Elena Pasini
@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
Giuseppe d’Orsi, Maria Teresa Di Claudio, Antonella Liantonio, Paola Imbrici, Cosimo Damiano Altomare, Orazio Palumbo, Pietro Palumbo, Mario Benvenuto, Nicola Gambacorta, Graziano Lolli,et al.
Springer Science and Business Media LLC
Abstract Background Lafora disease (LD) is an ultra-rare, autosomal recessive neurodegenerative disorder characterized by the accumulation of Lafora bodies in the brain, leading to drug-resistant epilepsy, myoclonus, progressive dementia, and cerebellar dysfunction. This retrospective study describes the clinical course and management challenges of LD in a cohort of patients from the Apulia region of Southern Italy, where the disease prevalence appears to be higher than in other populations. Methods We retrospectively analyzed clinical, electroencephalographic, and management data from six unrelated families with a confirmed diagnosis of LD, followed at the Neurology Unit of the Scientific Institute Casa Sollievo della Sofferenza Hospital between 2010 and 2024. Demographic information, clinical presentation, treatment history, disease progression, and outcomes were collected. Results Our analysis identified three distinct electroclinical stages: an initial Presenting Symptoms Stage with the onset of seizures and subsequent development of myoclonus; a Progressive Neurodegeneration Stage characterized by drug-resistant epilepsy, dementia, and ataxia; and a Terminal Stage marked by severe disability, frequent seizure emergencies, and medical complications. Management in the late stages proved particularly challenging, requiring a multidisciplinary approach to address refractory seizures, status epilepticus, and medical complications such as aspiration pneumonia and respiratory failure. Home-based care, with specialized team support, played a crucial role in minimizing hospitalizations. Discussion Our findings underscore the importance of early diagnosis and a multidisciplinary approach in the management of LD. The late stages of the disease are characterized by significant clinical challenges necessitating close collaboration among neurologists, epileptologists, and other healthcare professionals, supported by effective home-based care. The apparent higher prevalence in Apulia warrants further investigation into potential genetic or environmental factors. Conclusion This study highlights the significant clinical burden of LD and emphasizes the importance of multidisciplinary management, particularly in the advanced stages. Home-based care supported by specialized teams and caregivers is essential for optimizing patient well-being. Further research is needed to identify early biomarkers and develop targeted therapies for this devastating condition.
Elena Pasini, Greta Mainieri, Irene Minardi, Serena Mazzone, Maria Tappatà, Lorenzo Muccioli, Francesca Bisulli, Federica Provini, and Roberto Michelucci
Ovid Technologies (Wolters Kluwer Health)
Poul H. Espino, Krista Eschbach, Leah J. Blank, Mackenzie C. Cervenka, Eyal Muscal, Raquel Farias‐Moeller, Emily J. Gilmore, Margaret T. Gopaul, Hiba A. Haider, Aurelie Hanin,et al.
Wiley
AbstractWe propose and prioritize important outcome domains that should be considered for future research investigating long‐term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps. Subsequently, a consensus‐building process was performed to prioritize and rank important LTO domains for further research. The prioritization of LTO domains was qualitative, enabling the expert panel to generate ideas, share opinions, and provide reasons for the rankings. A second round took place to allow expansion and agreement regarding specific details for each domain. Outcomes were classified into eight main domains: (1) Function: Neuropsychological, Neurological (other than seizures), and Psychiatric (mood and behavior); (2) Quality of Life; (3) Epilepsy; (4) Nonneurological (medical); (5) Social; (6) Caregiver Burden; (7) Long‐Term Mortality; and (8) Health Care System Impact. In addition, the working group suggested obtaining outcome measures for each domain at 6 months and 1 year after discharge and annually thereafter until stability has been reached. There are no currently established time frames set for when LTO in NORSE begin or plateau, and previously there existed no consensus regarding which LTO should be considered. This consensus process identifies and recommends NORSE LTO domains that should be considered in future research studies to provide more consistent results that can be compared between studies. Survivors of NORSE should be evaluated serially and at fixed points over time to maximize our understanding of the recovery trajectory for all LTO domains. Establishing reliable and standardized data describing LTO (beyond seizures) after NORSE will support discussions with families during the acute stages, prognostication, the development of targeted management strategies for survivors, and future comparative research globally helping to identify biomarkers that may predict LTO.
