Neurophysiological Findings in Neuronal Ceroid Lipofuscinoses

Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of neurodegenerative diseases, characterized by progressive cerebral atrophy due to lysosomal storage disorder. Common clinical features include epileptic seizures, progressive cognitive and motor decline, and visual failure, which occur over different time courses according to subtypes. During the latest years, many advances have been done in the field of targeted treatments, and in the next future, gene therapies and enzyme replacement treatments may be available for several NCL variants. Considering that there is rapid disease progression in NCLs, an early diagnosis is crucial, and neurophysiological features might have a key role for this purpose. Across the different subtypes of NCLs, electroencephalogram (EEG) is characterized by a progressive deterioration of cerebral activity with slowing of background activity and disappearance of spindles during sleep. Some types of heterogeneous abnormalities, diffuse or focal, prevalent over temporal and occipital regions, are described in many NCL variants. Photoparoxysmal response to low-frequency intermittent photic stimulation (IPS) is a typical EEG finding, mostly described in CLN2, CLN5, and CLN6 diseases. Visual evoked potentials (VEPs) allow to monitor the visual functions, and the lack of response at electroretinogram (ERG) reflects retinal neurodegeneration. Taken together, EEG, VEPs, and ERG may represent essential tools toward an early diagnosis of NCLs

POLG1-Related Epilepsy. Review of Diagnostic and Therapeutic Findings

Background: The clinical spectrum associated with POLG1 gene mutations ranges from non-syndromic epilepsy or mild isolated neurological signs to neurodegenerative disorders. Our aim was to review diagnostic findings, therapeutic approaches and outcomes of reported cases of epilepsy related to POLG1 mutation. Methods: The articles for review were identified through a systematic research on PubMed and EMBASE databases from January 2003 to April 2020, searching for the terms "Epilepsy AND POLG OR polymerase gamma," OR "POLG1". Results: Forty-eight articles were selected for review, which included 195 patients. Two main peaks of age at epilepsy onset were found: at ages 1 and 13 years. The most frequent seizure type was myoclonic. The occurrence of Status Epilepticus was reported in 46.4% of cases. Epileptiform and slow abnormalities were most frequently seen over occipital regions. Brain Magnetic Resonance Imaging (MRI) revealed increased T2 signal intensities in thalamic regions. Genetic analysis revealed a prevalence of A467T, W748S and G848S (74.2% of patients) mutations. Survival at 5 years was estimated at very low levels (30.2% of patients). Conclusion: In this review, we included cases with both pediatric and adult epilepsy onset. The analysis of data regarding prognosis showed that survival is related to age at onset of epilepsy

Refractory Status Epilepticus in Genetic Epilepsy-Is Vagus Nerve Stimulation an Option?

Refractory and super-refractory status epilepticus (RSE, SRSE) are severe conditions that can have long-term neurological consequences with high morbidity and mortality rates. The usefulness of vagus nerve-stimulation (VNS) implantation during RSE has been documented by anecdotal cases and in systematic reviews; however, the use of VNS in RSE has not been widely adopted. We successfully implanted VNS in two patients with genetic epilepsy admitted to hospital for SRSE; detailed descriptions of the clinical findings and VNS parameters are provided. Our patients were implanted 25 and 58 days after status epilepticus (SE) onset, and a stable remission of SE was observed from the seventh and tenth day after VNS implantation, respectively, without change in anti-seizure medication. We used a fast ramp-up of stimulation without evident side effects. Our results support the consideration of VNS implantation as a safe and effective adjunctive treatment for SRSE

Insights into cognitive and behavioral comorbidities of SLC6A1-related epilepsy: five new cases and literature review

IntroductionSLC6A1 pathogenic variants have been associated with epilepsy and neurodevelopmental disorders. The clinical phenotype includes different seizure types, intellectual disability, and psychiatric symptoms affecting mood and behavior. Few data regarding neuropsychological features have been described, and details on cognitive profiles are often missing due to the lack of standardized tests.MethodsWe retrospectively reviewed the neuropsychological assessments of five subjects carrying heterozygous missense genetic variants in SLC6A1. We also collected data on epileptic features, EEGs, and brain MRIs. Additionally, we reviewed neuropsychological data from 204 previously reported patients with SLC6A1 pathogenic variants.ResultsIn our series, at the last evaluation (median 12.6 years), three patients had borderline intellectual functioning, one patient had mild cognitive impairment, and one patient presented with a moderate cognitive disability. Three out of five patients underwent at least two neuropsychological evaluations, which revealed a worsening of cognitive functions over time. We detected attention deficits in all patients. In addition, we observed anxiety, disruptive behavior disorder, emotional instability, and hetero aggressiveness. We also performed a literature review that highlighted that most of the patients with SLC6A1 pathogenic variants have mild-to-moderate intellectual disability and that one-third of cases have autistic traits.DiscussionBased on the literature review and the detailed description of our cases, we conclude that patients with SLC6A1-related epilepsy mostly present with mild-to-moderate intellectual disability, often associated with attention disorders. Such symptoms may worsen over time. Periodic standardized neuropsychological tests may be useful tools to follow development over time, and patient-specific rehabilitation programs could be tailored consistently

