Lafora disease (LD) is a rare fatal autosomal recessive form of progressive myoclonus epilepsy. It affects previously healthy children or adolescents, causing pharmacoresistant epilepsy, myoclonus ...and severe psychomotor deterioration. This work aims to describe the clinical course of LD and identify predictors of outcome by means of a prognostic systematic review with individual participant data meta-analysis.
A search was conducted on MEDLINE and Embase with no restrictions on publication date. Only studies reporting genetically confirmed LD cases were included. Kaplan-Meier estimate was used to assess probability of death and loss of autonomy. Univariable and multivariable Cox regression models with mixed effects (clustered survival data) were performed to evaluate prognostic factors.
Seventy-three papers describing 298 genetically confirmed LD cases were selected. Mean age at disease onset was 13.4 years (SD 3.7), with 9.1% aged ≥ 18 years. Overall survival rates in 272 cases were 93% 95% CI 89-96 at 5 years, 62% 95% CI 54-69 at 10 years and 57% 95% CI 49-65 at 15 years. Median survival time was 11 years. The probability of loss of autonomy in 110 cases was 45% 95% CI 36-55 at 5 years, 75% 95% CI 66-84 at 10 years, and 83% 95% CI 74-90 at 15 years. Median loss of autonomy time was 6 years. Asian origin and age at onset < 18 years emerged as negative prognostic factors, while type of mutated gene and symptoms at onset were not related to survival or disability.
This study documented that half of patients survived at least 11 years. The notion of actual survival rate and prognostic factors is crucial to design studies on the effectiveness of upcoming new disease-modifying therapies.
Purpose: To determine the incidence and the 30‐day case fatality of status epilepticus (SE) in the adult resident population of the city of Bologna, Italy.
Methods: Over a 1‐year period (March 1, ...1999 to February 29, 2000), all patients older than 20 years with SE were included. The case‐finding method was based on (a) a prospective surveillance of all public general hospitals in the city by neurologic units, and (b) a review of all discharge codes concerning epilepsy.
Results: The crude and standardized annual incidence rate of SE was 13.1 per 100,000 95% confidence interval (CI), 9.5–17.5 and 10.7 (95% CI, 7.5–13.8). It was higher in the elderly (older than 60 years) than in young adults (26.2 vs. 5.2) and in women than in men (14.9 vs. 11.0). Acute symptomatic SE accounted for 48%, and a cerebrovascular pathology was the most frequently associated etiologic condition (41%). A history of seizures was reported in 39% of patients. The 30‐day case fatality was 39% (33% excluding postanoxic patients).
Conclusions: This study reports the first data on the epidemiology of SE in Italy. The incidence rate found in the population of Bologna is in the same range as that of the other European countries. The 30‐day case fatality is higher than all the other population studies (both European and American), despite the broadly similar clinical features of patients. Indirect evidence suggests that some inaccurate patient management could have negatively influenced the outcome of SE.
Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized by symptoms such as excessive daytime sleepiness, sudden sleep episodes, disrupted nocturnal sleep, cataplexy, sleep ...paralysis, and hypnagogic hallucinations, which significantly impact the overall well-being and quality of life of individuals. While psychological factors have gained attention, there is limited research on the coping strategies employed by patients with NT1 and their association with quality of life. This study aimed to compare coping strategies in patients with NT1 and controls, as well as assess the relationship between coping strategies and quality of life in patients with NT1. A total of 122 individuals diagnosed with NT1 and 138 controls were enrolled in this cross-sectional study. Participants completed questionnaires assessing coping strategies and health-related quality of life. A Mann-Whitney U test was conducted to compare the use of different coping strategies by patients with NT1 and controls. Spearman's rho correlation was performed to examine the association between coping strategies and quality of life in the NT1 group. Results showed that patients with NT1 exhibited differences in the use of coping strategies compared to controls. They reported lower use of active coping, planning, instrumental, and emotional social support, and higher use of behavioral and mental disengagement. Denial and behavioral disengagement were significantly and negatively associated with quality of life. Identifying coping strategies and their association with quality of life may aid in the development of tailored interventions aimed at improving the adoption of effective coping strategies and reducing the use of maladaptive coping strategies.
Lafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1. With a few exceptions, the influence of genetic factors on disease ...progression has yet to be confirmed. We present a systematic review and meta-analysis of the known pathogenic variants to identify genotype-phenotype correlations.
We collected all reported cases with genetically-confirmed LD containing data on disease history. Pathogenic variants were classified into missense (MS) and protein-truncating (PT). Three genotype classes were defined according to the combination of the variants: MS/MS, MS/PT, and PT/PT. Time-to-event analysis was performed to evaluate survival and loss of autonomy.