Lidia Di Vito, Eleonora Matteo, Stefano Meletti, Corrado Zenesini, Giorgia Bernabè, Chiara Bomprezzi, Maria Chiara Casadio, Carlo Alberto Castioni, Edward Cesnik, Carlo Coniglio,et al.
Wiley
AbstractObjectiveThe STEPPER (Status Epilepticus in Emilia‐Romagna) study aimed to investigate the clinical characteristics, prognostic factors, and treatment approaches of status epilepticus (SE) in adults of the Emilia‐Romagna region (ERR), Northern Italy.MethodsSTEPPER, an observational, prospective, multicentric cohort study, was conducted across neurology units, emergency departments, and intensive care units of the ERR over 24 months (October 2019–October 2021), encompassing incident cases of SE. Patients were followed up for 30 days.ResultsA total of 578 cases were recruited (56% female, mean age = 70 years, 32% with previous diagnosis of epilepsy, 43% with in‐hospital onset, 35% stuporous/comatose, 46% with nonconvulsive SE). Etiology was known in 87% (acute 43%, remote 24%, progressive 17%, definite epileptic syndrome 3%). The mean pre‐SE Rankin Scale score was 2, the Status Epilepticus Severity Score was ≥4 in 33%, the Epidemiology‐Based Mortality Score in Status Epilepticus score was ≥64 in 61%, and 34% were refractory. The sequence of treatments followed current clinical practice guidelines in 63%. Benzodiazepines (BDZs) were underused as first‐line therapy (71%), especially in in‐hospital onset cases; 15% were treated with continuous intravenous anesthetic drugs. Mortality was 24%; 63% of survivors had functional worsening. At the two‐step multivariable analysis, incorrect versus correct treatment sequence with correct BDZ dose was the strongest predictor of failure to resolve SE in the in‐hospital group (odds ratio [OR] = 4.42, 95% confidence interval [CI] = 1.86–10.5), with a similar trend in the out‐of‐hospital group (OR = 2.22, 95% CI = .98–5.02). In turn, failure to resolve was the strongest predictor of 30‐day mortality (OR = 11.3, 95% CI = 4.16–30.9, out‐of‐hospital SE; OR = 6.42, 95% CI = 2.79–14.8, in‐hospital SE) and functional worsening (OR = 5.83, 95% CI = 2.05–16.6, out‐of‐hospital SE; OR = 9.30, 95% CI 2.22–32.3, in‐hospital SE).SignificanceThe STEPPER study offers insights into real‐world SE management, highlighting its significant morbidity and functional decline implications. Although nonmodifiable clinical factors contribute to SE severity, modifiable factors such as optimized first‐line therapies and adherence to guidelines can potentially influence prognosis.
Lorenzo Muccioli, Corrado Zenesini, Laura Licchetta, Laura Maria Beatrice Belotti, Lidia Di Vito, Lorenzo Ferri, Domenico Fiorillo, Barbara Mostacci, Elena Pasini, Patrizia Riguzzi,et al.
Wiley
AbstractBackgroundEpilepsy significantly impacts on morbidity and mortality. Understanding hospitalization and mortality risks in persons with epilepsy (PWE) is essential for improving healthcare strategies. We aimed to investigate the risk and causes of hospitalization and mortality in PWE compared to a matched general population cohort.MethodsThe EpiLink Bologna historical cohort study analyzed adult PWE in the period 2018–2019. A general population control cohort was used for comparison. Clinical data were linked with health administrative data. PWE were grouped into persons with focal epilepsy, idiopathic generalized epilepsy, and developmental and/or epileptic encephalopathy (PDEE). The primary outcome was the hospitalization rate. Emergency department (ED) visit rate and the risk of death for any cause were also assessed.ResultsThe study included 1438 PWE and 14,096 controls. PWE had higher incidence rate ratio (IRR) for ED visit (IRR 1.26, 95% CI 1.20–1.32), hospital admission (IRR 2.05, 95% CI 1.83–2.29), and death (IRR 1.5, 95% CI 1.1–2.2) compared to control cohort. The highest hospitalization risk was in the PDEE group (IRR 4.70; 95% CI 3.28–6.74). The increased hospitalization rate among PWE was due to both their higher ED visit and elective hospital admission rates. PWE on polytherapy were at higher risk of hospitalization for inflammation of jaw, acid–base/electrolyte imbalances, chronic cerebrovascular disease, major traumas and infections.ConclusionsDuring a 2‐year‐period, PWE in Bologna had a doubled risk of hospitalization and 50% higher risk of death compared to a matched general population cohort. Hospitalization risks varied significantly by epilepsy type and antiseizure therapy.