Anxiety and depression in Charcot-Marie-Tooth disease: data from the Italian CMT national registry

Background There is little information about neuropsychiatric comorbidities in Charcot-Marie-Tooth disease (CMT). We assessed frequency of anxiety, depression, and general distress in CMT.Methods We administered online the Hospital Anxiety-Depression Scale (HADS) to CMT patients of the Italian registry and controls. HADS-A and HADS-D scores >= 11 defined the presence of anxiety/depression and HADS total score (HADS-T) >= 22 of general distress. We analysed correlation with disease severity and clinical characteristics, use of anxiolytics/antidepressants and analgesic/anti-inflammatory drugs.Results We collected data from 252 CMT patients (137 females) and 56 controls. CMT patient scores for anxiety (mean +/- standard deviation, 6.7 +/- 4.8), depression (4.5 +/- 4.0), and general distress (11.5 +/- 8.1) did not differ from controls and the Italian population. However, compared to controls, the percentages of subjects with depression (10% vs 2%) and general distress (14% vs 4%) were significantly higher in CMT patients. We found no association between HADS scores and disease duration or CMT type. Patients with general distress showed more severe disease and higher rate of positive sensory symptoms. Depressed patients also had more severe disease. Nineteen percent of CMT patients took antidepressants/anxiolytics (12% daily) and 70% analgesic/anti-inflammatory drugs. Patients with anxiety, depression, and distress reported higher consumption of anxiolytics/antidepressants. About 50% of patients with depression and/or general distress did not receive any specific pharmacological treatment.Conclusions An appreciable proportion of CMT patients shows general distress and depression. Both correlated with disease severity and consumption of antidepressants/anxiolytics, suggesting that the disease itself is contributing to general distress and depression

Frequency, entity and determinants of fatigue in Charcot-Marie-Tooth disease

Fatigue, a disabling symptom in many neuromuscular disorders, has been reported also in Charcot-Marie-Tooth disease (CMT). The presence of fatigue and its correlations in CMT was investigated

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Gli indicatori di aderenza dei pazienti oncologici alla chemioterapia orale. Evidenze empiriche da una revisione sistematica della letteratura

Introduzione. L'indice di aderenza ha un ruolo fondamentale nel trattamento dei pazienti poichè influenza notevolmente l'efficacia di un trattamento terapeutico in termini di miglioramento della sopravvivenza globale, della speranza di vita, della qualití  della stessa e di riduzione dei costi sanitari. Esistono lacune nell'individuazione degli indicatori da utilizzare per valutare l'aderenza e le modalití  attraverso cui tali indicatori debbano essere adottati. L'obiettivo di questo lavoro è quello di individuare in letteratura gli indicatori di aderenza.Metodo. Revisione sistematica della letteratura di tipo quantitativo effettuata seguendo il metodo PRISMA. La ricerca è stata condotta su: Cinhal-EBSCO, Medline-PUBMED e Scopus. Sono stati ricercati studi che misurassero l'aderenza dei pazienti al trattamento in lingua inglese e pubblicati dal 2010 al 2016. La selezione è stata effettuate utilizzando criteri di inclusione ed esclusione. La qualití  degli articoli è stata valutata con la NewCastle Ottawa Scale per gli studi osservazionali e con la Cochrane Collaboration Risk of Bias per gli studi sperimentali.Risultati. Sono stati ritrovati in totale 7,368 articoli e di questi selezionati 15 (11 studi osservazionali, 4 RCT), per un totale di 1,396 pazienti. Gli indicatori individuati sono: strumenti self-report, conta pillola, tasso di ricarica del farmaco, misure continue, dosaggio dei metaboliti. Un paziente oncologico è considerato aderente al trattamento se assume una percentuale di farmaci ≥ 80% rispetto ai farmaci prescritti.Discussione. Si ottiene una valutazione migliore di aderenza mediante l'utilizzo di più strumenti contemporaneamente. Gli indicatori oggettivi derivano dall'utilizzo dei metodi di misurazione diretta dell'aderenza, quelli soggettivi da quella indiretta. Parole chiave: self-management support, oral chemioterapy, measure adherence, measure compliance.The Adherence's indicators of cancer patients to oral chemotherapy. A sistematic literature review.ABSTRACTIntroduction. Adherence has a key role in treating patients as influences the effectiveness of therapeutic treatment for improving overall survival, life expectancy, quality of life and reducing healthcare costs. There are gaps in identifying indicators to be used to evaluate adherence and ways in which these indicators should be adopted. The aim of this paper is to identify adherence's indicators in literature.Methods. Systematic review was carried out in, Cinhal-EBSCO, Medline-PUBMED and Scopus including studies of measure patient's adherence in English and published from 2010 to 2016. Inclusion and exclusion criteria were used. The quality of the articles was assessed with the NewCastle Ottawa Scale for observational studies and the Cochrane Collaboration Risk of Bias for experimental studies.Results. Of the 7,368 papers initially retrieved, 15 met the inclusion criteria (11 observational studies, 4 RCTs), for a total of 1,396 patients. The indicators found are: self-report tools, pill counts, drug recharge rate, continuous measures, metabolic dosage. A patient is considered adherent to the treatment if he or she assumes a percentage of drugs ≥ 80% of the prescribed medications. Discussion. A better adherence rating is obtained by using multiple instruments at the same time. The objective indicators derive from the direct measurement methods of adherence, the subjective ones from the indirect. Key words: self-management support, oral chemioterapy, measure adherence, measure compliance

