Giorgia Giussani

Background The neural network underlying social cognition (SC) may be vulnerable to different types of lesions, but also amenable to recovery through interventions that stimulate brain plasticity. This review assessed current non-pharmacological interventions (NPIs) and their effects on SC in neurological patients. Methods A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Randomized controlled studies, cohort studies, cross-sectional studies, case series, case reports, and literature reviews were included if they reported a precise description of the NPI in subjects older than 6 years, with brain or cerebellar lesion. Results Among 5.077 screened articles, 17 fulfilled the eligibility criteria. These articles provided 19 face-to-face, online or hybrid methods, involving 344 patients with multiple sclerosis, stroke, Parkinson disease, cerebellar ataxia, traumatic brain injuries or mixed acquired brain injuries. The methods were applied in observational and randomized study designs using group or individual settings, involving SC, general cognition, and relational aspects. These NPIs, classifiable into training, rehabilitation or combined interventions, improved SC in patients with various diagnosis and age. Conclusions Results show that NPIs for SC in neurological patients is being addressed with insightful methods and study designs with improvement possibility in children and adults suffering different pathologies. This is not sufficient for thorough consensus but can trigger a range of broader high-quality and interdisciplinary clinical and research applications.

Objectives For the past five years, COVID-19 has not only been a priority for health planning but also a hotspot for clinical research. Yet, the weight of the worldwide COVID-19 pandemic arises from the critical phase consequences due to the onset of acute disease, associated containment measures, and documented ongoing disabling symptoms. Investigating the global longitudinal effects on children and adolescents will inform future health directives tailored to this population’s needs. This review aimed to report the spectrum of persistent neurological sequelae in children and adolescents following SARS-CoV-2 infection. Methods Hence, we conducted a scoping review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We included the peer-reviewed articles from PubMed, Google Scholar, Web of Science, Cochrane Library, and WHO COVID database to identify relevant literature on long-COVID-19 neurological signs/symptoms among children and adolescents. The search covered the period between September 2020 and September 2024. Results The results of our analysis of 33 studies found long-COVID-19-related neurological signs/symptoms were predominantly: pain and sensory problems (N = 74,612/91,543; 81.5%), followed by sleep disturbances (N = 14,630/91,543; 15.9%), and cognitive difficulties (N = 2274/91,543; 2.4%). The global prevalence of long COVID-19 neurological signs/symptoms was estimated between 0.4% (20/5032; 95% CI = 2.1–3%) and 34% (27/79) based on data obtained through online questionnaire; while it varied between 1.8% (4/215) and 83.14% (74/89; 95%CI = − 0.12; 0.30) based on patient assessment. Long-COVID-19-related neurological signs/symptoms were more common in the 11–16 age group. Children with immunocompetent profiles were at higher risk of developing long-COVID-19-related neurological signs/symptoms. Conclusion Our results demonstrate a considerable burden of COVID-19-related persistent neurological signs/symptoms in children and adolescents, which should be taken into consideration in healthcare decision-making.

Objectives: The gold standard for distinguishing epileptic seizures (ES) from non‐epileptic events is video‐EEG monitoring. In some cases, video alone might suffice, leading to increased utilization of home videos, to support the diagnosis. This study aimed to assess the feasibility of such practice and its accuracy compared to video‐EEG, to identify key signs and symptoms of functional seizure (FS) and to establish if self‐reported questionnaires would improve diagnostic accuracy.Methods: All consecutive patients ≥14 years presenting to six Italian epilepsy centers with either recurrent paroxysmal events of uncertain nature or with confirmed ES were enrolled. Subjects had to record home videos of the events and to respond to ad‐hoc questionnaires. De‐identified data were randomly assigned to pairs of evaluators blinded to the gold standard diagnosis, one epileptologist and one neurologist, to predict the correct diagnosis in two steps: Step 1 (home video alone) and Step 2 (patient's and witness' questionnaires).Results: Ninety‐four videos (48 ES; 45 FS; 1 other), obtained from 36 patients, were independently evaluated by the 16 reviewers, providing a total of 188 assessments. Diagnostic accuracy for the whole group was 55.3% among epileptologists and 48.9% among neurologists (p = 0.6892) but was significantly higher in the FS subgroup (71.1%) compared to ES (41.7%) (p = 0.0043).Significance: Diagnostic accuracy was moderate, without significant differences between epileptologists and neurologists, while it was higher for FS compared to ES. The addition of questionnaires did not improve accuracy. Eye closure for FS and abrupt ending for ES emerged as the only diagnostic signs. Thus, homemade videos have a role in differentiating these disorders.Plain Language Summary: This study aimed to assess if home videos can distinguish epileptic seizures from functional seizures. Patients over 14 years from six Italian centers recorded videos of their episodes and answered questionnaires. Data were evaluated by epileptologists and neurologists. Results showed moderate diagnostic accuracy, with higher accuracy for functional seizures compared to epileptic seizures. Key diagnostic signs included eye closure for functional seizures and abrupt endings for epileptic seizures. Questionnaires did not improve accuracy. In conclusion, home videos can help differentiate these events.

