BACKGROUND: In epilepsy, seizure freedom is widely regarded as the primary therapeutic endpoint. However, equating recovery with seizure cessation alone may overlook relevant psychological, social, and existential dimens...BACKGROUND: In epilepsy, seizure freedom is widely regarded as the primary therapeutic endpoint. However, equating recovery with seizure cessation alone may overlook relevant psychological, social, and existential dimensions. The concept of the “burden of normality” describes the disequilibrium that can arise when individuals are expected to resume ordinary life after prolonged illness. We propose framing seizure freedom as the beginning of a transitional phase—analogous to developmental transitions—characterized by identity renegotiation and adjustment to new roles and expectations. METHODS: This paper stems from a multidisciplinary meeting held in Rome (June 2025) involving neurologists, a neuropsychologist, a medical anthropologist, and a patient representative. Through multidisciplinary discussion, participants explored the implications of seizure freedom across biomedical and psychosocial domains. Key themes were identified through qualitative synthesis and translated into practice-oriented considerations. RESULTS: Seizure freedom was conceptualized not as the end of illness experience but as the onset of a complex recovery phase. Key themes emerged, including: [1] recovery as a multidimensional process extending beyond symptom control; [2] psychosocial challenges, including identity disruption, emotional ambivalence, and relational strain; [3] persistent biological and neuropsychiatric burdens despite seizure control; and [4] gaps in current care models, which rarely address post-remission needs. CONCLUSIONS: Seizure freedom should be reframed as the start of a transitional recovery phase. Holistic care strategies and broader outcome measures are needed to support sustained reintegration and long-term well-being.
BACKGROUND: To investigate the safety and efficacy of transcatheter left atrial appendage occlusion (LAAO) in patients with concomitant atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) and high bleeding ris...BACKGROUND: To investigate the safety and efficacy of transcatheter left atrial appendage occlusion (LAAO) in patients with concomitant atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) and high bleeding risk that precludes long-term oral anticoagulation. METHODS: Consecutive patients with non-valvular AF and a CHA2DS2-VASc score ≥ 2 and concomitant CAA who underwent transcatheter LAAO between 2014 and 2022 at Parma University Hospital were included in the analysis. The primary endpoint was a composite of any ischemic/hemorrhagic events. The observed rates of ischemic and bleeding events were compared with those expected from the CHA2DS2-VASc score and HAS-BLED score. RESULTS: Twenty-four patients with probable CAA (median age 74.0 years; 66.7% males) qualified for inclusion. During follow up (median time 17 months), 2 ischemic strokes and 2 ICHs occurred. The rate of primary endpoint event was 8.34/100 patients-year compared to an expected rate of 13.80/100 patients-year, resulting in a 39.6% risk reduction. The risk reduction for systemic thromboembolism and major bleeding was respectively 55.2% and 7.3%. CONCLUSIONS: Transcatheter LAAO might be an effective strategy for thromboembolic prevention in patients with AF and concomitant CAA. Because of the potential shortcomings, this study can only be considered as hypothesis-generating.
BACKGROUND: Oculogyric crisis and other acute dystonic reactions have been reported as a rare adverse effect of aripiprazole, a third-generation antidopaminergic medication used for the treatment of multiple neuropsychia...BACKGROUND: Oculogyric crisis and other acute dystonic reactions have been reported as a rare adverse effect of aripiprazole, a third-generation antidopaminergic medication used for the treatment of multiple neuropsychiatric conditions, including psychotic disorders, affective disorders, obsessive-compulsive disorder, and neurodevelopmental disorders. CASE DESCRIPTION: We document two cases (two females aged 16 and 22 years) diagnosed with a neurodevelopmental tic disorder (Tourette syndrome), who developed oculogyric crisis while taking medium/high-dose aripiprazole 20-30 mg daily as a first-line anti-tic agent. Their acute dystonic manifestations completely regressed following dose reduction of aripiprazole. DISCUSSION: Aripiprazole-induced oculogyric crisis has previously been reported in a total of 18 cases (9 females, age range 11–28 years). Of these, only two (an 18-year-old male and a 21-year-old female) were taking aripiprazole for their tic disorder. In addition to further documenting treatment-emergent oculogyric crisis in patients with Tourette syndrome taking aripiprazole for the treatment of their tics, our reports raise the possibility of dose-dependent mechanisms underlying the development of oculogyric crisis, at least in selected cases.
