Quantitative EEG analysis of brivaracetam in drug-resistant epilepsy: A pharmaco-EEG study.

OBJECTIVE: Brivaracetam (BRV) is a recent antiseizure medication (ASM) approved as an add-on therapy for people with focal epilepsy. BRV has a good efficacy and safety profile compared to other ASMs. However, its specific effects on resting-state EEG activity and connectivity are unknown. The aim of this study is to evaluate quantitative EEG changes induced by BRV therapy in a population of adult people with drug-resistant epilepsy (PwE) compared to healthy controls (HC). METHODS: We performed a longitudinal, retrospective, pharmaco-EEG study on a population of 23 PwE and a group of 25 HC. Clinical outcome was dichotomized into drug-responders (i.e., >50% reduction in seizures' frequency; RES) and non-responders (N-RES) after two years of BRV. EEG parameters were compared between PwE and HC at baseline (pre-BRV) and after three months of BRV therapy (post-BRV). We investigated BRV-related variations in EEG connectivity using the phase locking value (PLV). RESULTS: BRV therapy did not induce modifications in power spectrum density across different frequency bands. PwE presented lower PLV connectivity values compared to HC in all frequency bands. RES exhibited lower theta PLV connectivity compared to HC before initiating BRV and experienced an increase after BRV, eliminating the significant difference from HC. CONCLUSIONS: This study shows that BRV does not alter the EEG power spectrum in PwE, supporting its favourable neuropsychiatric side-effect profile, and induces the disappearance of EEG connectivity differences between PwE and HC. SIGNIFICANCE: The integration of EEG quantitative analysis in epilepsy can provide insights into the efficacy, mechanism of action, and side effects of ASMs.

Overnight switch from carbamazepine to eslicarbazepine in a real-life clinical scenario: a retrospective study.

BACKGROUND: Carbamazepine (CBZ) is a first-choice anti-seizure medication (ASM) whose efficacy is often invalidated by adverse effects (AEs). Eslicarbazepine (ESL) is a structural derivative of CBZ with better pharmacokinetic/tolerability profiles. We describe our experience of the overnight CBZ to ESL switch in people with epilepsy (PwE) to improve seizure control, AEs, and ASMs adherence. METHODS: We retrospectively included 19 PwE (12 females, 53 ± 21 years old) who underwent CBZ to ESL overnight switch due to single/multiple issues: poor efficacy (pEff, N = 8, 42%), tolerability (pToll, N = 11, 58%), adherence (pAdh, N = 2, 10%). 9/19 (47%) had psychiatric comorbidities. Clinical variables, seizure frequency, and AEs were recorded at switch time (T0) after 3.5 ± 3 (T1) and 6.5 ± 1.5 months (T2). RESULTS: At T1, in pEff group, 1/8 (13%) was seizure free, 2/8 (25%) were responders (> 50% seizure reduction), 2/8 (25%) had no seizure changes, 3/8 (37%) had seizure worsening; the latter were those with the most severe epilepsy and encephalopathy. In pToll group, all PwE experienced AEs disappearance/amelioration. In pAdh group, all PwE reported adherence amelioration. Four dropouts. At T2, no changes were recorded within groups, while in the whole sample, 6/15 (40%) were responders, and 4/15 (27%) were seizure-free. No one complained of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation psychiatric worsening, while 6/19 (32%) experienced mood/behavior benefits. CONCLUSIONS: CBZ to ESL overnight switch offers an opportunity to improve efficacy, tolerability, adherence, and psychiatric symptoms.

Autoimmune encephalitis during pregnancy: A diagnostic and therapeutic challenge-A systematic review with individual patients' analysis and clinical recommendations.

Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the diagnostic and therapeutic approach to AE during pregnancy, highlighting the associated maternal and fetal clinical outcomes. A systematic search of the literature was performed. The following databases were used: PubMed, Google Scholar, EMBASE, and CrossRef. The revision was registered on the PROSPERO platform (CRD42022336357). Forty-nine patients were included. AE onset was mainly observed during the first and the second trimester of pregnancy with psychiatric manifestations and seizures as main onset symptoms. CSF analysis showed AE-specific autoantibody positivity in 33 patients (anti-NMDA receptor as the most frequent). EEG generally showed normal findings. MRI revealed pathological findings in less than half of patients. Tumor screening was positive in 14 cases. First-line immunotherapy (single or combined) was generally employed while second line was administered in a minority of patients. Levetiracetam was the most used antiseizure medication. Cesarean section was performed in 18 women. Most of the women had an excellent early outcome after delivery but 22 showed persistent neurological deficits in long-term follow-up. Fetal outcome was positive in 33 cases, whereas 12 cases of fetal death were reported. A logistic regression showed that no variable significantly influenced the odds of good/bad maternal and fetal clinical outcome. Diagnosis and treatment of AE during pregnancy is challenging. The rate of miscarriage in women with AE seems to be higher than the general population. In addition, mothers may show long-term neurological deficits.

EPIAMNE: A New Scoring System for Differentiating Transient EPIleptic AMNEsia from Transient Global Amnesia.

