Elena Pasini
Verified @isnb.it
UOC of Neurology
IRCCS Istituto delle Scienze Neurologiche di Bologna
- 01/06/2020-Today: Neurologist at Bellaria Hospital, UOC of Neurology, IRCCS of Neurological Sciences of Bologna
- 06/11/2017-31/05/2020: Neurologist at Maggiore Hospital, UOC of Neurology, IRCCS of Neurological Sciences of Bologna
- 14/03/2016-05/11/2017: Research project on “Clinical evaluation and therapeutic treatment of serious neurological diseases that need management in ICU through multiparametric and neurophysiological monitoring” at Bellaria Hospital, IRCCS of Neurological Sciences of Bologna
- 08/24/2009-05/14/2010: fellowship in PERNO project (Progetto Emiliano-Romagnolo in Neuro-Oncologia-Sottoprogetto Epilessia tumorale) at the Neurological Department of Bellaria Hospital (referent Dr. Michelucci)
- In 2008-2009 partecipation to two randomized clinical trials on new epileptic drugs at the Neurological Department of Bellaria Hospital (referent Dr. Michelucci)
EDUCATION
- Scientific-technological diploma in 2002 (vote 100/100)
- Nine months spent at the Pasteur University of Strasbourg, France, during university
- Undergraduate Introduction to Management Program, BU Global, Boston University (07-08/2007)
- Graduated in Medicine and Surgery at the “Alma Mater Studiorum University of Bologna” on May 12, 2008 with 110/110 and Praise. Title of thesis: “amyotrophic lateral sclerosis: genotype-phenotype correlation in patients with SOD1 gene mutation and etiopathogenic hypothesis. Supervisor: Prof. Carlo Alberto Tassinari.
- From the 24th March 2009 entered in the order of Bologna physicians
- 05/17/2010-01/02/2016 Neurological Fellowship at Bologna University (headmaster Prof. Paolo Tinuper).
- 25/2/2012-06/04/2012 “EFNS Department to Department Program” at the “National Hospital of Neurology and Neurosurgery-Department of Neurology, Queen Square, London” (Prof. Simon Shorvon)
RESEARCH INTERESTS
Epilepsy
EEG
Stereo-EEG
ICU-monitoring
FUTURE PROJECTS
Stereo-EEG
During 2022-2025 we expect to begin the stereo-electroencephalography study of the patient affected by cryptogenic focal pharmacoresistant epilepsy. All this project will be possible thanks to the collaboration with the collegues of Niguarda Hospital of Milan. Project financed by the Emilia-Romagna Region
Applications Invited
Neuro-critical care unit monitoring
During the last years we improve our experience in the field of the long term monitorig EEG and therapy of refractory and super refractory status epilepticus. At the same time we pursuit an important project of multidisciplinary evaluation of the long term prognosis in patients with severe brain injuries
Applications Invited
Lafora Disease
Clinical and electrophysiological characterization of Lafora affected patients
Applications Invited
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Elena Pasini, Patrizia Riguzzi, and Roberto Michelucci
Journal of the Neurological Sciences, ISSN: 0022510X, eISSN: 18785883, Volume: 434, Published: 15 March 2022
Elsevier BV
Lorenzo Muccioli, Corrado Zenesini, Lisa Taruffi, Laura Licchetta, Barbara Mostacci, Lidia Di Vito, Elena Pasini, Lilia Volpi, Patrizia Riguzzi, Lorenzo Ferri, Flavia Baccari, Francesco Nonino, Roberto Michelucci, Paolo Tinuper, Luca Vignatelli, and Francesca Bisulli
Epilepsia, ISSN: 00139580, eISSN: 15281167, Published: 2022
Wiley
OBJECTIVE
Data on COVID-19 outcomes in persons with epilepsy (PWE) are scarce and inconclusive. We aimed to study the risk of hospitalization and death for COVID-19 in a large cohort of PWE from 01 March 2020 to 31 October 2021.
METHODS
Historical cohort design (EpiLink Bologna), comparing adult PWE grouped in people with focal epilepsy (PFE), idiopathic generalized epilepsy (PIGE), developmental and/or epileptic encephalopathy (PDEE), and a matched population cohort (ratio 1:10) for age, sex, residence, and comorbidity (assessed with the multisource comorbidity score), living in the local health trust of Bologna (about 800,000 residents). Clinical data were linked to health administrative data.
