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

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

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

Epilepsy in elderly patients: focus on treatment

Epilepsy is a disorder widely distributed across all age groups, although its incidence and prevalence favours elderly patients. In this population the development of epilepsy is mainlyrelated to other brain disorders that facilitate the occurrence of late seizures, mostly of focal onset. Apart from the difficulties faced in current practice with the appropriate diagnosis of the epileptic nature of the episodes, old subjects require an individualised drug treatment, tailored on their characteristics, such as comorbidity, polytherapy, age-associated biological impairment and compliance. Among the various antiepileptic drugs available for the treatment of epilepsy, rational selection and combination of drugs should drive both initiation and maintenance of the treatment. Choice of antiepileptic drugs should first focus on avoidance of adverse effects and potential drug interactions. The pharmacological control of seizures is usually favourable at this age, with a good prognosis. However, alternative therapeutic options should be considered as soon as drug-response is unsatisfactory

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

A retrospective multicenter study on clinical and serological parameters in patients with MuSK myasthenia gravis with and without general immunosuppression

Introduction: Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied. Methods: We analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17–79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2–82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20–68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total IgG4 and total IgG in the sera by ELISA, RIA and nephelometry. Results: We observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum IgG4 levels were within the normal range, with IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission. Discussion: We conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum IgG4 concentrations and IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings

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