Publications by authors named "Stefano Meletti"

112 Publications

"Don't call me from the left side…": ischemic stroke in a patient with uncommon vertebral artery dissection.

Neurol Sci 2021 Jun 5. Epub 2021 Jun 5.

Neurology Clinic, Department of Neuroscience, University Hospital of Modena, via Giardini 1355 Baggiovara, ZIP 41100, Modena, Italy.

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http://dx.doi.org/10.1007/s10072-021-05369-xDOI Listing
June 2021

Combining perampanel and ketamine in super refractory post-traumatic status epilepticus: A case report.

Seizure 2021 May 9;89:59-61. Epub 2021 May 9.

Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena.

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http://dx.doi.org/10.1016/j.seizure.2021.04.026DOI Listing
May 2021

TeleNeurological evaluation and Support for the Emergency Department (TeleNS-ED): protocol for an open-label clinical trial.

BMJ Open 2021 05 19;11(5):e048293. Epub 2021 May 19.

Neurology Unit, Azienda Ospedaliero-Universitaria di Modena Ospedale Civile di Baggiovara, Modena, Italy

Introduction: The COVID-19 pandemic compelled health systems to protect patients and medical personnel during transit in hospitals by minimising transfers, prompting the use of telehealth systems. In the field of neurology, telemedicine has been used in emergency settings for acute stroke management between spoke and hub hospital networks, where good outcomes have been achieved. However, data on the use of telemedicine in non-stroke acute neurological conditions accessing the emergency department (ED) are currently missing.

Methods And Analyses: This is an interventional, open-label trial on the use of teleconsultation in the ED for neurological diseases other than stroke. The study aims to develop a remote consultancy system (TeleNeurological Evaluation and Support, TeleNS) for patients with acute neurological symptoms referred to hospital facilities without a 24-hour availability of a neurologist consultant (spoke hospitals). The study population will include 100 ED patients referred to two spoke hospitals in 6 months, who will be asked to perform teleconsultation instead of inperson visits. As a control group, retrospectively available data from patients admitted to the ED of spoke hospitals during the same time period over the last 2 years will be evaluated. The primary objective is to assess whether a TeleNS for the ED guarantees a faster but qualitatively non-inferior diagnostic/therapeutic work-up if compared with inperson examination, assuring the availability of all the necessary examinations and treatments with consistent time-saving.

Ethics And Dissemination: The trial was designed following the national guidelines on clinical investigation on telemedicine provided by the Italian Ministry of Health and according to the Standard Protocol Items for Randomized Trials statement guidelines. This research protocol was approved by Comitato Etico Area Vasta Emilia Nord in September 2020 (number/identification: 942/2020/DISP/AOUMO SIRER ID 805) and was written without patient involvement. Patients' associations will be involved in the dissemination of study design and results. The results of the study will be presented during scientific symposia or published in scientific journals.

Trial Registration Number: NCT04611295.
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http://dx.doi.org/10.1136/bmjopen-2020-048293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137206PMC
May 2021

Platelet Function Monitoring Performed after Carotid Stenting during Endovascular Stroke Treatment Predicts Outcome.

J Stroke Cerebrovasc Dis 2021 Jul 5;30(7):105800. Epub 2021 May 5.

Stroke Unit, Neurology Unit, Department of Neuroscience, Ospedale Civile, Azienda Ospedaliera Universitaria di Modena, Via Giardini 1355, Modena, Emilia Romagna 41126, Italy. Electronic address:

Objectives: Many studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting.

Materials And Methods: We performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting. Patients were divided according to validated cutoffs in acetylsalicylic acid and Clopidogrel responders and not responders. Group comparison and regression analyses were performed to identify differences between groups and outcome predictors.

Results: We included in the final analysis 54 patients. Acetylsalicylic acid resistance was an independent predictor of poor 90 days outcome (OR for modified Rankin scale (mRS) ≤ 2: 0.10 95% CI: 0.02 - 0.69) whereas Clopidogrel resistance was an independent predictor of good outcome (OR for mRS ≤ 2: 7.09 95%CI: 1.33 - 37.72). Acetylsalicylic acid resistance was also associated with increased 90-days mortality (OR: 18.42; 95% CI: 1.67 - 203.14).

Conclusion: We found a significant association between resistance to acetylsalicylic acid and poor 90-days functional outcome and between resistance to Clopidogrel and good 90-days functional outcome. If confirmed, our results might improve pharmacological management after acute carotid stenting.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105800DOI Listing
July 2021

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep.

