Barbara Mostacci

Purpose of ReviewMenopause is a neurobiological transition with important implications for neurologic care. This review summarizes the physiology and hormonal changes of spontaneous menopause and i...

Objective: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature mortality in people with epilepsy, particularly in those with tonic–clonic seizures (TCSs), developmental and epileptic encephalopathies (DEEs), and drug‐resistant epilepsy. Although awareness of SUDEP has increased, major uncertainties remain regarding individualized risk stratification, mechanistic interpretation, and implementation of preventive strategies in routine care. This Italian expert consensus statement was developed to formalize a shared multidisciplinary position on SUDEP risk profiles, pathophysiological mechanisms, and preventive and therapeutic strategies. Methods: The consensus was supported by a focused narrative appraisal of current evidence, rather than a systematic review, and developed through a structured multidisciplinary process based on a nominal group technique. The panel comprised 11 Italian experts: nine epileptologists from the Italian League Against Epilepsy (LICE) and its SUDEP Working Group, one cardiologist with expertise in epilepsy‐related cardiac complications and SUDEP, and one biomedical engineer with expertise in seizure‐detection devices and wearable technologies. Statements were generated across three macro‐areas, discussed in working groups and plenary sessions, prioritized through an initial in‐person vote, refined after discussion, and submitted to a second online round. Consensus was predefined as at least 75% agreement on a 5‐point Likert scale. Results: A final set of 33 statements was generated, of which 26 reached consensus; two of these (serotonergic modulation as a preventive strategy and fenfluramine's mechanisms beyond seizure control) reached the threshold only narrowly and are discussed as hypothesis‐generating rather than as established clinical guidance. The resulting framework supports an extension of seizure‐centered prevention toward an integrated, individualized, and mechanism‐informed approach, in which reduction of convulsive seizure burden remains central while post‐ictal respiratory, autonomic, cardiac, arousal, genetic, and treatment‐related vulnerabilities are considered in selected high‐risk patients. Significance: This consensus provides the first formalized Italian multidisciplinary position on SUDEP, offering an evidence‐informed and mechanism‐aware framework intended to support more consistent risk communication, individualized risk stratification, and preventive care in clinical practice. Plain Language Summary: Sudden unexpected death in epilepsy (SUDEP) is uncommon but is more likely in people with frequent tonic–clonic seizures and some severe epilepsy syndromes. An Italian multidisciplinary expert panel developed consensus statements on SUDEP risk, possible mechanisms, monitoring, and prevention. Reducing convulsive seizures and supporting treatment adherence remain the main preventive priorities; SUDEP information should be offered broadly, while counseling and additional measures should be tailored to individual risk. These statements reflect expert agreement and available evidence and are not formal clinical practice guidelines.

Purpose of the ReviewPerimenopause and menopause are reproductive stages marked by fluctuating and subsequent permanent loss of ovarian estrogen and progesterone production. There are important con...

Objective: Capillary microsampling offers a minimally invasive alternative to venipuncture for therapeutic drug monitoring (TDM) of anti‐seizure medications (ASMs). We evaluated the feasibility and reliability of volumetric absorptive microsampling (VAMS) and quantitative dried blood spot (qDBS) devices for ambulatory self‐collection and at‐home use in persons with epilepsy (PwE). Methods: PwE attending the Epilepsy Centre of the IRCCS‐Istituto delle Scienze Neurologiche di Bologna (Italy) were enrolled between October 2023 and October 2024. Participants performed supervised self‐collection using VAMS and qDBS in ambulatory setting and at‐home self‐collection with VAMS devices. Sample quality, delivery success, and patient‐reported outcomes (ease, pain, and clarity of instructions) were recorded. Carbamazepine, lacosamide, lamotrigine, and levetiracetam were quantified using a validated ultra‐high performance liquid chromatography‐tandem mass spectrometry (UHPLC–MS/MS) method. Reliability was assessed by comparing at‐home VAMS with ambulatory VAMS and cross‐validating qDBS with VAMS and venous plasma samples using Bland–Altman analysis and linear regression. Results: A total of 105 PwE (66% female, mean age 41 years) performed at‐home and ambulatory self‐collection using VAMS and qDBS devices. Most at‐home VAMS samples (88%) were received by the laboratory within 7 days, and 86.8% met high‐quality criteria. For lacosamide, lamotrigine, and levetiracetam, we found strong correlations between at‐home and ambulatory VAMS (Pearson's r ranging from .88 to .98) and low mean bias (60 years impacted sampling quality, particularly for qDBS ( p = .04). Significance: VAMS‐based self‐collection is feasible and reliable for at‐home TDM, provided that high‐quality sampling is ensured. qDBS represents a reliable alternative for ambulatory monitoring. Future work should focus on optimizing sampling procedures for older adults and improving logistics for home‐based microsampling.

