Publications by authors named "Antonietta Coppola"

110 Publications

Diagnosis and treatment of pneumonia, a common cause of respiratory failure in patients with neuromuscular disorders.

Acta Myol 2021 Sep 30;40(3):124-131. Epub 2021 Sep 30.

Unità of Fisiopatologia e Riabilitazione Respiratoria AO Ospedali dei Colli, Naples, Italy.

Patients with neuromuscular diseases, during their illness are more susceptible to respiratory infections due to predisposing factors. Ineffective cough and the presence of atelectasis and hypoventilation, dysphagia and drooling can represent risk factors for the development of respiratory infection and fatal respiratory failure. Infections of respiratory tract with acute respiratory failure are the most common reason for hospitalizations, and pneumonia is among the leading causes of morbidity and mortality worldwide. The setting in which pneumonia is acquired heavily influences diagnostic and therapeutic choices. We will focus on aetiopathogenesis, diagnosis and treatment of pneumonia in these subjects, particularly considering the disease severity, rates of antibiotic resistance and the possible complications. In this case consultations with specialized physicians are strongly recommended.
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http://dx.doi.org/10.36185/2532-1900-053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489170PMC
September 2021

Cortical and Subcortical Network Dysfunction in a Female Patient With Encephalopathy.

Front Neurol 2021 9;12:722664. Epub 2021 Sep 9.

Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy.

The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies. Recently, mutations have been shown to cause a DEE in females, characterized by myoclonic-atonic epilepsy and recurrent nonconvulsive status. Here we used advanced neuroimaging techniques in a patient with a novel mutation presenting with recurrent absence status with eyelid myoclonia, to reveal brain structural and functional changes that can bring the clinical phenotype to alteration within specific brain networks. Indeed, the alterations found in the patient involved the visual pericalcarine cortex and the middle frontal gyrus, regions that have been demonstrated to be a core feature in epilepsy phenotypes with visual sensitivity and eyelid myoclonia with absences.
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http://dx.doi.org/10.3389/fneur.2021.722664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459922PMC
September 2021

Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis.

EClinicalMedicine 2021 Sep 9:101125. Epub 2021 Sep 9.

Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy.

Background: We and others have previously demonstrated that the endothelium is a primary target of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and L-arginine has been shown to improve endothelial dysfunction. However, the effects of L-arginine have never been evaluated in coronavirus disease 2019 (COVID-19).

Methods: This is a parallel-group, double-blind, randomized, placebo-controlled trial conducted on patients hospitalized for severe COVID-19. Patients received 1.66 g L-arginine twice a day or placebo, administered orally. The primary efficacy endpoint was a reduction in respiratory support assessed 10 and 20 days after randomization. Secondary outcomes were the length of in-hospital stay, the time to normalization of lymphocyte number, and the time to obtain a negative real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab. This clinical trial had been registered at ClinicalTrials.gov, identifier: NCT04637906.

Findings: We present here the results of the initial interim analysis on the first 101 patients. No treatment-emergent serious adverse events were attributable to L-arginine. At 10-day evaluation, 71.1% of patients in the L-arginine arm and 44.4% in the placebo arm ( < 0.01) had the respiratory support reduced; however, a significant difference was not detected 20 days after randomization. Strikingly, patients treated with L-arginine exhibited a significantly reduced in-hospital stay placebo, with a median (interquartile range 25,75 percentile) of 46 days (45,46) in the placebo group 25 days (21,26) in the L-arginine group ( < 0.0001); these findings were also confirmed after adjusting for potential confounders including age, duration of symptoms, comorbidities, D-dimer, as well as antiviral and anticoagulant treatments. The other secondary outcomes were not significantly different between groups.

Interpretation: In this interim analysis, adding oral L-arginine to standard therapy in patients with severe COVID-19 significantly decreases the length of hospitalization and reduces the respiratory support at 10 but not at 20 days after starting the treatment.
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http://dx.doi.org/10.1016/j.eclinm.2021.101125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428476PMC
September 2021

Intermittent Abdominal Pressure Ventilation: An Alternative for Respiratory Support.

Can Respir J 2021 23;2021:5554765. Epub 2021 Aug 23.

Hospital General Universitario Morales Meseguer, Murcia, Spain.

Intermittent abdominal pressure ventilation is a positive pressure ventilation technique that works with abdominal compressions. It has been known since 1938; however, for many years, it was out of production. In recent years, a new device has been produced that has captured the attention to this old respiratory support technique. We considered eight patients with respiratory failure secondary to a neuromuscular disease (congenital myopathy, Duchenne dystrophy, and amyotrophic lateral sclerosis) intolerant to daytime noninvasive ventilation (NIV). IAPV was proposed as an alternative to NIV. We performed baseline and post-IAPV respiratory function assessment. All patients, two years later, are still using intermittent abdominal ventilation. Intermittent positive abdominal mechanical ventilation can be a valid alternative to noninvasive mechanical ventilation with a nasal or face mask. It improves gas exchange, symptoms, and quality of life, decreases the incidence of pneumonia, and can avert the need for intubation and tracheotomy.
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http://dx.doi.org/10.1155/2021/5554765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405303PMC
August 2021

The Angiotensin Converting Enzyme Deletion/Deletion Genotype Is a Risk Factor for Severe COVID-19: Implication and Utility for Patients Admitted to Emergency Department.

Medicina (Kaunas) 2021 Aug 20;57(8). Epub 2021 Aug 20.

Sub-Intensive Care Unit, Department of Respiratory Pathophysiology and Rehabilitation Monaldi-A.O. Dei Colli, 80131 Naples, Italy.

