Elena Pasini

- 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

Scopus Publications

Causes of hospitalization and mortality in persons with epilepsy: The EpiLink Bologna cohort, Italy
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.


New onset refractory status epilepticus: Long-term outcomes beyond seizures
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.


Parameter analysis in stereoelectroencephalography-guided radiofrequency thermocoagulation: A common basis for objective comparison between protocols
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



CASPR2-related epilepsy: A distinctive and unrecognized form of epilepsy in adult and elderly males
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.


VAL-1221 for the treatment of patients with Lafora disease: Study protocol for a single-arm, open-label clinical trial
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).


Cortical Connectivity Response to Hyperventilation in Focal Epilepsy: A Stereo-EEG Study
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.


Clinical practice guidelines on the management of status epilepticus in adults: A systematic review
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.


Myoclonus: Differential diagnosis and current management
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.


Heart Rate Variability as a Tool for Seizure Prediction: A Scoping Review
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.


Prognostic factors and impact of management strategies for status epilepticus: The STEPPER study in the Emilia-Romagna region, Italy
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.


The Heart and Seizures: Friends or Enemies?
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.


IRF2BPL as a novel causative gene for progressive myoclonus epilepsy
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.


An Explainable Convolutional Neural Network for the Early Diagnosis of Alzheimer’s Disease from 18F-FDG PET
Lisa Anita De Santi, Elena Pasini, Maria Filomena Santarelli, Dario Genovesi, and Vincenzo Positano
Springer Science and Business Media LLC



Risk of hospitalization and death for COVID-19 in persons with epilepsy over a 20-month period: The EpiLink Bologna cohort, Italy
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.


Convolution Neural Networks for the Automatic Segmentation of 18F-FDG PET Brain as an Aid to Alzheimer’s Disease Diagnosis
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.


Iatrogenic ictal asystole
Elena Pasini, Patrizia Riguzzi, and Roberto Michelucci
Elsevier BV



Hypoglycemia: The Great Chameleon: A Pseudo-Nonconvulsive Status Epilepticus
Roberto Michelucci, Stefania Testoni, Roberta Pantieri, Patrizia Riguzzi, and Elena Pasini
Elsevier BV



fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study
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.


Intravenous immunoglobulin therapy in COVID-19-related encephalopathy
Lorenzo Muccioli, Umberto Pensato, Giorgia Bernabè, Lorenzo Ferri, Maria Tappatà, Lilia Volpi, Ilaria Cani, Olivia J. Henry, Francesca Ceccaroni, Sabina Cevoli,et al.
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.


Fit and faint or faint and fit?
Elena Pasini and Roberto Michelucci
Elsevier BV



Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke
Umberto Pensato, Lorenzo Muccioli, Elena Pasini, Maria Tappatà, Lorenzo Ferri, Lilia Volpi, Laura Licchetta, Stella Battaglia, Giada Rossini, Isabella Bon,et al.
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.


EEG findings in COVID-19 related encephalopathy
Elena Pasini, Francesca Bisulli, Lilia Volpi, Irene Minardi, Maria Tappatà, Lorenzo Muccioli, Umberto Pensato, Patrizia Riguzzi, Paolo Tinuper, and Roberto Michelucci
Elsevier BV



Autosomal dominant lateral temporal lobe epilepsy associated with a novel reelin mutation
Roberto Michelucci, Emanuela Dazzo, Lilia Volpi, Elena Pasini, Patrizia Riguzzi, Raffaella Minardi, Anna Federica Marliani, Maria Tappatà, Francesca Bisulli, Carlo Alberto Tassinari,et al.
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.


LGI1 tumor tissue expression and serum autoantibodies in patients with primary malignant glioma
Emanuela Dazzo, Elena Pasini, Sandra Furlan, Dario de Biase, Matteo Martinoni, Roberto Michelucci, and Carlo Nobile
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.


Subcutaneous immunoglobulin treatment and thromboembolic risk
Veria Vacchiano, Rocco Liguori, Elena Pasini, Patrizia Avoni, and Vincenzo Donadio
Elsevier BV

RECENT SCHOLAR PUBLICATIONS

Prognostic factors and impact of management strategies for status epilepticus: The STEPPER study in the Emilia‐Romagna region, Italy
L Di Vito, E Matteo, S Meletti, C Zenesini, G Bernab, C Bomprezzi, ...
Epilepsia 66 (3), 753-767 2025



Causes of hospitalization and mortality in persons with epilepsy: The EpiLink Bologna cohort, Italy
L Muccioli, C Zenesini, L Licchetta, LMB Belotti, LD Vito, L Ferri, D Fiorillo, ...
European Journal of Neurology 32 (2), e16576 2025