RESULTS
In both cohorts (EpiLink N=1,576 subjects, 1128 PFE, 267 PIGE, 148 PDEE, 32 other, controls N=15,326 subjects), 52% were females, and the mean age was 50 years (SD 18). Hospital admissions for COVID-19 in the whole period were 49 (3.1%) in PWE and 225 (1.5%) in controls. The adjusted hazard ratio (aHR) in PWE was 1.9 (95% CI 1.4-2.7). The subgroups at higher risk were PFE (aHR 1.9, 95% CI 1.3-2.8) and PDEE (aHR 3.9, 95% CI 1.7- 8.7), while PIGE had a risk comparable to the controls (aHR 1.1, 95% CI 0.3-3.5). Stratified analyses of the two main epidemic waves (March-May 2020, October 2020-May 2021) disclosed a higher risk of COVID-19-related hospitalization during the first epidemic wave (March-May 2020) (aHR 3.8, 95% CI 2.2-6.7). Polytherapy with antiseizure medications contributed to a higher risk of hospital admission. 30-day risk of death after hospitalization was 14% both in PWE and controls.
SIGNIFICANCE
During the first 20 months since the outbreak of COVID-19 in Bologna, PWE had a doubled risk of COVID-19 hospital admission compared to a matched control population. Conversely, epilepsy did not represent a risk factor for COVID-19-related death.
Roberto Michelucci, Stefania Testoni, Roberta Pantieri, Patrizia Riguzzi, and Elena Pasini
American Journal of Medicine, ISSN: 00029343, eISSN: 15557162, Volume: 135, Pages: e11-e13, Published: January 2022
Elsevier BV
A. E. Vaudano, L. Mirandola, F. Talami, G. Giovannini, G. Monti, P. Riguzzi, L. Volpi, R. Michelucci, F. Bisulli, E. Pasini, P. Tinuper, L. Di Vito, G. Gessaroli, M. Malagoli, G. Pavesi, F. Cardinale, L. Tassi, L. Lemieux, and S. Meletti
Brain Topography, ISSN: 08960267, eISSN: 15736792, Pages: 632-650, Published: September 2021
Springer Science and Business Media LLC
Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.
Lorenzo Muccioli, Umberto Pensato, Giorgia Bernabè, Lorenzo Ferri, Maria Tappatà, Lilia Volpi, Ilaria Cani, Olivia J. Henry, Francesca Ceccaroni, Sabina Cevoli, Gloria Stofella, Elena Pasini, Giacomo Fornaro, Caterina Tonon, Simone Vidale, Rocco Liguori, Paolo Tinuper, Roberto Michelucci, Pietro Cortelli, and Francesca Bisulli
Journal of Neurology, ISSN: 03405354, eISSN: 14321459, Volume: 268, Pages: 2671-2675, Published: August 2021
Springer Science and Business Media LLC
Abstract Objective To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. Methods We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. Results Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19–55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1–10 days). No adverse events related to IVIg were observed. Conclusions Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.
Elena Pasini and Roberto Michelucci
Clinical Neurophysiology, ISSN: 13882457, eISSN: 18728952, Volume: 132, Pages: 178-179, Published: January 2021
Elsevier BV
Umberto Pensato, Lorenzo Muccioli, Elena Pasini, Maria Tappatà, Lorenzo Ferri, Lilia Volpi, Laura Licchetta, Stella Battaglia, Giada Rossini, Isabella Bon, Maria Carla Re, Luigi Cirillo, Luigi Simonetti, Laura Ludovica Gramegna, Roberto Michelucci, Pietro Cortelli, Andrea Zini, and Francesca Bisulli
Frontiers in Neurology, eISSN: 16642295, Published: 19 October 2020
Frontiers Media SA
Introduction: Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. Case: A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. Conclusions: We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment.