Neuroimage 2021 Apr 30;236:118117. Epub 2021 Apr 30.

MoMiLab Research Unit, IMT School for Advanced Studies Lucca, Piazza San Francesco, 19, Lucca 55100, Italy. Electronic address:

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118117DOI Listing
April 2021

Status epilepticus with prominent motor symptoms clusters into distinct electroclinical phenotypes.

Eur J Neurol 2021 May 1. Epub 2021 May 1.

Neurology Unit, OCB Hospital, AOU Modena, Modena, Italy.

Background And Purpose: Status epilepticus (SE) is a heterogeneous condition and considerable variability exists in its etiology, semiology, electroencephalographic correlates, and response to treatment. The aim of the present study was to explore whether distinct phenotypes may be identified within SE with prominent motor symptoms.

Methods: Consecutive episodes of SE with prominent motor symptoms in patients aged ≥14 years were included. Etiology of SE was defined as symptomatic (acute, remote, progressive) or unknown. Electroencephalogram (EEG) recordings were searched for lateralized periodic discharges (LPDs), generalized sharply and/or triphasic periodic potentials (GPDs), and spontaneous burst suppression (BS). According to treatment response, SE was classified into responsive, refractory and super-refractory. Average linkage hierarchical cluster analysis was performed with Pearson's correlation as a similarity measure.

Results: A total of 240 episodes of SE were identified. Three major clusters were found. The first cluster linked focal motor SE evolving into non-convulsive SE (NCSE), presence of LPDs/GPDs on EEG, unknown etiology and treatment refractoriness. The second cluster linked convulsive and myoclonic SE evolving into NCSE, presence of spontaneous BS on EEG, progressive symptomatic etiology and super-refractoriness. The third cluster linked convulsive and myoclonic SE not evolving into other semiologies, absence of LPDs/GPDs/spontaneous BS on EEG, acute symptomatic etiology and treatment responsiveness.

Conclusions: Distinct electroclinical phenotypes characterized by different response to pharmacological intervention can be identified within the heterogeneity of SE with prominent motor phenomena.
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http://dx.doi.org/10.1111/ene.14891DOI Listing
May 2021

Mild to Severe Neurological Manifestations of COVID-19: Cases Reports.

Int J Environ Res Public Health 2021 04 1;18(7). Epub 2021 Apr 1.

School of Anaesthesia and Intensive Care, University of Modena and Reggio Emilia, 41125 Modena, Italy.

The main focus of Coronavirus disease 2019 (COVID-19) infection is pulmonary complications through virus-related neurological manifestations, ranging from mild to severe, such as encephalitis, cerebral thrombosis, neurocognitive (dementia-like) syndrome, and delirium. The hospital screening procedures for quickly recognizing neurological manifestations of COVID-19 are often complicated by other coexisting symptoms and can be obscured by the deep sedation procedures required for critically ill patients. Here, we present two different case-reports of COVID-19 patients, describing neurological complications, diagnostic imaging such as olfactory bulb damage (a mild and unclear underestimated complication) and a severe and sudden thrombotic stroke complicated with hemorrhage with a low-level cytokine storm and respiratory symptom resolution. We discuss the possible mechanisms of virus entrance, together with the causes of COVID-19-related encephalitis, olfactory bulb damage, ischemic stroke, and intracranial hemorrhage.
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http://dx.doi.org/10.3390/ijerph18073673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036948PMC
April 2021

Intravenous brivaracetam in status epilepticus: A multicentric retrospective study in Italy.

Seizure 2021 Mar 30;86:70-76. Epub 2021 Jan 30.

Neurology Unit 2, Careggi University Hospital, Florence, Italy.

Purpose: to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE).

Methods: a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration.

Results: 56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50-300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39-202; p = 0.002). No severe treatment emergent adverse events were observed.

Conclusion: BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.
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http://dx.doi.org/10.1016/j.seizure.2021.01.014DOI Listing
March 2021

Olfactory function and viral recovery in COVID-19.

Brain Behav 2021 03 19;11(3):e02006. Epub 2021 Jan 19.

Neurology Unit, OCB Hospital, Azienda Ospedaliera-Universitaria, Modena, Italy.

Background: Olfactory and taste disorders were reported in up to 30%-80% of COVID-19 patients. The purpose of our study was to objectively assess smell impairment in COVID-19 patients and to correlate olfactory function with viral recovery.

