Il levetiracetam nella terapia dell'epilessia: relazione dose-efficacia e fattori predittivi di risposta al trattamento

L’obiettivo primario dello studio è quello di valutare se esiste una risposta dose correlata alla terapia con Levetiracetam. Obiettivi secondari sono stati quelli di valutare l’eventuale diversa efficacia della terapia in relazione a varie caratteristiche della popolazione in studio: tipo di crisi e sindrome epilettica, presenza di anomalie EEG e presenza di alterazioni RM. Abbiamo analizzato retrospettivamente una popolazione di 118 pazienti afferenti al Centro Regionale per la Diagnosi e la Terapia dell’Epilessia che assumono Levetiracetam da almeno due anni sia in mono che in politerapia. I dati rilevati nel corso dello studio sono stati sottoposti ad analisi statistica tramite il Test del Chi-quadro e il Test T di Student. Per la determinazione della significatività statistica dei risultati è stato considerato un livello di p<0.05. Dall’analisi dei nostri dati non è emersa una chiara correlazione tra incrementi del dosaggio del farmaco ed un corrispettivo aumento della risposta alla terapia; l’efficacia del trattamento, pertanto, sembrerebbe essere legata alle caratteristiche del farmaco stesso. Inoltre benché si siano rilevate delle percentuali di maggiore risposta alla terapia in alcuni gruppi di pazienti (P. con sindromi generalizzate, con forme sintomatiche e con anomalie EEG) queste differenze di efficacia non sono risultate statisticamente significative

Usefulness of a simple sleep-deprived EEG protocol for epilepsy diagnosis in de novo subjects.

OBJECTIVE: In case series concerning the role of EEG after sleep deprivation (SD-EEG) in epilepsy, patients' features and protocols vary dramatically from one report to another. In this study, we assessed the usefulness of a simple SD-EEG method in well characterized patients. METHODS: Among the 963 adult subjects submitted to SD-EEG at our Center, in the period 2003-2010, we retrospectively selected for analysis only those: (1) evaluated for suspected epileptic seizures; (2) with a normal/non-specific baseline EEG; (3) still drug-free at the time of SD-EEG; (4) with an MRI analysis; (5) with at least 1year follow-up. SD-EEG consisted in SD from 2:00 AM and laboratory EEG from 8:00 AM to 10:30 AM. We analyzed epileptic interictal abnormalities (IIAs) and their correlations with patients' features. RESULTS: Epilepsy was confirmed in 131 patients. SD-EEG showed IIAs in 41.2% of all patients with epilepsy, and a 91.1% specificity for epilepsy diagnosis; IIAs types observed during SD-EEG are different in generalized versus focal epilepsies; for focal epilepsies, the IIAs yield in SD-EEG is higher than in second routine EEG. CONCLUSIONS: This simple SD-EEG protocol is very useful in de novo patients with suspected seizures. SIGNIFICANCE: This study sheds new light on the role of SD-EEG in specific epilepsy populations

Controversial issues on EEG after sleep deprivation for the diagnosis of epilepsy

EEG after sleep deprivation (SD-EEG) is widely used in many epilepsy centers as an important tool in the epilepsy diagnosis process. However, after more than 40 years of use, there are a number of issues which still need to be clarified concerning its features and role. In particular, the many scientific papers addressing its role in epilepsy diagnosis often differ remarkably from each other in terms of the type of patients assessed, their description and study design. Furthermore, also the length and the type of EEG performed after SD, as well as the length of SD itself, vary dramatically from one study to another. In this paper we shortly underscore the abovementioned differences among the different reports, as well as some interpretations of the findings obtained in the different studies. This analysis emphasizes, if needed, how SD-EEG still represents a crucial step in epilepsy diagnosis, and how additional, controlled studies might further shape its precise diagnostic/prognostic role

Somatic mutations of thymic epithelial tumors with myasthenia gravis

BackgroundThymic epithelial tumors are rare malignant neoplasms that are frequently associated with paraneoplastic syndromes, especially myasthenia gravis. GTF2I is an oncogene mutated in a subgroup of thymomas that is reputed to drive their growth. However, for GTF2I wild-type tumors, the relevant mutations remain to be identified.MethodsWe performed a meta-analysis and identified 4,208 mutations in 339 patients. We defined a panel of 63 genes frequently mutated in thymic epithelial tumors, which we used to design a custom assay for next-generation sequencing. We sequenced tumor DNA from 67 thymomas of patients with myasthenia gravis who underwent resection in our institution.ResultsAmong the 67 thymomas, there were 238 mutations, 83 of which were in coding sequences. There were 14 GTF2I mutations in 6 A, 5 AB, 2 B2 thymomas, and one in a thymoma with unspecified histology. No other oncogenes showed recurrent mutations, while sixteen tumor suppressor genes were predicted to be inactivated. Even with a dedicated assay for the identification of specific somatic mutations in thymic epithelial tumors, only GTF2I mutations were found to be significantly recurrent.ConclusionOur evaluation provides insights into the mutational landscape of thymic epithelial tumors, identifies recurrent mutations in different histotypes, and describes the design and implementation of a custom panel for targeted resequencing. These findings contribute to a better understanding of the genetic basis of thymic epithelial tumors and may have implications for future research and treatment strategies