: Insertion/deletion polymorphisms of angiotensin-converting enzyme (ACE) have been previously described in association with adult respiratory distress syndrome (ARDS) and correlated to outcome. The ACE deletion/deletion(D/D)genotype represents a marker of thrombosis in subjects apparently without predisposing factors and/or traditional thrombophilic alterations and increases the risk of venous thromboembolism in subjects in whom a thrombogenic condition occurs. Thrombosis seems to play a role very early in the disease caused by SARS-CoV-2, in particular in those with severe COVID-19 pneumonia. The counterbalance between angiotensin-converting enzyme (ACE) and ACE2 activities in COVID-19 disease may play a crucial role in the thrombo-inflammatory process. We hypothesised that a genetic predisposition could condition the severity and complications of SARS-CoV-2 infection. : We conducted a spontaneous, single centre observational study in the Sub-Intensive Care Unit of A.O.R.N. Ospedali dei Colli, Cotugno Hospital, Naples (Italy). In this study, we performed genetic screening for ACE D/D genotype and other thrombophilic mutations in 20 patients affected by ARDS related to COVID-19 pneumonia, compared to 19 age- and sex-matched healthy controls. : All tested patients had multiple polymorphisms and, in particular, a significantly higher prevalence of ACE D/D polymorphism in severe COVID-19 patients : We found that the majority of patients who tested positive for ACE D-D genotype and who were not associated with other risk factors for VTE showed an evolution to ARDS. This finding could have a predicting role in the selection of patients more prone to developing severe COVID-19 during clinical observation in emergency department.
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http://dx.doi.org/10.3390/medicina57080844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400776PMC
August 2021

Role of endothelial miR-24 in COVID-19 cerebrovascular events.

Crit Care 2021 08 25;25(1):306. Epub 2021 Aug 25.

Departments of Medicine (Cardiology) and Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Einstein-Sinai Diabetes Research Center , Albert Einstein College of Medicine, New York, NY, USA.

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http://dx.doi.org/10.1186/s13054-021-03731-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385482PMC
August 2021

KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum.

Brain 2021 Jun 11. Epub 2021 Jun 11.

Pediatric Neurology Department, Lyon University Hospital, 69500 Bron, France.

Variants in KCNT1, encoding a sodium-gated potassium channel (subfamily T member 1), have been associated with a spectrum of epilepsies and neurodevelopmental disorders. These range from familial autosomal dominant or sporadic sleep-related hypermotor epilepsy ((AD)SHE) to epilepsy of infancy with migrating focal seizures (EIMFS) and include developmental and epileptic encephalopathies (DEE). This study aims to provide a comprehensive overview of the phenotypic and genotypic spectrum of KCNT1 mutation-related epileptic disorders in 248 individuals, including 66 unpreviously published and 182 published cases, the largest cohort reported so far. Four phenotypic groups emerged from our analysis: i) EIMFS (152 individuals, 33 previously unpublished); ii) DEE other than EIMFS (non-EIMFS DEE) (37 individuals, 17 unpublished); iii) (AD)SHE (53 patients, 14 unpublished); iv) other phenotypes (6 individuals, 2 unpublished). In our cohort of 66 new cases, the most common phenotypic features were: a) in EIMFS, heterogeneity of seizure types, including epileptic spasms, epilepsy improvement over time, no epilepsy-related deaths; b) in non-EIMFS DEE, possible onset with West syndrome, occurrence of atypical absences, possible evolution to DEE with SHE features; one case of sudden unexplained death in epilepsy (SUDEP); c) in (AD)SHE, we observed a high prevalence of drug-resistance, although seizure frequency improved with age in some individuals, appearance of cognitive regression after seizure onset in all patients, no reported severe psychiatric disorders, although behavioural/psychiatric comorbidities were reported in about 50% of the patients, SUDEP in one individual; d) other phenotypes in individuals with mutation of KCNT1 included temporal lobe epilepsy, and epilepsy with tonic-clonic seizures and cognitive regression. Genotypic analysis of the whole cohort of 248 individuals showed only missense mutations and one inframe deletion in KCNT1. Although the KCNT1 mutations in affected individuals were seen to be distributed among the different domains of the KCNT1 protein, genotype-phenotype considerations showed many of the (AD)SHE-associated mutations to be clustered around the RCK2 domain in the C-terminus, distal to the NADP domain. Mutations associated with EIMFS/non-EIMFS DEE did not show a particular pattern of distribution in the KCNT1 protein. Recurrent KCNT1 mutations were seen to be associated with both severe and less severe phenotypes. Our study further defines and broadens the phenotypic and genotypic spectrums of KCNT1-related epileptic conditions and emphasizes the increasingly important role of this gene in the pathogenesis of early onset DEEs as well as in focal epilepsies, namely (AD)SHE.
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http://dx.doi.org/10.1093/brain/awab219DOI Listing
June 2021

Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.

Front Neurol 2021 20;12:673135. Epub 2021 May 20.

Pediatric Neurology and Epileptology Unit, Brotzu Hospital Trust, Cagliari, Italy.

Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox-Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period. Thirty centers were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg per day. Adverse effects and liver function tests were assessed after 2 weeks; 1, 3, and 6 months of treatment; and periodically thereafter. Seizure endpoints were the percentage of patients with ≥50 and 100% reduction in seizures compared to baseline. A total of 93 patients were enrolled and included in the safety analysis. Eighty-two patients [27 (32.9%) DS, 55 (67.1%) LGS] with at least 3 months of treatment have been included in the effectiveness analysis; median previously failed antiseizure medications was eight. Pediatric and adult patients were uniformly represented in the cohort. At 3-month follow-up, compared to the 28-day baseline period, the percentage of patients with at least a 50% reduction in seizure frequency was 40.2% (plus 1.2% seizure-free). Retention rate was similar according to diagnosis, while we found an increased number of patients remaining under treatment in the adult group. CBD was mostly coadministered with valproic acid (62.2%) and clobazam (41.5%). In the safety dataset, 29 (31.2%) dropped out: reasons were lack of efficacy [16 (17.2%)] and adverse events (AEs) [12 (12.9%)], and one met withdrawal criteria (1.1%). Most reported AEs were somnolence (22.6%) and diarrhea (11.9%), followed by transaminase elevation and loss of appetite. CBD is associated with improved seizure control also in a considerable proportion of highly refractory patients with DS and LGS independently from clobazam use. Overall, CBD safety and effectiveness are not dose-related in this cohort.
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http://dx.doi.org/10.3389/fneur.2021.673135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173151PMC
May 2021

The Role of High Flow Nasal Cannula in COVID-19 Associated Pneumomediastinum and Pneumothorax.

Healthcare (Basel) 2021 May 22;9(6). Epub 2021 May 22.

Sub-intensive Care Unit, Department of Respiratory Pathophysiology and Rehabilitation Monaldi-A.O. Dei Colli, Via Gaetano Quagliariello 54, 80131 Naples, Italy.

Background: Pneumomediastinum, subcutaneous emphysema and pneumothorax are not rarely observed during the COVID-19 pandemic. Such complications can worsen gas exchange and the overall prognosis in critical patients. The aim of this study is to investigate what predisposing factors are related to pneumomediastinum and pneumothorax in SARS-CoV2-Acute Respiratory Distress Syndrome (ARDS), what symptoms may predict a severe and potentially fatal complication and what therapeutical approach may provide a better outcome.

Methods: In this single center cohort study, we recorded data from 45 critically ill COVID-19 patients who developed one or more complicating events among pneumomediastinum, subcutaneous emphysema and pneumothorax. All patients showed ARDS and underwent non-invasive ventilation (NIV) at baseline. Patients with mild to moderate ARDS and pneumomediastinum/pneumothorax ( = 25) received High Flow Nasal Cannula (HFNC), while patients with severe ARDS and pneumomediastinum/pneumothorax underwent HFNC ( = 10) or invasive mechanical ventilation (IMV) ( = 10).

Results: Pneumomediastinum/pneumothorax developed in 10.5% of subjects affected by SARS-coV2-ARDS. Dyspnea affected 40% and cough affected 37% of subjects. High resolution computed tomography of the chest showed bilateral diffuse ground glass opacities (GGO) in 100% of subjects. Traction bronchiolectasis, reticulation, crazy paving and distortion were observed in 64%. Furthermore, 36% showed subcutaneous emphysema. Non-severe ARDS cases received HFNC, and 76% patients recovered from pneumomediastinum/pneumothorax over a median follow up of 5 days. Among severe ARDS cases the recovery rate of pneumomediastinum/pneumothorax was 70% with the HFNC approach, and 10% with IMV.

Conclusion: HFNC is a safe and effective ventilatory approach for critical COVID-19 and has a positive role in associated complications such as pneumomediastinum and pneumothorax.
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http://dx.doi.org/10.3390/healthcare9060620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224766PMC
May 2021

Alpha-1 antitrypsin deficiency in the elderly: a case report.

J Med Case Rep 2021 May 10;15(1):231. Epub 2021 May 10.

UOC Pathophysiology and Respiratory Rehabilitation, Intensive Care Department, Monaldi Hospital, Naples, Italy.

Background: Generally, alpha-1 antitrypsin deficiency (AATD) is suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic gaps and are misdiagnosed with chronic obstructive pulmonary disease (COPD), asthma, and airway hyperresponsiveness (AHR), as AATD may present with nonspecific respiratory symptoms. It is never too late to suspect AATD, especially in a patient with an unusual medical history. In recent years, evidence is beginning to emerge that there may be value in identifying and treating patients who do not already have deterioration of functional parameters.

Case Presentation: We describe a case of a 69-year-old Caucasian female patient, late diagnosis of AATD, with both severe bronchial hyperreactivity and numerous exacerbations due to the peculiar clinical history and the presence of a rare mutation; although not presenting forced expiratory volume in 1 second (FEV) between 30 and 65%, the patient was treated with alpha-1 antitrypsin (AAT) augmentation therapy and achieved clinical and functional improvement.

Conclusion: AATD should always be suspected. The Alpha-1 Foundation recommendations for the diagnosis and management of AATD in adult patients indicate that treatment should be provided for patients with FEV between 30 and 65%. It may be useful to evaluate and treat patients based on clinical symptoms, even outside the established parameters, in particular cases.
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http://dx.doi.org/10.1186/s13256-021-02847-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108364PMC
May 2021

Alpha-1 Antitrypsin Deficiency: Home Therapy.

Front Pharmacol 2021 15;12:575402. Epub 2021 Apr 15.

Department of Respiratory Pathophysiology Monaldi Hospital, Naples, Italy.

While available in only a few countries, home therapy is a possible strategy for the treatment of alpha-1 antitrypsin deficiency. We want to describe our experience in the management of human alpha-1 antitrypsin using home care intravenous augmentation therapy during this emergency period caused by SARS-CoV2 infection. We assessed the safety of the home treatment and the quality of life of patients enrolled in the program.
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http://dx.doi.org/10.3389/fphar.2021.575402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082418PMC
April 2021

Alpha-1 Antitrypsin Screening in a Selected Cohort of Patients Affected by Chronic Pulmonary Diseases in Naples, Italy.