Methods: Between 15 and 30 April 2020, hospitalized patients with confirmed SARS-CoV-2 infection underwent an objective assessment of olfactory function with the Smell Identification subtest of the Sniffin' Sticks Test (SI-SST). Association between viral recovery and SI-SST performance was evaluated.

Results: 51 patients were enrolled (49% males, mean age 66.2 ± 14.6 years). At the time of test administration, 45% were clinically recovered and 39% were virus-free. Objective hyposmia/anosmia was found in 45% of the patients. Subjective olfactory disorders showed no association with the clinical or viral recovery status of the patients. On the contrary, none of the patients with anosmia and the 5% of hyposmic patients at test had viral recovery. The relative risk for hyposmic patients to be still positive at swab test was 10.323 (95% CI 1.483-71.869, p < .0001). Logistic regression analysis showed an independent and significant correlation between viral clearance and SI-SST scores (OR = 2.242; 95% CI 1.322-3.802, p < .003). ROC curve analysis confirmed that a SI-SST > 10.5 predicts viral clearance with 79% sensitivity and 87% specificity (AUC = 0.883).

Conclusion: Hyposmia is part of COVID-19 symptoms; however, only objectively assessed olfactory function is associated with viral recovery. SI-SST is an easy and safe instrument, and further large multicentric studies should assess its value to predict infection and recovery.
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http://dx.doi.org/10.1002/brb3.2006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994699PMC
March 2021

Developmental and epileptic encephalopathies: Is prognosis related to different epileptic network dysfunctions?

Epilepsy Behav 2020 Dec 18:107654. Epub 2020 Dec 18.

Division of Pediatric Neurology, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; Study Group for Intensive and Integrated Care of Pediatric Central Nervous System (iCNS Group), Chang Gung Children's Hospital, Taoyuan, Taiwan. Electronic address:

Developmental and epileptic encephalopathies are a group of rare, severe epilepsies, which are characterized by refractory seizures starting in infancy or childhood and developmental delay or regression. Developmental changes might be independent of epilepsy. However, interictal epileptic activity and seizures can further deteriorate cognition and behavior. Recently, the concept of developmental and epileptic encephalopathies has moved from the lesions associated with epileptic encephalopathies toward the epileptic network dysfunctions on the functioning of the brain. Early recognition and differentiation of patients with developmental and epileptic encephalopathies is important, as precision therapies need to be holistic to address the often devastating symptoms. In this review, we discuss the evolution of the concept of developmental and epileptic encephalopathies in recent years, as well as the current understanding of the genetic basis of developmental and epileptic encephalopathies. Finally, we will discuss the role of epileptic network dysfunctions on prognosis for these severe conditions.
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http://dx.doi.org/10.1016/j.yebeh.2020.107654DOI Listing
December 2020

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

Epilepsia 2021 01 12;62(1):e1-e6. Epub 2020 Dec 12.

Epilepsy Center, Neurology Unit, Venice, Italy.

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [ HR] = 1.07, 95% CI = 1.02-1.13, P = .009) and baseline monthly seizure frequency ( HR = 1.004, 95% CI = 1.001-1.008, P = .028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.
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http://dx.doi.org/10.1111/epi.16769DOI Listing
January 2021

Kappa Index Versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders.

Diagnostics (Basel) 2020 Oct 21;10(10). Epub 2020 Oct 21.

Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, Italy.

Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID).

Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer.

Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis.

Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information.
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http://dx.doi.org/10.3390/diagnostics10100856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589948PMC
October 2020

Middle cerebral artery ischemic stroke and COVID-19: a case report.

J Neurovirol 2020 12 8;26(6):967-969. Epub 2020 Sep 8.

Stroke Unit - Neurology Clinic, Department of Neuroscience, Ospedale Civile di Baggiovara, Azienda Ospedaliera Universitaria di Modena, Modena, Italy.

We present a clinical case of a patient with SARS-CoV-2 infection and respiratory symptoms, complicated with a pro-thrombotic state involving multiple vascular territories and concomitant interleukin-6 increase. This case underlines the possibility to develop a COVID-19-related coagulopathy.
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http://dx.doi.org/10.1007/s13365-020-00898-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478241PMC
December 2020

Spatio-temporal dynamics of interictal activity in musicogenic epilepsy: Two case reports and a systematic review of the literature.

Clin Neurophysiol 2020 10 18;131(10):2393-2401. Epub 2020 Jul 18.

Department of Biomedical, Metabolic, and Neuronal Sciences, University of Modena and Reggio Emilia, Modena, Italy; Department of Neurology, OCB Hospital, AOU Modena, Modena, Italy.

