Publications by authors named "Antonio Gambardella"

226 Publications

Neuroma of the Inferior Alveolar Nerve: A Treatable Mimic of Refractory Trigeminal Neuralgia.

Neurol Clin Pract 2021 Aug;11(4):e582-e584

Institute of Neurology (FF, MT, AG); and Institute of Odontostomatology (LF), University Magna Graecia of Catanzaro, Italy.

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http://dx.doi.org/10.1212/CPJ.0000000000000938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382427PMC
August 2021

Hyper-religiosity and visual hallucinations in a patient with frontotemporal dementia carrying a double variant in GRN gene.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Aug 26:1-4. Epub 2021 Aug 26.

Neuroscience Centre, Magna Graecia University, Catanzaro, Italy, and.

: Hyper-religiosity has been reported in patients affected by frontotemporal dementia (FTD) with asymmetrical, predominantly right-sided frontotemporal atrophy. : We report a FTD patient carrying a double genetic variant (p.Cys139Arg and c.*78C > T) in the progranulin (GRN) gene who showed an unusual clinical phenotype characterized by hyper-religiosity behavior and visual hallucinations with exclusively religious content. Noteworthy, this patient exhibited a slow clinical and radiological rate of disease progression and a predominantly left-sided frontotemporal atrophy. : The simultaneous presence of these GRN variants in our FTD patient with predominant atrophy in the left (dominant) hemisphere could determine the unusual phenotype with hyper-religiosity and visual hallucinations with exclusively religious content and influence the slow rate of disease progression.
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http://dx.doi.org/10.1080/21678421.2021.1946087DOI Listing
August 2021

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.

Neuropathol Appl Neurobiol 2021 Aug 13. Epub 2021 Aug 13.

Neuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Aims: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis.

Methods: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy.

Results: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia.

Conclusions: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.
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http://dx.doi.org/10.1111/nan.12758DOI Listing
August 2021

Guillain-Barré syndrome following BNT162b2 COVID-19 vaccine.

Neurol Sci 2021 Aug 4. Epub 2021 Aug 4.

Department of Medical and Surgical Sciences, Institute of Neurology, Magna Græcia University, V.le Europa, 88100, Catanzaro, Italy.

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http://dx.doi.org/10.1007/s10072-021-05523-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331323PMC
August 2021

Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study.

Neuroimage Clin 2021 24;31:102765. Epub 2021 Jul 24.

Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany; Institute for Diagnostic and Interventional Radiology, Pediatric and Neuroradiology, University Medical Centre Rostock, Rostock, Germany.

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.
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http://dx.doi.org/10.1016/j.nicl.2021.102765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346685PMC
September 2021

Predictive factors of Status Epilepticus and its recurrence in patients with adult-onset seizures: A multicenter, long follow-up cohort study.

Seizure 2021 Oct 18;91:397-401. Epub 2021 Jul 18.

Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, National Council of Research, Institute of Clinical Physiology, Reggio Calabria, Italy.

Purpose: Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures.

Methods: We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model.

Results: Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p<0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p<0.001).

Conclusions: In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.
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http://dx.doi.org/10.1016/j.seizure.2021.07.009DOI Listing
October 2021

Postictal Psychosis in Epilepsy: A Clinicogenetic Study.

Ann Neurol 2021 Sep 3;90(3):464-476. Epub 2021 Aug 3.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.

Objective: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy-related psychoses, and has unknown causation.

Methods: We conducted a case-control cohort study including patients diagnosed with postictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile, and outcomes. After screening 3,288 epilepsy patients, we identified 83 with psychosis; 49 had postictal psychosis. Controls were 98 adults, matched by age and epilepsy type, with no history of psychosis. Logistic regression was used to investigate clinical factors associated with postictal psychosis; univariate associations with a p value < 0.20 were used to build a multivariate model. Polygenic risk scores for schizophrenia were calculated.