250 cases described in 70 articles were included. The mutated gene was NHLRC1 in 56% and EPM2A in 44% of cases. 114 pathogenic variants (67 EPM2A; 47 NHLRC1) were identified. The NHLRC1 genotype PT/PT was associated with shorter survival HR 2.88; 95% CI 1.23-6.78 and a trend of higher probability of loss of autonomy HR 2.03, 95% CI 0.75-5.56 at the multivariable Cox regression analysis. The population carrying the homozygous p.Asp146Asn variant of NHLRC1 genotype was confirmed to have a more favourable prognosis in terms of disease duration.
This study demonstrates the existence of prognostic genetic factors in LD, namely the genotype defined according to the functional impact of the pathogenic variants. Although the reasons why NHLRC1 genotype PT/PT is associated with a poorer prognosis have yet to be fully elucidated, it may be speculated that malin plays a pivotal role in LD pathogenesis.
ABSTRACT
The concept of epilepsy syndromes, introduced in 1989, was defined as “clusters of signs and symptoms customarily occurring together”. Definition of epilepsy syndromes based on ...electro‐clinical features facilitated clinical practice and, whenever possible, clinical research in homogeneous groups of patients with epilepsies. Progress in the fields of neuroimaging and genetics made it rapidly clear that, although crucial, the electro‐clinical description of epilepsy syndromes was not sufficient to allow much needed development of targeted therapies and a better understanding of the underlying pathophysiological mechanisms of seizures. The 2017 ILAE position paper on Classification of the Epilepsies recognized that “as a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking”. The concept of “epilepsy syndromes” evolved, incorporating issues related to aetiologies and comorbidities. A comprehensive update (and revision where necessary) of the EEG diagnostic criteria in the light of the 2017 revised terminology and concepts was deemed necessary. Part 2 covers the neonatal and paediatric syndromes in accordance with the age of onset. Published with educational EEG plates at www.epilepticdisorders.com.
We explored the impact of the coronavirus disease-19 (COVID-19) emergency on the health of people with epilepsy (PwE). We also investigated their attitude toward telemedicine.
The PubMed database up ...to September 10, 2020 was searched for questionnaire-based studies conducted in PwE during the COVID-19 emergency, and the literature retrieved was reviewed. In addition, all patients who had a telephone consultation with our center between May 7 and July 31, 2020 were invited to fill in a 57-item online questionnaire focusing on epilepsy and comorbidities, any changes in lifestyle or clinical conditions and any emergency-related problems arising during the COVID-19 emergency, and their views on telemedicine. Associations between variables were detected through
test and Fisher's exact test. Univariate and multivariate logistic regression models were used to evaluate the effects of different factors on clinical conditions.
Twelve studies met the literature search criteria. They showed that the rate of seizure worsening during the emergency ranged from 4 to 35% and was mainly correlated with epilepsy severity, sleep disturbances and COVID-19-related issues. Our questionnaire was filled in by 222 PwE or caregivers. One hundred (76.6%) reported unchanged clinical conditions, 25 (11.3%) an improvement, and 27 (12%) a deterioration. Reported clinical worsening was associated with a psychiatric condition and/or medication (OR = 12.59,
< 0.001), sleep disorders (OR = 8.41,
= 0.001), limited access to healthcare (OR = 4.71,
= 0.016), and experiencing seizures during the emergency (OR = 4.51,
= 0.007). Telemedicine was considered acceptable by 116 subjects (52.3%).
Most PwE did not experience a significant change in their clinical conditions during the COVID-19 emergency. However, severity of epilepsy, concomitant disability, comorbid psychiatric conditions, sleep disorders and limited access to healthcare may affect their health.
Narcolepsy is a rare chronic sleep disorder that typically begins in youth. Excessive daytime sleepiness is the main disabling symptom, but the disease is often associated with severe ...endocrine-metabolic and psychosocial issues, worsened by a long diagnostic delay, requiring a multidisciplinary approach. The scarcity of reference Sleep Centres forces the patient and family to travel for seeking medical consultations, increasing the economic and psychosocial burden of the disease. Growing evidence suggests that Telemedicine may facilitate patient access to sleep consultations and its non-inferiority in terms of patient satisfaction, adherence to treatment, and symptom improvement for sleep disorders. However, Telemedicine clinical and economic benefits for patients with narcolepsy are still unknown.