Objective: To explore neurophysiological features of musicogenic epilepsy (ME), discussing experimental findings in the framework of a systematic review on ME.

Methods: Two patients with ME underwent high-density-electroencephalography (hd-EEG) while listening to ictogenic songs. In one case, musicogenic seizures were elicited. Independent component analysis (ICA) was applied to hd-EEG, and components hosting interictal and ictal elements were identified and localized. Finally, the temporal dynamics of spike-density was studied relative to seizures. All findings were compared against the results of a systematic review on ME, collecting 131 cases.

Results: Interictal spikes appeared isolated in specific fronto-temporal independent components, whose cortical generators were located in the anterior temporal and inferior frontal lobe. In the patient undergoing seizure, ictal discharge relied in the same component, with the interictal spike-density decreasing before the seizure onset.

Conclusion: Our study shows how ICA can isolate neurophysiological features of ictal and interictal discharges in ME, highlighting a fronto-temporal localization and a suppression of spike-density preceding the seizure onset.

Significance: While the localization of ME activity could indicate which aspect within the musical stimulus might trigger musicogenic seizures for each patient, the study of ME dynamics could contribute to the development of models for seizure-prediction and their validation.
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http://dx.doi.org/10.1016/j.clinph.2020.06.028DOI Listing
October 2020

Valproate Use Is Associated With Posterior Cortical Thinning and Ventricular Enlargement in Epilepsy Patients.

Front Neurol 2020 2;11:622. Epub 2020 Jul 2.

Neurology Unit, OCSAE Hospital, AOU Modena, Modena, Italy.

Valproate is a drug widely used to treat epilepsy, bipolar disorder, and occasionally to prevent migraine headache. Despite its clinical efficacy, prenatal exposure to valproate is associated with neurodevelopmental impairments and its use in children and adults was associated with rare cases of reversible brain atrophy and ventricular enlargement. To determine whether valproate use is related with structural brain changes we examined through a cross-sectional study cortical and subcortical structures in a group of 152 people with epilepsy and a normal clinical brain MRI. Patients were grouped into those currently using valproate ( = 54), those taking drugs other than valproate ( = 47), and drug-naïve patients ( = 51) at the time of MRI, irrespectively of their epilepsy syndrome. Cortical thickness and subcortical volumes were analyzed using Freesurfer, version 5.0. Subjects exposed to valproate (either in mono- or polytherapy) showed reduced cortical thickness in the occipital lobe, more precisely in the cuneus bilaterally, in the left lingual gyrus, and in left and right pericalcarine gyri when compared to patients who used other antiepileptic drugs, to drug-naïve epilepsy patients, and to healthy controls. Considering the subgroup of patients using valproate monotherapy ( = 25), both comparisons with healthy controls and drug-naïve groups confirmed occipital lobe cortical thickness reduction. Moreover, patients using valproate showed increased left and right lateral ventricle volume compared to all other groups. Notably, subjects who were non-valproate users at the time of MRI, but who had valproate exposure in the past ( = 27) did not show these cortical or subcortical brain changes. Cortical changes in the posterior cortex, particularly in the visual cortex, and ventricular enlargement, are present in people with epilepsy using valproate, independently from clinical and demographical variables. These findings are relevant both for the efficacy and adverse events profile of valproate use in people with epilepsy.
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http://dx.doi.org/10.3389/fneur.2020.00622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351506PMC
July 2020

Anti-NMDA receptor encephalitis presenting as new onset refractory status epilepticus in COVID-19.

Seizure 2020 10 15;81:18-20. Epub 2020 Jul 15.

Neurology Unit, OCB Hospital, Azienda Ospedaliera Universitaria di Modena, Italy; Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena Italy. Electronic address:

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http://dx.doi.org/10.1016/j.seizure.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362825PMC
October 2020

Intraoperative neurophysiological monitoring in aneurysm clipping: Does it make a difference? A systematic review and meta-analysis.

Clin Neurol Neurosurg 2020 09 29;196:105954. Epub 2020 May 29.

Neurosurgery Unit, Department of Biomedical, Metabolic, and Neuroscience, University of Modena and Reggio Emilia, AOU, Modena, Italy.