Results: Cases were more likely to have seizure clustering (odds ratio [OR] = 7.59, p < 0.001), seizures with a recollected aura (OR = 2.49, p = 0.013), and a family history of psychiatric disease (OR = 5.17, p = 0.022). Cases showed predominance of right temporal epileptiform discharges (OR = 4.87, p = 0.007). There was no difference in epilepsy duration, neuroimaging findings, or antiseizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of postictal psychosis cases (n = 58) were significantly higher than in 1,366 epilepsy controls (R  = 3%, p = 6 × 10 ), but not significantly different from 945 independent patients with schizophrenia (R  = 0.1%, p = 0.775).

Interpretation: Postictal psychosis occurs under particular circumstances in people with epilepsy with a heightened genetic predisposition to schizophrenia, illustrating how disease biology (seizures) and trait susceptibility (schizophrenia) may interact to produce particular outcomes (postictal psychosis) in a common disease. ANN NEUROL 2021;90:464-476.
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http://dx.doi.org/10.1002/ana.26174DOI Listing
September 2021

Selection of antiseizure medications for first add-on use: A consensus paper.

Epilepsy Behav 2021 09 24;122:108087. Epub 2021 Jun 24.

Division of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.

Introduction: When monotherapy used alone or sequentially fails to achieve seizure control, a trial of combination therapy may be considered.

Objective: To define optimal criteria to guide choice of an antiseizure medication (ASM) for use as first add-on.

Methods: A standardized Delphi procedure was applied to produce a list of consensus statements. First, an Expert Board consisting of 5 epileptologists agreed on a set of 46 statements relevant to the objective. The statements were then finalized through an iterative process by a Delphi Panel of 84 Italian pediatric and adult neurologists with expertise in the management of epilepsy. Panel members provided anonymous ratings of their level of agreement with each statement on a 9-point Likert scale.

Results: Consensus, defined as agreement by at least 80% of Panel members, was reached for 36 statements. Medication-related factors considered to be important for drug selection included efficacy, tolerability and safety, interaction potential, mechanism of action, and ease of use. The need to optimize adherence and to tailor drug selection to individual characteristics was emphasized.

Conclusions: Choice of an ASM for first add-on requires consideration of many factors, many of which also apply to choose initial treatment. Factors more specifically relevant to add-on use include drug interaction potential and the preference for an ASM with a different mechanism of action.
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http://dx.doi.org/10.1016/j.yebeh.2021.108087DOI Listing
September 2021

Orbito-frontal thinning together with a somatoform dissociation might be the fingerprint of PNES.

Epilepsy Behav 2021 08 26;121(Pt A):108044. Epub 2021 May 26.

Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Italy; Neuroscience Research Center, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Italy; Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy.

Objective: To investigate neuroanatomical changes in patients with psychogenic nonepileptic seizures (PNES) compared to major depressive disorder (MDD) and healthy controls.

Methods: Forty-two drug-naïve PNES subjects and 25 patients with MDD, matched for demographic characteristics and level of depression (as measured by Beck Depression Inventory-II, BDI-II), were consecutively recruited. Patients performed an extensive neuropsychiatric assessment including: Hamilton Anxiety Rating Scale, Traumatic Experience Checklist, Dissociative Experiences Scale, Toronto Alexithymia Scale and Somatoform Dissociation Questionnaire (SDQ-20). All patients, together with 78 healthy matched controls, underwent 3T brain MRI followed by surface-based morphometry.

Results: Cortical thickness analysis revealed significant cortical thinning in bilateral medial orbitofrontal cortex (OFC) and left rostral anterior cingulate cortex (ACC) in patients with MDD compared to subjects with PNES and controls. Interestingly, increased thickness of the right pars triangularis was found in PNES subjects compared to controls. PNES showed higher scores in SDQ-20 (p < 0.001) compared to MDD, which was corroborated by neuroimaging data, where somatoform dissociation scores correlated with morphological changes in the left medial OFC.

Conclusion: Our results show selective cortical thinning over the medial OFC in patients with PNES compared to wider regions of thinning in patients with MDD. Somatoform dissociation was the only psychopathological assessment significantly different in PNES and MDD.
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http://dx.doi.org/10.1016/j.yebeh.2021.108044DOI Listing
August 2021

Diagnostic and therapeutic approach to drug-resistant juvenile myoclonic epilepsy.