New onset refractory status epilepticus: Long‐term outcomes beyond seizures
PH Espino, K Eschbach, LJ Blank, MC Cervenka, E Muscal, ...
Epilepsia 2025



Parameter analysis in stereoelectroencephalography-guided radiofrequency thermocoagulation: A common basis for objective comparison between protocols
L Zanuttini, F Mason, L Ferri, E Pasini, L Di Vito, R Mai, L Tassi, L Castana, ...
Epilepsy Research 208, 107472 2024



CASPR2‐related epilepsy: A distinctive and unrecognized form of epilepsy in adult and elderly males
R Michelucci, E Pasini, P Riguzzi, M Tappat, MP Giannoccaro, ...
Epileptic Disorders 26 (6), 753-760 2024



What temporal plus epilepsy does really imply?
E Pasini, M Martinoni, L Ferri, L Di Vito, F Cardinale, R Mai, R Michelucci
EPILEPSIA 65, 258-258 2024



Seizures and autoimmune encephalitis: A case series
G Carrozzo, L Licchetta, E Pasini, L Muccioli, L Ferri, L Di Vito, B Mostacci, ...
EPILEPSIA 65, 95-95 2024



Detection of somatic and germline pathogenic variants in epileptogenic lesions
L Ferri, E Cifaldi, L Licchetta, P Dimartino, R Minardi, A Perciavalle, M Seri, ...
EPILEPSIA 65, 289-290 2024



Cortical Connectivity Response to Hyperventilation in Focal Epilepsy: A Stereo-EEG Study.
L Ferri, F Mason, L Di Vito, E Pasini, R Michelucci, F Cardinale, R Mai, ...
Applied Sciences (2076-3417) 14 (18) 2024



Desynchronization Index: a New Approach for Exploring Complex Epileptogenic Networks in Stereoelectroencephalography
F Mason, L Ferri, L Di Vito, L Alvisi, L Zanuttini, M Martinoni, R Mai, ...
arXiv preprint arXiv:2408.16347 2024



Clinical practice guidelines on the management of status epilepticus in adults: A systematic review
L Vignatelli, V Tontini, S Meletti, M Camerlingo, S Mazzoni, G Giovannini, ...
Epilepsia 65 (6), 1512-1530 2024



Myoclonus: Differential diagnosis and current management
A Riva, G D'Onofrio, E Ferlazzo, A Pascarella, E Pasini, S Franceschetti, ...
Epilepsia Open 9 (2), 486-500 2024



Heart rate variability as a tool for seizure prediction: a scoping review
F Mason, A Scarabello, L Taruffi, E Pasini, G Calandra-Buonaura, ...
Journal of clinical medicine 13 (3), 747 2024



Combining depth electrodes and intraoperative ultrasound to overcome limits of intraoperative electrocorticography in epilepsy surgery
L Zanuttini, E Pasini, L Ferri, L Di Vito, A Caruso, F Blasioli, ML Alvisi, ...
Brain and Spine 4, 103468 2024



STEPPER (Status Epilepticus in Emilia Romagna): therapeutic interventions and quality of care in Emilia-Romagna Region, Italy
L Di Vito, P Tinuper, R Michelucci, S Meletti, G Giovannini, E Pasini, ...
EPILEPSIA 64, 176-176 2023



Autoimmune-associated epilepsy as the outcome of autoimmune encephalitis with NORSE presentation
S Matricardi, S Lattanzi, A Vogrig, G Pauletto, G Giovannini, S Meletti, ...
EPILEPSIA 64, 492-493 2023



The Heart and Seizures: Friends or Enemies?
E Pasini, R Michelucci
Journal of Clinical Medicine 12 (18), 5805 2023



IRF2BPL as a novel causative gene for progressive myoclonus epilepsy
E Gardella, R Michelucci, HM Christensen, CD Fenger, C Reale, ...
Epilepsia 64 (8), e170-e176 2023



Guidelines on Status Epilepticus neglet the quality domain of applicability: a systematic review
L Vignatelli, V Tontini, S Mazzoni, M Camerlingo, F Bisulli, G Giovannini, ...
EUROPEAN JOURNAL OF NEUROLOGY 30, 118-119 2023



Long-term outcomes of autoimmune encephalitis with NORSE presentation
S Matricardi, S Lattanzi, A Vogrig, G Pauletto, S Meletti, G Giovannini, ...
EUROPEAN JOURNAL OF NEUROLOGY 30, 173-174 2023

