3, 95% CI 7.1-7.5) followed the Poisson distribution (goodness-of-fit test: λ = 7.3, χ 2  = 8082, 12 freedom degrees, p > 0.70). The prevalence rate decreased with the distance between the patients' residence and the UHFe (χ 2 for trend = 82.9, p < 0.001). The commonest clinical conditions requiring UNCs were acute cerebrovascular disorders (28%), headache (14%), and vertigo (9%). The hospital admission rate was 32.5% which increased with age (χ 2 for trend = 35.8, p < 0.001). The commonest discharge diagnoses of the admitted cases were ischemic stroke (57.3%), epilepsy (7%), TIA (6%), and intraparenchymal hemorrhage (5.5%). Acute cerebrovascular disease accounted for 69% of the discharge diagnoses. The survey showed that the UNCs' demand was higher than previous Italian data confirming that acute cerebrovascular disease is the most frequent acute neurological condition requiring attention in the ER. It also suggested that the UNCs could be poorly appropriate. These findings would require the healthcare administrators attention.

Published
2018
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45. Can the age at onset give a clue to the pathogenesis of ALS?

Author

Govoni V, Della Coletta E, Cesnik E, Casetta I, and Granieri E

Subjects
Age Distribution, Aged, Female, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Risk Factors, Sex Distribution, Age of Onset, Amyotrophic Lateral Sclerosis epidemiology, Amyotrophic Lateral Sclerosis etiology
Abstract

Pathogenesis could play an important role in the mid- to late-life onset of symptoms in amyotrophic lateral sclerosis (ALS). An analysis of the age at onset of ALS among the incident cases occurring in the population in the Health District of Ferrara, Italy, in the period 1064-2009 was carried out. Two subsequent 23-year time intervals (1964-1986 and 1987-2009) were considered. The mean age at onset (MAAO) was estimated in relation to gender, onset type and area of residence (urban or extra-urban) at disease onset among the incident cases which occurred in the two subsequent time intervals. An uneven increase in the MAAO over time was observed as it was significant only among the female cases (from 56.7 95 % CI 51.6-61.7 years to 65.4 95 % CI 61.8-69.0 years), the overall bulbar onset cases (from 58.0 95 % CI 54.0-62.1 years to 69.3 95 % CI 66.2-72.4 years), the overall cases occurring in the extra-urban population (from 54.5 95 % CI 49.0-60.1 years to 65.1 95 % CI 60.4-69.8 years) and the bulbar onset cases occurring in the extra-urban population (from 57.1 95 % CI 53.5-60.7 years to 69.6 95 % CI 66.3-73.7 years). Although the increasing age of the population combined with improvements in ALS diagnosis among the elderly may have played a part, these uneven findings among the incident cases occurring in a well-defined homogeneous population with a stable ALS incidence would seem to suggest the involvement of risk factors associated with the extra-urban environment.

Published
2017
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46. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.

Author

Doronin VB, Parkhomenko TA, Castellazzi M, Cesnik E, Buneva VN, Granieri E, and Nevinsky GA

Subjects
Adult, Antibodies, Antinuclear blood, Antibodies, Antinuclear cerebrospinal fluid, Antibodies, Antinuclear chemistry, Antibodies, Catalytic chemistry, Cerebrospinal Fluid Proteins chemistry, Chromatography, Affinity, Chromatography, Gel, Chromatography, High Pressure Liquid, DNA analysis, Female, Humans, Hydrolysis, Immunoglobulin G blood, Immunoglobulin G cerebrospinal fluid, Immunoglobulin G chemistry, Isoelectric Focusing, Male, Middle Aged, Myelin Basic Protein blood, Myelin Basic Protein cerebrospinal fluid, Retrospective Studies, Young Adult, Amylases blood, Amylases cerebrospinal fluid, Antibodies, Catalytic blood, Antibodies, Catalytic cerebrospinal fluid, Multiple Sclerosis blood, Multiple Sclerosis cerebrospinal fluid
Abstract

We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed.

Published
2016
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47. Posterior reversible encephalopathy associated with nocturnal blood pressure non-dipping pattern.

Author

Casetta I, Cesnik E, and Pedelini F

Subjects
Aged, Humans, Hypertensive Encephalopathy therapy, Male, Posterior Leukoencephalopathy Syndrome therapy, Blood Pressure physiology, Hypertension physiopathology, Hypertensive Encephalopathy physiopathology, Posterior Leukoencephalopathy Syndrome physiopathology
Abstract

We report the case of a 70-year-old man who presented with a recent history of headache, altered mental status and sleepiness. He was known to have type II diabetes mellitus, and a mild, treated and apparently well controlled hypertension. Brain magnetic resonance imaging demonstrated extensive abnormalities in the parieto-occipital white matter, suggestive of posterior reversible encephalopathy syndrome (PRES). An extensive diagnostic evaluation did not allow the detection of any known cause of the syndrome. Twenty-four-hour non-invasive ambulatory blood pressure monitoring showed a mild to moderate hypertension, with non-dipping pattern. This case suggests that, in the context of an overnight blunted blood pressure profile, even a mild or moderate hypertension can result in cerebral vasogenic oedema, underlining the diagnostic importance of 24-h blood pressure monitoring in patients with PRES without severe hypertension or other commonly recognized causes of posterior reversible encephalopathy.