BACKGROUND: Cenobamate is increasingly used as adjunctive treatment in adults with drug-resistant focal epilepsy. In clinical practice, the combination with clobazam is common and sedation-related adverse events (SRAEs)...BACKGROUND: Cenobamate is increasingly used as adjunctive treatment in adults with drug-resistant focal epilepsy. In clinical practice, the combination with clobazam is common and sedation-related adverse events (SRAEs) have been reported. METHODS: We conducted a retrospective single-centre analysis of adult patients with drug-resistant epilepsy treated with cenobamate between January and September 2025. Clinical data, concomitant antiseizure medications, and adverse events were collected during routine follow-up. SRAEs occurring within three months of cenobamate initiation were classified as early. Particular attention was paid to patients receiving concomitant clobazam. Pharmacogenetic data were available as part of routine clinical assessment. RESULTS: SRAEs were observed more frequently among patients receiving the cenobamate-clobazam combination and were mostly reported within the first three months of treatment. Among affected patients, clobazam doses ranged between 10 and 30 mg/day. When pharmacogenetic data were considered, a higher proportion of SRAEs was observed among intermediate CYP2C19 metabolizers compared with other phenotypes, although the sample size was limited. CONCLUSIONS: In this real-world cohort, early SRAEs were observed in a subset of patients receiving the cenobamate-clobazam combination, particularly among individuals with reduced CYP2C19 metabolic activity. Further prospective studies are needed to clarify the pharmacokinetic and pharmacogenetic contributions to these adverse events.
Ros-Arlanzón P, Valverde-Mata N, Almarcha-Menargues ML
… +8 more, Patiño Á, Alonso-Cánovas A, Pérez-Torre P, López-Sendón JL, Fanjul S, Kurtis MM, Martínez-Castrillo JC, Pareés I
BACKGROUND: Oral levodopa is currently the most effective treatment for Parkinson’s disease (PD). However, many patients will suffer fluctuations as the disease progresses. CVT-301, an inhaled levodopa powder, has shown...BACKGROUND: Oral levodopa is currently the most effective treatment for Parkinson’s disease (PD). However, many patients will suffer fluctuations as the disease progresses. CVT-301, an inhaled levodopa powder, has shown promise in clinical trials for managing OFF periods without severe side effects, yet real-world data are lacking. OBJECTIVES: To assess clinical effectiveness and tolerance of inhaled levodopa in PD patients. METHODS: observational study based on a retrospective chart review of consecutive PD patients treated with inhaled levodopa from April 2023 to May 2024. RESULTS: twenty-eight patients were included. Twenty (71.4%) reported improvement of OFF symptoms, with benefits appearing within 10 min in most patients. Adverse events were common. Only 2 (7.1%) discontinued treatment due to severe coughing. CONCLUSIONS: Inhaled levodopa offers rapid improvement in PD symptoms with acceptable tolerance. This real-world study underscores its potential benefit for PD-related fluctuations, widening on demand options for patients inadequately controlled by oral medications.
BACKGROUND: Data on cognitive impairment in patients with Long-COVID remain controversial. METHODS: The study analyzed in patients followed for Long-COVID the frequency and risk factors for cognitive impairment (defined...BACKGROUND: Data on cognitive impairment in patients with Long-COVID remain controversial. METHODS: The study analyzed in patients followed for Long-COVID the frequency and risk factors for cognitive impairment (defined by a Montreal Cognitive Assessment [MoCA] score < 24 points), its associations with subjectively reported cognitive and psychological symptoms, and the evolution of cognitive impairment and cognitive symptoms over time. RESULTS: At a mean interval of 259 days from COVID-19, the mean MoCA score recorded among 118 individuals was 25.5, with 32.2% of them showing scores < 24 points. Eighty-five patients (72.0%) presented persisting symptoms, predominantly represented by fatigue (35.6%), dyspnea (28.8%) and cognitive symptoms (24.6%). A MoCA score < 24 was significantly associated with older age, hospitalization during acute disease and female sex. Individuals with persisting cognitive symptoms had significantly lower MoCA scores compared to individuals without such symptoms, with a mean difference of 1.4 points. Anxiety and depression were not associated with lower MoCA scores. In a subsequent evaluation conducted in 66 individuals (55.9%) at an average interval of 959 days from COVID-19, the mean MoCA score decreased by 1.3 points (95%CI 0.5-2, p = 0.001), the frequency of a MoCA score < 24 increased from 25.8% to 36.4% (p = 0.090), and the prevalence of cognitive symptoms increased from 27.3% to 53.0% (p = 0.002). DISCUSSION: Cognitive impairment in Long-COVID appeared common and persisting. Cognitive symptoms, unlike psychological symptoms, were associated with lower cognitive scores and tended to accumulate during follow-up. Advanced age, severity of acute SARS-CoV-2 disease and female sex should be considered as potential risk factors.