The use of intraoperative neurophysiological monitoring (IOM) has been proposed to prevent new neurological deficit during aneurysm clipping. The purpose of this meta-analysis was to evaluate if IOM can prevent neurological injury during clipping of intracranial aneurysm. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analysis, we reviewed clinical comparative studies who evaluate the rate of new neurological deficit in patients who had a surgical clipping with and without IOM. Of the 268 citations screened, four studies (including 873 patients) met the inclusion criteria and were included in the meta-analysis. Patients who received surgery with IOM had less new neurological deficit than those who underwent surgery without it (p = 0,04). This finding was more significant in the subgroup analysis of two studies focused on middle cerebral artery (MCA) aneurysm (p = 0,02). However, a specific analysis of the three studies reporting the results of IOM to prevent permanent deficit revealed that there is only a trend for less neurological events in monitored patients without statistically significance (p = 0,05). The use of IOM during clipping of intracranial aneurysm was associated with less new neurological deficit with the obtained evidence of the included studies. However, at long-term follow-up the use of IOM did not correlate with a significant improvement in neurological outcome.
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http://dx.doi.org/10.1016/j.clineuro.2020.105954DOI Listing
September 2020

Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review.

Neurol Sci 2020 Nov 10;41(11):3075-3084. Epub 2020 Jun 10.

Institute of Neurology, University Magna Graecia, Germaneto (CZ), Italy.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients.

Material And Methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included.

Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies.

Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.
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http://dx.doi.org/10.1007/s10072-020-04479-2DOI Listing
November 2020

Clinical outcomes and treatments effectiveness in status epilepticus resolved by antiepileptic drugs: A five-year observational study.

Epilepsia Open 2020 Jun 2;5(2):166-175. Epub 2020 Mar 2.

Neurology Unit OCB Hospital Azienda Ospedaliera-Universitaria Modena Italy.

Objective: To evaluate clinical outcomes and treatment effectiveness of status epilepticus finally resolved by nonbenzodiazepine antiepileptic drugs (AEDs).

Methods: All consecutive SE episodes observed from September 1, 2013, to September 1, 2018, and resolved by AEDs were considered. Diagnosis and classification of SE followed the 2015 ILAE proposal. Nonconvulsive status (NCSE) diagnosis was confirmed according to the Salzburg EEG criteria. The modified Rankin Scale and deaths at 30 days from onset were used to evaluate outcomes.

Results: A total of 277 status episodes (mean age 71 years; 61% female) were treated and resolved by antiepileptic drugs after 382 treatment trials. 68% of the SE resolved after AED use as first/second treatment line, while subsequent trials with AEDs gave an additional 32% resolution. A return to baseline conditions was observed in 48% of the patients, while overall mortality was 19% without significant changes across the study years. Mortality was higher in NCSE than in convulsive SE (22.5% vs 12.9%;  < .05), while mortality did not differ in SE episodes resolved by a first/second AED trial (17.2%) versus SE resolved by successive treatment trials (18.9%). The resolution rate of intravenous AEDs was 82% for valproate, 77% for lacosamide, 71% for phenytoin, and 62% for levetiracetam. No significant differences were found in head-to-head comparison, but for the valproate-levetiracetam one that was related to NCSE episodes in which valproate resulted to be effective in 86% of the trials while levetiracetam in 62% ( < .002).

Significance: A high short-term mortality, stable over time, was observed in SE despite resolution of seizures, especially in SE with nonconvulsive semiology. Comparative AED efficacy showed no significant differences except for higher resolution rate for valproate versus levetiracetam in NCSE.
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http://dx.doi.org/10.1002/epi4.12383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278543PMC
June 2020

The ENIGMA-Epilepsy working group: Mapping disease from large data sets.

Hum Brain Mapp 2020 May 29. Epub 2020 May 29.

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.
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http://dx.doi.org/10.1002/hbm.25037DOI Listing
May 2020

The Relation Between Aortic Arch Branching Types and the Laterality of Cardio-Embolic Stroke.

J Stroke Cerebrovasc Dis 2020 Jul 13;29(7):104917. Epub 2020 May 13.

Department of Neuroscience, Stroke Unit - Neurology Clinic, Ospedale Civile di Baggiovara, AOU di Modena, Italy; Faculty of Medicine, Department of Neurology, Mansoura University, Mansoura 35511, Egypt. Electronic address:

Background And Purpose: The trajectory of cardiogenic emboli could be affected by anatomical and flow characteristics of the aortic arch. We aimed to study the relation between the different aortic arch patterns and the laterality of cardiogenic emboli.