Transient epileptic amnesia (TEA) is a rare cause of acute amnestic syndromes (AAS), often misdiagnosed as transient global amnesia (TGA). We proposed a scoring system­the EPIlepsy AMNEsia (EPIAMNE) score­using quantitative EEG (qEEG) analysis to obtain a tool for differentiating TEA from TGA. We retrospectively reviewed clinical information and standard EEGs (stEEG) of 19 patients with TEA and 21 with TGA. We computed and compared Power Spectral Density, demonstrating an increased relative theta power in TGA. We subsequently incorporated qEEG features in EPIAMNE score, together with clinical and stEEG features. ROC curve models and pairwise ROC curve comparison were used to evaluate and compare the diagnostic accuracy for TEA detection of EPIAMNE score, presence of symptoms atypical for TGA (pSymAT) and identification of anomalies (interictal epileptiform or temporal focal spiky transients) at stEEG (PosEEG). Area Under the Curve (AUC) of EPIAMNE score revealed to be higher than PosEEG and pSymAT (AUCEPIAMNE = 0.95, AUCpSymAT = 0.85, AUCPosEEG = 0.67) and this superiority proved to be statistically significant (p-valueEPIAMNE-PosEEG and p-valueEPIAMNE-pSymAT < 0.05). In conclusion, EPIAMNE score classified TEA with higher accuracy than PosEEG and pSymAT. This approach could become a promising tool for the differential diagnosis of AAS, especially for early TEA detection.

Levetiracetam Modulates EEG Microstates in Temporal Lobe Epilepsy.

To determine the effects of Levetiracetam (LEV) therapy using EEG microstates analysis in a population of newly diagnosed Temporal Lobe Epilepsy (TLE) patients. We hypothesized that the impact of LEV therapy on the electrical activity of the brain can be globally explored using EEG microstates. Twenty-seven patients with TLE were examined. We performed resting-state microstate EEG analysis and compared microstate metrics between the EEG performed at baseline (EEGpre) and after 3 months of LEV therapy (EEGpost). The microstates A, B, C and D emerged as the most stable. LEV induced a reduction of microstate B and D mean duration and occurrence per second (p < 0.01). Additionally, LEV treatment increased the directional predominance of microstate A to C and microstate B to D (p = 0.01). LEV treatment induces a modulation of resting-state EEG microstates in newly diagnosed TLE patients. Microstates analysis has the potential to identify a neurophysiological indicator of LEV therapeutic activity. This study of EEG microstates in people with epilepsy opens an interesting path to identify potential LEV activity biomarkers that may involve increased neuronal inhibition of the epileptic network.

Understanding and managing the impact of the COVID-19 pandemic and lockdown on patients with epilepsy.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic represented a relevant issue for people with epilepsy (PwE). Medical care and social restrictions exposed PwE to a high risk of seizure worsening. Medical institutions answered to the pandemic assuring only emergency care and implementing a remote assistance that highlighted the technological obsolescence of the medical care paradigms for PwE. AREA COVERED: We reviewed the literature on the COVID-19-related factors influencing the epilepsy course, from the evidence of seizure risk in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected PwE to anti-Sars-Cov-2 drugs interactions with antiseizure medications and the perceived changes of seizures in PwE. EXPERT OPINION: COVID-19 pandemic was a problematic experience for PwE. We must make treasure of the lessons learned during this period of social restrictions and employ the recent technological advances to improve PwE assistance, in particular telemedicine and electronic media for patients' education.

Machine learning for predicting levetiracetam treatment response in temporal lobe epilepsy.

OBJECTIVE: To determine the predictive power for seizure-freedom of 19-channels EEG, measured both before and after three months the initiation of the use of Levetiracetam (LEV), in a cohort of people after a new diagnosis of temporal-lobe epilepsy (TLE) using a machine-learning approach. METHODS: Twenty-three individuals with TLE were examined. We dichotomized clinical outcome into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG effective power in different frequency bands was compared using baseline EEG (T0) and the EEG after three months of LEV therapy (T1) between SF and NSF patients. Partial Least Square (PLS) analysis was used to test and validate the prediction of the model for clinical outcome. RESULTS: A total of 152 features were extracted from the EEG recordings. When considering only the features calculated at T1, a predictive power for seizure-freedom (AUC = 0.750) was obtained. When employing both T0 and T1 features, an AUC = 0.800 was obtained. CONCLUSIONS: This study provides a proof-of-concept pipeline for predicting the clinical response to anti-seizure medications in people with epilepsy. SIGNIFICANCE: Future studies may benefit from the pipeline proposed in this study in order to develop a model that can match each patient to the most effective anti-seizure medication.

Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications.

Chronic pain is one of the leading causes of disability and disease burden worldwide, accounting for a prevalence between 6.9% and 10% in the general population. Pharmacotherapy alone results ineffective in about 70-60% of patients in terms of a satisfactory degree of pain relief. Focused ultrasound is a promising tool for chronic pain management, being approved for thalamotomy in chronic neuropathic pain and for bone metastases-related pain treatment. FUS is a noninvasive technique for neuromodulation and for tissue ablation that can be applied to several tissues. Transcranial FUS (tFUS) can lead to opposite biological effects, depending on stimulation parameters: from reversible neural activity facilitation or suppression (low-intensity, low-frequency ultrasound, LILFUS) to irreversible tissue ablation (high-intensity focused ultrasounds, HIFU). HIFU is approved for thalamotomy in neuropathic pain at the central nervous system level and for the treatment of facet joint osteoarthritis at the peripheral level. Potential applications include HIFU at the spinal cord level for selected cases of refractory chronic neuropathic pain, knee osteoarthritis, sacroiliac joint disease, intervertebral disc nucleolysis, phantom limb, and ablation of peripheral nerves. FUS at nonablative dosage, LILFUS, has potential reversible and tissue-selective effects. FUS applications at nonablative doses currently are at a research stage. The main potential applications include targeted drug and gene delivery through the Blood-Brain Barrier, assessment of pain thresholds and study of pain, and reversible peripheral nerve conduction block. The aim of the present review is to describe the approved and potential applications of the focused ultrasound technology in the field of chronic pain management.