Expert Rev Neurother 2021 May 25:1-9. Epub 2021 May 25.

Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.

Introduction: Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of generalized epilepsy of presumed genetic origin representing up to 10% of all epilepsy cases. Despite adequate anti-seizure medication (ASM) treatment, seizures persist in one-third of JME patients.

Areas Covered: A literature search was conducted using Pubmed search on the topics of drug-resistant JME.

Expert Opinion: About 30% of JME patients are drug-resistant. Valproate (VPA) is considered the first-choice drug. In women of childbearing potential, levetiracetam (LEV) should represent the first-choice treatment. Alternative monotherapy or add-on therapy should be considered in subjects with resistant seizures after the exclusion of pseudo-drug resistance. The choice of the add-on ASM depends on the predominant seizure type. In subjects with persistent bilateral tonic-clonic seizures, LEV or lamotrigine should be firstly considered. In patients with difficult-to-treat myoclonic seizures, clonazepam or LEV are recommended. In case of persistent absences, ethosuximide should be considered. With appropriate selection and safeguards in place, VPA should remain available as an option in women of childbearing potential whose seizures are resistant to other treatments.
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http://dx.doi.org/10.1080/14737175.2021.1931126DOI Listing
May 2021

Incidental evidence of hypointensity in brain grey nuclei on routine MR imaging: when to suspect a neurodegenerative disorder?

Neurol Sci 2021 May 1. Epub 2021 May 1.

Neuroscience Centre, Magna Graecia University, Catanzaro, Italy.

Deep grey nuclei of the human brain accumulate minerals both in aging and in several neurodegenerative diseases. Mineral deposition produces a shortening of the transverse relaxation time which causes hypointensity on magnetic resonance (MR) imaging. The physician often has difficulties in determining whether the incidental hypointensity of grey nuclei seen on MR images is related to aging or neurodegenerative pathology. We investigated the hypointensity patterns in globus pallidus, putamen, caudate nucleus, thalamus and dentate nucleus of 217 healthy subjects (ages, 20-79 years; men/women, 104/113) using 3T MR imaging. Hypointensity was detected more frequently in globus pallidus (35.5%) than in dentate nucleus (32.7%) and putamen (7.8%). A consistent effect of aging on hypointensity (p < 0.001) of these grey nuclei was evident. Putaminal hypointensity appeared only in elderly subjects whereas we did not find hypointensity in the caudate nucleus and thalamus of any subject. In conclusion, the evidence of hypointensity in the caudate nucleus and thalamus at any age or hypointensity in the putamen seen in young subjects should prompt the clinician to consider a neurodegenerative disease.
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http://dx.doi.org/10.1007/s10072-021-05292-1DOI Listing
May 2021

Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes.

Am J Hum Genet 2021 04;108(4):722-738

Neurology - Neurophysiology Unit, ASST dei Sette Laghi, Galmarini Tradate Hospital, Tradate 21049, Italy.

Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies.
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http://dx.doi.org/10.1016/j.ajhg.2021.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059372PMC
April 2021

Facemask headache: a new nosographic entity among healthcare providers in COVID-19 era.

Neurol Sci 2021 Apr 27;42(4):1267-1276. Epub 2021 Jan 27.

Institute of Neurology, Department of Medical and Surgical Sciences, AOU Mater Domini - Magna Græcia University, V.le Europa, 88100, Catanzaro, Italy.

Background: SARS-CoV-2 is a novel infectious agent causing coronavirus disease 2019, which has been declared as pandemic in March 2020. Personal protective equipment has been mandatory for healthcare workers in order to contain the outbreak of pandemic disease. Mild neurological disturbances such as headache have been related to the extensive utilization of facemask. This study aims to examine headache variations related to the intensive utilization of facemask among a cohort of healthcare professionals in a setting of low-medium risk of exposure to SARS-CoV-2.