J Clin Med 2021 Apr 7;10(8). Epub 2021 Apr 7.

Unit of Respiratory Physiopathology, Department of Critic Area, Monaldi Hospital, 80131 Naples, Italy.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition associated with several respiratory diseases in patients with severe protein deficiency. AATD is often late diagnosed or underdiagnosed. Diagnosis frequently occurs in patients with chronic obstructive pulmonary disease and emphysema characterized by frequent exacerbations and over ten years' duration. The purpose of this study was to evaluate the incidence of alpha-1 antitrypsin deficiency in patients with the chronic pulmonary disease after a thorough screening in the city of Naples in southern Italy.

Materials And Methods: Two hundred patients suffering from respiratory pathology (chronic obstructive pulmonary disease (COPD), emphysema, asthma, or bronchiectasis) were examined and evaluated in our outpatients' clinic and tested for serum levels of AAT. Patients who had a respiratory disease suspected of AATD and/or serum AAT < 120 mg/dL underwent genetic testing. Genetic screening was performed on samples from 141 patients.

Results: A total of 36 patients had an intermediate deficiency of AAT levels. Among them, 8 were PI*MZ, 6 were PI*MS and 22 had rare pathological mutations. Five patients had a severe AATD, all were composite heterozygous with S or Z allele, while the other allele had a rare pathological mutation.

Conclusions: The incidence of genetic defects as AATD in the population of patients affected by chronic respiratory disorders is always a matter of discussion because of the frequent interaction between genes and environmental causes. In our series, numerous rare variants and compound heterozygosity have been described. No homozygous patients have been described. The present is one of few studies available on the incidence of rare variants in the geographic area of the city of Naples. So, our results could be considered interesting not only to know the incidence of AATD and its related rare mutations but also to support early diagnosis and treatments for patients with chronic pulmonary disease and frequent exacerbation and to fight the association with environmental causes of pulmonary damages as smoking.
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http://dx.doi.org/10.3390/jcm10081546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067626PMC
April 2021

Home Management of Patients with Moderate or Severe Respiratory Failure Secondary to COVID-19, Using Remote Monitoring and Oxygen with or without HFNC.

Pathogens 2021 Apr 1;10(4). Epub 2021 Apr 1.

Department of Respiratory Pathophysiology, Monaldi-Cotugno Hospital, 80131 Naples, Italy.

Background: Home treatment of patients affected by COVID-19 is still a matter of daily debate. During the clinical evolution of the disease, there are high risks of lung failure, which requires oxygen therapy. Here, we report our clinical experience with at-home treatment using high-flow nasal cannula in non-hospitalised patients with confirmed COVID-19.

Patients And Methods: In this study, 18 patients with moderate-to-severe respiratory failure secondary to COVID-19 were monitored at home daily for temperature and SpO2 measurements. Other parameters such as saturation of peripheral oxygen (SpO2), SpO2/FiO2 (fraction of inspired oxygen), temperature, and lung performance were monitored periodically. Depending on oxygen requirements, the patients also received either standard oxygen via a face mask or, if higher FiO2 required, high-flow nasal cannula (HFNC).

Results: All 18 patients had favourable outcomes and recovered from COVID-19. No death was recorded in this group.

Conclusion: Our clinical experience proves that high-flow nasal cannula oxygen therapy may be considered for at-home treatment of COVID-19 patients with moderate lung failure. This could be useful for further treatment during the pandemic and may also be considered in future epidemics.
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http://dx.doi.org/10.3390/pathogens10040413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065650PMC
April 2021

Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.

J Neurol Neurosurg Psychiatry 2021 Oct 26;92(10):1044-1052. Epub 2021 Apr 26.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, and Chalfont Centre for Epilepsy, Gerrard Cross, UK

Objective: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.

Methods: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.

Results: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).

Significance: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
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http://dx.doi.org/10.1136/jnnp-2020-325932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458055PMC
October 2021

Daytime alternatives for non-invasive mechanical ventilation in neuromuscular disorders.

Acta Myol 2021 Mar 31;40(1):51-60. Epub 2021 Mar 31.

Unit of Respiratory Pathophysiology, Monaldi-Cotugno Hospital, Naples, Italy.

Mechanical ventilation in recent years has benefited from the development of new techniques and interfaces. These developments allowed clinicians to offer increasingly personalised therapies with the combination of different complementary techniques for treating respiratory insufficiency in patients with neuromuscular diseases. The mouthpiece ventilation, intermittent abdominal pressure ventilator and the negative pressure ventilation can offer many patients alternative therapy options when ventilation is required for many hours a day. In this non-systematic review, we will highlight the use of alternative methods to non-invasive mechanical ventilation at positive pressure in neuromuscular patients, to ensure the optimal interface for each patient.
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http://dx.doi.org/10.36185/2532-1900-042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033425PMC
March 2021

Temporal-parietal-occipital epilepsy in GEFS+ associated with SCN1A mutation.

Epileptic Disord 2021 Apr;23(2):397-401

Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Napoli, Italy.