TENAR is a two-part project, including: 1. a cross-sectional study (involving 250 children and adults with suspected narcolepsy) evaluating the accuracy of Teletriage (i.e., a synchronous live interactive sleep assessment through a Televisit) for narcolepsy diagnosis compared to the reference standard; and 2. a two-arm, parallel, open randomized controlled trial (RCT) to demonstrate the non-inferiority of the multidisciplinary care of narcolepsy through Televisits versus standard care. In this RCT, 202 adolescents (> 14 y.o.) and adults with narcolepsy will be randomly allocated (1:1 ratio) either to Televisits via videoconference or to standard in-person outpatient follow-up visits (control arm). The primary outcome is sleepiness control (according to the Epworth Sleepiness Scale). Secondary outcomes are other symptoms control, compliance with treatment, metabolic control, quality of life, feasibility, patient and family satisfaction with care, safety, and disease-related costs. At baseline and at 12 months, patients will undergo neurologic, metabolic, and psychosocial assessments and we will measure primary and secondary outcomes. Primary outcomes will be also measured at 6 months (remotely or in person, according to the arm).
TENAR project will assess, for the first time, the feasibility, accuracy, efficacy and safety of Telemedicine procedures applied to the diagnosis and the multidisciplinary care of children and adults with narcolepsy. The study may be a model for the remote management of other rare disorders, offering care access for patients living in areas lacking medical centres with specific expertise.
Number of the Tele-multidisciplinary care study NCT04316286. Registered 20 March 2020.
Introduction
We aimed to create standardized protocol for language examination in patients who underwent video-EEG recording and assessed its efficacy in the characterization of ictal language ...impairment, its ability to differentiate this from impaired awareness, and interobserver reliability in clinical practice.
Methods
From our database of video-EEG recordings, we selected a representative sample of 63 focal seizures with presumed language impairment. A multidisciplinary team of epileptologists, EEG technicians, and speech therapists analyzed the selected videos to highlight the critical issues of ordinary ictal language evaluation. We subsequently followed a multi-step process to develop the protocol and assess its interobserver reliability.
Results
A protocol based on seven tests in hierarchical succession was created, summed up in the acronym CA-P-S C-A-R-E (Closed Answers, Pro-speak question, Simple orders, Common object denomination, Audio repetition, Reading, Evoke). Following its preliminary administration for 5 months, we assessed the inter-observer reliability of 16 healthcare professionals in distinguishing between language impairment and impaired awareness among a sample of 10 seizures, finding a substantial agreement (kappa 0.61).
Conclusion
The proposed protocol, made of simple and easy to memorize tests, is an effective tool that evaluates multiple domains beyond language. Its use could help to recognize ictal aphasia effectively and differentiate it from impaired awareness, minimizing inter-examiner variability.
IntroductionEpilepsy is a chronic condition requiring consistent follow-up aimed at seizure control, and monitoring of anti-seizure medication (ASM) levels and side effects. Telemedicine (TM) offers ...invaluable support to patient follow-up, guaranteeing the prompt availability of a team of experts for persons with epilepsy (PWE) widely distributed across the country. Although many health institutions have endorsed the use of TM, robust data on effectiveness, safety and costs of TM applied to epilepsy are lacking. TELEmedicine for EPIlepsy Care (TELE-EPIC) will evaluate the effectiveness of video consultation (VC) via TM compared with usual care (UC) for the monitoring of PWE (TELE-EPIC_RCT). Moreover, TELE-EPIC will apply an innovative Volumetric Absorptive Microsampling (VAMS) device for quantitation of ASM through finger prick blood sampling as an alternative to venipuncture sampling (TELE-EPIC_VAMS).Methods and analysisTELE-EPIC_RCT is a multicentre, open, pragmatic two-arm randomised controlled trial prospectively including adult and paediatric outpatients with established diagnosis of epilepsy consecutively attending the Epilepsy Centres of Bologna and Rome, respectively. The primary outcome is the non-inferiority of VC on seizure control compared with UC after an 18-month follow-up. Secondary outcomes are adherence to treatment, ASM-related adverse events, quality of life, mood disorders, patient and caregiver satisfaction, safety and costs. TELE-EPIC_VAMS is a cross-validation study for blood ASM quantitation through a novel, VAMS-based device, comparing (1) VAMS versus plasma samples (reference standard method); and (2) nurse-collected versus self-collected blood by VAMS device.Ethics and disseminationThe study has been approved by the local ethics committee (349-2019-SPER-AUSLBO). Complete information about the state of project, relevant events and results will be regularly updated on the project’s webpage on ClinicalTrials.gov. The project’s results and data on the potential impact of TM in epilepsy will be disseminated on social media. A closeout meeting will be convened for the communication and dissemination of the project, highlighting its main achievements and impacts.Trial registration numberNCT04496310
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