Lorenzo Muccioli, Lidia Di Vito, Elena Pasini, Lorenzo Ferri, Giovanni Vitale, Alessandro Granito, Barbara Mostacci, Manuel Moneti, Laura Licchetta, Rocco Liguori,et al.
Frontiers Media SA
ObjectivesTo describe the occurrence of secondary sclerosing cholangitis in critically ill patients (SC-CIP) with febrile infection-related epilepsy syndrome (FIRES).MethodsMonocentric retrospective analysis of all adult patients with FIRES admitted from January 2020 to December 2024.ResultsFour patients (3 males) with a mean age of 24 years (range: 18–40 years) and no significant medical history presented with cryptogenic FIRES. They required treatment with antiseizure medications (mean: 9; range: 8–10), anesthetics (propofol, midazolam and ketamine in all cases), and immunotherapies. The average duration of status epilepticus (SE) was 57 days (range: 34–90 days), while the mean duration of intensive care unit (ICU) stay was 82 days (range: 58–117 days). All patients developed cholestatic liver disease during their ICU stay, reversible in one case. In the three cases with persistent injury (75%), SC-CIP was diagnosed with MR-colangiography after a mean of 106 days from SE onset.DiscussionThe high incidence of SC-CIP in our cohort of patients with FIRES suggests a link between these two rare conditions, likely related to prolonged intensive care, hyperinflammation and polytherapy, including ketamine use. Vigilant monitoring of liver disease progression in critically ill patients with FIRES and similar predisposing factors may allow early recognition of SC-CIP and improved patient outcomes.
Lorenzo Muccioli, Francesca Bisulli, Raffaella Minardi, Maria Lucia Valentino, Micaela De Simone, Rodrigo Almeida Paroni, Edward Cesnik, Elisa Fallica, Luigi Bonan, Eleonora Pizzi,et al.
Wiley
AbstractWe report two cases of dual genetic diagnoses involving Lafora disease (LD) and co‐occurring neurodevelopmental disorders caused by pathogenic variants in TRIO and SHANK3, respectively. LD is an ultra‐rare, autosomal recessive, severe form of progressive myoclonus epilepsy affecting previously healthy children or adolescents. In both patients, the presence of developmental delay, intellectual disability, and behavioral abnormalities was consistent with a primary genetic disorder—TRIO‐related neurodevelopmental disorder in one, and Phelan‐McDermid syndrome in the other. However, the onset of epilepsy with atypical features, coupled with progressive neurological decline in one patient and a positive family history of LD in the other, prompted the additional diagnosis of LD. These cases illustrate how overlapping clinical presentations can obscure the presence of concomitant genetic conditions, potentially delaying diagnosis and appropriate management. Our findings underscore the importance of considering dual diagnoses and show that phenotypical variability in ultra‐rare disorders such as LD may be influenced by concurrent genetic conditions.Plain Language SummaryThis report describes two patients who have both Lafora disease, an ultra‐rare, progressive type of epilepsy, and other rare genetic disorders that affect development and behavior. In one case, the patient showed a progressive and unusual neurological deterioration, while the other had atypical epileptic seizures and a family history of Lafora disease. These cases highlight how different genetic conditions can share similar symptoms, making it difficult to identify all the issues a patient may have. Understanding these overlaps is important for proper diagnosis and treatment.
Roberto Michelucci, Giada Pauletto, Antonio Silvani, Elena Pasini, Tamara Ius, Matteo Martinoni, Carlo Alberto Castioni, Andrea Salmaggi, Sofia Asioli, Marta Maschio,et al.