Most families with genetic epilepsy with febrile seizures plus show a mutation in the sodium channel alpha 1 subunit gene, however, but there is much phenotypic heterogeneity and focal epilepsy remains relatively rare. Here, we report a family with electroclinical features indicative of temporal-parietal-occipital carrefour epilepsy with common occurrence of post-ictal migraine. We studied a four-generation family including nine affected subjects by means of EEG and MRI. Genetic testing was performed by targeted re-sequencing (gene panel). In most patients, seizure semiology included cognitive, autonomic, and emotional symptoms, eventually evolving towards sensory visual phenomena. Focal sensory vestibular seizures and changes in body perception were also reported in some cases. Post-ictal migraine was common, occurring in five out of the six (83%) epilepsy patients. A missense mutation (c.1130 G>A; p.R377Q) affecting the S5-S6 segment (pore region) of the sodium channel alpha 1 subunit was identified in all affected and four unaffected subjects. Temporal-parietal-occipital carrefour epilepsy is part of the genetic epilepsy with febrile seizures plus spectrum. The electroclinical features in this family support the involvement of a genetically impaired neural network. High prevalence of post-ictal migraine suggests the role of posterior brain areas in the clinical expression of this gene defect.
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http://dx.doi.org/10.1684/epd.2021.1266DOI Listing
April 2021

Perampanel Improves Cortical Myoclonus and Disability in Progressive Myoclonic Epilepsies: A Case Series and a Systematic Review of the Literature.

Front Neurol 2021 24;12:630366. Epub 2021 Mar 24.

Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, Italy.

Progressive myoclonic epilepsies (PMEs) are a heterogenous group of genetic diseases presenting with epilepsy, cognitive impairment, and severe action myoclonus, which can severely affect daily life activities and independent walking ability. Perampanel is a recent commercially available antiseizure medication with high efficacy against generalized seizures. Some reports supported the role of perampanel in ameliorating action myoclonus in PMEs. Here, we aimed to describe a case series and provide a systematic literature review on perampanel effects on PMEs. We report the perampanel effectiveness on myoclonus, daily life activities, and seizures on an original Italian multicenter case series of 11 individuals with PMEs. Then, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we performed a systematic review on perampanel effect on myoclonus and disability in PMEs. We searched PubMed, Scopus, and Google Scholar articles on perampanel and PMEs up to June 2020. No prospective trials were found. We reviewed 11 case series manuscripts reporting 104 cases of different PMEs. Here, we are reporting the effectiveness of perampanel in five individuals affected by Unverricht-Lundborg disease, three by Lafora disease, two by sialidosis, and one by an undetermined PME. Nine out of 11 individuals improved their disability related to the action myoclonus (two with Lafora disease did not). Among the 104 persons with PMEs collected by the systematic review, we found that more than half of the patients receiving perampanel exhibited an amelioration of action myoclonus and, consequently, of their independence in daily life activities. The Unverricht-Lundborg disease seemed to show the best clinical response to perampanel, in comparison with the other more severe PMEs. A significant seizure reduction was achieved by almost all persons with active epilepsy. Only 11% of PME patients dropped out due to inefficacy. Perampanel demonstrated a beneficial effect with regard to action myoclonus, disability, and seizures and was well-tolerated in people with PMEs, independently from their genetic diagnosis. Given the limited scientific evidence, broader prospective trials should be encouraged.
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http://dx.doi.org/10.3389/fneur.2021.630366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024635PMC
March 2021

Bleeding events in COVID-19: the other side of the coin?

Monaldi Arch Chest Dis 2021 Apr 1. Epub 2021 Apr 1.

Department of Respiratory Pathophysiology, Monaldi-Cotugno Hospital, Naples.

We present three cases of patients affected by severe SARS-CoV-2-related pneumonia treated with a low molecular weight heparin for prevention or treatment of pulmonary embolism, who presented a major bleed, in particular an ileopsoas haematoma that caused severe anaemia; in one case it was fatal. In the recent outbreak of novel coronavirus infection, significantly abnormal coagulation parameters in SARS-CoV-2 infection occur very often, but complications in the opposite direction such as bleeding diathesis are very rare. In these cases, there are different levels of gravity: for one patient the major bleed required the anticoagulant therapy to be stopped until bleeding stabilized, one patient needed interventional radiology and one patient died.
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http://dx.doi.org/10.4081/monaldi.2021.1739DOI Listing
April 2021

Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: a multicenter study on 313 Covid-19 patients.

Clin Chem Lab Med 2021 08 26;59(9):e354-e357. Epub 2021 Mar 26.

Division of Clinical Pathology, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1515/cclm-2021-0168DOI Listing
August 2021

Genotype-phenotype correlations in patients with de novo pathogenic variants.

Neurol Genet 2020 Dec 30;6(6):e528. Epub 2020 Nov 30.