OBJECTIVE: To develop an early diagnostic prediction model to differentiate cavernous sinus inflammation (inflammation group) from microvascular ischemic ocular motor cranial nerve (CN) palsy (ischemic group) at early pr...OBJECTIVE: To develop an early diagnostic prediction model to differentiate cavernous sinus inflammation (inflammation group) from microvascular ischemic ocular motor cranial nerve (CN) palsy (ischemic group) at early presentation. METHODS: A total of 66 and 117 patients within 2 weeks of symptom onset were enrolled in the inflammation and ischemic groups. Twenty-two potential predictors were evaluated; predictors that remained significant after Benjamini-Hochberg adjustment (false discovery rate 0.05) were entered into a multivariable logistic regression model. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC), and calibration by the Hosmer -Lemeshow goodness-of-fit test. RESULTS: Significant predictors included vascular risk factor scores (VRFs), ocular motor nerve palsy scale (OMNPS) score, aggregate index of systemic inflammation (AISI), history of diabetes, and cavernous sinus thickness. The AUC was 0.899 (95% confidence interval, 0.838 to 0.939). At the optimal probability cutoff(0.674), sensitivity and specificity were 72.3% and 89.7%, respectively. The Hosmer-Lemeshow test yielded χ2 = 4.262, P = 0.833. CONCLUSIONS: The logistic regression–based model showed good discrimination and calibration for differentiating cavernous sinus inflammation from microvascular ischemic ocular motor CN palsy during early presentation, and may assist early clinical decision-making.
BACKGROUND: The prevalence of Mild Cognitive Impairment (MCI) is increasing worldwide, while the scarce evidence regarding clinical practice requires real-life research and consensus. This study examined real-life practi...BACKGROUND: The prevalence of Mild Cognitive Impairment (MCI) is increasing worldwide, while the scarce evidence regarding clinical practice requires real-life research and consensus. This study examined real-life practices regarding the diagnosis and management of subjects with MCI in Italy. METHODS: Data were collected from a modified Delphi study conducted in April-December 2023. The study involved 12 advisors and 16 specialists working in Italian Memory Clinics. The 50 statements proposed by the 12 advisors were rated on a 1–6 Likert scale in a two-round survey. Consensus was a priori defined when the rates of each statement in each round reached a mean value ≥ 5. The ratings of each statement were collected using an Excel spreadsheet. The data were analysed using Microsoft Excel and expressed as mean, median, and standard deviation (SD). RESULTS: The response rate was 100% for both voting rounds. In the first round, 40 statements reached a consensus, while 8 did in the second. The SD of the eight final statements in the first round of voting ranged from 0.91 to 1.74, and that of the second round from 0.57 to 1.71. CONCLUSIONS: This consensus study emphasized the need to standardize investigations, set cut-off thresholds, and establish quantitative reporting standards. Building on this, the study recommended combining biomarker studies to stratify risks and predict decline. Furthermore, it advised integrating genetic data into risk algorithms and increasing testing and clinical criteria. Additionally, the consensus valued promoting specialized and integrative training, while fostering structured relationships with general practitioners.
