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OBJECTIVE: To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug-resistant focal epilepsy. METHODS: Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6-month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment-related variables were assessed by using a stepwise logistic regression model. RESULTS: At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re-assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow-up, whereas no association was identified with sociodemographic and epilepsy-related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6-month re-assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two-fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes. SIGNIFICANCE: Almost 1 in 5 adults with drug-resistant focal epilepsy who screen negative for depression become positive when re-assessed 6 months after a treatment change. At re-assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline.
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Epilepsia Refractaria , Epilepsias Parciales , Epilepsia , Suicidio , Adulto , Humanos , Ideación Suicida , Depresión/etiología , Suicidio/psicología , Convulsiones/complicaciones , Epilepsia/complicaciones , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/complicaciones , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/complicacionesRESUMEN
OBJECTIVE: This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy. METHODS: This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses. RESULTS: A total of 236 subjects with a median age of 38 (Q1-Q3 = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q1-Q3 = 2.50-4.47) at baseline to 2.50 (Q1-Q3 = 1.67-3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel. SIGNIFICANCE: Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.
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OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. METHODS: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM- remains to be elucidated.
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Epilepsia Generalizada , Epilepsia Refleja , Mioclonía , Humanos , Secuenciación del Exoma , Helicasa Inducida por Interferón IFIH1/genética , Epilepsia Refleja/genética , Electroencefalografía , Párpados , Proteínas Portadoras/genética , Proteínas del Tejido Nervioso/genéticaRESUMEN
Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.
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Epilepsia Generalizada , Epilepsia , Embarazo , Humanos , Femenino , Topiramato/efectos adversos , Anticonvulsivantes/efectos adversos , Teratógenos/toxicidad , Estudios Retrospectivos , Estudios de Cohortes , Fructosa/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Levetiracetam/efectos adversos , Inmunoglobulina E/uso terapéuticoRESUMEN
OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.
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OBJECTIVE: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. METHODS: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models. RESULTS: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM. SIGNIFICANCE: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics.
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Epilepsias Parciales , Epilepsia , Nitrilos , Piridonas , Masculino , Adulto , Humanos , Femenino , Anticonvulsivantes/efectos adversos , Epilepsias Parciales/tratamiento farmacológico , Estudios Retrospectivos , Levetiracetam/uso terapéutico , Lacosamida/uso terapéutico , Epilepsia/tratamiento farmacológico , Pirrolidinonas/uso terapéutico , Resultado del TratamientoRESUMEN
AIM: Biallelic mutations in the PTRH2 gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features. METHODS: Extensive neurological and neurophysiological evaluations have been conducted on the two affected brothers and their healthy mother since 1996. The diagnosis of peripheral neuropathy of probable hereditary origin was confirmed through a sural nerve biopsy. Exome sequencing was performed after the analysis of major neuropathy-associated genes yielded negative results. RESULTS: Whole-exome sequencing analysis identified the homozygous substitution c.256C>T (p.Gln86Ter) in the PTRH2 gene in the two siblings. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant has been classified as pathogenic. At 48 years old, the proband's reevaluation confirmed a demyelinating sensorimotor polyneuropathy with bilateral sensorineural hearing loss that had been noted since he was 13. Additionally, drug-resistant epileptic seizures occurred when he was 32 years old. No hepatic or endocrinological signs developed. The younger affected brother, 47 years old, has an overlapping clinical presentation without epilepsy. INTERPRETATION: Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to PTRH2 variants. We thereby hope to better define IMNEPD and facilitate the identification and diagnosis of this novel disease entity.
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Enfermedades Pancreáticas , Humanos , Masculino , Italia , Femenino , Enfermedades Pancreáticas/genética , Enfermedades Pancreáticas/fisiopatología , Persona de Mediana Edad , Codón sin Sentido , Linaje , AdultoRESUMEN
OBJECTIVE: Functional seizures (FS) are brief, involuntary changes in behaviour or consciousness, distinct from epileptic seizures, potentially associated with psychological dissociation. Binge eating disorder (BED) was linked to psychological and somatic dissociation also. However, any connection between FS and BED is insufficiently explored. We aimed to assess BED prevalence in individuals with FS, anxiety/depression (AD), and healthy subjects (HS), to investigate dissociation's link to binge eating, and to explore psychological characteristics of FS individuals. METHOD: Participants underwent evaluations based on ILAE guidelines and DSM-5 criteria, including questionnaires assessing binge eating, dissociation, anxiety, depression and personality traits. Inclusion criteria were age > 18 years, no history of substance abuse, no history of epilepsy, and no use of medications inducing eating disorders. RESULTS: We found significantly more frequent and severe binge-eating symptoms in individuals with FS and AD compared to HS. Depression and dissociation correlated with binge-eating symptoms in both AD and FS groups. The PID-5 facet 'Perseveration' predicted binge-eating attitudes only in FS individuals; they reported more childhood emotional neglect and increased disinhibition compared do AD people. DISCUSSION: This study underscores the commonality of binge-eating symptoms in FS individuals, emphasizing its association with dissociation symptoms. This finding support the hypothesis of a link between dissociation and eating disorders. Unique clinical characteristics in individuals with FS were identified, as a compulsive dimension related to binge-eating symptoms, providing a comprehensive understanding of their psychological profile and guiding targeted therapeutic interventions.