Wiley
AbstractSeizures are a common and challenging symptom in brain tumors, affecting approximately 60% of patients. Tumor‐related epilepsy (TRE) in glioma patients requires personalized and dynamic management in a multidisciplinary environment, especially for its intricate pathophysiology and unpredictable disease evolution. This investigation provides an updated overview about the pathophysiological mechanisms and treatment options of TRE associated with gliomas, based on expert contributions belonging to different areas. By combining the most recent discoveries and expert opinions, this study seeks to provide useful advice for TRE management in glioma patients. To improve patient outcomes and quality of life, prospective, standardized, multicentric studies should be promoted to optimize TRE patient care and refine therapeutic approaches.
Martin Guillemaud, Aurélie Hanin, James J. Riviello, Mario Chavez, Ayush Batra, Megan Berry, Francesca Bisulli, Carlos Castillo‐Pinto, Carla Cobos‐Hernandez, Sophie Demeret,et al.
Wiley
AbstractObjectiveWe investigated whether complete blood count (CBC) analyses during intensive care unit stay could predict 12‐month outcomes in patients with cryptogenic febrile infection–related epilepsy syndrome (FIRES), a subset of new‐onset refractory status epilepticus (NORSE).MethodsOutcomes at 12 months were classified as “unfavorable” (Glasgow Outcome Score [GOS] 1–3) or “favorable” (GOS 4–5). Demographic, clinical, and serial CBC data were collected across treatment phases: (1) no immunotherapy (before initiation or no treatment), (2) first‐line immunotherapy, and (3) second‐line immunotherapy. For each treatment phase, predictive models stratified outcomes based on CBC features using decision tree regression, with separate models for adults and children. Model performance was tested using a leave‐one‐patient‐out approach.ResultsWe studied 63 patients (34 adults, 29 children) from 12 centers. Unfavorable outcomes occurred in 18 adults and 12 children. Children were more likely to receive second‐line immunotherapy. We analyzed 1530 CBCs (adults: 997 CBCs, including 539 for unfavorable outcomes; children: 533 CBCs, including 415 for unfavorable outcomes). Subgroup analyses revealed differences in CBC levels according to the outcomes and the treatment received. Adults with unfavorable outcomes notably had higher neutrophil‐to‐lymphocyte ratios (NLRs) and monocyte‐to‐lymphocyte ratios (MLRs), whereas children with unfavorable outcomes had higher red cell distribution width. NLRs and MLRs increased when CBCs were collected after the initiation of immunotherapy for both adults and children. The variables of interest differed in the different predictive models but always included the proportion of at least one subtype of leukocyte. Prediction accuracy with our models was higher in children (87% overall, with the best performance in no‐treatment and first‐line phases) than in adults (83% overall, with the best performance during/after the initiation of second‐line).SignificanceFindings suggest the potential for standard CBCs to serve as a rapid, accessible tool for early prognostication in cryptogenic FIRES, particularly in children.
Giuseppe Didato, Federico Vigevano, Laura Tassi, Renzo Guerrini, Marco de Curtis, Luca De Palma, Giancarlo Di Gennaro, Lino Nobili, Matteo Martinoni, Stefano Meletti,et al.
