Sex-based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia

Although a striking female preponderance has been consistently reported in epilepsy with eyelid myoclonia (EEM), no study has specifically explored the variability of clinical presentation according to sex in this syndrome. Here, we aimed to investigate sex-specific electroclinical differences and prognostic determinants in EEM. Data from 267 EEM patients were retrospectively analyzed by the EEM Study Group, and a dedicated multivariable logistic regression analysis was developed separately for each sex. We found that females with EEM showed a significantly higher rate of persistence of photosensitivity and eye closure sensitivity at the last visit, along with a higher prevalence of migraine with/without aura, whereas males with EEM presented a higher rate of borderline intellectual functioning/intellectual disability. In female patients, multivariable logistic regression analysis revealed age at epilepsy onset, eyelid myoclonia status epilepticus, psychiatric comorbidities, and catamenial seizures as significant predictors of drug resistance. In male patients, a history of febrile seizures was the only predictor of drug resistance. Hence, our study reveals sex-specific differences in terms of both electroclinical features and prognostic factors. Our findings support the importance of a sex-based personalized approach in epilepsy care and research, especially in genetic generalized epilepsies

The spectrum of epilepsy with eyelid myoclonia: delineation of disease subtypes from a large multicenter study

Objective Epilepsy with eyelid myoclonia (EEM) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission and to a less favorable neuropsychiatric outcome. However, much work is still needed to better delineate this epilepsy syndrome. Methods In this multicenter retrospective cohort study, we included 267 EEM patients from nine countries. Data on electroclinical and demographic features, intellectual functioning, migraine with or without aura, family history of epilepsy, and epilepsy syndromes in relatives were collected in each patient. The impact of age at epilepsy onset (AEO) on EEM clinical features was investigated, along with the distinctive clinical characteristics of patients showing sporadic myoclonia involving body regions other than eyelids (body-MYO). Results Kernel density estimation revealed a trimodal distribution of AEO, and Fisher-Jenks optimization disclosed three EEM subgroups: early onset (EO-EEM), intermediate onset (IO-EEM), and late onset (LO-EEM). EO-EEM was associated with the highest rate of intellectual disability, antiseizure medication refractoriness, and psychiatric comorbidities and with the lowest rate of family history of epilepsy. LO-EEM was associated with the highest proportion of body-MYO and generalized tonic-clonic seizures (GTCS), whereas IO-EEM had the lowest observed rate of additional findings. A family history of EEM was significantly more frequent in IO-EEM and LO-EEM compared with EO-EEM. In the subset of patients with body-MYO (58/267), we observed a significantly higher rate of migraine and GTCS but no relevant differences in other electroclinical features and seizure outcome. Significance Based on AEO, we identified consistent EEM subtypes characterized by distinct electroclinical and familial features. Our observations shed new light on the spectrum of clinical features of this generalized epilepsy syndrome and may help clinicians toward a more accurate classification and prognostic profiling of EEM patients

Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU·μ L−1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV-2 pandemic.This research was funded by grants number COV20-00080 and COV20-00173 of the 2020 Emergency Call for Research Projects about the SARS-CoV-2 virus and the COVID-19 disease of the Institute of Health ‘Carlos III’, Spanish Ministry of Science and Innovation, and by grant number EQC2019-006240-P of the 2019 Call for Acquisition of Scientifc Equipment, FEDER Program, Spanish Ministry of Science and Innovation. This work has been supported by the European Commission through the JRC HUMAINT project. ABR was supported by grant number RTI2018-094465-J funded by the Spanish National Agency of Research

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings.This research was funded by Grants Number COV20-00080 and COV20-00173 of the 2020 Emergency Call for Research Projects about the SARS-CoV-2 virus and the COVID-19 disease of the Institute of Health ‘Carlos III’, Spanish Ministry of Science and Innovation, and by Grant Number EQC2019-006240-P funded by MICIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. ABR was supported by Grant Number RTI2018-094465-J-I00 funded by MICIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This work has been supported by the European Commission through the Joint Research Center (JRC) HUMAINT project

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings

Electroclinical Features and Long-term Seizure Outcome in Patients With Eyelid Myoclonia With Absences