BACKGROUND: Delayed encephalopathy due to acute carbon monoxide poisoning (DEACMP) is a severe complication after carbon monoxide (CO) poisoning. However, the sensitivity and specificity of known risk factors for predict...BACKGROUND: Delayed encephalopathy due to acute carbon monoxide poisoning (DEACMP) is a severe complication after carbon monoxide (CO) poisoning. However, the sensitivity and specificity of known risk factors for predicting the development of DEACMP remain suboptimal. This study aimed to explore the role of cognitive reserve (CR)-an active mechanism modulating cognitive function in neurological diseases, on the development of DEACMP. METHODS: Ninety-four patients with first-ever CO poisoning were recruited from Nanchong Central Hospital. Cognitive assessments were conducted at 3 and 12 months post-CO poisoning. Logistic regression and linear mixed-effect regression were used to elucidate the influence of CR on DEACMP occurrence and developmental trajectories of cognition. RESULTS: Our results indicated that CR score, C-reactive protein (CRP) level, hyperbaric oxygen (HBO) sessions and glucocorticoid treatment were identified as independent factors associated with DEACMP development. The area under Receiver-operating characteristic (ROC) curve was 0.910 for CR score, with 86.7% sensitivity and 84.4% specificity for predicting DEACMP. Furthermore, our results revealed that higher CR score was associated with slower deterioration in Mental State Examination (MMSE), Activities of Daily Living (ADL) and clinical dementia rating (CDR) scores in post-CO poisoning patients. CONCLUSIONS: Our study suggests that CR acts as an early predictive factor for DEACMP development, and proactive administration of HBO and glucocorticoid treatments are crucial for preventing DEACMP occurrence. Furthermore, CR predicts a better cognitive trajectory, suggesting that cognitive training may delay cognitive decline in patients after acute CO poisoning.
BACKGROUND: Fatigue is a common and debilitating non-motor symptom in Parkinson's disease (PD), significantly impairing patient quality of life and often observed in clinical management. Its pathophysiology involves comp...BACKGROUND: Fatigue is a common and debilitating non-motor symptom in Parkinson's disease (PD), significantly impairing patient quality of life and often observed in clinical management. Its pathophysiology involves complex interactions among dopaminergic, non-dopaminergic, and neuroinflammatory pathways. Although fatigue is highly prevalent, evidence-based treatment strategies remain limited. METHODS: This review is based on a targeted literature search focusing on recent advances in research on PD-related fatigue. Using a combination of keywords such as "Parkinson's disease", "fatigue", "non-invasive brain neurostimulation techniques", "repetitive transcranial magnetic stimulation ", and "transcranial direct current stimulation ", relevant articles published between 2000 and 2025 were selected. RESULT: While pharmacological approaches, such as rasagiline, have shown some promise, their therapeutic effects remain inconsistent and limited. Recently, non-invasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have emerged as promising non-pharmacological interventions. Preliminary studies indicate that rTMS may help quantify central fatigue through motor evoked potential (MEP) modulation, while tDCS applied to cortical targets like M1 and DLPFC appears to reduce fatigue severity and improve cognitive processing. Despite theirpotential, current evidence is restrained by small sample sizes, heterogeneity in protocols, and a lack of standardized outcome measures. CONCLUSION: This review summarizes the clinical features, diagnostic criteria, and current therapeutic strategies for PD-related fatigue,with a focus on the emerging role of NIBS. Future research should prioritize well-designed, large-scale randomized controlled trials tooptimize stimulation parameters and validate the long-term efficacy of NIBS in fatigue management for PD patients.
OBJECTIVES: This study investigates the global burden of common central nervous system (CNS) disorders—including late-onset multiple sclerosis (LOMS), Parkinson’s disease (PD), Alzheimer’s disease and other dementias (AD...OBJECTIVES: This study investigates the global burden of common central nervous system (CNS) disorders—including late-onset multiple sclerosis (LOMS), Parkinson’s disease (PD), Alzheimer’s disease and other dementias (ADOD)—among adults aged 55 years and older, covering the period from 1990 to 2021 with projections extending through 2050. METHODS: Data from the Global Burden of Disease (GBD) Study 2021, spanning the years 1990 to 2021, were analyzed to evaluate the number of incident and prevalent cases, deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), and their corresponding age-standardized rates. These metrics were stratified by socio-demographic index (SDI) regions, sex, and age groups. Future trends were forecasted using the Bayesian age–period–cohort (BAPC) model up to the year 2036 and the Autoregressive Integrated Moving Average (ARIMA) model up to 2050. RESULTS: In 2021, global cases reached 0.76 million for LOMS, 10.76 million for PD, and 20.84 million for ADOD. ADOD exhibited the highest burden across all metrics. Females bore greater LOMS and ADOD burden; males bore higher PD burden. High SDI regions had highest LOMS burden; high-middle SDI regions led in PD and ADOD burden. Population growth was the primary burden driver. China faced the highest PD and ADOD burden due to rapid aging. CONCLUSION: Urgent health policies must target elderly populations with sex-specific approaches—focusing on women for LOMS/ADOD and men for PD—alongside strategies for high-risk demographic groups.