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Cognizione sociale in epilessia: uno studio del dominio Theory of Mind nell'Epilessia Mioclonica Giovanile

L'epilessia mioclonica giovanile (JME) è una delle più frequenti sindromi epilettiche generalizzate genetiche. Nonostante sia considerata una sindrome “benigna”, recenti studi hanno dimostrato la presenza di deficit cognitivi lievi e alterazioni comportamentali, correlabili con disfunzioni a carico dei lobi frontali, nei pazienti con JME. Inoltre, questa sindrome si associa spesso a un outcome sociale insoddisfacente. Nessuno studio ha finora indagato in questi pazienti la Teoria della Mente (ToM), che è l’abilità di definire gli stati mentali propri ed altrui per interpretare i comportamenti e guidare la condotta sociale e sembra coinvolgere i lobi frontali. Scopo di questo studio è quello di valutare la performance ToM dei pazienti con JME, esaminando eventuali correlazioni con alcuni parametri clinici e con le funzioni esecutive. Venti pazienti con JME e venti controlli sani sono stati sottoposti a valutazione cognitiva con Test di Attribuzione delle Emozioni (EAT), Strange Stories Task (SST), Faux Pas Task (FPT), Reading the Mind in the Eyes Task e Test delle Situazioni Sociali, oltre che con test neuropsicologici per la valutazione di funzioni esecutive, memoria verbale e visuo-spaziale, abilità visuo-spaziali e fluenze verbali. I due gruppi sono risultati omogenei per età, scolarità e QI. La differenza tra le performance di pazienti e controlli è risultata statisticamente significativa per il riconoscimento della rabbia in EAT, SST, FPT e in alcuni test per le funzioni esecutive, la memoria verbale e visuo-spaziale e la fluenza verbale. Il deficit della ToM evidenziato in questi pazienti potrebbe essere correlato a una disfunzione dei lobi frontali, in accordo con i recenti dati di neuroimaging nella JME. Potrebbe, inoltre, spiegare almeno in parte l’outcome sociale spesso insoddisfacente di questi soggetti

Social cognition in idiopathic generalized epilepsies and potential neuroanatomical correlates

Social cognition allows us to elaborate mental representations of social relationships and use them appropriately in a social environment. One of its main attributes is the so-called Theory of Mind (ToM), which consists of the ability to attribute beliefs, intentions, emotions, and feelings to self and others. Investigating social cognition may help understand the poor social outcome often experienced by persons with Idiopathic Generalized Epilepsies (IGE), who otherwise present with normal intelligence. In recent years, several studies have addressed social cognition in subjects with focal epilepsies, while literature on social cognition in IGE is scarce, and findings are often conflicting. Some studies on samples of patients with mixed IGE showed difficulties in emotion attribution tasks, which were not replicated in a homogeneous population of patients with Juvenile Myoclonic Epilepsy alone. Impairment of higher order social skills, such as those assessed by Strange Stories Test and Faux Pas Tasks, were consistently found by different studies on mixed IGE, suggesting that this may be a more distinctive IGE-associated trait, irrespective of the specific syndrome subtype. Though an interplay between social cognition and executive functions (EF) was suggested by several authors, and their simultaneous impairment was shown in several epilepsy syndromes including IGE, no formal correlations among the two domains were identified in most studies. People with IGE exhibit subtle brain structural alterations in areas potentially involved in sociocognitive functional networks, including mesial prefrontal and temporoparietal cortices, which may relate to impairment in social cognition. Heterogeneity in patient samples, mostly consisting of groups with mixed IGE, and lack of analyses in specific IGE subsyndromes, represent evident limitations of the current literature. Larger studies, focusing on specific subsyndromes and implementing standardized test batteries, will improve our understanding of sociocognitive processing in IGE. Concomitant high-resolution structural and functional neuroimaging may aid the identification of its neural correlates. This article is part of the Special Issue “Epilepsy and social cognition across the lifespan”

Reversible MRI abnormalities in mesial temporal lobe epilepsy: a case report

The question regarding  the existence of abnormalities in the neuroimaging exams immediately after status epilecticus or epileptic seizures, but showing complete reversibility after a proper antiepileptic therapy, has long been debated. The first reports attempting to demonstrate their existence date back to the 1980s, and relied upon computed tomography as the imaging method of choice. After the introduction of MRI, a more appropriate characterization of these abnormalities was obtained along with the description of their most frequent features: (a) T2 signal hyperintensity in the white matter and, occasionally, (b) reduced apparent diffusion coefficient (ADC) and increased signal in DWI sequences. The MRI abnormalities induced by epileptic activity pose a broad differential diagnosis including infections, inflammatory autoimmune encephalopathies, neoplasms. It remains a diagnosis of exclusion and requires proper diagnostic iter in order to reduce the risk of misdiagnosis and unnecessary intervention. In this case report, a thorough presentation will be outlined about MRI alterations in the left mesial temporal lobe, which resulted completely reversible after a proper antiepileptic therapy