Safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of central nervous system: A single center experience.

Introduction: Concern of a correlation between disease relapse in patients with acquired demyelinating disorders of central nervous system (CNS) and SARS-CoV2 vaccines has been raised. In this single center study, we retrospectively evaluated safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of CNS. Materials and methods: Patients with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) with disease onset before 18 years of age were included. Demographic and clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Results: We included nine patients with MOGAD. Six patients received SARS-CoV2 vaccination and complained pain at injection site while only one had fever and fatigue. Median follow-up was 28 weeks (range 20-48). Seven patients had COVID-19 occurring with mild flu-like symptoms and median follow-up was 28 weeks (range 24-34). Nobody had disease relapse. Five patients with NMOSD were included. All patients received SARS-CoV2 vaccination (BNT162b2-Pfizer-BioNTech). The median follow-up was 20 weeks (range 14-24) and only two patients complained pain at injection site, fever and fatigue. Three patients had also COVID-19 with mild flu-like symptoms, despite two of them being under immunosuppressive treatment. Lastly, forty-three patients with MS were included. 35 out of 43 received SARS-CoV2 vaccination with a median follow-up of 24 weeks (range 8-36). Fourteen patients had no side effects, while 21 complained mild side effects (mainly pain at injection site) and one experienced a disease relapse with complete recovery after steroid therapy. At vaccination, all but one were under treatment. Sixteen patients had COVID-19 occurring with mild symptoms. Discussion: COVID-19 outcome was good although many patients were under immunosuppressive treatment. Vaccine-related side effects were frequent but were mild and self-limited. Only one MS patient had a post-vaccination relapse with complete recovery after steroid therapy. In conclusion, our data support the safety of SARS-CoV-2 vaccines in pediatric MS, MOGAD and NMOSD.

Safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of central nervous system: A single center experience

Introduction Concern of a correlation between disease relapse in patients with acquired demyelinating disorders of central nervous system (CNS) and SARS-CoV2 vaccines has been raised. In this single center study, we retrospectively evaluated safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of CNS. Materials and methods Patients with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) with disease onset before 18 years of age were included. Demographic and clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Results We included nine patients with MOGAD. Six patients received SARS-CoV2 vaccination and complained pain at injection site while only one had fever and fatigue. Median follow-up was 28 weeks (range 20-48). Seven patients had COVID-19 occurring with mild flu-like symptoms and median follow-up was 28 weeks (range 24-34). Nobody had disease relapse. Five patients with NMOSD were included. All patients received SARS-CoV2 vaccination (BNT162b2-Pfizer-BioNTech). The median follow-up was 20 weeks (range 14-24) and only two patients complained pain at injection site, fever and fatigue. Three patients had also COVID-19 with mild flu-like symptoms, despite two of them being under immunosuppressive treatment. Lastly, forty-three patients with MS were included. 35 out of 43 received SARS-CoV2 vaccination with a median follow-up of 24 weeks (range 8-36). Fourteen patients had no side effects, while 21 complained mild side effects (mainly pain at injection site) and one experienced a disease relapse with complete recovery after steroid therapy. At vaccination, all but one were under treatment. Sixteen patients had COVID-19 occurring with mild symptoms. Discussion COVID-19 outcome was good although many patients were under immunosuppressive treatment. Vaccine-related side effects were frequent but were mild and self-limited. Only one MS patient had a post-vaccination relapse with complete recovery after steroid therapy. In conclusion, our data support the safety of SARS-CoV-2 vaccines in pediatric MS, MOGAD and NMOSD.

Long-Term Effects of COVID-19 Pandemic on Migraine in Adolescents. A Retrospective Analysis of the Population Attending the Headache Center in Different Phases of the Pandemic.

BACKGROUND: Literature data report that the first COVID-19 pandemic had an impact on the progression of migraine both in adults and children. The present study aimed to verify how the migraine course and psychological aspects varied in adolescent patients in relation to some of the different phases of the COVID-19 pandemic and compared with the months before COVID-19. In addition, the relationship between the characteristics of headache episodes and psychological and school-related aspects were analyzed. METHODS: The study included 418 adolescents. Based on the timing of the evaluation, they were categorized into patients observed before the COVID-19 pandemic (pre COVID) or during the first (COVID 1) or second (COVID 2) wave of the pandemic. Subjects were also categorized into three further groups: those who had high or low frequency of migraine attacks during the month, those who had mild or severe pain during the attack, and those who were taking prophylactic drugs. The Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) scales were utilized to assess depression and anxiety. RESULTS: We observed a significant increase in the frequency of attacks and the use of prophylactic drugs during the COVID 2 period compared to the COVID 1 and pre-COVID periods (p < 0.05). Patients showed higher levels of anxiety and depression during each of the two COVID periods compared with the pre-COVID months (p < 0.05), especially during the COVID 2 period (p < 0.05). CONCLUSION: Our results show long-term negative impacts of the COVID-19 pandemic on clinical parameters and psychological symptoms in adolescents with migraine.

Case report: A pediatric case of Bickerstaff brainstem encephalitis after COVID-19 vaccination and Mycoplasma pneumoniae infection: Looking for the culprit.

