A retrospective multicentric study on the effectiveness of intravenous brivaracetam in seizure clusters: Data from the Italian experience.

OBJECTIVE: Nearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. METHODS: Retrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. RESULTS: 97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 - 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 - 9.7). No severe treatment emergent adverse events were observed. SIGNIFICANCE: In our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.

Need for a standardized technique of nap EEG recordings: results of a national online survey in Italy.

The aim of this study is to report current clinical practice for sleep induction in Italian epilepsy centers. We administered an online-structured survey between March and November 2017 and collected data from pediatric and adult neurophysiologists belonging to 73 epilepsy centers. The preferred time for EEG recording is variable, depending on daily schedule of each laboratory. To facilitate spontaneous sleep during nap EEGs, almost all centers require sleep deprivation before the examination, with partial loss preferred to total deprivation in most centers (58/73 vs 12/73, p < 0.001). Other non-pharmacological procedures include breast/bottle feeding or listening to music (encouraged in most centers). Pharmacological sleep induction is performed in 40% of laboratories, more commonly in children than in adults (27/60 vs 7/42, p = 0.003). Melatonin is the most frequently prescribed drug to facilitate spontaneous sleep (one third of participating centers). Our study highlights the great heterogeneity among Italian epilepsy centers in current clinical practice for sleep EEG recordings. Expert consensus for sleep induction procedure is warranted.

An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample.

Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy and is usually associated with hippocampal sclerosis (Hs). The pathogenesis of MTLE involves many biological pathways, some of which seem to be regulated by microRNAs (miRNAs). Increasing evidence shows that single nucleotide polymorphisms (SNPs) or mutations in miRNAs sequence may affect the processing and function of miRNAs and participate in the occurrence of diseases. In this study, the effect of the SNP of one neuronal miRNA, miR-124, on susceptibility to MTLE was investigated using a case control study. To understand the role, a common C/G polymorphism designated rs531564 in the molecular mechanisms of MTLE, we sought to determine whether this genetic variant could influence susceptibility to disease in a cohort of 307 MTLE patients and 306 healthy controls, using TaqMan allelic discrimination assay, on an Applied Biosystems PCR platform. No statistically significant differences were found in the allele or genotype distributions of the miR-124 rs531564 polymorphism among MTLE patients and MTLE-free control subjects (p > 0.05). Our results demonstrate that this SNP has no major role in genetic susceptibility to MTLE, at least in the population studied here.

Cerebellar involvement in essential tremor with and without resting tremor: A Diffusion Tensor Imaging study.

OBJECTIVE: Essential Tremor with resting tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without resting tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI). METHODS: We studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres. RESULTS: MD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). Interestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM. CONCLUSION: Our results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology.

Individual differences in depression are associated with abnormal function of the limbic system in multiple sclerosis patients.

BACKGROUND: Depression is common in patients with multiple sclerosis (MS), although the brain mechanisms of this psychiatric condition in MS are poorly understood. Specifically, it remains to be determined whether depression in MS is related to altered activity and functional connectivity patterns within limbic circuits. METHODS: Seventy-seven MS patients with variable levels of depression (as assessed via the Beck Depression Inventory) underwent functional magnetic resonance imaging while performing an emotional processing task. To conduct the functional connectivity analyses, the bilateral amygdala and hippocampus, two areas critically involved in the pathophysiology of depression, were chosen as 'seed' regions. Multiple regression models were used to assess how depression in MS patients was correlated with the activity and functional connectivity patterns within the limbic system. RESULTS: Depression scores in MS patients were negatively correlated: (1) with the activity in the subgenual cingulate cortex; (2) with the functional connectivity between the hippocampus and orbitofrontal cortex as well as the dorsolateral prefrontal cortex, and (3) with the functional connectivity between the amygdala and dorsolateral prefrontal cortex. CONCLUSIONS: Our study showed that individual differences in depression in MS patients were significantly associated with altered regional activity and functional connectivity patterns within the limbic system.