Wiley
AbstractObjectiveTo study the current practice of epilepsy surgery in Italy and the relative impact of coronavirus disease 2019 (COVID‐19) pandemic on it.MethodsWe launched a survey through the Italian National Virtual Epilepsy Institute, to identify centers with epilepsy surgery programs and collect data on the current preoperative and surgical practices. We reported changes in surgical volumes and complications and seizure outcomes between 2018 and 2022, that is, before and after the COVID‐19 pandemic in Italy.ResultsA total of 21 of the 26 surveyed centers (80.7%) responded. Eleven centers (52.4%) reported having an established epilepsy surgery program, with most performing complex procedures, such as multilobar, disconnective, and hemispheric interventions. However, only a few carry out minimally invasive surgeries. Presurgical evaluation protocols vary across centers, but in keeping with international standards. Globally, 618 surgeries were performed in children and 621 in adults (total 1239) between 2018 and 2022. The most frequent type of surgery was unilobar extratemporal lobectomy for children (38.7%, p < 0.0001) and unilobar temporal lobectomy for adults (63.3%, p < 0.0001). Hemispheric surgeries were more frequent in children than in adults (11.5% vs 2.1%, p = 0.001), whereas interventions in unrevealing magnetic resonance (MRI) cases were more frequent in adults than in children (p = 0.030). At the onset of COVID‐19outbreak in Italy (March 2020), we observed a significant decrease in the total number of operations compared to 2019, especially for hemispheric interventions (p = 0.027). Surgical volumes resumed in 2021, particularly for temporal lobe epilepsies and in adult cohorts. Surgical complications increased significantly in 2020 (Incidence Rate Ratio [IRR] = 13.13), whereas seizure outcome did not change significantly between 2018 and 2022.SignificanceAdvanced pre‐ and postsurgical evaluation protocols are currently implemented across Italy, with a great variability between centers. Starting in 2021, epilepsy surgery volumes have regained their pre‐pandemic levels, albeit with a slight loss of complexity, whereas seizure outcome has remained stable.
Roberto Michelucci, Elena Pasini, Patrizia Riguzzi, Maria Tappatà, Maria Pia Giannoccaro, Elisa Micalizzi, Anastasia Lechiara, Pietro Mattioli, Luana Benedetti, and Flavio Villani
Wiley
AbstractObjectiveThe aim of this study was to describe the clinical features of contactin‐associated protein‐like 2 (CASPR2)‐IgG‐associated seizures.MethodsNine patients were retrospectively collected from two epilepsy centers. For each patient we obtained a full clinical, neurophysiological, and MRI study along with detection of antineuronal autoantibodies from serum and CSF. The patients were followed up for 1–6 years.ResultsThe patients were nine male subjects aged 56–85 years (mean: 66) with a 1‐ to 14‐year (mean: 6,3 median: 6) history of seizures. The seizures were classified as focal onset seizures with impaired awareness, usually preceded by epigastric aura (two), piloerection (two), olfactory hallucinations (two), nausea and dizziness (one). Tonic–clonic seizures were present in five patients. Seizure frequency was high in six cases and sporadic in three. Most patients reported memory impairment (eight) or behavioral/mood changes (four). Interictal EEGs usually showed bilateral or unilateral temporal epileptiform abnormalities. A number of seizures arising from the temporal lobes, with bilateral asynchronous onset, were recorded on long‐term video‐EEG monitoring in two patients. MRI disclosed nonspecific white matter T2 hyperintensities suggestive of chronic vascular changes in four patients and bilateral T2‐FLAIR amygdalo‐hippocampal hyperintensity in three cases. Neuropsychological study demonstrated various degrees of cognitive impairment in the majority of cases. Increased titers of CASPR2 autoantibodies were detected in the serum and CSF, which persisted over time in four cases. Drug resistance to common anti‐seizure medications was present in seven cases who benefited from immunotherapy.SignificanceCASPR2‐IgG testing should be performed among old male patients with a recent or even not recent onset of focal seizures with impaired awareness particularly when these seizures are accompanied by cognitive impairment or behavioral disturbances. In these cases, anti‐seizure medications may be ineffective while immunotherapy may lead to a prompt improvement of seizures and cognitive deficits.
Luca Zanuttini, Federico Mason, Lorenzo Ferri, Elena Pasini, Lidia Di Vito, Roberto Mai, Laura Tassi, Laura Castana, Gianfranco Vornetti, Lorenzo Muccioli,et al.