Elena Pasini, Francesca Bisulli, Lilia Volpi, Irene Minardi, Maria Tappatà, Lorenzo Muccioli, Umberto Pensato, Patrizia Riguzzi, Paolo Tinuper, and Roberto Michelucci
Clinical Neurophysiology, ISSN: 13882457, eISSN: 18728952, Volume: 131, Pages: 2265-2267, Published: September 2020
Elsevier BV
Roberto Michelucci, Emanuela Dazzo, Lilia Volpi, Elena Pasini, Patrizia Riguzzi, Raffaella Minardi, Anna Federica Marliani, Maria Tappatà, Francesca Bisulli, Carlo Alberto Tassinari, and Carlo Nobile
Epileptic Disorders, ISSN: 12949361, eISSN: 19506945, Pages: 443-448, Published: 1 August 2020
John Libbey Eurotext
Reelin mutations are responsible for a minority of families with autosomal dominant lateral temporal lobe epilepsy. Here, we report a novel nuclear family with distinct clinical and neuroradiological findings. We studied the proband and her mother by means of EEG, video-EEG, 3T MRI, FDG-PET and genetic testing. Both patients had a focal drug-resistant epilepsy with onset at the age of 16 and focal seizures with typical auditory features combined with fear, followed by loss of contact or evolving to bilateral tonic-clonic seizures. The proband's ictal EEG showed clear left temporal seizure onset, and cerebral MRI revealed subtle left temporal changes (mild hypotrophy, slight blurring of the white and grey matter and hyperintensity) with corresponding left temporal mesial focal hypometabolism on FDG-PET. Genetic testing identified a missense variant, c.6631C>T (p.Arg2211Cys), in reelin repeat #5 in both patients, which markedly affected the secretion of the protein. The data from this family support previous findings indicating that reelin mutations are a cause of autosomal dominant lateral temporal lobe epilepsy which has a clinical spectrum that may also encompass drug-resistant epilepsy associated with mild MRI temporal changes.
Emanuela Dazzo, Elena Pasini, Sandra Furlan, Dario de Biase, Matteo Martinoni, Roberto Michelucci, and Carlo Nobile
Clinical Neurology and Neurosurgery, ISSN: 03038467, eISSN: 18726968, Volume: 170, Pages: 27-33, Published: July 2018
Elsevier BV
OBJECTIVES
The Leucine-rich glioma inactivated 1 (LGI1) protein is thought to be implicated in malignant progression of glioma tumors, and mutations in the encoding gene, LGI1, cause autosomal dominant lateral temporal epilepsy, a genetic focal epilepsy syndrome. The aim of this study was to investigate the possible involvement of LGI1 in high-grade glioma-associated epilepsy by analyzing its expression in tumor specimens of patients with and without epilepsy and by searching for LGI1 autoantibodies in the sera these patients.
PATIENTS AND METHODS
We examined tumor tissue samples from 24 patients with high-grade gliomas (12 with and 12 without epilepsy) by immunoblot and detected variable amounts of LGI1 in tumor tissues from 9/24 (37%) patients.
RESULTS
LGI1 was detected in 7/12 (58%) patients with epilepsy and in 2/12 (16%) patients without epilepsy (p = 0.0894; Fisher's exact test). Moreover, testing blood sera of five patients for antibodies against LGI1 revealed LGI1 autoantibodies in two patients, both suffering from epilepsy and expressing LGI1 in tumor tissue.
CONCLUSION
Our findings suggest that there may be a preferential expression of LGI1 in high-grade glioma tumors of patients with epilepsy. We also unveil the presence of serum LGI1 autoantibodies in some patients with high-grade gliomas, where they might play an epileptogenic role.