Department of Neurosciences (F. Malerba, G.B., E.A., A. Riva, V.S., L.N., C. Minetti, F.Z., P.S.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova; Pediatric Neurology and Muscular Diseases Unit (F. Malerba, G.B., F. Marchese, E.A., A. Riva, M.S.V., V.S., C. Minetti, P.S.), IRCCS Istituto G. Gaslini; Center for Synaptic Neuroscience and Technology ([email protected]) (G.A., L.M., F.B.), Istituto Italiano di Tecnologia; Department of Experimental Medicine (G.A.), Università degli Studi di Genova; Laboratory of Human Genetics (E.G.); Unit of Medical Genetics (F. Madia, F.Z.), IRCCS Istituto G. Gaslini, Genova, Italy; Child Neurology and Neurorehabilitation Unit (M.A.), Department of Pediatrics, Central Hospital of Bolzano, Bolzano; Child Neurology and Psychiatry Unit (L.G., P.A., P.M.), ASST Spedali Civili, Brescia; Neurology Unit (M. Trivisano, N.S.), Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Roma; Child Neurology Unit (A. Russo, G.G.), IRCCS, Institute of Neurological Sciences of Bologna; Child Neuropsychiatry Unit (F.R.), U.O.N.P.I.A. ASST-Rhodense, Rho, Milano; Neurology Unit and Laboratories (T.P.), A. Meyer Children's Hospital, Firenze; Child Neurology and Psychiatric Unit (C. Marini), Pediatric Hospital G. Salesi, United Hospital of Ancona; Child Neuropsychiatry Unit (M.M.M., L.N.), IRCCS Istituto G. Gaslini, Genova; Department of Pediatric Neuroscience (E.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B. Castellotti), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano; Department of Child Neuropsychiatry (G.C.), Epilepsy Center, C. Poma Hospital, Mantova; Fondazione Poliambulanza Brescia (G.C.); Epilepsy Center (A.C.), Department of Neuroscience, Reproductive and Odontostomatological Sciences, Università degli Studi di Napoli Federico II, Napoli; Department of Pediatrics (A.V.), University of Perugia; Section of Pharmacology (F. Miceli, M. Taglialatela), Department of Neuroscience, Reproductive and Odontostomatological Sciences, Università degli Studi di Napoli Federico II, Napoli; IRCCS Ospedale Policlinico San Martino (L.M., F.B.), Genova, Italy; Division of Pediatric Neurology (M.R.C.), Saint-Luc University Hospital, and Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium; Department of Epilepsy Genetics and Personalized Treatment (K.M.J., R.S.M.), The Danish Epilepsy Center Filadelfia, Dianalund, Denmark; Institute for Regional Health Services (K.M.J., R.S.M.), University of Southern Denmark, Odense, Denmark; Department of Neurology (B. Ceulemans, S.W.), University Hospital Antwerp; Applied & Translational Neurogenomics Group (S.W.), VIB-Center for Molecular Neurology; Laboratory of Neurogenetics (S.W.), Institute Born-Bunge, University of Antwerp, Belgium; and Department of Life and Environmental Sciences (L.M.), Polytechnic University of Marche, Ancona, Italy.

Objective: Early identification of de novo variants in patients with epilepsy raises prognostic issues toward optimal management. We analyzed the clinical and genetic information from a cohort of patients with de novo pathogenic variants to dissect genotype-phenotype correlations.

Methods: Patients with de novo pathogenic variants were identified from Italy, Denmark, and Belgium. Atomic resolution Kv7.2 structures were also generated using homology modeling to map the variants.

Results: We included 34 patients with a mean age of 4.7 years. Median seizure onset was 2 days, mainly with focal seizures with autonomic signs. Twenty-two patients (65%) were seizure free at the mean age of 1.2 years. More than half of the patients (17/32) displayed severe/profound intellectual disability; however, 4 (13%) of them had a normal cognitive outcome.A total of 28 de novo pathogenic variants were identified, most missense (25/28), and clustered in conserved regions of the protein; 6 variants recurred, and 7 were novel. We did not identify a relationship between variant position and seizure offset or cognitive outcome in patients harboring missense variants. Besides, recurrent variants were associated with overlapping epilepsy features but also variable evolution regarding the intellectual outcome.

Conclusions: We highlight the complexity of variant interpretation to assess the impact of a class of de novo mutations. Genetic modifiers could be implicated, but the study paradigms to successfully address the impact of each single mutation need to be developed.
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http://dx.doi.org/10.1212/NXG.0000000000000528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803337PMC
December 2020

ACE Gene I/D Polymorphism and Acute Pulmonary Embolism in COVID19 Pneumonia: A Potential Predisposing Role.

Front Med (Lausanne) 2020 21;7:631148. Epub 2021 Jan 21.

Department of Intensive Care, A.O.R.N. Ospedali dei Colli, Naples, Italy.

Most recent studies have stressed a high risk of thromboembolism in patients with SARS-CoV-2 infection, particularly in those with severe COVID-19 pneumonia. Counterbalance between angiotensin-converting-enzyme (ACE) and ACE2 activities in COVID-19 disease may be crucially involved in the thrombo-inflammatory process. Currently, no study has investigated ACE I/D polymorphism involvement in COVID-19 disease complicated by pulmonary embolism, hence the aim of the present pilot study. This is a retrospective, single-center observational case-control study, conducted at the Sub-Intensive Care Unit of A.O.R.N. Ospedali dei Colli, Cotugno Hospital, Naples (Italy). We included 68 subjects with severe/critical COVID-19 pneumonia. COVID-19 patients were divided according to occurrence of PE (PE+, = 25) or absence of thromboembolic complications (PE-, = 43). Assessment of ACE I/D polymorphisms showed a statistically significant difference between PE+ and PE- patients ( = 0.029). Particularly, prevalence of D/D homozygous polymorphism was significantly higher in PE+ COVID-19 patients than in PE- (72 vs. 46.5%; = 0.048), while heterozygote I/D polymorphism was significantly lower expressed in PE+ patients than in PE- (16 vs. 48.8%; = 0.009). Computed tomographic pulmonary angiography showed predominantly mono/bilateral sub-segmental embolisms. In conclusion, our findings let us hypothesize a genetic susceptibility to thromboembolism in COVID-19 disease. ACE D/D polymorphism might represent a genetic risk factor, although studies on larger populations are needed.
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http://dx.doi.org/10.3389/fmed.2020.631148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874110PMC
January 2021

Temporal lobe malformations, focal epilepsy, and FGFR3 mutations: a non-causal association?

Neurol Sci 2021 May 3;42(5):2063-2067. Epub 2021 Jan 3.

