Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

Prevalence of ictal injuries in functional (psychogenic nonepileptic) seizures: A systematic review and meta-analysis.

OBJECTIVE: Ictal injuries have long been considered typical signs of epileptic seizures. However, studies have shown that patients with functional seizures (FS)-also named psychogenic nonepileptic seizures-can also present these signs, misleading physicians and delaying a correct diagnosis. This systematic review aimed to assess the prevalence of injuries from FS. METHODS: A literature search was performed in PubMed, Embase, LILACS (Latin American and Caribbean Health Sciences Literature), Scopus, Web of Science, PsycINFO, Google Scholar, OpenGrey, and ProQuest. Observational studies were included. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist for studies reporting prevalence data. RStudio was used for meta-analyses. Cumulative evidence was evaluated according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: From the 2607 identified records, 41 studies were included in the qualitative synthesis, and 28 were included in meta-analyses. A meta-analysis of 13 studies, including 1673 individuals, resulted in an overall lifetime prevalence of injuries due to FS per person of 25% (95% confidence interval [CI] = 19%-32%, I2 = 88%). Considering a limited period (video-electroencephalographic [VEEG] monitoring days), a meta-analysis of 13 studies, including 848 individuals, resulted in an injury prevalence due to FS per person of .7% (95% CI = 0%-3%, I2 = 73%). Also, a meta-analysis of eight studies, including 1000 individuals, resulted in a prevalence of injuries per FS of .1% (95% CI = 0%-.98%, I2 = 49%). The certainty in cumulative evidence assessed by GRADE was rated "very low" for lifetime prevalence of injuries per person, "low" for prevalence per person during VEEG monitoring, and "moderate" for prevalence per number of FS. SIGNIFICANCE: Overall pooled lifetime prevalence of injuries due to FS per person was 25%. In comparison, the prevalence of injuries per person during VEEG monitoring and per functional seizure was .7% and .1%, respectively. [Correction added on 07 October 2023, after first online publication: In the preceding sentence, 'consecutively' was corrected to 'respectively'.] The evidence of the occurrence of injuries due to FS breaks the paradigm that epileptic seizures can cause injuries but FS cannot.

Seizure rescue medications are missing from in-flight medical emergency kits.

OBJECTIVE: We aimed to inquire whether any seizure rescue medications are included in the in-flight medical emergency kits of the main airlines in the world. This data could help the airline authorities update their strategies in light of any shortcomings. METHODS: First, we identified ten major airlines in the world. Then, we searched the Google engine with the following keywords: "name of the airline" and "in-flight medical emergency" or "first aid kit" or "emergency kit". In case there was no information on the web, we emailed the airlines and inquired about the contents of their in-flight medical emergency kits. We also investigated some of the major aviation organizations' websites [i.e., Aerospace Medical Association (AsMA), International Civil Aviation Organization (ICAO), and International Air Transport Association (IATA)]. RESULTS: None of the major airlines were equipped with easily applicable seizure rescue medications (i.e., buccal midazolam, a nasal spray of midazolam, or intranasal diazepam). The AsMA and ICAO recommend including injectable sedative anticonvulsant drugs in the in-flight medical emergency kits without any further specifications. The IATA does not provide specific recommendations for including seizure rescue medications in the in-flight medical emergency kits. CONCLUSION: A seizure is a significant in-flight medical emergency event. The use of easily applicable seizure rescue medications during prolonged or repeated seizures is significantly associated with fewer sequelae for the affected person. Easily applicable seizure rescue medications should be included in the in-flight medical emergency kits, and the cabin crew should receive training on how and when to use them.

Epilepsy care during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID-19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well-being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID-19 pandemic, including access to health services and impact on mental health, including the 6-item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new-onset seizures or an exacerbation of seizures in the context of COVID-19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well-being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p<0.01). An increase in telemedicine use during the COVID-19 pandemic was reported by health care professionals, with 40% of consultations conducted by this method. Although 74.9% of health care providers thought that this impacted positively, barriers to care were also identified. As we move forward, there is a need to ensure ongoing support and care for PWE to prevent a parallel pandemic of unmet health care needs.

Epilepsy and school in the Middle East and North Africa (MENA) region: The current situation, challenges, and solutions.

Education is a human right that plays a key role in social and economic development. Children having active epilepsy may not be properly schooled in ordinary school structures. Students with epilepsy (SWE) are often faced with academic barriers. The lack of information about the current status of special education for SWE obliged the researchers to try to describe the existing reality of the special education practices in the Middle East and North Africa (MENA) region. We disseminated a simple self-administered questionnaire via email to main healthcare professionals involved in epilepsy care in the MENA region, and we also did a literature search on the PubMed, Google Scholar, and Embase engines. We ranked the countries in terms of their educational system. The 1st group contains the most advanced educational system, including specialized schools for SWE. The 2nd group contains an educational system with specialized but less structured schools. The 3rd group includes countries using integrated classes or classes mixing many children with cognitive disabilities. The 4th group includes countries with ordinary classes for SWE, and finally, the 5th group with no schooling for children with epilepsy (CWE). This study indicates that 60% of the countries in the MENA region belong to the 3rd group; there is only one country in each of the first two groups. This work highlights the need to develop structured environments for schooling for SWE in the MENA region.