In a clinical setting, exome sequencing (ES) with copy number variant (CNV) analysis is currently the most effective approach for developmental and epileptic encephalopathies (DEE). However, trio‐based ES is often not feasible in adults, its costs remain prohibitive in certain health care settings, and computational tools for CNV calling still lack sufficient accuracy. Chromosomal microarray (CMA) is indicated as a first‐tier test for CNV detection in patients with DEE, dysmorphisms, and comorbidities. We investigate the role of CNVs in the etiology of DEE in an adult cohort, to define the most appropriate diagnostic approach in this population. A total of 219 patients (male/female: 104/115) with undiagnosed DEE underwent array‐based comparative genomic hybridization/single nucleotide polymorphism arrays as adults. Causative CNVs were identified in 18 patients (8.2%); 14 were deletions (mean size ≈ 2.96 Mb), and four were duplications/triplications (mean size ≈ 3.63 Mb). Thirteen were responsible for known deletion/microduplication syndromes, and four were deletions involving haploinsufficient genes associated with epilepsy/neurodevelopmental disorders. For one deletion, population evidence, reports with overlapping deletions, and clinical databases support a likely pathogenic role. The mean age at CMA diagnosis was 32.4 ± 13 years. An additional 46 patients (21%) then received a molecular diagnosis through alternative approaches. Despite a diagnostic delay of 24.2 ± 14.5 years, CMA enabled a genetic diagnosis in 8.2% of our adult DEE patients, especially in those with dysmorphisms. The diagnostic yield rises to 10.4% when excluding patients diagnosed using other methods. A total of 66.7% of solved cases had direct implications from the diagnosis, supporting the clinical utility of CNV analysis inclusion in the diagnostic workflow for adult patients with DEE.

Epileptologists and psychiatrists have long observed a correlation between epilepsy and personality disorders (PDs) in their clinical practice. We conducted a comprehensive PubMed search looking for evidence on PDs in people with epilepsy (PwE). Out of over 600 results obtained without applying any time restriction, we selected only relevant studies (both analytical and descriptive) limited to English, Italian, French and Spanish languages, with a specific focus on PDs, rather than traits or symptoms, thus narrowing our search down to 23 eligible studies. PDs have been investigated in focal epilepsy (predominantly temporal lobe epilepsy - TLE), juvenile myoclonic epilepsy (JME) and psychogenic non-epileptic seizures (PNES), with heterogeneous methodology. Prevalence rates of PDs in focal epilepsy ranged from 18 to 42% in surgical candidates or post-surgical individuals, with Cluster C personality disorders or related traits and symptoms being most common. In JME, prevalence rates ranged from 8 to 23%, with no strong correlation with any specific PDs subtype. In PNES, prevalence rates ranged from 30 to 60%, with a notable association with Cluster B personality disorders, particularly borderline personality disorder. The presence of a PD in PwE, irrespective of subtype, complicates treatment management. However, substantial gaps of knowledge exist concerning the neurobiological substrate, effects of antiseizure medications and epilepsy surgery on concomitant PDs, all of which are indeed potential paths for future research.

Epilepsy with auditory features (EAF) is a focal epilepsy belonging to the focal epileptic syndromes with onset at variable age according to the new ILAE Classification. It is characterized by seizures with auditory aura or receptive aphasia suggesting a lateral temporal lobe involvement of the epileptic discharge. Etiological factors underlying EAF are largely unknown. In the familial cases with an autosomal dominant pattern of inheritance several genes have been involved, among which the first discovered, LGI1, was thought to be predominant. However, increasing evidence now points to a multifactorial etiology, as familial and sporadic EAF share a virtually identical electro-clinical characterization and only a few have a documented genetic etiology. Patients with EAF usually have an unremarkable neurological examination and a good response to antiseizure medications. However, it must be underscored that total remission might be lower than expected and that treatment withdrawal might lead to relapses. Thus, a proper understanding of this condition is in order for better patient treatment and counseling. Further studies are still required to further characterize the many facets of EAF.