Methods: 192 cardioembolic strokes were classified into 3 groups according to the type of the aortic arch; type 1 (n = 69), type 2 (n = 49), type 3 (n = 74). The side and site of the cerebral vessels occlusion were divided into anterior and posterior circulation strokes, and anterior strokes were further subdivided into right or left internal carotid, middle or anterior cerebral arteries occlusion.

Results: Overall, the anterior circulation embolic occlusions were more common than the posterior, and middle cerebral artery more commonly affected than internal carotid artery. The left side propensity was higher either in the total patients' pool or after segregation into atrial fibrillation (AF) and non AF cardio-embolic cases in all types of aortic arch except for type 1 aortic arch in the non AF cases. This propensity tended to get higher with advancement of the aortic arch types but failed to show statistically significant difference between the 3 arch types, however combination of type 2 and 3 arches into a single group showed statistically significant rise in the left side propensity in the total cardioembolic cases (P = 0.039) and in the non AF cardioembolic cases (P = 0.029). The bovine arch also showed increased left side propensity.

Conclusion: Cardioemboli tends to have left anterior cerebrovascular predilection especially with AF. Different geometrical patterns of aortic arch branching seem to affect the laterality of cardioemboli and increase its left side predilection.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104917DOI Listing
July 2020

The EEG diagnosis of NCSE: Concordance between clinical practice and Salzburg Criteria for NCSE.

Seizure 2020 Jul 24;79:1-7. Epub 2020 Apr 24.

Neurology Department, OCB Hospital, AOU Modena, Italy; PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy.

Purpose: To evaluate the concordance between the EEG diagnosis of non-convulsive status epilepticus (NCSE) made by the treating physician and the application of the Salzburg Consensus Criteria (SCC) on consecutive urgent EEG requested for acute alteration of consciousness not otherwise explained.

Methods: Retrospective evaluation of all urgent EEGs acquired between January 1st and March 31st 2018 in adolescents and adult patients (≥14 years old). The 'reference' was the neurologist who first evaluated the patient and reported the corresponding EEG diagnosis. All were blind to the SCC. All included EEG were evaluated and classified by three neurologists trained in the application of SCC blind to the clinical diagnosis.

Results: 181 consecutive EEGs entered the study. The treating clinician diagnosed a NCSE in 17 cases (9%). According to the SCC, 12 EEGs were classified as Definite NCSE (7%), 71 (39 %) as Possible NCSE, and 98 (54 %) as no NCSE. A perfect concordance was found for the Definite- and No-NCSE categories, while only 5 patients with a Possible-NCSE were diagnosed by the treating clinician as having NCSE. It is relevant to note that aamong the 66 patients with a Possible NCSE not diagnosed as SE by the treating clinician, only two presented an evolution toward a definite SE.

Conclusion: SCC have optimal performances for the 'Definite NCSE', and to exclude the presence of a NCSE. Conversely, the Possible NCSE category is still a a grey land of debate that could potentially include many different conditions.
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http://dx.doi.org/10.1016/j.seizure.2020.04.010DOI Listing
July 2020

Reply to Dr. Capovilla on "Reply to the article "Management of status epilepticus in adults. Position paper of the Italian League Against Epilepsy".

Epilepsy Behav 2020 06 6;107:107048. Epub 2020 Apr 6.

IRCCS Istituto delle Scienze Neurologiche, Bellaria Hospital, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.

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http://dx.doi.org/10.1016/j.yebeh.2020.107048DOI Listing
June 2020

Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes.

Front Neurol 2019 19;10:1316. Epub 2019 Dec 19.

Neurology Unit, OCB Hospital, AOU Modena, Modena, Italy.

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of "self-limited focal epilepsies." In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 ± 11.46. Two independent general linear model models were created for each patient based on the effect of interest: "individual CTS" in model 1 and "CTS density" in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical-subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood-oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks.
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http://dx.doi.org/10.3389/fneur.2019.01316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930928PMC
December 2019

Motor and Limbic System Contribution to Emotional Laughter across the Lifespan.

Cereb Cortex 2020 05;30(5):3381-3391

Department of Biomedical, Metabolic, and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 41121 Modena, Italy.