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BACKGROUND: Antiseizure medications remain the cornerstone of treatment for epilepsy, although a proportion of individuals with the condition will continue to experience seizures despite appropriate therapy. Treatment choices for epilepsy are based on variables related to both the individual patient and the available medications. Brivaracetam is a third-generation agent antiseizure medication. METHODS: We carried out a Delphi consensus exercise to define the role of brivaracetam in clinical practice and to provide guidance about its use as first add-on ASM and in selected clinical scenarios. A total of 15 consensus statements were drafted by an expert panel following review of the literature and all were approved in the first round of voting by panelists. The consensus indicated different clinical scenarios for which brivaracetam can be a good candidate for treatment, including first add-on use. RESULTS: Overall, brivaracetam was considered to have many advantageous characteristics that render it a suitable option for patients with focal epilepsy, including a fast onset of action, favorable pharmacokinetic profile with few drug-drug interactions, broad-spectrum activity, and being well tolerated across a range of doses. Brivaracetam is also associated with sustained clinical response and good tolerability in the long term. CONCLUSIONS: These characteristics also make it suitable as an early add-on for the elderly and for patients with post-stroke epilepsy or status epilepticus as highlighted by the present Delphi consensus.
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Anticonvulsivantes , Consenso , Técnica Delphi , Epilepsias Parciales , Pirrolidinonas , Humanos , Pirrolidinonas/uso terapéutico , Pirrolidinonas/administración & dosificación , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/administración & dosificación , Epilepsias Parciales/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
INTRODUCTION: High-density EEG (hdEEG) is a validated tool in presurgical evaluation of people with epilepsy. The aim of this national survey is to estimate diffusion and knowledge of hdEEG to develop a network among Italian epilepsy centers. METHODS: A survey of 16 items (and 15 additional items) was distributed nationwide by email to all members of the Italian League Against Epilepsy and the Italian Society of Clinical Neurophysiology. The data obtained were analyzed using descriptive statistics. RESULTS: A total of 104 respondents were collected from 85 centers, 82% from the Centre-North of Italy; 27% of the respondents had a hdEEG. The main applications were for epileptogenic focus characterization in the pre-surgical evaluation (35%), biomarker research (35%) and scientific activity (30%). The greatest obstacles to hdEEG were economic resources (35%), acquisition of dedicated personnel (30%) and finding expertise (17%). Dissemination was limited by difficulties in finding expertise and dedicated personnel (74%) more than buying devices (9%); 43% of the respondents have already published hdEEG data, and 91% of centers were available to participate in multicenter hdEEG studies, helping in both pre-processing and analysis. Eighty-nine percent of respondents would be interested in referring patients to centers with established experience for clinical and research purposes. CONCLUSIONS: In Italy, hdEEG is mainly used in third-level epilepsy centers for research and clinical purposes. HdEEG diffusion is limited not only by costs but also by lack of trained personnel. Italian centers demonstrated a high interest in educational initiatives on hdEEG as well as in clinical and research collaborations.
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Epilepsia , Humanos , Electroencefalografía , Epilepsia/diagnóstico , Italia , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST). METHODS: BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5-20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6. RESULTS: A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5-20, and >20 seizures per month (p < .001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p < .001). SSR was reached by 51.2% and 26.5% participants with a history of 1-5 and ≥6 ASMs (p < .001); the corresponding rates of SSF were 24.7% and 4.5% (p < .001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p < .001), and in participants with history of ≥6 prior ASMs compared to those with history of 1-5 ASMs (19.6% vs. 12.2%, p = .002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs. SIGNIFICANCE: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy.