Methods: This is a cross-sectional study among healthcare providers from different hospital and clinics in Italy. Each participant completed a specifically designed self-administered questionnaire. Headache features and outcome measures' change from baseline were evaluated over a 4-month period, in which wearing facemask has become mandatory for Italian healthcare workers.

Results: A total of 400 healthcare providers completed the questionnaire, 383 of them met the inclusion criteria. The majority were doctors, with a mean age of 33.4 ± 9.2 years old. Among 166/383 subjects, who were headache free at baseline, 44 (26.5%) developed de novo headache. Furthermore, 217/383 reported a previous diagnosis of primary headache disorder: 137 were affected by migraine and 80 had tension-type headache. A proportion (31.3%) of these primary headache sufferers experienced worsening of their pre-existing headache disorder, mainly for migraine frequency and attack mean duration.

Conclusions: Our data showed the appearance of de novo associated facemask headache in previous headache-free subjects and an exacerbation of pre-existing primary headache disorders, mostly experienced by people with migraine disease.
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http://dx.doi.org/10.1007/s10072-021-05075-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838234PMC
April 2021

Opicapone-induced reversible myopathy in a patient with advanced Parkinson's disease and familial hyperCKemia.

Neurol Sci 2021 06 25;42(6):2583-2585. Epub 2021 Jan 25.

Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Magna Graecia University, Catanzaro, Italy.

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http://dx.doi.org/10.1007/s10072-021-05071-yDOI Listing
June 2021

Circulating microRNA: The Potential Novel Diagnostic Biomarkers to Predict Drug Resistance in Temporal Lobe Epilepsy, a Pilot Study.

Int J Mol Sci 2021 Jan 12;22(2). Epub 2021 Jan 12.

Department of Medical and Surgical Sciences, Institute of Neurology, University "Magna Graecia", Germaneto, 88100 Catanzaro, Italy.

MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as new potential epigenetic biomarkers. Here, we evaluate the efficacy of six circulating miRNA previously described in the literature as biomarkers for the diagnosis of temporal lobe epilepsy (TLE) and/or as predictive biomarkers to antiepileptic drug response. We measured the differences in serum miRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays in a cohort of 27 patients (14 women and 13 men; mean ± SD age: 43.65 ± 17.07) with TLE compared to 20 healthy controls (HC) matched for sex, age and ethnicity (11 women and 9 men; mean ± SD age: 47.5 ± 9.1). Additionally, patients were classified according to whether they had drug-responsive ( = 17) or drug-resistant ( = 10) TLE. We have investigated any correlations between miRNAs and several electroclinical parameters. Three miRNAs (miR-142, miR-146a, miR-223) were significantly upregulated in patients (expressed as average expression ± SD). In detail, miR-142 expression was 0.40 ± 0.29 versus 0.16 ± 0.10 in TLE patients compared to HC (-test, < 0.01), miR-146a expression was 0.15 ± 0.11 versus 0.07 ± 0.04 (-test, < 0.05), and miR-223 expression was 6.21 ± 3.65 versus 1.23 ± 0.84 (-test, < 0.001). Moreover, results obtained from a logistic regression model showed the good performance of miR-142 and miR-223 in distinguishing drug-sensitive vs. drug-resistant TLE. The results of this pilot study give evidence that miRNAs are suitable targets in TLE and offer the rationale for further confirmation studies in larger epilepsy cohorts.
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http://dx.doi.org/10.3390/ijms22020702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828221PMC
January 2021

Management of status epilepticus in patients with liver or kidney disease: a narrative review.

Expert Rev Neurother 2020 Dec 28:1-14. Epub 2020 Dec 28.

Regional Epilepsy Centre, Great Metropolitan "Bianchi-Melacrino-Morelli" Hospital, Reggio, Italy.