Elsevier BV
Lorenzo Muccioli, Luca Vignatelli, Maria Tappatà, Serena Mazzone, Corrado Zenesini, Dustin Armstrong, , Roberto Michelucci, and Francesca Bisulli
BMJ
IntroductionLafora disease (LD) is an ultrarare fatal progressive myoclonic epilepsy, causing drug-resistant epilepsy, myoclonus and psychomotor deterioration. LD is caused by mutations in EPM2A or NHLRC1, which lead to the accumulation of polyglucosans in the brain and neurodegeneration. There are no approved treatments for LD. VAL-1221 is a fusion protein comprising the Fab portion of a cell-penetrating antibody and recombinant human acid alpha glucosidase, and has demonstrated an ability to clear polyglucosans. We hypothesise that intravenous infusion of VAL-1221 might be able to degrade cerebral polyglucosans and stabilise or improve disease outcomes. The aim of this study is to assess the safety and preliminary efficacy of VAL-1221 in patients with LD.Methods and analysisThe study is a phase 2, single-arm, open-label, baseline-controlled clinical trial which will be conducted in a single investigational study centre in Italy, namely the sponsor ‘IRCCS Istituto delle Scienze Neurologiche di Bologna—Azienda USL di Bologna’. The study will enrol six genetically confirmed patients with mid- to late-stage LD. The global duration of the study for each participant will be 18 months, including screening period, open-label treatment (12 months) and follow-up period. VAL-1221 20 mg/kg will be administered as an intravenous infusion every week for 3 weeks, then every other week. Patients will undergo full clinical assessments at baseline, at an intermediate and at the end-of-treatment visit. The primary objective is to evaluate the safety. The exploratory efficacy endpoints will be related to epilepsy, neuropsychological and motor functions, global assessment and disease burden, in addition to biomarkers. Statistical analyses will be primarily descriptive.Ethics and disseminationThe study protocol was approved by the local ethics committee (number 232-2023-FARM-AUSLBO-23020, 22 March 2023). The results of this study will be disseminated by the investigators through presentations at international scientific conferences and reported in peer-reviewed scientific journals.Trial registration numberEuropean Union Clinical Trials Register (EudraCT 2023-000185-34).
Lorenzo Ferri, Federico Mason, Lidia Di Vito, Elena Pasini, Roberto Michelucci, Francesco Cardinale, Roberto Mai, Lara Alvisi, Luca Zanuttini, Matteo Martinoni,et al.
MDPI AG
Hyperventilation (HV) is an activation technique performed during clinical practices to trigger epileptiform activities, supporting the neurophysiological evaluation of patients with epilepsy. Although the role of HV has often been questioned, especially in the case of focal epilepsy, no studies have ever assessed how cortical structures respond to such a maneuver via intracranial EEG recordings. This work aims to fill this gap by evaluating the HV effects on the Stereo-EEG (SEEG) signals from a cohort of 10 patients with drug-resistant focal epilepsy. We extracted multiple quantitative metrics from the SEEG signals and compared the results obtained during HV, awake status, non-REM sleep, and seizure onset. Our findings show that the cortical connectivity, estimated via the phase transfer entropy (PTE) algorithm, strongly increases during the HV maneuver, similar to non-REM sleep. The opposite effect is observed during seizure onset, as ictal transitions involve the desynchronization of the brain structures within the epileptogenic zone. We conclude that HV promotes a conductive environment that may facilitate the propagation of epileptiform activities but is not sufficient to trigger seizures in focal epilepsy.
Luca Vignatelli, Valentina Tontini, Stefano Meletti, Maria Camerlingo, Stefania Mazzoni, Giada Giovannini, Elena Pasini, Roberto Michelucci, Francesca Bisulli, Paolo Tinuper,et al.
Wiley
AbstractObjectiveStatus epilepticus (SE) is the second most common neurological emergency in adults. Despite improvements in the management of acute neurological conditions over the last decade, mortality is still durably high. Because a gap has emerged between SE management based on clinical practice guidelines (CPGs) and actual clinical practice, we conducted a systematic review of CPGs, assessing their quality, outlining commonalities and discrepancies in recommendations, and highlighting research gaps.MethodsWe searched the PubMed and EMBASE databases and other gray literature sources (nine among guideline registries, evidence‐based medicine databases, point‐of‐care tools; seven websites of governmental organizations and international neurologic societies) in December 2021 (updated in November 2023). The units of analysis were CPGs that included recommendations on the diagnostic and/or therapeutic management of SE in adults. The quality of the CPGs was assessed using the AGREE II tool.ResultsFifteen CPGs were included. The “Applicability” domain was assigned the lowest median score of 10%. The domains “Stakeholder Involvement”, “Rigor of Development,” and “Editorial Independence” were as well generally underrated. Recommendations on general and diagnostic management and on organizational interventions were fragmented and scattered. Recommendations on pre‐hospital and hospital treatment of early‐onset and refractory SE were broadly agreed, whereas there was less agreement on the treatment model and medications for established SE and super‐refractory SE.SignificanceThe CPGs for the management of SE developed in recent years are flawed by several methodological issues and discrepancies in the coverage of important topics. The gap between CPG‐based management of SE and actual clinical practice may be due in part to the inherent limitations of the CPGs produced so far.