OBJECTIVE: To compare the genotype-phenotype relationships betweenchildren with PRRT2 gene variants and 16p11.2 microdeletion syndrome. METHODS: A retrospective analysis was performed on clinical data from 68 patients wi...OBJECTIVE: To compare the genotype-phenotype relationships betweenchildren with PRRT2 gene variants and 16p11.2 microdeletion syndrome. METHODS: A retrospective analysis was performed on clinical data from 68 patients with PRRT2 variants and 16 patients with 16p11.2 microdeletionsyndrome at the Children’s Hospital of Chongqing Medical Universitybetween February 2015 and August 2024. Genetic testing included whole-exome sequencing and copy number variation sequencing. RESULTS: (1) PRRT2 Cohort (n=68): Clinical diagnoses included benign familial infantile epilepsy (49/68), paroxysmal kinesigenic dyskinesia (4/68),infantile convulsions with paroxysmal choreoathetosis (8/68), and otherepilepsy subtypes (7/68). Genetic analysis revealed frameshift variants in 89.7% (61/68), with c.649dupC as the predominant mutation(penetrance:77.2%). Electroencephalography detected epileptiformdischarges in 45.6% of cases. Brain MRI showed nonspecific abnormalities,including widened extra-axial spaces (75%). Oxcarbazepine showed bettertherapeutic efficacy than levetiracetam. (2) 16p11.2 microdeletion cohort (n=16): This group exhibited moresevere phenotypes: The incidence of persistent status epilepticus may behigher (18.8% vs 2.9%, P=0.045, q=0.084), with 87.5% being de novovariants and 81.2% having negative family history. Compared with the PRRT2 group, these patients had significantly increased risks of congenitalheart disease, global developmental delay, and structural brainabnormalities (all P < 0.05). CONCLUSION: PRRT2-related disorders are characterized by incompletepenetrance and benign clinical courses, whereas 16p11.2 microdeletionsyndrome manifests complex phenotypic spectra due to polygenicinvolvement, necessitating distinct diagnostic and therapeutic strategies.
BACKGROUND: Anti-Sez6L2 (seizure-related 6 homolog-like 2) antibody–associated autoimmune cerebellar ataxia is an exceptionally rare neuroimmunological disorder, with only a limited number of cases reported to date. Its...BACKGROUND: Anti-Sez6L2 (seizure-related 6 homolog-like 2) antibody–associated autoimmune cerebellar ataxia is an exceptionally rare neuroimmunological disorder, with only a limited number of cases reported to date. Its clinical spectrum and optimal therapeutic strategies remain incompletely characterized. CASE PRESENTATION: We report a 77-year-old woman who developed a subacute-to-chronic progressive cerebellar ataxia accompanied by oculomotor abnormalities, a forward-leaning posture, and gait initiation failure.. Neuroimaging studies revealed no structural or neoplastic lesions sufficient to account for the neurological deterioration. Cell-based assays detected anti-Sez6L2 IgG antibodies in both serum and cerebrospinal fluid. The patient exhibited only limited and unsustained improvement following first-line immunotherapies, including corticosteroids and intravenous immunoglobulin. After confirmation of an antibody-mediated mechanism, treatment was escalated to B-cell–depleting therapy with rituximab, resulting in clinical improvement accompanied by a reduction in cerebrospinal fluid antibody titers. CONCLUSION: This case represents a rare presentation of anti-Sez6L2 antibody–associated autoimmune cerebellar ataxia and provides additional clinical and immunological evidence supporting the relevance of this antibody. Furthermore, it suggests that rituximab may represent a potentially valuable therapeutic option in patients with insufficient responses to first-line immunotherapies.