Laughter is a universal human behavior generated by the cooperation of different systems toward the construction of an expressive vocal pattern. Given the sensitivity of neuroimaging techniques to movements, the neural mechanisms underlying laughter expression remain unclear. Herein, we characterized the neural correlates of emotional laughter using the onsets and the duration of laughter bursts to inform functional magnetic resonance imaging. Laughter-related blood oxygen level-dependent (BOLD) increases involved both the motor (motor cortex, supplementary motor area, frontal operculum) and the emotional/limbic (anterior cingulate cortex, amygdala, n. accumbens, hippocampus) systems, as well as modulatory circuitries encompassing the basal ganglia, thalamus, and cerebellum. BOLD changes related to the 2 s preceding the laughter outbreak were selectively observed at the temporo-occipital junction and the periaqueductal gray matter, supporting the role of the former in the detection of incongruity and the gating role of the latter in the initiation of spontaneous laughter. Moreover, developmental changes were identified in laughter processing, consisting in a greater engagement of the reward circuitry in younger subjects; conversely, the default mode network appears more activated in older participants. Our findings contribute valuable information about the processing of real-life humorous materials and suggest a close link between laughter-related motor, affective, and cognitive elements, confirming its complex and multi-faceted nature.
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http://dx.doi.org/10.1093/cercor/bhz316DOI Listing
May 2020

Management of status epilepticus in adults. Position paper of the Italian League against Epilepsy.

Epilepsy Behav 2020 01 22;102:106675. Epub 2019 Nov 22.

IRCCS Istituto delle Scienze Neurologiche, Bellaria Hospital, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy. Electronic address:

Since the publication of the Italian League Against Epilepsy guidelines for the treatment of status epilepticus in 2006, advances in the field have ushered in improvements in the therapeutic arsenal. The present position paper provides neurologists, epileptologists, neurointensive care specialists, and emergency physicians with updated recommendations for the treatment of adult patients with status epilepticus. The aim is to standardize treatment recommendations in the care of this patient population.
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http://dx.doi.org/10.1016/j.yebeh.2019.106675DOI Listing
January 2020

The effect of chronic neuroglycopenia on resting state networks in GLUT1 syndrome across the lifespan.

Hum Brain Mapp 2020 02 11;41(2):453-466. Epub 2019 Nov 11.

Neurology Unit, OCSAE Hospital, AOU Modena, Modena, Italy.

Glucose transporter type I deficiency syndrome (GLUT1DS) is an encephalopathic disorder due to a chronic insufficient transport of glucose into the brain. PET studies in GLUT1DS documented a widespread cortico-thalamic hypometabolism and a signal increase in the basal ganglia, regardless of age and clinical phenotype. Herein, we captured the pattern of functional connectivity of distinct striatal, cortical, and cerebellar regions in GLUT1DS (10 children, eight adults) and in healthy controls (HC, 19 children, 17 adults) during rest. Additionally, we explored for regional connectivity differences in GLUT1 children versus adults and according to the clinical presentation. Compared to HC, GLUT1DS exhibited increase connectivity within the basal ganglia circuitries and between the striatal regions with the frontal cortex and cerebellum. The excessive connectivity was predominant in patients with movement disorders and in children compared to adults, suggesting a correlation with the clinical phenotype and age at fMRI study. Our findings highlight the primary role of the striatum in the GLUT1DS pathophysiology and confirm the dependency of symptoms to the patients' chronological age. Despite the reduced chronic glucose uptake, GLUT1DS exhibit increased connectivity changes in regions highly sensible to glycopenia. Our results may portrait the effect of neuroprotective brain strategy to overcome the chronic poor energy supply during vulnerable ages.
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http://dx.doi.org/10.1002/hbm.24815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313681PMC
February 2020

Plasma neurofilaments correlate with disability in progressive multiple sclerosis patients.

Acta Neurol Scand 2020 Jan 26;141(1):16-21. Epub 2019 Aug 26.

Department of Neurosciences, Ospedale Civile, Azienda Ospedaliero-Universitaria, Modena, Italy.

Objectives: Cerebrospinal fluid (CSF) and blood neurofilaments (NFLs) are markers of axonal damage and are being investigated, mostly in relapsing-remitting (RR) MS, as a marker of disease activity and of response to treatment, while there are less data in progressive MS patients. Primary aim was to measure NFL in plasma samples of untreated patients with primary (PP) and secondary (SP) progressive MS and to correlate them with disability, disease severity, and prior/subsequent disability progression.

Materials And Methods: Neurofilament concentrations were measured using SIMOA (Single Molecule Array, Simoa HD-1 Analyzer; Quanterix).