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Anticonvulsivantes , Epilepsias Parciales , Adulto , Humanos , Anticonvulsivantes/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Quimioterapia Combinada , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Epilepsias Parciales/tratamiento farmacológico , Pirrolidinonas/uso terapéuticoRESUMEN
BACKGROUND: The GLA c.337T > C (p.Phe113Leu) is a known pathogenic variant associated to late-onset Fabry disease phenotype with predominant cardiac manifestations. A founder effect was demonstrated in a large cohort in the Portuguese region of Guimarães. Herein we report an in-depth phenotype description of a cluster of five Southern Italy families. METHODS: Family pedigrees of five index males with the p.Phe113Leu variant were obtained and all at-risk relatives underwent biochemical and genetical screening test. Carriers of GLA p.Phe113Leu variant underwent subsequent multidisciplinary clinical and instrumental evaluation. RESULTS: Thirty-one (16 M, 15 F) individuals with p.Phe113Leu pathogenic variant were identified. Sixteen out of 31 patients (51.6%) had cardiac manifestations. Notably, myocardial fibrosis was found in 7/8 patients, of whom 2 were under 40 years. Stroke occurred in 4 patients. White matter lesions were detected in 12/19 patients and occurred in 2/10 of subjects under 40 years. Seven females complained of acroparesthesias. Renal involvement occurred in 10 patients. Angiokeratomas were evident in 9 subjects. Eyes, ear, gastrointestinal and pulmonary involvement occurred in the minority of subjects. CONCLUSION: This study demonstrates that a cluster of subjects with p.Phe113Leu pathogenic variant is also present in Southern Italy. Disease manifestations are frequent in both sexes and may occur early in life. Cardiac involvement represents the core manifestation, but neurological and renal involvement is also frequent, suggesting that extra-cardiac complications deserve clinical attention.
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Enfermedad de Fabry , Accidente Cerebrovascular , Femenino , Humanos , Masculino , alfa-Galactosidasa/genética , Enfermedad de Fabry/epidemiología , Enfermedad de Fabry/genética , Heterocigoto , Fenotipo , Accidente Cerebrovascular/genéticaRESUMEN
OBJECTIVE: To describe the clinical and paraclinical findings, treatment options and long-term outcomes in autoimmune encephalitis (AE), with a close look to epilepsy. METHODS: In this retrospective observational cohort study, we enrolled patients with new-onset seizures in the context of AE. We compared clinical and paraclinical findings in patients with and without evidence of antibodies. RESULTS: Overall, 263 patients (138 females; median age 55 years, range 4-86) were followed up for a median time of 30 months (range 12-120). Antineuronal antibodies were detected in 63.50%.Antibody-positive patients had multiple seizure types (p=0.01) and prevalent involvement of temporal regions (p=0.02). A higher prevalence of episodes of SE was found in the antibody-negative group (p<0.001).Immunotherapy was prescribed in 88.60%, and effective in 61.80%. Independent predictors of favourable outcome of the AE were early immunotherapy (p<0.001) and the detection of antineuronal surface antibodies (p=0.01).Autoimmune-associated epilepsy was the long-term sequela in 43.73%, associated with cognitive and psychiatric disturbances in 81.73%. Independent predictors of developing epilepsy were difficult to treat seizures at onset (p=0.04), a high number of antiseizure medications (p<0.001), persisting interictal epileptiform discharges at follow-up (p<0.001) and poor response to immunotherapy during the acute phase (p<0.001). CONCLUSIONS: The recognition of seizures secondary to AE represents a rare chance for aetiology-driven seizures management. Early recognition and treatment at the pathogenic level may reduce the risk of long-term irreversible sequelae. However, the severity of seizures at onset is the major risk factor for the development of chronic epilepsy.This study provides class IV evidence for management recommendations.
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BACKGROUND: Identifying late epileptic seizures (LS) following cerebral venous thrombosis (CVT) can be useful for prognosis and management. We systematically reviewed the literature to identify risk factors for LS due to CVT. METHODS: We systematically searched PubMed, Scholar, and Scopus databases (May 2021) to identify studies reporting data on prevalence and risk factors for CVT-LS. The methodological quality was assessed with the Ottawa-Newcastle Scale. The risk of developing CVT-LS was summarized in meta-analyses and expressed as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using random-effects models. RESULTS: Out of the 332 records retrieved, four studies were eventually included with a total of 1309 patients with CVT and 142 (11%) with CVT-LS. The most relevant predictors of CVT-LS were symptomatic seizures (OR 5.66, 95% CI 3.83-8.35), stupor/coma (OR 6.81, 95% CI 1.18-39.20), focal neurologic signs (OR 6.81, 95% CI 1.18-39.2), hemorrhagic component (OR 3.52, 95% CI 2.45-5.06), and superior sagittal sinus involvement (OR 1.52, 95% CI 1.04-2.21). CONCLUSION: There are several risk factors for CVT-LS that should be considered in clinical practice. Further high-quality studies are warranted to develop predictive models for individualized risk stratification and prediction of CVT-LS.