Background and objectives: Eyelid myoclonia with absences (EMA) is a generalized epilepsy syndrome whose prognosis and clinical characteristics are still partially undefined. We investigated electroclinical endophenotypes and long-term seizure outcome in a large cohort of EMA patients. Methods: In this multicenter retrospective study, EMA patients with ≥5 years of follow-up were included. We investigated prognostic patterns and sustained terminal remission (STR), along with their prognostic factors. Moreover, a two-step cluster analysis was used to investigate the presence of distinct EMA endophenotypes. Results: We included 172 patients, with a median age at onset of 7 years (interquartile range (IQR) 5-10) and a median follow-up duration of 14 years (IQR 8.25-23.75). Sixty-six patients (38.4%) displayed a non-remission pattern, whereas remission and relapse patterns were encountered in 56 (32.6%) and 50 (29.1%) subjects. Early epilepsy onset, history of febrile seizures (FS) and eyelid myoclonia (EM) status epilepticus significantly predicted a non-remission pattern according to multinomial logistic regression analysis. STR was achieved by 68 (39.5%) patients with a mean latency of 14.05 years (SD ± 12.47). Early epilepsy onset, psychiatric comorbidities, and a history of FS and generalized tonic-clonic seizures (GTCS) were associated with a lower probability of achieving STR according to a Cox regression proportional hazards model. Antiseizure medication (ASM) withdrawal was attempted in 62/172 patients, and seizures relapsed in 74.2%. Cluster analysis revealed two distinct clusters with 86 patients each. Cluster 2, which we defined as "EMA-plus", was characterized by an earlier age at epilepsy onset, higher rate of intellectual disability, EM status epilepticus, generalized paroxysmal fast activity, self-induced seizures, FS, and poor ASM response, whereas Cluster 1, the "EMA-only" cluster, was characterized by a higher rate of seizure remission and more favorable neuropsychiatric outcome. Discussion: Early epilepsy onset was the most relevant prognostic factor for poor treatment response. A long latency between epilepsy onset and ASM response was observed, suggesting the impact of age-related brain changes in EMA remission. Finally, our cluster analysis showed a clear-cut distinction of EMA patients into an EMA-plus insidious subphenotype and an EMA-only benign cluster that strongly differed in terms of remission rates and cognitive outcomes

Electroclinical Features and Long-term Seizure Outcome in Patients With Eyelid Myoclonia With Absences

BACKGROUND AND OBJECTIVES Eyelid myoclonia (EM) with absences (EMA) is a generalized epilepsy syndrome with a prognosis and clinical characteristics that are still partially undefined. We investigated electroclinical endophenotypes and long-term seizure outcome in a large cohort of patients with EMA. METHODS In this multicenter retrospective study, patients with EMA with ≥5 years of follow-up were included. We investigated prognostic patterns and sustained terminal remission (STR), along with their prognostic factors. Moreover, a 2-step cluster analysis was used to investigate the presence of distinct EMA endophenotypes. RESULTS We included 172 patients with a median age at onset of 7 years (interquartile range [IQR] 5-10 years) and a median follow-up duration of 14 years (IQR 8.25-23.75 years). Sixty-six patients (38.4%) displayed a nonremission pattern, whereas remission and relapse patterns were encountered in 56 (32.6%) and 50 (29.1%) participants. Early epilepsy onset, history of febrile seizures (FS), and EM status epilepticus significantly predicted a nonremission pattern according to multinomial logistic regression analysis. STR was achieved by 68 (39.5%) patients with a mean latency of 14.05 years (SD ±12.47 years). Early epilepsy onset, psychiatric comorbid conditions, and a history of FS and generalized tonic-clonic seizures were associated with a lower probability of achieving STR according to a Cox regression proportional hazards model. Antiseizure medication (ASM) withdrawal was attempted in 62 of 172 patients, and seizures recurred in 74.2%. Cluster analysis revealed 2 distinct clusters with 86 patients each. Cluster 2, which we defined as EMA-plus, was characterized by an earlier age at epilepsy onset, higher rate of intellectual disability, EM status epilepticus, generalized paroxysmal fast activity, self-induced seizures, FS, and poor ASM response, whereas cluster 1, the EMA-only cluster, was characterized by a higher rate of seizure remission and more favorable neuropsychiatric outcome. DISCUSSION Early epilepsy onset was the most relevant prognostic factor for poor treatment response. A long latency between epilepsy onset and ASM response was observed, suggesting the effect of age-related brain changes in EMA remission. Last, our cluster analysis showed a clear-cut distinction of patients with EMA into an EMA-plus insidious subphenotype and an EMA-only benign cluster that strongly differed in terms of remission rates and cognitive outcomes