Published
2014
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48. Incidence of epilepsy in Ferrara, Italy.

Author

Cesnik E, Pedelini F, Faggioli R, Monetti VC, Granieri E, and Casetta I

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Incidence, Infant, Infant, Newborn, Italy epidemiology, Male, Middle Aged, Young Adult, Epilepsy epidemiology
Abstract

Few studies have been carried out in the same area at different times, allowing an assessment of the incidence of epilepsy (E.), including all ages, over time. The available data on temporal trend show a decrease in E. incidence in childhood and an increase in the elderly. We sought to update the incidence of E. in the province of Ferrara, where a previous study estimated an incidence rate of 33.1 per 100,000, 35.8, if standardized to the European population. Newly diagnosed patients aged up to 14 years were drawn from a community-based prospective multi-source registry, and adult onset E. cases were collected through multiple overlapping sources of case collection. Cases were included and classified according to ILAE recommendations. During the study period (2007-2008), 141 newly diagnosed cases (66 men and 75 women) living in the study area were identified. The crude incidence rate was 46.1 per 100,000 person-years (95 % CI 39.0-54.5), 35.5 (95 % CI 28.0-43.0) if adjusted to the European population. The incidence of childhood and adolescence epilepsy was 57.0 per 100,000 person-years (95 % CI 33.8-90.0), lower than that reported in our previous study, and it was 44.8 (95 % CI 37.4-53.6) for adult onset E., which is significantly higher as compared to our previous study. The overall incidence of E. in northern Italy is stable over time. We detected a significant decrease in incidence of childhood and adolescence E. and an increase in adult-onset E. The burden of epilepsy will increase as the population continues to age.

Published
2013
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49. Gait measures with a triaxial accelerometer among patients with neurological impairment.

Author

Fazio P, Granieri G, Casetta I, Cesnik E, Mazzacane S, Caliandro P, Pedrielli F, and Granieri E

Subjects
Adult, Age Factors, Aged, Aged, 80 and over, Analysis of Variance, Ataxia diagnosis, Ataxia etiology, Female, Humans, Male, Middle Aged, Nervous System Diseases complications, Severity of Illness Index, Walking physiology, Young Adult, Accelerometry methods, Gait Disorders, Neurologic diagnosis, Gait Disorders, Neurologic etiology
Abstract

The purpose of the present study is to evaluate accelerometric parameters of gait in different neurological conditions with pathological gait impairment compared to healthy subjects. We studied 17 patients affected by Parkinson's disease, 24 with ataxic gait due to different diseases and 24 healthy subjects supplied with a triaxial accelerometer with a portable datalogger which measures acceleration and deceleration on an anterior-posterior, mediolateral and vertical plane at an approximate level of the center of mass (back sacral localization) and in other two positions (sternal and frontal sacral region) during a steady-state walking. Analyses of the basic accelerometric parameters associated with a jerk analysis allowed us to differentiate between the population groups. We observed a significant reduction of acceleration parameters in neurological patients when compared with healthy subjects, with a reduction of the mean acceleration of 0.30 m/s(2) for ataxic and 0.64 m/s(2) for parkinsonian patients (t test, p < 0.01). The root-mean square of the accelerations was used to quantify the attenuations of accelerations. This study suggests that a triaxial accelerometer is a good practical and an economic tool for assessing the alteration of perambulation. Moreover, it is plausible to use these data to obtain objective parameters in the evaluation of the progression of the disease and the efficacy of therapeutic tools.

Published
2013
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50. Technical, Anatomical, and Functional Study after Removal of a Symptomatic Cavernous Angioma Located in Deep Wernicke's Territories with Cortico-Subcortical Awake Mapping.

Author

Sarubbo S, Basso G, Chioffi F, Cesnik E, Paradiso B, Grandi E, Fainardi E, Tugnoli V, Farneti M, and Granieri E

Abstract

Introduction. The subcortical region underneath Wernicke's area (WA) is a critical crossing of the eloquent language pathways involved in all semantic, phonological, syntactic, and working memory elaboration. We report the resection of a CA located underneath the dominant WA discussing the functional and anatomical evidence provided by fMRI, dissections with Klingler's technique, and intraoperative mapping during awake surgery. Case Report. A 64-year-old right-handed female affected by daily complex focal seizures underwent f-MRI, showing language activations in the middle and inferior temporal gyri and an unusual free entry zone in the "classical" WA. The cortical intraoperative mapping partially confirmed the f-MRI results, and we approached the lesion directly through WA. Subcortical DES allowed the identification of the eloquent language pathways and the radical resection of the perilesional gliotic rim. The patient did not report deficits and she is seizures and drug free after 1-year surgery. Discussion. Cortical DES demonstrated the variability of the eloquent areas within the cortex of the dominant temporal lobe. The subcortical DES confirmed the crucial role in language elaboration and the anatomical course of the bundles underneath WA. Conclusions. Awake surgery with DES represents a reliable and dynamic technique also for safer and functional-customized resection of CAs.

Published
2013
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