Association of Human Leukocyte Antigen Alleles with Carbamazepine- or Lamotrigine-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in an Iranian Population: A Case-control Study.

Background: Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN. Methods: A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher's exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant. Results: CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07). Conclusion: Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.

Nano-delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives.

Epilepsy is a common chronic neurological disorder caused by aberrant neuronal electrical activity. Antiseizure medications (ASMs) are the first line of treatment for people with epilepsy (PWE). However, their effectiveness may be limited by their inability to cross the blood-brain barrier (BBB), among many other potential underpinnings for drug resistance in epilepsy. Therefore, there is a need to overcome this issue and, hopefully, improve the effectiveness of ASMs. Recently, synthetic nanoparticle-based drug delivery systems have received attention for improving the effectiveness of ASMs due to their ability to cross the BBB. Furthermore, exosomes have emerged as a promising generation of drug delivery systems because of their potential benefits over synthetic nanoparticles. In this narrative review, we focus on various synthetic nanoparticles that have been studied to deliver ASMs. Furthermore, the benefits and limitations of each nano-delivery system have been discussed. Finally, we discuss exosomes as potentially promising delivery tools for treating epilepsy.

Is Shunt Location a Risk Factor for the Development of De Novo Post-shunt Seizures?

Background: While ventriculo-extracranial shunting procedures have been the standard treatment option for hydrocephalus for a long time, their long-term morbidity, including the development of post-shunt de Novo seizures, should be taken into account. This study aimed to investigate the rate and risk factors of the occurrence of de Novo post-shunt seizures in patients with hydrocephalus. Methods: In this retrospective longitudinal study, all patients with hydrocephalus who had ventriculo-peritoneal shunt insertion from 2014 to 2017 at Namazi Hospital, (Shiraz, Iran) were studied. Phone calls were made to all patients to obtain their postoperative seizure outcome and other data (e.g., sex, age at surgery, shunt insertion location, history of seizures before surgery, history of seizures after surgery, any other type of brain surgery, and the etiology of their hydrocephalus). The Pearson Chi Square was used for the analysis of binary variable (e.g., sex) differences, and the t test for the analysis of differences in the means of numerical variables (e.g., age). Bonferroni correction tests were also utilized. P values less than 0.05 were considered significant. Results: A total of 114 patients were included in the study. Overall, 68 (60%) patients had a frontal location of shunt insertion and 46 (40%) had a parietal site. Twenty-four (21%) patients reported experiencing de Novo post-shunt seizures, 15 of which had a frontal location and nine a parietal location for shunt insertion (P=0.824). Conclusion: De Novo post-shunt seizures are common occurrences. However, shunt location is not a significant risk factor for the development of de Novo post-shunt seizures.

Vasovagal syncope treated as epilepsy for 16 years.

The differentiation of vasovagal syncope and epileptic seizure is sometimes problematic, since vasovagal syncope may mimic epileptic seizures in many ways. The present report describes a patient who had been diagnosed and treated as having epilepsy with medically-refractory seizures for 16 years. Often, unlike epileptic seizures, tonic-clonic convulsions and postictal confusion are uncommon features of vasovagal syncope, but these may occur. Our patient was subjected to subcutaneous injection of one ml normal saline, which caused asystole leading to hypoxia and consequently a typical tonic-clonic convulsion. This patient was proved to have vasovagal syncope. The findings in the present case suggest that the possibility of vasovagal syncope should always be taken into consideration when evaluating patients with medically-refractory or unusual pattern of seizures. In such a circumstance, simultaneous video-electroencephalogram/electocardiogram monitoring may help achieve the correct diagnosis.

The Neurological Manifestations of H1N1 Influenza Infection; Diagnostic Challenges and Recommendations.

BACKGROUND: World Health Organization declared pandemic phase of human infection with novel influenza A (H1N1) in April 2009. There are very few reports about the neurological complications of H1N1 virus infection in the literature. Occasionally, these complications are severe and even fatal in some individuals. The aims of this study were to report neurological complaints and/or complications associated with H1N1 virus infection. METHODS: The medical files of all patients with H1N1 influenza infection admitted to a specified hospital in the city of , from October through November 2009 were reviewed. More information about the patients were obtained by phone calls to the patients or their care givers. All patients had confirmed H1N1 virus infection with real-time PCR assay. RESULTS: Fifty-five patients with H1N1 infection were studied. Twenty-three patients had neurological signs and/or symptoms. Mild neurological complaints may be reported in up to 42% of patients infected by H1N1 virus. Severe neurological complications occurred in 9% of the patients. The most common neurological manifestations were headache, numbness and paresthesia, drowsiness and coma. One patient had a Guillain-Barre syndrome-like illness, and died in a few days. Another patient had focal status epilepticus and encephalopathy. CONCLUSIONS: The H1N1 infection seems to have been quite mild with a self-limited course in much of the world, yet there appears to be a subset, which is severely affected. We recommend performing diagnostic tests for H1N1influenza virus in all patients with respiratory illness and neurological signs/symptoms. We also recommend initiating treatment with appropriate antiviral drugs as soon as possible in those with any significant neurological presentation accompanied with respiratory illness and flu-like symptoms.