Antonella Riva, Gianluca D'Onofrio, Edoardo Ferlazzo, Angelo Pascarella, Elena Pasini, Silvana Franceschetti, Ferruccio Panzica, Laura Canafoglia, Aglaia Vignoli, Antonietta Coppola,et al.
Wiley
AbstractMyoclonus classically presents as a brief (10–50 ms duration), non‐rhythmic jerk movement. The etiology could vary considerably ranging from self‐limited to chronic or even progressive disorders, the latter falling into encephalopathic pictures that need a prompt diagnosis. Beyond the etiological classification, others evaluate myoclonus' body distribution (i.e., clinical classification) or the location of the generator (i.e., neurophysiological classification); particularly, knowing the anatomical source of myoclonus gives inputs on the observable clinical patterns, such as EMG bursts duration or EEG correlate, and guides the therapeutic choices. Among all the chronic disorders, myoclonus often presents itself as a manifestation of epilepsy. In this context, myoclonus has many facets. Myoclonus occurs as one, or the only, seizure manifestation while it can also present as a peculiar type of movement disorder; moreover, its electroclinical features within specific genetically determined epileptic syndromes have seldom been investigated. In this review, following a meeting of recognized experts, we provide an up‐to‐date overview of the neurophysiology and nosology surrounding myoclonus. Through the dedicated exploration of epileptic syndromes, coupled with pragmatic guidance, we aim to furnish clinicians and researchers alike with practical advice for heightened diagnostic management and refined treatment strategies.Plain Language SummaryIn this work, we described myoclonus, a movement characterized by brief, shock‐like jerks. Myoclonus could be present in different diseases and its correct diagnosis helps treatment.
Federico Mason, Anna Scarabello, Lisa Taruffi, Elena Pasini, Giovanna Calandra-Buonaura, Luca Vignatelli, and Francesca Bisulli
MDPI AG
The most critical burden for People with Epilepsy (PwE) is represented by seizures, the unpredictability of which severely impacts quality of life. The design of real-time warning systems that can detect or even predict ictal events would enhance seizure management, leading to high benefits for PwE and their caregivers. In the past, various research works highlighted that seizure onset is anticipated by significant changes in autonomic cardiac control, which can be assessed through heart rate variability (HRV). This manuscript conducted a scoping review of the literature analyzing HRV-based methods for detecting or predicting ictal events. An initial search on the PubMed database returned 402 papers, 72 of which met the inclusion criteria and were included in the review. These results suggest that seizure detection is more accurate in neonatal and pediatric patients due to more significant autonomic modifications during the ictal transitions. In addition, conventional metrics are often incapable of capturing cardiac autonomic variations and should be replaced with more advanced methodologies, considering non-linear HRV features and machine learning tools for processing them. Finally, studies investigating wearable systems for heart monitoring denoted how HRV constitutes an efficient biomarker for seizure detection in patients presenting significant alterations in autonomic cardiac control during ictal events.
Elena Pasini and Roberto Michelucci
MDPI AG
The heart and seizures are closely linked by an indissoluble relationship that finds its basis in the cerebral limbic circuit whose mechanisms remain largely obscure. The differential diagnosis between seizures and syncopes has always been a cornerstone of the collaboration between cardiologists and neurologists and is renewed as a field of great interest for multidisciplinary collaboration in the era of the diffusion of prolonged telemonitoring units. The occurrence of ictal or post-ictal arrhythmias is currently a cause of great scientific debate with respect to the role and risks that these complications can generate (including sudden unexpected death in epilepsy). Furthermore, the study of epileptic seizures and the arrhythmological complications they cause (during and after seizures) also allows us to unravel the mechanisms that link them. Finally, intercritical arrhythmias may represent great potential in terms of the prevention of cardiological risk in epileptic patients as well as in the possible prediction of the seizures themselves. In this paper, we review the pertaining literature on this subject and propose a scheme of classification of the cases of arrhythmia temporally connected to seizures.