: Status epilepticus (SE) is a neurologic and medical emergency with significant related morbidity and mortality. Hepatic or renal dysfunction can considerably affect the pharmacokinetics of drugs used for SE through a variety of direct or indirect mechanisms.: This review aims to focus on the therapeutic management of SE in patients with hepatic or renal impairment, highlighting drugs' selection and dose changes that may be necessary due to altered drug metabolism and excretion. The references for this review were identified by searches of PubMed and Google Scholar until May 2020.: According to literature evidence and clinical experience, in patients with renal disease, the authors suggest considering lorazepam as the drug of choice in pre-hospital and intra-hospital early-stage SE, phenytoin in definite SE, propofol in refractory or super-refractory SE. In patients with liver disease, the authors suggest the use of lorazepam as drug of choice in pre-hospital and intra-hospital early-stage SE, lacosamide in definite SE, propofol in refractory or super-refractory SE. A list of preferred drugs for all SE stages is provided.
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http://dx.doi.org/10.1080/14737175.2021.1862649DOI Listing
December 2020

Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study.

Sci Adv 2020 Nov 18;6(47). Epub 2020 Nov 18.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria 3010, Australia.

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.
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http://dx.doi.org/10.1126/sciadv.abc6457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673818PMC
November 2020

Objective bilateral tinnitus from palatal nystagmus. Audio and video features of a rare case of palatal myoclonus.

Am J Otolaryngol 2020 Nov - Dec;41(6):102739. Epub 2020 Sep 19.

Department of Experimental and Clinical Medicine, Unit of Audiology, Regional Centre for Cochlear Implants and ENT Diseases, Magna Graecia University, Catanzaro, Italy.

Tinnitus is one of the most represented otological symptom, affecting 15% of adults, worldwide. Literature describes subjective tinnitus when it's perceived by the patient only, and objective tinnitus when it's heard both, by patient and examiner. An objective tinnitus can be caused by a large variety of anomalies and diseases; one of them is Palatal Myoclonus, characterized by rhytmic movements of soft palatal muscles and, only occasionally, involving other near districts. Case presentation. We observed a rare case of essential palatal myoclonus in a 54 y.o. female, suffering from chronic objective bilateral tinnitus, since 35 years, who underwent a wide number of clinical evaluations over the years, without receiving any conclusive diagnosis. In this video, we illustrate all the districts involved in clonic movements: soft palate, larynx and nasal wings. At the same time, we report the spectrographic analysis of tinnitus, recorded in esternal ear canal, taken together with the muscle movements. Palatal Myoclonus has to be considered in the etiological diagnosis of each objective tinnitus and should always be investigated properly.
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http://dx.doi.org/10.1016/j.amjoto.2020.102739DOI Listing
December 2020

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study.

Brain 2020 08;143(8):2454-2473

Department of Neurology, Medical University of South Carolina, Charleston 29425 SC, USA.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
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http://dx.doi.org/10.1093/brain/awaa200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567169PMC
August 2020

The impact of sexual abuse on psychopathology of patients with psychogenic nonepileptic seizures.

Neurol Sci 2021 Apr 13;42(4):1423-1428. Epub 2020 Aug 13.

Institutes of Neurology, Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, 88100, Catanzaro, Italy.

Objectives: In the present study, we evaluated if the presence of sexual abuse in the clinical history of patients with psychogenic non-epileptic seizures (PNES) is associated with a different psychopathological profile.

Materials And Methods: In a consecutive population of 63 PNES patients, we compared two demographically and clinically matched groups of patients with (no. 15) and without (no. 48) a history of sexual abuse using a comprehensive psychopathological assessment (Beck Depression Inventory, Hamilton Anxiety Rating Scale, Dissociative Experience Scale, Somatoform Dissociation Questionnaire, and Toronto Alexithymia Scale).

Results: We found that the group of patients reporting sexual abuse is characterized by higher scores on Dissociative Experience Scale (p = 0.003) and Beck Depression Inventory (p = 0.001) with respect to the other group. No significant statistical differences in Hamilton Anxiety Rating Scale (p = 0.103), Toronto Alexithymia Scale (p = 0.137), and Somatoform Dissociation Questionnaire (p = 0.486) were captured. Moreover, we found that the negative effect on dissociate symptoms was also hampered by the increasing of seizure frequency.