Veria Vacchiano, Rocco Liguori, Elena Pasini, Patrizia Avoni, and Vincenzo Donadio
Annals of Allergy, Asthma and Immunology, ISSN: 10811206, eISSN: 15344436, Volume: 120, Pages: 433-435, Published: April 2018
Elsevier BV
Enrico Franceschi, Alicia Tosoni, Santino Minichillo, Roberta Depenni, Alexandro Paccapelo, Stefania Bartolini, Maria Michiara, Giacomo Pavesi, Benedetta Urbini, Girolamo Crisi, Michele A. Cavallo, Luigino Tosatto, Claudio Dazzi, Claudia Biasini, Giuseppe Pasini, Damiano Balestrini, Francesca Zanelli, Vania Ramponi, Antonio Fioravanti, Ermanno Giombelli, Dario De Biase, Agostino Baruzzi, Alba A. Brandes, A. Baruzzi, F. Albani, F. Calbucci, R. D'Alessandro, R. Michelucci, A. Brandes, V. Eusebi, S. Ceruti, E. Fainardi, R. Tamarozzi, E. Emiliani, M. Cavallo, E. Franceschi, A. Tosoni, M. Cavallo, F. Fiorica, A. Valentini, R. Depenni, C. Mucciarini, G. Crisi, E. Sasso, C. Biasini, L. Cavanna, D. Guidetti, N. Marcello, A. Pisanello, A.M. Cremonini, G. Guiducci, S. de Pasqua, S. Testoni, R. Agati, G. Ambrosetto, A. Bacci, E. Baldin, A. Baldrati, E. Barbieri, S. Bartolini, E. Bellavista, F. Bisulli, E. Bonora, F. Bunkheila, V. Carelli, M. Crisci, P. Dall'Occa, D. de Biase, S. Ferro, C. Franceschi, G. Frezza, V. Grasso, M. Leonardi, G. Marucci, L. Morandi, B. Mostacci, G. Palandri, E. Pasini, M. Pastore Trossello, A. Pession, R. Poggi, P. Riguzzi, R. Rinaldi, S. Rizzi, G. Romeo, F. Spagnolli, P. Tinuper, C. Trocino, M. Dall'Agata, M. Frattarelli, G. Gentili, A. Giovannini, P. Iorio, U. Pasquini, G. Galletti, C. Guidi, W. Neri, A. Patuelli, S. Strumia, M. Faedi, M. Casmiro, A. Gamboni, F. Rasi, G. Cruciani, P. Cenni, C. Dazzi, A.R. Guidi, F. Zumaglini, A. Amadori, G. Pasini, M. Pasquinelli, E. Pasquini, A. Polselli, A. Ravasio, B. Viti, M. Sintini, A. Ariatti, F. Bertolini, G. Bigliardi, P. Carpeggiani, F. Cavalleri, S. Meletti, P. Nichelli, E. Pettorelli, G. Pinna, E. Zunarelli, F. Artioli, I. Bernardini, M. Costa, G. Greco, R. Guerzoni, C. Stucchi, C. Iaccarino, M. Ragazzi, R. Rizzi, G. Zuccoli, P. Api, F. Cartei, M. Colella, E. Fallica, M. Farneti, A. Frassoldati, E. Granieri, F. Latini, C. Monetti, A. Saletti, R. Schivalocchi, S. Sarubbo, S. Seraceni, M.R. Tola, B. Urbini, G. Zini, C. Giorgi, E. Montanari, D. Cerasti, P. Crafa, I. Dascola, I. Florindo, E. Giombelli, S. Mazza, V. Ramponi, F. Servadei, E.M. Silini, P. Torelli, P. Immovilli, N. Morelli, C. Vanzo, and C. Nobile
World Neurosurgery, ISSN: 18788750, eISSN: 18788769, Volume: 112, Pages: e342-e347, Published: 1 April 2018
Elsevier BV
BACKGROUND
Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients.
METHODS
We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment.
RESULTS
A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P < 0.001) were significantly correlated with survival.
CONCLUSIONS
Survival was consistently longer among MGMT methylated females compared with males. Gender can be considered as a further prognostic factor.
Elena Pasini, Federica Provini, and Roberto Michelucci
BMJ Case Reports, eISSN: 1757790X, Volume: 2018, Published: 2018
BMJ
A 61-year-old woman affected by nocturnal hypermotor seizures since the age of 2 years complained of epigastric discomfort and chocking sensation before seizure onset for the last 25 years. Telemetry unit monitoring revealed several focal seizures with left frontotemporal onset complicated with ictal asystole and apnoea. After pacemaker (PM) implantation, video-EEG monitoring coupled with extensive respiratory montage confirmed the presence of ictal central apnoea. Despite this huge ictal autonomic imbalance which is claimed to be a risk factor for sudden unexpected death in epilepsy, the patient had a 25-year history of similar seizures, questioning the need to perform PM implantation and assisted ventilation.
Enrico Franceschi, , Roberta Depenni, Alexandro Paccapelo, Mario Ermani, Marina Faedi, Carmelo Sturiale, Maria Michiara, Franco Servadei, Giacomo Pavesi, Benedetta Urbini, Anna Pisanello, Girolamo Crisi, Michele A. Cavallo, Claudio Dazzi, Claudia Biasini, Federica Bertolini, Claudia Mucciarini, Giuseppe Pasini, Agostino Baruzzi, and Alba A. Brandes
Journal of Neuro-Oncology, ISSN: 0167594X, eISSN: 15737373, Volume: 136, Pages: 221-222, Published: 1 January 2018
Springer Science and Business Media LLC
The members of the PERNO Study Group were not individually captured in the metadata of the original publication. They are included in the metadata of this publication.