BACKGROUND AND AIMS: Embolic stroke of undetermined source (ESUS) is biologically heterogeneous and often presumed cardioembolic (CE). We investigated whether thrombus composition can capture etiologic heterogeneity with...BACKGROUND AND AIMS: Embolic stroke of undetermined source (ESUS) is biologically heterogeneous and often presumed cardioembolic (CE). We investigated whether thrombus composition can capture etiologic heterogeneity within ESUS, clarifying its overall similarity to CE stroke and exploring whether selected radiological features are associated with atherothrombotic-like thrombus patterns. METHODS: Retrospective single-center study of anterior-circulation ischemic stroke patients treated with mechanical thrombectomy (MT) (2022-2025) with available thrombus, classified as large-artery atherosclerosis (LAA), CE, or ESUS. Thrombus composition (RBCs, fibrin, leukocytes; % thrombus area) was analyzed using prespecified non-parametric hierarchical comparisons with Bonferroni correction (k = 3). Reference analyses compared LAA vs. CE; primary analyses ESUS vs. LAA and CE; secondary and tertiary analyses stratified ESUS by ipsilateral high-risk non-stenotic carotid plaque (hrNSCP - vs. hrNSCP+, defined by CTA-based Plaque-RADS score 3-4). Robustness was assessed using isometric log-ratio transformation and exploratory multivariable models. RESULTS: Among 344 MT-treated patients, 159 (46.2%) were included (91 CE, 18 LAA, 50 ESUS). LAA and CE showed distinct thrombus profiles, with higher RBC and lower fibrin content in LAA compared with CE (p < 0.01). ESUS thrombi were descriptively CE-like, without significant differences versus CE or LAA after correction. After stratification, two distinct and biologically coherent thrombus phenotypes emerged: ESUS hrNSCP- (n = 42) thrombi overlapped with CE, whereas ESUS hrNSCP+ (n = 8) thrombi were indistinguishable from LAA; these patterns were confirmed by compositional and multivariable analyses. CONCLUSIONS: When etiologic heterogeneity is taken into account, thrombus composition reveals distinct cardioembolic-like and atherothrombotic-like patterns within ESUS, supporting its role as a complementary tool for etiologic attribution alongside clinical and imaging data.
BACKGROUND AND OBJECTIVE: The accurate prediction of symptomatic intracranial heamorrhage (sICH) risk after intravenous thrombolysis (IVT) is essential for clinical decision-making in patients with acute ischaemic stroke...BACKGROUND AND OBJECTIVE: The accurate prediction of symptomatic intracranial heamorrhage (sICH) risk after intravenous thrombolysis (IVT) is essential for clinical decision-making in patients with acute ischaemic stroke(AIS).We aimed to develop and validate machine learning-based models for sICH risk prediction and compare their performance against that of established clinical scores. METHODS: For this retrospective study,611 AIS patients(2017–2024)were included for model development and internal validation (70/30 split),along with an independent external cohort (n = 100) for testing.Using artificial neural network (ANN) and decision tree (DT) algorithms,we constructed predictive models incorporating 14 demographic,clinical,and neuroimaging variables.A simplified bedside “ANN score” was derived.The performance was compared against that of seven conventional scales (ASPECTS, GRASPS, MSS, HAT, SEDAN, THRIVE, and DRAGON) using the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of sICH was 9.3% in the primary cohort and 11% in the external cohort.The ANN model demonstrated superior predictive performance,with AUCs of 0.988 (95% CI: 0.977–1.000) in the training,0.996 (95% CI: 0.988–1.000) internal validation,and 0.997 (0.990–1.000) external validation cohorts.The derived ANN-score also maintained high accuracy (external AUCs: 0.932).The core infarction volume (ICV) was identified as the strongest predictor. Among conventional scores,the SEDAN performed best (external AUC:0.919),yet the superiority of the ANN model remained significant (p < 0.001). CONCLUSION: The ANN-based model and its derived simplified score provide a reliable approach for sICH risk stratification.Compared with traditional scoring systems,this model offers enhanced precision,potentially aiding clinicians in identifying high-risk patients more effectively.