Objective: The STANDLOW trial investigated whether first‐line antiseizure monotherapy with low doses has a similar efficacy to standard doses, but with fewer adverse events, improved quality of life, and reduced costs for the National Health System.Methods: Multicenter, randomized, parallel‐arm, single‐blind, non‐inferiority trial, comparing low dose versus standard dose of antiseizure medications (carbamazepine, levetiracetam, valproate, zonisamide, oxcarbazepine, topiramate, lamotrigine, gabapentin, lacosamide) in adults with newly diagnosed focal epilepsy.Results: The intention‐to‐treat (ITT) population consisted of 58 randomized patients, 29 in the low dose arm and 29 in the standard dose arm, 27 (46.6%) females and 31 (53.4%) males, with an age between 18 and 87 years (median 54.9, IQR 32–71). The seizure type was focal impaired awareness seizures in 44 (75.9%) and focal aware seizures in 14 (24.1%). Etiology was unknown in 43 (74.1%) and structural in 15 (25.9%). At study entry, EEG was epileptiform in 28 (48.2%) and seizure frequency was low (≤2 seizures/month) in 41 (70.7%). The estimated relapse proportions at 12 months were 47% for the low dose and 48% for the standard dose, with a difference of 1% (95% CI: −30%; 27%). At the end of the study visit (12 months of follow‐up, or immediately after seizure relapse or study withdrawal for other reasons, whichever came first), no differences in the number or severity of adverse events or quality of life measures were observed between the two treatment groups. The total drug‐related costs over the entire study period were lower in the low dose arm (median per participant 253 € versus 475 € in the standard dose arm).Significance: Although the efficacy of low doses versus standard doses appeared similar, non‐inferiority could not be demonstrated due to slow recruitment and premature termination of the trial. Although statistically inconclusive, our findings suggest that a low dose of antiseizure medications may be considered as a first‐line option in adult patients with a new diagnosis of focal epilepsy of unknown etiology and low seizure frequency.Plain Language Summary: This study aimed to see if low doses of anti‐seizure medications (ASMs) could be as effective as standard doses in treating adults with newly diagnosed epilepsy. Subjects were assigned to receive either a low or standard dose of ASMs. 58 adults participated. Both low and standard doses seemed to have a similar effect on controlling seizures. The study was stopped early due to slow enrollment, making it difficult to definitively prove that low doses were non‐inferior to standard doses. Low doses of ASMs might be a reasonable option for adults with newly diagnosed epilepsy with no clear cause and few seizures.

Introduction: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. Methods: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. Results: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. Discussion: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected, witnessed or unwitnessed, non‐traumatic and non‐drowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus in which postmortem examination does not reveal other causes of death. Lower diagnostic levels are assigned when cases met most or all of these criteria, but data suggested more than one possible cause of death. The incidence of SUDEP ranged from 0.09 to 2.4 per 1000 person‐years. Differences can be attributed to the age of the study populations (with peaks in the 20–40‐year age group) and the severity of the disease. Young age, disease severity (in particular, a history of generalized TCS), having symptomatic epilepsy, and the response to antiseizure medications (ASMs) are possible independent predictors of SUDEP. The pathophysiological mechanisms are not fully known due to the limited data available and because SUDEP is not always witnessed and has been electrophysiologically monitored only in a few cases with simultaneous assessment of respiratory, cardiac, and brain activity. The pathophysiological basis of SUDEP may vary according to different circumstances that make that particular seizure, in that specific moment and in that patient, a fatal event. The main hypothesized mechanisms, which could contribute to a cascade of events, are cardiac dysfunction (included potential effects of ASMs, genetically determined channelopathies, acquired heart diseases), respiratory dysfunction (included postictal arousal deficit for the respiratory mechanism, acquired respiratory diseases), neuromodulator dysfunction, postictal EEG depression and genetic factors.

In an aging world, it is important to know the burden of epilepsy affecting populations of older persons. We performed a selective review of epidemiological studies that we considered to be most informative, trying to include data from all parts of the world. We emphasized primary reports rather than review articles. We reviewed studies reporting the incidence and prevalence of epilepsy that focused on an older population as well as studies that included a wider age range if older persons were tabulated as a subgroup. There is strong evidence that persons older than approximately 60 years incur an increasing risk of both acute symptomatic seizures and epilepsy. In wealthier countries, the incidence of epilepsy increases sharply after age 60 or 65 years. This phenomenon was not always observed among reports from populations with lower socioeconomic status. This discrepancy may reflect differences in etiologies, methods of ascertainment, or distribution of ages; this is an area for more research. We identified other areas for which there are inadequate data. Incidence data are scarcer than prevalence data and are missing for large areas of the world. Prevalence is lower than would be expected from cumulative incidence, possibly because of remissions, excess mortality, or misdiagnosis of acute symptomatic seizures as epilepsy. Segmentation by age, frailty, and comorbidities is desirable, because “epilepsy in the elderly” is otherwise too broad a concept. Data are needed on rates of status epilepticus and drug‐resistant epilepsy using the newer definitions. Many more data are needed from low‐income populations and from developing countries. Greater awareness of the high rates of seizures among older adults should lead to more focused diagnostic efforts for individuals. Accurate data on epilepsy among older adults should drive proper allocation of treatments for individuals and resources for societies.