Laura Canafoglia, Edoardo Ferlazzo, Roberto Michelucci, Pasquale Striano, Adriana Magaudda, Antonio Gambardella, Elena Pasini, Vincenzo Belcastro, Patrizia Riguzzi, Martina Fanella, Tiziana Granata, Francesca Beccaria, Claudia Trentini, Amedeo Bianchi, Umberto Aguglia, Ferruccio Panzica, and Silvana Franceschetti
Neurology, ISSN: 00283878, eISSN: 1526632X, Pages: 1691-1697, Published: 17 October 2017
Ovid Technologies (Wolters Kluwer Health)
Objective:To explore the course of Unverricht-Lundborg disease (EPM1) and identify the risk factors for severity, we investigated the time course of symptoms and prognostic factors already detectable near to disease onset.Methods:We retrospectively evaluated the features of 59 Italian patients carrying the CSTB expansion mutation, and coded the information every 5 years after the disease onset in order to describe the cumulative time-dependent probability of reaching disabling myoclonus, relevant cognitive impairment, and inability to work, and evaluated the influence of early factors using the log-rank test. The risk factors were included in a Cox multivariate proportional hazards regression model.Results:Disabling myoclonus occurred an average of 32 years after disease onset, whereas cognitive impairment occurred a little later. An age at onset of less than 12 years, the severity of myoclonus at the time of first assessment, and seizure persistence more than 10 years after onset affected the timing of disabling myoclonus and cognitive decline. Most patients became unable to work years before the appearance of disabling myoclonus or cognitive decline.Conclusions:A younger age at onset, early severe myoclonus, and seizure persistence are predictors of a more severe outcome. All of these factors may be genetically determined, but the greater hyperexcitability underlying more severe seizures and myoclonus at onset may also play a role by increasing cell damage due to reduced cystatin B activity.
Maria Pia Giannoccaro, Anna Bartoletti-Stella, Silvia Piras, Annalisa Pession, Patrizia De Massis, Federico Oppi, Michelangelo Stanzani-Maserati, Elena Pasini, Simone Baiardi, Patrizia Avoni, Piero Parchi, Rocco Liguori, and Sabina Capellari
Journal of Neurology, ISSN: 03405354, eISSN: 14321459, Volume: 264, Pages: 1426-1433, Published: 1 July 2017
Springer Science and Business Media LLC
The C9orf72 repeat expansion (RE) is one of the most frequent causative mutations of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, it is still unclear how the C9orf72 RE can lead to a heterogeneous phenotype. Several reports have shown the coexistence of mutations in multiple ALS/FTD causative genes in the same family, suggesting an oligogenic etiology for ALS and FTD. Our aim was to investigate this phenomenon in an Italian group of ALS/FTD pedigrees carrying the C9orf72 RE. We included 11 subjects from 11 pedigrees with ALS/FTD and the C9orf72 RE. Mutation screening of FUS, SOD1 and TARDBP genes was performed by direct sequencing. A dementia-specific custom-designed targeted next-generation sequencing panel was used for screening dementia-associated genes mutations. We found genetic variants in additional ALS or dementia-related genes in four pedigrees, including the p.V47A variant in the TYROBP gene. As a group, double mutation carriers displayed a tendency toward a younger age at onset and a higher frequency of positive familiar history and of parkinsonism. Our observation supports the hypothesis that the co-presence of mutations in different genes may be relevant for the clinical expression of ALS/FTD and of their oligogenic nature.