MOST CITED SCHOLAR PUBLICATIONS

LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy
C Nobile, R Michelucci, S Andreazza, E Pasini, SCE Tosatto, P Striano
Human mutation 30 (4), 530-536 2009
Citations: 172



Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy
E Dazzo, M Fanciulli, E Serioli, G Minervini, P Pulitano, S Binelli, ...
The American Journal of Human Genetics 96 (6), 992-1000 2015
Citations: 147



Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I–III
M Visani, D De Biase, G Marucci, S Cerasoli, E Nigrisoli, MLB Reggiani, ...
Molecular oncology 8 (2), 417-430 2014
Citations: 118



Lateral temporal lobe epilepsies: clinical and genetic features
R Michelucci, E Pasini, C Nobile
Epilepsia 50, 52-54 2009
Citations: 90



Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K⁺ channel properties
KL Oliver, S Franceschetti, CJ Milligan, M Muona, SA Mandelstam, ...
Annals of neurology 81 (5), 677-689 2017
Citations: 82



The prognostic roles of gender and O6-methylguanine-DNA methyltransferase methylation status in glioblastoma patients: the female power
E Franceschi, A Tosoni, S Minichillo, R Depenni, A Paccapelo, S Bartolini, ...
World neurosurgery 112, e342-e347 2018
Citations: 58



Myoclonus and seizures in progressive myoclonus epilepsies: pharmacology and therapeutic trials
R Michelucci, E Pasini, P Riguzzi, E Andermann, R Klviinen, P Genton
Epileptic Disorders 18 (s2), S145-S153 2016
Citations: 56



Epilepsy in primary cerebral tumors: The characteristics of epilepsy at the onset (results from the PERNO study–P roject of E milia R omagna R egion on N euro‐O ncology)
R Michelucci, E Pasini, S Meletti, E Fallica, R Rizzi, I Florindo, A Chiari, ...
Epilepsia 54, 86-91 2013
Citations: 55



Mild L afora disease: clinical, neurophysiologic, and genetic findings
E Ferlazzo, L Canafoglia, R Michelucci, A Gambardella, E Gennaro, ...
Epilepsia 55 (12), e129-e133 2014
Citations: 53



Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned
F Bianco, F Salomone, I Milesi, X Murgia, S Bonelli, E Pasini, R Dellac, ...
Respiratory Research 22, 1-31 2021
Citations: 52



From bench to bedside: in vitro and in vivo evaluation of a neonate-focused nebulized surfactant delivery strategy
F Bianco, F Ricci, C Catozzi, X Murgia, M Schlun, A Bucholski, U Hetzer, ...
Respiratory research 20, 1-11 2019
Citations: 52



EEG findings in COVID-19 related encephalopathy
E Pasini, F Bisulli, L Volpi, I Minardi, M Tappat, L Muccioli, U Pensato, ...
Clinical Neurophysiology 131 (9), 2265 2020
Citations: 50



The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations
R Michelucci, P Pulitano, C Di Bonaventura, S Binelli, C Luisi, E Pasini, ...
Epilepsy & Behavior 68, 103-107 2017
Citations: 50



Intravenous immunoglobulin therapy in COVID-19-related encephalopathy
L Muccioli, U Pensato, G Bernab, L Ferri, M Tappat, L Volpi, I Cani, ...
Journal of neurology 268, 2671-2675 2021
Citations: 49



DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy
P Striano, E Serioli, L Santulli, I Manna, A Labate, E Dazzo, E Pasini, ...
Epilepsia 56 (10), e168-e171 2015
Citations: 48



Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in ASAH1
G Rubboli, P Veggiotti, A Pini, A Berardinelli, G Cantalupo, E Bertini, ...
Epilepsia 56 (5), 692-698 2015
Citations: 47



Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a
AA Brandes, E Franceschi, M Ermani, A Tosoni, F Albani, R Depenni, ...
Neuro-oncology practice 1 (4), 166-171 2014
Citations: 46



Multiple variants in families with amyotrophic lateral sclerosis and frontotemporal dementia related to C9orf72 repeat expansion: further observations on their
MP Giannoccaro, A Bartoletti-Stella, S Piras, A Pession, P De Massis, ...
Journal of neurology 264, 1426-1433 2017
Citations: 45



Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without LGI1 mutations
R Michelucci, E Pasini, S Malacrida, P Striano, CD Bonaventura, ...
Epilepsia 54 (7), 1288-1297 2013
Citations: 43



Genetics of epilepsy and relevance to current practice
R Michelucci, E Pasini, P Riguzzi, L Volpi, E Dazzo, C Nobile
Current neurology and neuroscience reports 12, 445-455 2012
Citations: 36