Conclusions: This study reinforces the importance of traumatic screening in the clinical spectrum of PNES in order to implement and improve specific therapeutic strategies.
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http://dx.doi.org/10.1007/s10072-020-04652-7DOI Listing
April 2021

Perampanel as first add-on choice on the treatment of mesial temporal lobe epilepsy: an observational real-life study.

Neurol Sci 2021 Apr 9;42(4):1389-1394. Epub 2020 Aug 9.

Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.

Purpose: To evaluate the efficacy of perampanel (PER) in patients with a diagnosis of mesial temporal lobe epilepsy (MTLE) taking PER as first add-on option due to inefficacy of first antiepileptic drug (AED), rather than late add-on choice.

Methods: Thirty-seven MTLE patients aged ≥ 12 years were recruited consecutively with a minimum duration of follow-up of 1 year and intermediate follow-up of 3 months. Patients were divided into two groups: 20/37 taking PER as first add-on due to inefficacy of first AED (first group) and 17/37 taking PER as late add-on due to inefficacy of ≥ 2 AEDs (second group). Efficacy, retention rate, and safety were evaluated.

Results: At 3 months, the 70% of the first group had a reduction > 50% of seizure frequency, with six patients becoming also seizure free, while in the second group, only the 23.5% had a reduction > 50% of seizure frequency and none became seizure free (p = 0.005). Six patients of first group were also switched to a monotherapy of PER and five out of six remained seizure free at 12 months. At 1 year of follow-up, efficacy of PER was 70% for the first group, while only of 29.4% for the second group (p = 0.014). Retention rate of the first group at 3 months and 1 year was 85%, while for the second group was, respectively, 82.3% and 64.7%.

Conclusion: PER was significantly successful and tolerated in MTLE patients when used as first add-on option rather than as late add-on.
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http://dx.doi.org/10.1007/s10072-020-04636-7DOI Listing
April 2021

Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis.

Ann Clin Transl Neurol 2020 09 5;7(9):1726-1731. Epub 2020 Aug 5.

Institute of Neurology, University Magna Graecia, Catanzaro, Italy.

We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss-of-function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the Na 1.1 loss-of-function, in addition to the typical GABA-current rundown, a hallmark of sporadic MTLE. Our results give evidence that a pharmacological rescuing of the GABAergic dysfunction may represent a promising strategy for the treatment of these patients.
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http://dx.doi.org/10.1002/acn3.51150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480916PMC
September 2020

Coverage of the requirements of first and second level stroke unit in Italy.

Neurol Sci 2021 Mar 31;42(3):1073-1079. Epub 2020 Jul 31.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova and IRCCS ICS Maugeri, Genova, Pavia, Italy.

Background And Aim: In the scientific literature, there is unanimous consensus that hospitalization in stroke unit (SU) is the most important treatment for stroke patients. In this regard, the Act number 70/2015 by the Italian government identified specific skills that contribute to a classification of SU and outlined a "hub and spoke" stroke network. The aim of our study was to check the coverage of requirements of first and second level SU in the national territory and to shed light on any deficit or misdistribution of resources.

Material And Methods: In 2019, a survey on the current situation related to stroke care in Italy was carried out by the Italian Society of Neurology (SIN), The Italian Stroke Organization (ISO), and the Association for the Fight against Stroke (A.L.I.Ce).

Results: First level SU was found to be 58 against a requirement, according to the Act 70/2015, of 240. Second level SU was found to be 52 compared with an expected requirement of 60. Neurointerventionists were 280 nationally, with a requirement of 240. A misdistribution of resources within individual regions was often seen.

Conclusions: The survey demonstrated a severe shortage of beds dedicated to cerebrovascular diseases, mainly because of lack of first level SU, especially in central and southern Italy. It also suggests that the current hub and spoke system is not yet fully implemented across the country and that resources should be better distributed in order to ensure uniform and fair care for all stroke patients on the whole territory.
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http://dx.doi.org/10.1007/s10072-020-04616-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870770PMC
March 2021

Looking for indicative magnetic resonance imaging signs of hippocampal developmental abnormalities in patients with mesial temporal lobe epilepsy and healthy controls.