Karen L. Oliver, Silvana Franceschetti, Carol J. Milligan, Mikko Muona, Simone A. Mandelstam, Laura Canafoglia, Anna M. Boguszewska-Chachulska, Amos D. Korczyn, Francesca Bisulli, Carlo Di Bonaventura, Francesca Ragona, Roberto Michelucci, Bruria Ben-Zeev, Rachel Straussberg, Ferruccio Panzica, João Massano, Daniel Friedman, Arielle Crespel, Bernt A. Engelsen, Frederick Andermann, Eva Andermann, Krystyna Spodar, Anetta Lasek-Bal, Patrizia Riguzzi, Elena Pasini, Paolo Tinuper, Laura Licchetta, Elena Gardella, Matthias Lindenau, Annette Wulf, Rikke S. Møller, Felix Benninger, Zaid Afawi, Guido Rubboli, Christopher A. Reid, Snezana Maljevic, Holger Lerche, Anna-Elina Lehesjoki, Steven Petrou, and Samuel F. Berkovic
Annals of Neurology, ISSN: 03645134, eISSN: 15318249, Pages: 677-689, Published: May 2017
Wiley
To comprehensively describe the new syndrome of myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK), including cellular electrophysiological characterization of observed clinical improvement with fever.
Roberto Michelucci, Patrizia Pulitano, Carlo Di Bonaventura, Simona Binelli, Concetta Luisi, Elena Pasini, Salvatore Striano, Pasquale Striano, Giangennaro Coppola, Angela La Neve, Anna Teresa Giallonardo, Oriano Mecarelli, Elena Serioli, Emanuela Dazzo, Manuela Fanciulli, and Carlo Nobile
Epilepsy and Behavior, ISSN: 15255050, eISSN: 15255069, Pages: 103-107, Published: 1 March 2017
Elsevier BV
Objective To describe the clinical phenotype of 7 families with Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) related to Reelin (RELN) mutations comparing the data with those observed in 12 LGI1-mutated pedigrees belonging to our series. Methods Out of 40 Italian families with ADLTE, collected by epileptologists participating in a collaborative study of the Commission for Genetics of the Italian League against Epilepsy encompassing a 14-year period (2000–2014), 7 (17.5%) were found to harbor heterozygous RELN mutations. The whole series also included 12 (30%) LGI1 mutated families and 21 (52.5%) non-mutated pedigrees. The clinical, neurophysiological, and neuroradiological findings of RELN and LGI1 mutated families were analyzed. Results Out of 28 affected individuals belonging to 7 RELN mutated families, 24 had sufficient clinical data available for the study. In these patients, the epilepsy onset occurred at a mean age of 20 years, with focal seizures characterized by auditory auras in about 71% of the cases, associated in one-third of patients with aphasia, visual disturbances or other less common symptoms (vertigo or déjà-vu). Tonic–clonic seizures were reported by almost all patients (88%), preceded by typical aura in 67% of cases. Seizures were precipitated by environmental noises in 8% of patients and were completely or almost completely controlled by antiepileptic treatment in the vast majority of cases (96%). The interictal EEG recordings showed epileptiform abnormalities or focal slow waves in 80% of patients, localized over the temporal regions, with marked left predominance and conventional 1,5T MRI scans were not contributory. By comparing these findings with those observed in families with LGI1 mutations, we did not observe significant differences except for a higher rate of left-sided EEG abnormalities in the RELN group. Significance Heterozygous RELN mutations cause a typical ADLTE syndrome, indistinguishable from that associated with LGI1 mutations.
Elisa Baldin, , Stefania Testoni, Silvia de Pasqua, Salvatore Ferro, Fiorenzo Albani, Agostino Baruzzi, and Roberto D’Alessandro
Neurological Sciences, ISSN: 15901874, eISSN: 15903478, Pages: 263, Published: 1 February 2017
Springer Science and Business Media LLC
Agati R., Ambrosetto G., Bacci A., Baldin E., Baldrati A., Barbieri E., Bartolini S., Bellavista E., Bisulli F., Bonora E., Bunkheila F., Carelli V., Cerasoli S., Crisci M., Dall’Occa P., de Biase D., Ferro S., Franceschi C., Frezza G., GrassoV., Leonardi M., Marucci G., Morandi L., Mostacci B., Palandri G., Pasini E., Pastore Trossello M., Pession A., Poggi R., Riguzzi P., Rinaldi R., Rizzi S., Romeo G., Spagnolli F., Tinuper P., Trocino C., Visani M. (Bologna), Dall’Agata M., Faedi M., Frattarelli M., Gentili G., Giovannini A., Iorio P., Pasquini U., Galletti G., Guidi C., Neri W., Patuelli A.., Strumia S. (ForlÍ-Cesena), Casmiro M., Gamboni A., Rasi F. (Faenza, RA), Cruciani G. (Lugo, RA), Cenni P., Dazzi C., Guidi A.R., Zumaglini F. (Ravenna), Amadori A., Pasini G., Pasquinelli M., Pasquini E., Polselli A., Ravasio A., Viti B. (Rimini), Sintini M. (Cattolica, RN), Ariatti A., Bertolini F., Bigliardi G., Carpeggiani P., Cavalleri F., Meletti S., Nichelli P., Pettorelli E., Pinna G., Zunarelli E. (Modena), Artioli F., Bernardini I., Costa M., Greco G., Guerzoni R., Stucchi C. (Carpi, MO), Iaccarino C., Ragazzi M., Rizzi R., Zuccoli G. (Reggio Emilia), Api P., Cartei F., Fallica E., Granieri E., Latini F., Lelli G., Monetti C., Saletti A., Schivalocchi R., Seraceni S., Tola M.R., Urbini B. (Ferrara), Giorgi C., Montanari E. (Fidenza, PR), Cerasti D., Crafa P., Dascola I., Florindo I., Giombelli E., Mazza S., Ramponi V., Servadei F., Silini EM., Torelli P. (Parma), Immovilli P., Morelli N., Vanzo C. (Piacenza), Nobile C. (Padova).