The spectrum of epilepsy with eyelid myoclonia: delineation of disease subtypes from a large multicenter study

Epilepsy with eyelid myoclonia (EEM) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission and to a less favorable neuropsychiatric outcome. However, much work is still needed to better delineate this epilepsy syndrome

Electroclinical Features and Long-term Seizure Outcome in Patients With Eyelid Myoclonia With Absences

BACKGROUND AND OBJECTIVES: Eyelid myoclonia with absences (EMA) is a generalized epilepsy syndrome whose prognosis and clinical characteristics are still partially undefined. We investigated electroclinical endophenotypes and long-term seizure outcome in a large cohort of EMA patients. METHODS: In this multicenter retrospective study, EMA patients with ≥5 years of follow-up were included. We investigated prognostic patterns and sustained terminal remission (STR), along with their prognostic factors. Moreover, a two-step cluster analysis was used to investigate the presence of distinct EMA endophenotypes. RESULTS: We included 172 patients, with a median age at onset of 7 years (interquartile range (IQR) 5-10) and a median follow-up duration of 14 years (IQR 8.25-23.75). Sixty-six patients (38.4%) displayed a non-remission pattern, whereas remission and relapse patterns were encountered in 56 (32.6%) and 50 (29.1%) subjects. Early epilepsy onset, history of febrile seizures (FS) and eyelid myoclonia (EM) status epilepticus significantly predicted a non-remission pattern according to multinomial logistic regression analysis. STR was achieved by 68 (39.5%) patients with a mean latency of 14.05 years (SD ± 12.47). Early epilepsy onset, psychiatric comorbidities, and a history of FS and generalized tonic-clonic seizures (GTCS) were associated with a lower probability of achieving STR according to a Cox regression proportional hazards model. Antiseizure medication (ASM) withdrawal was attempted in 62/172 patients, and seizures relapsed in 74.2%. Cluster analysis revealed two distinct clusters with 86 patients each. Cluster 2, which we defined as "EMA-plus", was characterized by an earlier age at epilepsy onset, higher rate of intellectual disability, EM status epilepticus, generalized paroxysmal fast activity, self-induced seizures, FS, and poor ASM response, whereas Cluster 1, the "EMA-only" cluster, was characterized by a higher rate of seizure remission and more favorable neuropsychiatric outcome. DISCUSSION: Early epilepsy onset was the most relevant prognostic factor for poor treatment response. A long latency between epilepsy onset and ASM response was observed, suggesting the impact of age-related brain changes in EMA remission. Finally, our cluster analysis showed a clear-cut distinction of EMA patients into an EMA-plus insidious subphenotype and an EMA-only benign cluster that strongly differed in terms of remission rates and cognitive outcomes

The spectrum of epilepsy with eyelid myoclonia: delineation of disease subtypes from a large multicenter study

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission and to a less favorable neuropsychiatric outcome. However, much work is still needed to better delineate this epilepsy syndrome. METHODS: In this multicenter retrospective cohort study, we included 267 EEM patients from 9 countries. Data about electroclinical and demographic features, intellectual functioning, migraine with or without aura, family history of epilepsy and epilepsy syndromes in relatives were collected in each patient. The impact of age at epilepsy onset (AEO) on EEM clinical features was investigated, along with the distinctive clinical characteristics of patients showing sporadic myoclonia over body regions other than eyelids (body-MYO). RESULTS: Kernel density estimation revealed a trimodal distribution of AEO and Fisher-Jenks optimization disclosed three EEM subgroups: early-onset (EO-EEM), intermediate-onset (IO-EEM) and late-onset subgroup (LO-EEM). EO-EEM was associated with the highest rate of intellectual disability, antiseizure medication refractoriness and psychiatric comorbidities and with the lowest rate of family history of epilepsy. LO-EEM was associated with the highest proportion of body-MYO and generalized tonic-clonic seizures (GTCS), whereas IO-EEM had the lowest observed rate of additional findings. A family history of EEM was significantly more frequent in IO-EEM and LO-EEM compared with EO-EEM. In the subset of patients with body-MYO (58/267), we observed a significantly higher rate of migraine and GTCS but no relevant differences in other electroclinical features and seizure outcome. SIGNIFICANCE: Based on AEO, we identified consistent EEM subtypes characterized by distinct electroclinical and familial features. Our observations shed new light on the spectrum of clinical features of this generalized epilepsy syndrome and may help clinicians towards a more accurate classification and prognostic profiling of EEM patients