Epilepsia 2020 08 22;61(8):1714-1722. Epub 2020 Jul 22.

Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University of Catanzaro, Catanzaro, Italy.

Objective: To evaluate the frequency of qualitative features for hippocampal developmental abnormalities (HiDeA) definition on magnetic resonance imaging (MRI) in mesial temporal lobe epilepsy (MTLE) patients and healthy controls, highlighting which were more sensitive and specific to the epileptic syndrome.

Methods: We enrolled 93 healthy controls and 187 MTLE patients. Among patients, 133 were MRI-negative and 54 had hippocampal sclerosis (HS). Two blinded, trained investigators defined HiDeA if three signs were present, including at least one of the following: (1) globular hippocampal shape (HCS), (2) verticalized collateral sulcus, and (3) medial positioning of hippocampus (HCP). After evaluating the prevalence of HiDeA in MTLE and controls, we assessed the frequency of each sign. Then, we classified differences in type or number of HiDeA diagnostic features, calculating their sensitivity and specificity. Fisher exact test was used to assess statistical significance.

Results: HiDeA was detected in 36 of 187 MTLE cases (19.25%) and in eight of 93 (8.6%) controls. In particular, HiDeA was present in 25 of 133 (18.8%) patients with MRI-negative MTLE. Among all visual criteria here considered, HCS showed higher sensitivity both in the MRI-negative MTLE group (88%) and in the HS-MTLE group (91%). HCP, thickened subiculum, and reduction of the upper horizontal portion of the parahippocampal gyrus (HCTH) signs demonstrated a 100% specificity in both groups. In healthy controls, HCS was confirmed to have the highest sensitivity (100%), whereas HCP showed the highest specificity (98.8%). All these criteria were statistically associated with HiDeA. Electroencephalographic focus was concordant with the HiDeA side in 52.2% of MTLE patients. An association was not found among signs of HiDeA and treatment responsiveness.

Significance: We identified characteristic signs of HiDeA, such as HCTH or HCP, differentiating HiDeA features between MTLE and healthy controls. The identification of sensitive and, more importantly, specific criteria of HiDeA could be helpful to make a more confident visual diagnosis.
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http://dx.doi.org/10.1111/epi.16608DOI Listing
August 2020

A Family With a Complex Phenotype Caused by Two Different Rare Metabolic Disorders: GLUT1 and Very-Long-Chain Fatty Acid Dehydrogenase (VLCAD) Deficiencies.

Front Neurol 2020 23;11:514. Epub 2020 Jun 23.

Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

GLUT1 Deficiency Syndrome (GLUT1-DS) is a rare and potentially treatable neurometabolic condition, caused by a reduced glucose transport into the brain and clinically characterized by an epileptic encephalopathy with movement disorders. A wide inter-intrafamilial phenotypic variability has been reported. Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited metabolic disorder of mitochondrial long-chain fatty acid oxidation (FAO) with also a variable age of onset and clinical presentation including cardiomyopathy, hypoketotic hypoglycemia, and liver disease. Sometimes, VLCAD manifests later with a prevalent muscle involvement characterized by exercise intolerance and recurrent rhabdomyolysis. We report a 40-year-old man with mild mental retardation and sporadic choreo-athetoid movements, who complained of recurrent episodes of rhabdomyolysis triggered by exercise or fasting since his twenties. His 15-year-old son had a psychomotor developmental delay with episodes of drowsiness mainly at fasting and exercise-induced choreo-athetoid movements but no history of pigmenturia. Clinical and laboratory findings in the son suggested a diagnosis of GLUT1-DS confirmed by genetic analysis that revealed a heterozygous mutation c.997C>T (p.R333W) that was also found in the proband. However, the presence in the latter of recurrent exercise-induced rhabdomyolysis, never reported in GLUT1-DS, implied a second metabolic disorder. Increased plasma C14:1-carnitine levels and the identification of two known heterozygous mutations c. 553G>A (p.G185S) and c.1153C>T (p.R385W) in confirmed the additional diagnosis of VLCAD deficiency in the proband. Nowadays, there is an increasing evidence of "double trouble" cases of genetic origin. Consequently, when atypical features accompany a known phenotype, associated comorbidities should be considered.
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http://dx.doi.org/10.3389/fneur.2020.00514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324651PMC
June 2020

Focal neuromyotonia associated with a C9ORF72 expansion mutation.