Epilepsy Centre, Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

Temporal lobe abnormalities and focal epilepsy have been documented in FGFR3-related clinical condition, including hypochondroplasia and Muenke syndrome. FGFR3 is expressed in the brain during development and could play a role in nervous system development and hippocampal formation. These observations suggest a non-casual association between temporal malformation, epilepsy, and FGFR3 mutations. Herein, we report clinical, electroclinical, and neuroimaging findings of three additional cases of focal epilepsy and temporal lobe malformations occurring in children with FGFR3 gene mutations.
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http://dx.doi.org/10.1007/s10072-020-04923-3DOI Listing
May 2021

Dual diagnosis in a child with familial SCN8A-related encephalopathy complicated by a 1p13.2 deletion involving NRAS gene.

Neurol Sci 2021 05 17;42(5):2115-2117. Epub 2020 Nov 17.

Department of Translational Medical Sciences, Child Neurology, University of Naples Federico II, Naples, Italy.

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http://dx.doi.org/10.1007/s10072-020-04898-1DOI Listing
May 2021

Cortical tremor: a tantalizing conundrum between cortex and cerebellum.

Brain 2020 10;143(10):e87

Paediatric Neurology and Muscular Diseases Unit, IRCCS "G. Gaslini" Institute, Genova, Italy.

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http://dx.doi.org/10.1093/brain/awaa260DOI Listing
October 2020

Late Reactivation of SARS-CoV-2: A Case Report.

Front Med (Lausanne) 2020 20;7:531. Epub 2020 Aug 20.

Department of Respiratory Pathophysiology, Monaldi - Cotugno Hospital, Naples, Italy.

SARS-CoV-2 is a betacoronavirus that belongs to the family Coronaviridae and the order Nidovirales (1). During December 2019, a series of pneumonia cases caused by a SARS-CoV-2 outbreak was identified in Wuhan, Hubei, China, and rapidly spread across the world. The spectrum of SARS-CoV-2 disease (COVID 19) varies from asymptomatic or paucisymptomatic forms to clinical conditions characterized by respiratory failure that necessitate mechanical ventilation and support in an intensive care unit (ICU), multiorgan and systemic manifestations, and, in terms of sepsis, septic shock, and multiple organ dysfunction syndromes (MODS) (2). Whilst many reports have characterized the clinical, epidemiological, laboratory, and radiological features, as well as treatment and clinical outcomes of patients with COVID-19 pneumonia, information on SARS-CoV-2 reactivation remains unreported. Curative and eradicative therapy for COVID-19 is not currently available (3). We report a case of a patient with PCR-confirmed COVID-19 pneumonia who experienced reactivation after 43 days and negative PCR sampling.
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http://dx.doi.org/10.3389/fmed.2020.00531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468504PMC
August 2020

MPV promote adherence to nocturnal NIV in a Duchenne patient.

Acta Myol 2020 Jun 1;39(2):101-104. Epub 2020 Jun 1.

UOC Pathophysiology and Respiratory Rehabilitation, Intensive Care, Department, Azienda Ospedaliera dei Colli, Naples, Italy.

We described a case of a patient 20 years old, affected by Duchenne dystrophy with obstructive sleep apnoea syndrome and severe nocturnal desaturation. He was not compliant to non-invasive ventilation (NIV) for claustrophobia and panic attacks. Mouthpiece ventilation was successfully used in this patient, who later accepted the nighttime NIV.
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http://dx.doi.org/10.36185/2532-1900-014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460732PMC
June 2020

Bergmeister's papilla in a young patient with type 1 sialidosis: case report.

BMC Ophthalmol 2020 Aug 31;20(1):356. Epub 2020 Aug 31.

Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania L. Vanvitelli, 80131, Naples, Italy.

Background: Sialidosis is a rare genetic lysosomal storage disorder caused by a deficit of neuraminidase enzyme activity. Patients with sialidosis present various neurological disorders such as: myoclonic epilepsy and hypotonia, often associated with visual impairment. A typical aspect of sialidosis is the finding of a macular cherry-red spot on ocular fundus examination. In this paper we describe a unilateral case of Bergmeister's papilla (BP) in a young female patient suffering from type 1 sialidosis.

Case Presentation: A 28-year-old young woman suffering from type 1 sialidosis, confirmed by previously described compound heterozigosity Leu91Arg and Gly328Ser on N-acetyl-alpha-neuraminidase - 1 (NEU1) gene, underwent an opthalmological examination at the Eye Clinic of the University of Campania L. Vanvitelli, for bilateral visual deterioration. The patient was suffering from myoclonic epilepsy with hypotonia and severe motor disability. Fundoscopic examination showed a typical macular cherry-red spot with retinal pigment epithelium dystrophy in the middle periphery, in both eyes. Furthermore, in the left eye (OS), a vitreous thickening was observed in the nasal sector of the optic disc, remnant of fetal vasculature on the optic disc (Bergmeister's papilla). Optical coherence tomography (OCT) showed, in both eyes, a thickening of the ganglion cell layer (GCL) with a hyperreflective opacity as a cap on the left optic disc.

Conclusions: In our paper we have described, for the first time in literature, a case of BP in a patient with type 1 sialidosis. The detection of BP with thickening of the peripapillary vitreous by SD-OCT is useful in monitoring any vitreo-retinal change that could cause future visual deterioration.
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http://dx.doi.org/10.1186/s12886-020-01628-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460740PMC
August 2020

Diagnosis and Management of Type 1 Sialidosis: Clinical Insights from Long-Term Care of Four Unrelated Patients.

Brain Sci 2020 Aug 1;10(8). Epub 2020 Aug 1.

Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy.

: Sialidosis is a rare autosomal recessive disease caused by mutations, leading to neuraminidase deficiency and accumulation of sialic acid-containing oligosaccharides and glycopeptides into the tissues. Sialidosis is divided into two clinical entities, depending on residual enzyme activity, and can be distinguished according to age of onset, clinical features, and progression. Type 1 sialidosis is the milder, late-onset form, also known as non-dysmorphic sialidosis. It is commonly characterized by progressive myoclonus, ataxia, and a macular cherry-red spot. As a rare condition, the diagnosis is often only made after few years from onset, and the clinical management might prove difficult. Furthermore, the information in the literature on the long-term course is scarce. : We describe a comprehensive clinical, neuroradiological, ophthalmological, and electrophysiological history of four unrelated patients affected by type 1 sialidosis. The long-term care and novel clinical and neuroradiological insights are discussed. : We report the longest follow-up (up to 30 years) ever described in patients with type 1 sialidosis. During the course, we observed a high degree of motor and speech disability with preserved cognitive functions. Among the newest antiseizure medication, perampanel (PER) was proven to be effective in controlling myoclonus and tonic-clonic seizures, confirming it is a valid therapeutic option for these patients. Brain magnetic resonance imaging (MRI) disclosed new findings, including bilateral gliosis of cerebellar folia and of the occipital white matter. In addition, a newly reported variant (c.914G > A) is described.
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http://dx.doi.org/10.3390/brainsci10080506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465165PMC
August 2020

Epilepsy Care in the Time of COVID-19 Pandemic in Italy: Risk Factors for Seizure Worsening.

Front Neurol 2020 3;11:737. Epub 2020 Jul 3.

Department of Human Neurosciences, "Sapienza" University of Rome, Rome, Italy.

In early 2020, Italy struggled with an unprecedented health emergency related to the COVID-19 pandemic. Medical care of chronic neurological diseases, such as epilepsy, is being sorely neglected. In this national survey, we aimed at understanding the impact of COVID-19 lockdown on the care of people with epilepsy (PwE) and identifying PwE risk factors for seizure worsening to direct telemedicine efforts. We administered a 48-items online survey (published on April 11, 2020) including socio-demographic, epilepsy-related, and psychometric variables (BDI-II for depression, GAD-7 for anxiety, and PSQI for sleep) to PwE and people without epilepsy (PwoE). Regression analysis identified predictors of seizure worsening. We collected responses from 456 PwE (344 females) and 472 PwoE (347 females). Outpatient examinations of PwE were postponed in 95% of cases. One-third of PwE complained of issues with epilepsy management, but only 71% of them reached the treating physician and solved their problems. PwE had worse depressive and anxiety symptoms (higher BDI-II and GAD-7 scores; < 0.001) than PwoE. Sleep quality was equally compromised in both groups (47 and 42%). Sixty-seven PwE (18%) reported seizure worsening, which was best explained by the number of anti-seizure medications (ASM) of chronic therapy and the severity of sleep disorder. During the current COVID-19 pandemic, a significant percentage of PwE experienced difficulties in follow-up and a seizure number increase, in particular those chronically taking more ASMs and with poor sleep quality. This dramatic experience outlines the urgent need for validation and implementation of telemedicine services for epileptic patients in order to provide regular follow-up.
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http://dx.doi.org/10.3389/fneur.2020.00737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350269PMC
July 2020

Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study).

Front Neurol 2020 25;11:592. Epub 2020 Jun 25.

Center for Tumor-Related Epilepsy, UOSD Neuroncology, IRCCS IFO Regina Elena National Cancer Institute, Rome, Italy.

Epilepsy is one of the most common symptoms of brain tumors. It is often drug resistant and generally worsen patients' quality of life (QoL). Brain tumors release glutamate among other mediators, contributing to seizures onset, and this is accompanied by an increased AMPA receptors' expression on neuronal cells' membrane. Perampanel (PER) is a relatively new antiseizure medication (ASM) that acts as a selective non-competitive AMPA receptors' antagonist. Given its mechanism of action, we aimed to evaluate through a prospective, observational study, the efficacy and safety of PER as an add-on treatment in patients with brain tumor-related epilepsy (BTRE). The study was called PERADET. Thirty-six adult patients (intention to treat population-ITT) affected by BTRE, with uncontrolled focal-onset seizures treated with 1-3 ASMs were recruited from four Italian epilepsy centers. Perampanel was added-on, titrated from 2 mg/day up to a maximum of 12 mg/day. Tumor history and therapy, type, and seizures frequency, previous ASMs were collected at 6 and 12 months. A battery of QoL tests were administered at baseline, 6 and 12 months. The primary endpoint was to assess the efficacy of PER by calculating the percent change in seizure frequency and the responder rate. The secondary endpoints were tolerability, retention rate at 12 months, and improvement in quality of life. At the end of 12 months, 21 patients (per protocol population-PP) were available for evaluation. In this population the responder rate (percentage of patients who experienced a 50% or greater reduction in seizure frequency) was 90.4 with 33.3% of patients being seizure-free. In the ITT group the responder rate at the end of 12 months was 66.6 with 25% of patients being seizure free. PER was well tolerated (30.6% of patients experienced an adverse event, none was severe; three needed a treatment interruptions). Our study indicate that PER may be efficacious against BTRE as suggested by its mechanism of action and our current knowledge on mechanisms of brain tumor epileptogenicity. (Prot. n° 0008872.25-06-2019); RS 919/17.
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http://dx.doi.org/10.3389/fneur.2020.00592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336340PMC
June 2020
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