Elena Gardella, Roberto Michelucci, Hanne M. Christensen, Christina D. Fenger, Chiara Reale, Patrizia Riguzzi, Elena Pasini, Luca Albini‐Riccioli, Valentina Papa, Maria Pia Foschini,et al.
Wiley
IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multi-systemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia, and pyramidal signs. We describe a novel IRF2BPL phenotype consistent with progressive myoclonic epilepsy (PME) in three novel subjects and review the features of the 31 subjects with IRF2BPL-related disorders previously reported. Our three probands, aged 28-40 years, harbored de novo nonsense variants in IRF2BPL [c.370C>T, p.(Gln124*) and c.364C>T; p.(Gln122*) respectively]. From late childhood/adolescence, they presented with severe myoclonus epilepsy, stimulus-sensitive myoclonus, and progressive cognitive, speech, and cerebellar impairment, consistent with a typical PME syndrome. The skin biopsy revealed massive intracellular glycogen inclusions in one proband, suggesting a similar pathogenic pathway with other storage disorders. While the two older probands were severely affected, the younger had a milder PME phenotype, partially overlapping with some of the previously reported IRF2BPL cases, suggesting that some of them might be unrecognized PME. Interestingly, all three patients harbored protein truncating variants clustered in a proximal, highly conserved gene region around the "coiled-coil" domain. Our data show that PME can be an additional phenotype within the spectrum of IRF2BPL-related disorders and suggest IRF2BPL as a novel causative gene for PME.
Lisa Anita De Santi, Elena Pasini, Maria Filomena Santarelli, Dario Genovesi, and Vincenzo Positano
Springer Science and Business Media LLC
Lorenzo Muccioli, Corrado Zenesini, Lisa Taruffi, Laura Licchetta, Barbara Mostacci, Lidia Di Vito, Elena Pasini, Lilia Volpi, Patrizia Riguzzi, Lorenzo Ferri,et al.
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.
Elena Pasini, Dario Genovesi, Carlo Rossi, Lisa Anita De Santi, Vincenzo Positano, Assuero Giorgetti, and Maria Filomena Santarelli
MDPI AG
Our work aims to exploit deep learning (DL) models to automatically segment diagnostic regions involved in Alzheimer’s disease (AD) in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) volumetric scans in order to provide a more objective diagnosis of this disease and to reduce the variability induced by manual segmentation. The dataset used in this study consists of 102 volumes (40 controls, 39 with established Alzheimer’s disease (AD), and 23 with established mild cognitive impairment (MCI)). The ground truth was generated by an expert user who identified six regions in original scans, including temporal lobes, parietal lobes, and frontal lobes. The implemented architectures are the U-Net3D and V-Net networks, which were appropriately adapted to our data to optimize performance. All trained segmentation networks were tested on 22 subjects using the Dice similarity coefficient (DSC) and other similarity indices, namely the overlapping area coefficient (AOC) and the extra area coefficient (EAC), to evaluate automatic segmentation. The results of each labeled brain region demonstrate an improvement of 50%, with DSC from about 0.50 for V-Net-based networks to about 0.77 for U-Net3D-based networks. The best performance was achieved by using U-Net3D, with DSC on average equal to 0.76 for frontal lobes, 0.75 for parietal lobes, and 0.76 for temporal lobes. U-Net3D is very promising and is able to segment each region and each class of subjects without being influenced by the presence of hypometabolic regions.
Elena Pasini, Patrizia Riguzzi, and Roberto Michelucci
Elsevier BV
Roberto Michelucci, Stefania Testoni, Roberta Pantieri, Patrizia Riguzzi, and Elena Pasini
Elsevier BV
A. E. Vaudano, L. Mirandola, F. Talami, G. Giovannini, G. Monti, P. Riguzzi, L. Volpi, R. Michelucci, F. Bisulli, E. Pasini,et al.
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.