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Epilepsia , Trombosis Intracraneal , Trombosis de la Vena , Epilepsia/complicaciones , Humanos , Trombosis Intracraneal/complicaciones , Trombosis Intracraneal/epidemiología , Factores de Riesgo , Convulsiones/diagnóstico , Convulsiones/epidemiología , Convulsiones/etiología , Trombosis de la Vena/complicaciones , Trombosis de la Vena/epidemiologíaRESUMEN
PURPOSE: To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. METHODS: This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. RESULTS: The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. CONCLUSIONS: Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.
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Epilepsia , Estado Epiléptico , Adulto , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Recurrencia , Convulsiones/tratamiento farmacológico , Estado Epiléptico/tratamiento farmacológicoRESUMEN
Fabry disease is a rare X-linked lysosomal storage disorder due to pathogenic variants of the galactosidase alpha (GLA) gene, leading to a deficiency of alpha-galactosidase A. The inadequate enzymatic activity leads to progressive glycosphingolipids accumulation within tissues and subsequent multi-systemic dysfunction, with predominant involvement of heart, kidney, and nervous system. Two subtypes are recognized: the classic type and the late-onset type. We here describe the clinical characteristics of a patient with late-onset Fabry disease carrying a not previously identified GLA gene variant. This 50-year-old man came to hospital because of an acute ischemic stroke. He also complained of acroparesthesia and had angiokeratomas in the nape and the back. Blood alpha-galactosidase A activity was low, plasmatic lyso-Gb3 level was borderline, cardiac MRI showed cardiac fibrosis, brain MRI documented cerebrovascular disease, and skin biopsy revealed small fiber neuropathy without globotriaosylceramide-3 skin deposits. Genetic study by means of targeted next-generation sequencing analysis disclosed a missense substitution c.1139C>T (p.Pro380Leu) in the GLA gene. We suggest that this novel variant should be considered as pathogenic and associated with a late-onset variant of Fabry disease with a predominant neurological phenotype.
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Enfermedad de Fabry , Accidente Cerebrovascular Isquémico , Masculino , Humanos , alfa-Galactosidasa/genética , Enfermedad de Fabry/genética , Galactosidasas/genética , Fenotipo , MutaciónRESUMEN
The differential diagnosis of epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) may be difficult, due to the lack of distinctive clinical features. The interictal electroencephalographic (EEG) signal may also be normal in patients with ES. Innovative diagnostic tools that exploit non-linear EEG analysis and deep learning (DL) could provide important support to physicians for clinical diagnosis. In this work, 18 patients with new-onset ES (12 males, 6 females) and 18 patients with video-recorded PNES (2 males, 16 females) with normal interictal EEG at visual inspection were enrolled. None of them was taking psychotropic drugs. A convolutional neural network (CNN) scheme using DL classification was designed to classify the two categories of subjects (ES vs. PNES). The proposed architecture performs an EEG time-frequency transformation and a classification step with a CNN. The CNN was able to classify the EEG recordings of subjects with ES vs. subjects with PNES with 94.4% accuracy. CNN provided high performance in the assigned binary classification when compared to standard learning algorithms (multi-layer perceptron, support vector machine, linear discriminant analysis and quadratic discriminant analysis). In order to interpret how the CNN achieved this performance, information theoretical analysis was carried out. Specifically, the permutation entropy (PE) of the feature maps was evaluated and compared in the two classes. The achieved results, although preliminary, encourage the use of these innovative techniques to support neurologists in early diagnoses.