Muscle Nerve 2020 10 5;62(4):E63-E65. Epub 2020 Aug 5.

Institute of Neurology, Magna Graecia University, Catanzaro, Italy.

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http://dx.doi.org/10.1002/mus.27009DOI Listing
October 2020

Listeria infection after treatment with alemtuzumab: a case report and literature review. Would antibiotic prophylaxis be considered?

Infez Med 2020 Jun;28(2):258-262

Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit, "Magna Graecia" University, Catanzaro, Italy.

Few cases of complicated infections with Listeria monocytogenes (LM) have been reported to date in patients with multiple sclerosis (MS) treated with alemtuzumab. Primary prevention strategies may be suggested in such patients to avoid infections. However, these may be ineffective because patients may already be carriers of LM. We report herein a case of bloodstream infection due to LM in a 25-year-old woman with MS treated with alemtuzumab. We searched the UMC/WHO Vigibase system for all reported cases of LM in patients treated with alemtuzumab and found 29 cases overall up to 21 July 2019. We also performed a literature review of MS cases with LM on alemtuzumab, in order to evaluate epidemiology, clinical characteristics, and outcome of this complication. Since the published cases (N=8) were mainly reported in recent years but more cases were found in the UMC/WHO Vigibase system (although not necessarily in patients with MS), we hypothesize that this complication is more frequent than currently believed and may become even more important in the future. Therefore, it is worth reaching a consensus on appropriate algorithms to stratify individuals by risk so as to implement targeted prevention strategies (whether primary or secondary).
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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

COVID-19 risk contagion: Organization and procedures in a South Italy geriatric oncology ward.

J Geriatr Oncol 2020 09 22;11(7):1187-1188. Epub 2020 May 22.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

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http://dx.doi.org/10.1016/j.jgo.2020.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242974PMC
September 2020

The efficacy of perampanel as adjunctive therapy in drug-resistant focal epilepsy in a "real world" context: focus on temporal lobe epilepsy.

J Neurol Sci 2020 Aug 15;415:116903. Epub 2020 May 15.

Institute of Neurology, University "Magna Graecia", Catanzaro, Italy. Electronic address:

Background: Perampanel (PER) is a novel antiepileptic drug approved as an add-on therapy for focal onset seizures with or without generalization and primary generalized tonic-clonic seizures. Aim of this study was to evaluate PER efficacy and tolerability as add-on therapy in patients with drug-resistant focal onset seizures and especially temporal lobe epilepsy (TLE).

Methods: An observational, prospective, multicentre study on adult with drug-resistant focal epilepsy consecutively recruited from six Italian tertiary epilepsy centres. All patients received add-on PER according to indication and clinical judgement. Seizure frequency and adverse events (AEs) were recorded at 6 and 12 months after PER introduction.

Results: Study sample comprised 246 patients, 77 of which with TLE. Seventy-five (35.9%) out of 209 and 66 (38.8%) out of 170 patients still taking PER resulted to be responders (i.e. ≥50% of seizure frequency or seizure free) after six and 12 months, respectively. In the TLE group, 39 (57.3%) out of 68 subjects on PER after 6 months and 32 (60.4%) out of 53 subjects taking PER after 12 months were responders. Overall reported incidence of AEs was 26.1%. In 28 cases (11.3%) AEs lead/contributed to PER discontinuation. The most frequently reported AE were dizziness (14/84) and somnolence (14/84). Regarding TLE patients, 25.9% of them experienced at least one AE and discontinuation for AEs occurred in eight (10.4%).

Conclusions: This study confirmed the good efficacy and safety of PER for drug-resistant focal epilepsy in real-life conditions and, above all, for the first time provide its effectiveness in patients with TLE.
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http://dx.doi.org/10.1016/j.jns.2020.116903DOI Listing
August 2020
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