Results: Neurofilament concentrations were measured on plasma samples of 70 progressive (27 PP and 43 SP), 21 RRMS patients, and 10 HCs. Longitudinal plasma NFL (pNFL) concentrations (median interval between sampling: 25 months) were available for nine PP/SP patients. PNFL concentrations were significantly higher in PP/SP compared to RRMS patients. They correlated with EDSS and MS Severity Score values. There was no difference in pNFL levels between PP/SP patients with EDSS progression in the preceding year (14% of patients) or during a median follow-up of 27 months (41%). In the longitudinal sub-study, pNFL levels increased in all patients between sampling by a mean value of 23% while EDSS mostly remained stable (77% of cases).

Conclusion: In PP/SP progressive MS patients, pNFL levels correlate with disability and increase over time, but are not associated with prior/subsequent disability progression, as measured by EDSS, which may not be a sufficiently sensitive tool in this context.
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http://dx.doi.org/10.1111/ane.13152DOI Listing
January 2020

Tumor-associated status epilepticus in patients with glioma: Clinical characteristics and outcomes.

Epilepsy Behav 2019 12 10;101(Pt B):106370. Epub 2019 Jul 10.

Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy; Neurology Unit, OCB Hospital, AOU Modena, Italy.

Between 3 and 12% of all adult status epilepticus (SE) are caused by a brain tumor. Gliomas, and in particular, high-grade gliomas (HGGs), are at high risk of SE development. In this study, we aimed to describe the clinical characteristic and outcomes of tumor-associated SE (TASE) in a population of adult patients with glioma prospectively collected between 2013 and 2019. In the aforementioned period, we observed 26 TASE (median age: 68 years). Overall, 22 patients (85%) presented a HGG (one anaplastic astrocytoma and 21 a glioblastoma) while 4 had a LGG (two diffuse astrocytoma and two ganglioglioma). All the lesions were supratentorial, and the temporal lobe was the most frequently involved (20 patients). Fourteen patients (54%) had the SE episode as the first manifestation of the tumor; in the remaining 12 (all patients with a HGG), the development of SE heralded tumor progression or reappearance. When TASE outcomes were compared with the ones observed in the general population of SE (SEGP), the response to treatment was not different between the two populations (refractory SE (RSE)/super-refractory SE (SRSE) 12% versus 13%, p = 0.75). In the short-term, group with TASE had a significantly lower global disability (modified Rankin scale (mRS) < 3 at discharge: 60% versus 32%, p < 0.001; at 30 days follow-up: 62% versus 30%, p < 0.001) and mortality (30 days mortality: 4% versus 27%, p = 0.008). Six months and 1 year mortality did not show any difference between the two groups (6 months: 46% and 45%, respectively, p = 0.9; 1 year: 68% and 52%, respectively, p = 0.22). The appearance of TASE often heralds tumor grow and progression. Even in this context, it appears to be as treatment-responsive as SEGP and the short-term disability and mortality related to SE episode are lower than those observed in the SEGP. Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.
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http://dx.doi.org/10.1016/j.yebeh.2019.06.014DOI Listing
December 2019

When the brain hurts the heart: status epilepticus inducing tako-tsubo cardiomyopathy.

Epileptic Disord 2019 Jun;21(3):235-243

Unit of Neurology, OCSAE Hospital, AOU, Modena, Department of Biomedical, Metabolic and Neural Sciences; Centre for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy.

Tako-tsubo cardiomyopathy (TTC) is a transient myocardial dysfunction mainly affecting the left ventricle, mimicking an acute coronary syndrome. This condition can be precipitated either by psychological/physical stressful events or by a number of medical conditions among which are seizures and status epilepticus (SE). The evolution is mostly favourable but sometimes TTC can evolve into life-threatening conditions. We searched for cases of TTC among all consecutive SE episodes observed at our department during the period 2013-2018. In addition, we searched MEDLINE (accessed through PubMed from inception to August 31, 2018) to identify reports of patients with TTC associated with an SE episode. Three TTC cases among 392 SE episodes were identified. Adding our cases to those previously reported, overall, we identified 45 cases of TTC induced by SE. The majority were females of around 60 years of age experiencing a first episode of SE with prominent motor phenomena, mostly in the context of remote aetiology. The most frequent presenting symptom was mild hypotension but cases with a severe presentation were also reported. The overall evolution was positive in all cases but some severe complications such as pulmonary oedema, cardiogenic shock, ventricular fibrillation, and a giant apical thrombus were also reported (19%). TTC may be a rare potentially life-threatening consequence of SE. It is frequently unrecognized, and therefore underdiagnosed. Clinicians dealing with SE should be aware of this entity.
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http://dx.doi.org/10.1684/epd.2019.1068DOI Listing
June 2019