Elisa Baldin, , Stefania Testoni, Silvia de Pasqua, Salvatore Ferro, Fiorenzo Albani, Agostino Baruzzi, and Roberto D’Alessandro
Neurological Sciences, ISSN: 15901874, eISSN: 15903478, Pages: 255-262, Published: 1 February 2017
Springer Science and Business Media LLC
Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4–11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3–10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4–0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3–8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population.
Enrico Franceschi, , Roberta Depenni, Alexandro Paccapelo, Mario Ermani, Marina Faedi, Carmelo Sturiale, Maria Michiara, Franco Servadei, Giacomo Pavesi, Benedetta Urbini, Anna Pisanello, Girolamo Crisi, Michele A. Cavallo, Claudio Dazzi, Claudia Biasini, Federica Bertolini, Claudia Mucciarini, Giuseppe Pasini, Agostino Baruzzi, and Alba A. Brandes
Journal of Neuro-Oncology, ISSN: 0167594X, eISSN: 15737373, Volume: 128, Pages: 157-162, Published: 1 May 2016
Springer Science and Business Media LLC
The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly patients with glioblastoma (GBM) remains unclear. We evaluated the outcome of patients >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. For this analysis the criteria for selecting patients enrolled in the PERNO study were: age >70 years; PS 0–3; histologically confirmed GBM; postoperative radiotherapy (RT) after surgery with or without concomitant temozolomide (TMZ) or postsurgical TMZ alone. Between January 2009 and December 2010, 76 GBM elderly patients were identified in the prospective PERNO study. Twenty-three patients did not receive any treatment after surgery, and 53 patients received postsurgical treatments (25 patients received RT alone and 28 patients RT/TMZ). Median survival was 11.1 months (95 % CI 8.8–13.5), adding temozolomide concomitant and adjuvant to radiotherapy it was 11.6 months (95 % CI 8.6–14.6), and 9.3 months (95 % CI 8.1–10.6) in patients treated with RT alone (P = 0.164). However, patients with MGMT methylated treated with RT/TMZ obtained a better survival (17.2 months, 95 % CI 11.5–22.9) (P = 0.042). No difference in terms of survival were observed if patients with MGMT unmethylated tumor received RT alone, or RT/TMZ or, in MGMT methylated tumor, if patients received radiotherapy alone. In elderly patients RT/TMZ represent a widely used approach but it is effective with methylated MGMT tumors only.
