Levetiracetam in patients with generalised epilepsy and myoclonic seizures: An open label study

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Tauroursodeoxycholic acid in patients with amyotrophic lateral sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative rare disease that affects motor neurons in the brain, brainstem, and spinal cord, resulting in progressive weakness and atrophy of voluntary skeletal muscles. Although much has been achieved in understanding the disease pathogenesis, treatment options are limited, and in Europe, riluzole is the only approved drug. Recently, some other drugs showed minor effects. Methods: The TUDCA-ALS trial is a phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The study aims to enroll 320 patients in 25 centers across seven countries in Europe. Enrolled patients are randomized to one of two treatment arms: TUDCA or identical placebo by oral route. The study measures disease progression during the treatment period and compares it to natural progression during a no-treatment run-in phase. Clinical data and specific biomarkers are measured during the trial. The study is coordinated by a consortium composed of leading European ALS centers. Conclusion: This trial is aimed to determine whether TUDCA has a disease-modifying activity in ALS. Demonstration of TUDCA efficacy, combined with the validation of new biomarkers, could advance ALS patient care. Clinical trial registration: ClinicalTrials.gov, identifier: NCT03800524

Monotherapy for partial epilepsy: focus on levetiracetam

Antonio Gambardella1,2, Angelo Labate1,2, Eleonora Colosimo1, Roberta Ambrosio1, Aldo Quattrone1,21Institute of Neurology, University Magna Græcia, Catanzaro, Italy; 2Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, ItalyAbstract: Levetiracetam (LEV), the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is a recently licensed antiepileptic drug (AED) for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Five randomized, double-blind, placebo-controlled trials enrolling adult or pediatric patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (≥50% reduction in seizure frequency) of 28%–45%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for 6 months of the study and 8% seizure-free for 1 year. More recent studies illustrated successful conversion to monotherapy in patients with refractory epilepsy, and its effectiveness as a single agent in partial epilepsy. LEV has also efficacy in generalized epilepsies. Adverse effects of LEV, including somnolence, lethargy, and dizziness, are generally mild and their occurrence rate seems to be not significantly different from that observed in placebo groups. LEV also has no clinically significant pharmacokinetic interactions with other AEDs, or with commonly prescribed medications. The combination of effective antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive therapy for partial seizures.Keywords: levetiracetam, partial epilepsy, antiepileptic drug

Electroclinical Features of a Family with Simple Febrile Seizures and Temporal Lobe Epilepsy Associated with SCN1A Loss-of-Function Mutation

Purpose: To report in detail the electroclinical features of a large family in which we recently identified a missense mutation (M145T) of a well-conserved amino acid in the first transmembrane segment of domain I of the human SCN1A. We showed that the mutation is associated with a loss of SCN1A function. Methods: The family originates from southern Italy and contains 35 members spread over four generations. Of the 14 affected individuals, the 13 still living members (7 males, mean age 36.6 +/- 20.4) underwent a complete electroclinical evaluation. Results: All 13 affected family members had febrile seizures (FS) up to the age of 6 years. Age at onset of FS ranged from 5 to 45 months with a mean age of 12.8 +/- 12.9 months. One of the 13 was affected by post-traumatic epilepsy. Three of the 13 later developed temporal lobe epilepsy (TLE) with both simple focal seizures, and also very rare focal complex or nocturnal secondary generalized tonic-clonic seizures. In two of the three patients who later developed TLE, the MRI studies revealed mesial temporal sclerosis. Conclusions: Our findings illustrate that SCN1A mutations can cause simple FS associated with TLE, which differ from the characteristic clinical spectrum of GEFS+. It is open to conjecture if this unusual phenotype might at least in part be related to the fact that M145T is the first missense mutation found in DIS1 of SCN1A

Transradial versus Transfemoral Access for Hepatic Chemoembolization: Intrapatient Prospective Single-Center Study

Purpose To compare transfemoral approach (TFA) and transradial approach (TRA) in patients undergoing hepatic chemoembolization in terms of safety, feasibility, and procedural variables, including fluoroscopy time, radiation dose (reference air kerma [RAK]), and patient preference. Materials and Methods A single-center prospective intrapatient comparative study was conducted with 42 consecutive patients with hepatic malignancies who received 2 consecutive treatment sessions of unilobar hepatic chemoembolization within a 4-week interval over a 6-month period with both TRA and TFA. All procedures were performed by 1 interventional radiologist who assessed the eligibility of patients for inclusion in the study. The primary endpoint was intraprocedural conversion rate. Secondary endpoints were access site complications, angiographic and procedural variables, and evaluation of patient discomfort and preferences. Results A 100% technical success rate and a crossover rate of 0% were recorded. There were no major vascular complications and similar rates of minor complications (4.8% for TRA, 7.1% for TFA; P =.095), which were self-limited and without any clinical sequelae. TRA treatments required a significantly longer preparation time for the procedure (P =.008) with no significant differences for other procedural variables. Greater discomfort at the access route and patient inability to perform basic activities after the procedure were recorded for TFA (P <.001). TRA was preferred by 35 patients (35/42) for potential future transarterial procedures. Conclusions TRA is safe and feasible for transarterial hepatic chemoembolization, with high technical success, low overall complications, and improved patient comfort