Impact of COVID-19 pandemic on pediatric patients with epilepsy - The caregiver perspective

The recent COVID-19 pandemic has disrupted care systems around the world. We assessed how the COVID-19 pandemic affected children with epilepsy in Italy, where lockdown measures were applied from March 8 to May 4, 2020. We compiled an Italian-language online survey on changes to healthcare and views on telehealth. Invitations were sent to 6631 contacts of all patients diagnosed with epilepsy within the last 5 years at the BambinoGesu Children's Hospital in Rome. Of the 3321 responses received, 55.6% of patients were seizure-free for at least 1 year before the COVID-19-related lockdown, 74.4% used anti-seizure medications (ASMs), and 59.7% had intellectual disability. Only 10 patients (0.4%) became infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Seizure frequency remained stable for most patients during the lockdown period (increased in 13.2%; decreased in 20.3%), and seizure duration, use of rescue medications, and adherence to treatment were unchanged. Comorbidities were more affected (behavioral problems worsened in 35.8%; sleep disorder worsened in 17.0%). Visits were canceled/postponed for 41.0%, but 25.1% had remote consultation during the lockdown period (93.9% were satisfied). Most responders (67.2%) considered continued remote consultations advantageous. Our responses support that patients/caregivers are willing to embrace telemedicine for some scenarios. (C) 2020 Elsevier Inc. All rights reserved

[The Adherence's indicators of cancer patients to oral chemotherapy. A sistematic literature review]

INTRODUZIONE. L\u2019indice di aderenza ha un ruolo fondamentale nel trattamento dei pazienti poich\ue8 influenza notevolmente l\u2019efficacia di un trattamento terapeutico in termini di miglioramento della sopravvivenza globale, della speranza di vita, della qualit\ue0 della stessa e di riduzione dei costi sanitari. Esistono lacune nell\u2019individuazione degli indicatori da utilizzare per valutare l\u2019aderenza e le modalit\ue0 attraverso cui tali indicatori debbano essere adottati. L\u2019obiettivo di questo lavoro \ue8 quello di individuare in letteratura gli indicatori di aderenza. METODO. Revisione sistematica della letteratura di tipo quantitativo effettuata seguendo il metodo PRISMA. La ricerca \ue8 stata condotta su: Cinhal-EBSCO, Medline-PUBMED e Scopus. Sono stati ricercati studi che misurassero l\u2019aderenza dei pazienti al trattamento in lingua inglese e pubblicati dal 2010 al 2016. La selezione \ue8 stata effettuate utilizzando criteri di inclusione ed esclusione. La qualit\ue0 degli articoli \ue8 stata valutata con la NewCastle Ottawa Scale per gli studi osservazionali e con la Cochrane Collaboration Risk of Bias per gli studi sperimentali. RISULTATI. Sono stati ritrovati in totale 7,368 articoli e di questi selezionati 15 (11 studi osservazionali, 4 RCT), per un totale di 1,396 pazienti. Gli indicatori individuati sono: strumenti self-report, conta pillola, tasso di ricarica del farmaco, misure continue, dosaggio dei metaboliti. Un paziente oncologico \ue8 considerato aderente al trattamento se assume una percentuale di farmaci superiore all'80% rispetto ai farmaci prescritti. DISCUSSIONE. Si ottiene una valutazione migliore di aderenza mediante l\u2019utilizzo di pi\uf9 strumenti contemporaneamente. Gli indicatori oggettivi derivano dall\u2019utilizzo dei metodi di misurazione diretta dell\u2019aderenza, quelli soggettivi da quella indiretta.INTRODUCTION: Adherence has a key role in treating patients as influences the effectiveness of therapeutic treatment for improving overall survival, life expectancy, quality of life and reducing healthcare costs. There are gaps in identifying indicators to be used to evaluate adherence and ways in which these indicators should be adopted. The aim of this paper is to identify adherence's indicators in literature. METHODS: Systematic review was carried out in, Cinhal-EBSCO, Medline-PUBMED and Scopus including studies of measure patient's adherence in English and published from 2010 to 2016. Inclusion and exclusion criteria were used. The quality of the articles was assessed with the NewCastle Ottawa Scale for observational studies and the Cochrane Collaboration Risk of Bias for experimental studies. RESULTS: Of the 7,368 papers initially retrieved, 15 met the inclusion criteria (11 observational studies, 4 RCTs), for a total of 1,396 patients. The indicators found are: self-report tools, pill counts, drug recharge rate, continuous measures, metabolic dosage. A patient is considered adherent to the treatment if he or she assumes a percentage of drugs 65 80% of the prescribed medications. DISCUSSION: A better adherence rating is obtained by using multiple instruments at the same time. The objective indicators derive from the direct measurement methods of adherence, the subjective ones from the indirect