Roberto Michelucci, Elena Pasini, Patrizia Riguzzi, Eva Andermann, Reetta Kälviäinen, and Pierre Genton
Epileptic Disorders, ISSN: 12949361, eISSN: 19506945, Pages: S145-S153, Published: 2016
John Libbey Eurotext
Generalized motor seizures, usually tonic-clonic, tonic-vibratory, myoclonic or clonic, and stimulus-sensitive/action myoclonus are typical features of progressive myoclonus epilepsies (PMEs). Despite the introduction of many anticonvulsants, the treatment of these symptoms, particularly myoclonus, remains challenging, due to the incomplete and often transitory effects of most drugs. Moreover, treatment is only symptomatic, since therapy targeting the underlying aetiology for these genetic conditions is in its infancy. Traditional antiepileptic drugs for the treatment of PMEs are valproate, clonazepam, and phenobarbital (or primidone). These drugs may improve the overall performance of PME patients by decreasing their generalized seizures and, to a lesser extent, their myoclonic jerks. Newer drugs which have been shown to be effective include piracetam, levetiracetam, topiramate, zonisamide, and possibly perampanel for Lafora disease. The potential of other drugs (such as L-triptophan and N-acetylcysteine) and procedures (such as vagal and deep brain stimulation) has also been discussed. The available data on the efficacy of drugs are mainly based on small series or anecdotal reports. Two prospective, randomized, double blind studies investigating the novel SV2A ligand, brivaracetam, in genetically confirmed Unverricht-Lundborg patients have been performed with disappointing results. When treating PMEs, particular care should be paid to avoid drugs known to aggravate myoclonus or myoclonic seizures, such as phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin. The emergency treatment of motor status, which often complicates the course of PMEs, consists of intravenous administration of benzodiazepines, valproate, or levetiracetam.
Pasquale Striano, Elena Serioli, Lia Santulli, Ida Manna, Angelo Labate, Emanuela Dazzo, Elena Pasini, Antonio Gambardella, Roberto Michelucci, Salvatore Striano, and Carlo Nobile
Epilepsia, ISSN: 00139580, eISSN: 15281167, Pages: e168-e171, Published: 1 October 2015
Wiley
Mutations in the DEPDC5 (DEP domain–containing protein 5) gene are a major cause of familial focal epilepsy with variable foci (FFEVF) and are predicted to account for 12–37% of families with inherited focal epilepsies. To assess the clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we screened a collection of Italian families with either autosomal dominant lateral temporal epilepsy (ADLTE) or familial mesial temporal lobe epilepsy (FMTLE). The probands of 28 families classified as ADLTE and 17 families as FMTLE were screened for DEPDC5 mutations by whole exome or targeted massive parallel sequencing. Putative mutations were validated by Sanger sequencing. We identified a DEPDC5 nonsense mutation (c.918C>G; p.Tyr306*) in a family with two affected members, clinically classified as FMTLE. The proband had temporal lobe seizures with prominent psychic symptoms (déjà vu, derealization, and forced thoughts); her mother had temporal lobe seizures, mainly featuring visceral epigastric auras and anxiety. In total, we found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies.
Timothy Pok Chi Yeung, , Yong Wang, Wenqing He, Benedetta Urbini, Roberta Gafà, Linda Ulazzi, Slav Yartsev, Glenn Bauman, Ting-Yim Lee, and Enrico Fainardi
Journal of Neuro-Oncology, ISSN: 0167594X, eISSN: 15737373, Volume: 125, Pages: 223-224, Published: 1 October 2015
Springer Science and Business Media LLC
Baruzzi A. (Chair), Albani F., Calbucci F., D’Alessandro R., Michelucci R. (IRCCS Institute of Neurological Sciences, Bologna, Italy), Brandes A. (Department of Medical Oncology, Bellaria-Maggiore Hospitals, Bologna, Italy), Eusebi V. (Department of Hematology and Oncological Sciences ‘‘L. & A. Seragnoli’’, Section of Anatomic Pathology at Bellaria Hospital, Bologna, Italy), Ceruti S., Fainardi E., Tamarozzi R. (Neuroradiology Unit, Department of Neurosciences and Rehabilitation, S. Anna Hospital, Ferrara, Italy), Emiliani E. (Istituto Oncologico Romagnolo, Department of Medical Oncology, Santa Maria delle Croci Hospital, Ravenna, Italy), Cavallo M. (Division of Neurosurgery, Department of Neurosciences and Rehabilitation, S. Anna Hospital, Ferrara, Italy).
Roberto Michelucci, Elena Pasini, Federica Anna Marliani, and Luigi Cirillo
Neurology, ISSN: 00283878, eISSN: 1526632X, Pages: e15-e16, Published: 1 July 2015
Ovid Technologies (Wolters Kluwer Health)
A 34-year-old man developed since age 18 years epilepsia partialis continua followed over the years by progressive ataxic hemiparesis involving the left side (figure 1).