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RATIONALE: Juvenile myoclonic epilepsy (JME) and juvenile absence epilepsy (JAE) are generalized epileptic syndromes presenting in the same age range. To explore whether uneven network dysfunctions may underlie the two different phenotypes, we examined drug-naive patients with JME and JAE at the time of their earliest presentation. METHODS: Patients were recruited based on typical JME (nâ¯=â¯23) or JAE (nâ¯=â¯18) presentation and compared with 16 age-matched healthy subjects (HS). We analyzed their awake EEG signals by Partial Directed Coherence and graph indexes. RESULTS: Out-density and betweenness centrality values were different between groups. With respect to both JAE and HS, JME showed unbalanced out-density and out-strength in alpha and beta bands on central regions and reduced alpha out-strength from fronto-polar to occipital regions, correlating with photosensitivity. With respect to HS, JAE showed enhanced alpha out-density and out-strength on fronto-polar regions. In gamma band, JAE showed reduced Global/Local Efficiency and Clustering Coefficient with respect to HS, while JME showed more scattered values. CONCLUSIONS: Our data suggest that regional network changes in alpha and beta bands underlie the different presentation distinguishing JME and JAE resulting in motor vs non-motor seizures characterizing these two syndromes. Conversely, impaired gamma-activity within the network seems to be a non-local marker of defective inhibition.
Asunto(s)
Epilepsia Tipo Ausencia , Epilepsia Mioclónica Juvenil , Preparaciones Farmacéuticas , Electroencefalografía , Epilepsia Tipo Ausencia/diagnóstico , Humanos , Epilepsia Mioclónica Juvenil/diagnóstico , Lóbulo Occipital , ConvulsionesRESUMEN
OBJECTIVE: To identify early structural alterations preceding the development of drug-resistance in mild mesial temporal lobe epilepsy (mMTLE), a drug-responsive syndrome ideal for investigating epilepsy pathophysiology and potential prognostic markers of long-term clinical outcome, using magnetic resonance imaging (MRI) at baseline and after 12-year follow-up. METHODS: Since 2002, a total of 55 participants with a baseline diagnosis of mMTLE underwent three-dimensional (3D) T1 1.5T MRI. Based on long-term outcome (follow-up 12 ± 3 years), we identified 39 patients with stable mMTLE (smMTLE) and 16 patients who had developed drug-resistance overtime (refractory MTLE [rMTLE]). At follow-up, 21 smMTLE and 13 rMTLE patients underwent 3T-MRI including diffusion-weighted scans. Structural images were processed using longitudinal voxel-based morphometry and standard Freesurfer analysis. Statistical analyses were carried out accounting for age, age at onset, gender, hippocampal volume, and hippocampal sclerosis (Hs). RESULTS: Patients presented similar demographic, clinical, and Hs features. White matter volume of the arcuate fasciculi, corticospinal tracts, left retrosplenial cingulum, and left inferior longitudinal fasciculus was reduced only in rMTLE patients before the development of drug-resistance. At follow-up, rMTLE showed decreased fractional anisotropy in the corpus callosum, superior longitudinal fasciculi, and major bundles of the right hemisphere. SIGNIFICANCE: White matter temporal and extratemporal abnormalities are preexisting in patients with mild MTLE who will develop drug-resistance, independently from the presence of Hs. Thus, these changes might be due to an inherited genetic alteration rather than a subordinate worsening after repeated seizures, multiple antiepileptic drugs, or initial precipitating factors.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia Refractaria/patología , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Sustancia Blanca/patología , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética , Resistencia a Medicamentos , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/patología , Femenino , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
AIMS: Stroke is the most commonly identified cause of late-onset epilepsy. Risk factors for poststroke epilepsy (PSE) are partially elucidated, and many studies have been performed in recent years. We aimed to update our previous systematic review and meta-analysis on risk factors for PSE. METHODS: PubMed, Google Scholar, and Scopus databases were searched. Articles published in English (1987-2019) were included. Odds ratios (OR) and mean values were calculated for examined variables. RESULTS: Thirty studies with different designs were included, enrolling 26,045 patients who experienced stroke, of whom 1800 had PSE, corresponding to a prevalence of 7%. Cortical lesions (OR: 3.58, 95% confidence interval (CI): 2.35-5.46, pâ¯<â¯0.001), hemorrhagic component (OR: 2.47, 95% CI: 1.68-3.64, pâ¯<â¯0.001), early seizures (ES) (OR: 4.88, 95% CI: 3.08-7.72, pâ¯<â¯0.001), and younger age at stroke onset (difference in means: 2.97â¯years, 95% CI: 0.78 to 5.16, pâ¯=â¯0.008) favor PSE. Sex and acute treatment with recombinant tissue plasminogen activator (rtPA) do not predict the occurrence of PSE. CONCLUSION: Despite limitations due to the uneven quality and design of the studies, the present meta-analysis confirms that cortical involvement, hemorrhagic component, and ES are associated with a higher risk of PSE. In this update, younger age at stroke onset but not thrombolytic treatment seems to increase the risk for PSE. This article is part of the Special Issue "Seizures & Stroke".