Bickerstaff brainstem encephalitis (BBE) is a rare, immune-mediated disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance. It has a complex multifactorial etiology, and a preceding infectious illness is seen in the majority of cases. Immune-mediated neurological syndromes following COVID-19 vaccination have been increasingly described. Here we report the case of a child developing BBE 2 weeks after COVID-19 vaccination. Despite nerve conduction studies and CSF analysis showing normal results, BBE was diagnosed on clinical ground and immunotherapy was started early with a complete recovery. Later, diagnosis was confirmed by positive anti-GQ1b IgG in serum. Even if there was a close temporal relationship between disease onset and COVID-19 vaccination, our patient also had evidence of a recent Mycoplasma pneumoniae infection that is associated with BBE. Indeed, the similarity between bacterial glycolipids and human myelin glycolipids, including gangliosides, could lead to an aberrantly immune activation against self-antigens (i.e., molecular mimicry). We considered the recent Mycoplasma pneumoniae infection a more plausible explanation of the disease onset. Our case report suggests that suspect cases of side effects related to COVID-19 vaccines need a careful evaluation in order to rule out well-known associated factors before claiming for a causal relationship.

From the New Diagnostic Criteria to COVID-19 Pandemic Passing Through the Placebo Effect. What Have We Learned in the Management of Pediatric Migrane Over the Past 5 Years?

In 2018, the Food and Drug Administration (FDA) approval of anti-calcitonin gene-related peptide (CGRP) therapies for the treatment of migraine represented a milestone for the management of the disease in adults. On the contrary, the novelties in the field of pediatric migraine are inserted in a different scenario and still concern: (1) diagnostic criteria of the international classification of headache disorders-3 (ICHD-3) that show numerous limits of applicability in the developmental age; (2) the release of the results of the Childhood and Adolescent Migraine Prevention (CHAMP) study that raised doubts about the usefulness of traditional drugs for the treatment of pediatric migraine; (3) the Coronavirus disease 2019 (COVID-19) pandemic has put the spotlight on the importance of managing the psychological factors associated with the disease. In this mini review we discuss the most relevant news in pediatric migraine over the last 5 years.

Subacute Sclerosing Panencephalitis in Children: The Archetype of Non-Vaccination.

Subacute sclerosing panencephalitis (SSPE) is a late complication of measles virus infection that occurs in previously healthy children. This disease has no specific cure and is associated with a high degree of disability and mortality. In recent years, there has been an increase in its incidence in relation to a reduction in vaccination adherence, accentuated by the COVID-19 pandemic. In this article, we take stock of the current evidence on SSPE and report our personal clinical experience. We emphasise that, to date, the only effective protection strategy against this disease is vaccination against the measles virus.

Vaccination and childhood epilepsies.

INTRODUCTION: The evidence relating vaccination to febrile seizures and epilepsy is evaluated with an emphasis on febrile seizures (FS), Dravet syndrome (DS), West syndrome, and other developmental and epileptic encephalopathies. METHODS: A systematic literature review using search words vaccination/immunization AND febrile seizures/epilepsy/Dravet/epileptic encephalopathy/developmental encephalopathy was performed. The role of vaccination as the cause/trigger/aggravation factor for FS or epilepsies and preventive measures were analyzed. RESULTS: From 1428 results, 846 duplicates and 447 irrelevant articles were eliminated; 120 were analyzed. CONCLUSIONS: There is no evidence that vaccinations cause epilepsy in healthy populations. Vaccinations do not cause epileptic encephalopathies but may be non-specific triggers to seizures in underlying structural or genetic etiologies. The first seizure in DS may be earlier in vaccinated versus non-vaccinated patients, but developmental outcome is similar in both groups. Children with a personal or family history of FS or epilepsy should receive all routine vaccinations. This recommendation includes DS. The known risks of the infectious diseases prevented by immunization are well established. Vaccination should be deferred in case of acute illness. Acellular pertussis DTaP (diphtheria-tetanus-pertussis) is recommended. The combination of certain vaccine types may increase the risk of febrile seizures however the public health benefit of separating immunizations has not been proven. Measles-containing vaccine should be administered at age 12-15 months. Routine prophylactic antipyretics are not indicated, as there is no evidence of decreased FS risk and they can attenuate the antibody response following vaccination. Prophylactic measures (preventive antipyretic medication) are recommended in DS due to the increased risk of prolonged seizures with fever.

Neonatal Cerebral Venous Thrombosis following Maternal SARS-CoV-2 Infection in Pregnancy.

A possible consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the development of an exacerbated thrombophilic status, and cerebral venous thrombosis (CVT) is a rare but possible complication of SARS-CoV-2 infection reported both in adults and in children. The present case report describes the clinical course of a term neonate showing extended CVT of unclear origin, whose mother had developed SARS-CoV-2 infection during the third trimester of pregnancy. We speculate that the prothrombotic status induced by maternal SARS-CoV-2 infection may have played a pathophysiological role in the development of such severe neonatal complication. Further investigations are required to confirm such hypothesis.

TELEmedicine for EPIlepsy Care (TELE-EPIC): protocol of a randomised, open controlled non-inferiority clinical trial.

INTRODUCTION: Epilepsy 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 ANALYSIS: TELE-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 DISSEMINATION: The 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 NUMBER: NCT04496310.

I stay at home with headache. A survey to investigate how the lockdown for COVID-19 impacted on headache in Italian children.

OBJECTIVE: The present Italian multicenter study aimed at investigating whether the course of primary headache disorders in children and adolescents was changed during the lockdown necessary to contain the COVID-19 emergency in Italy. METHODS: During the lockdown, we submitted an online questionnaire to patients already diagnosed with primary headache disorders. Questions explored the course of headache, daily habits, psychological factors related to COVID-19, general mood and school stress. Answers were transformed into data for statistical analysis. Through a bivariate analysis, the main variables affecting the subjective trend of headache, and intensity and frequency of the attacks were selected. The significant variables were then used for the multivariate analysis. RESULTS: We collected the answers of 707 patients. In the multivariate analysis, we found that reduction of school effort and anxiety was the main factor explaining the improvement in the subjective trend of headache and the intensity and frequency of the attacks (p < 0.001). The greater the severity of headache, the larger was the clinical improvement (p < 0.001). Disease duration was negatively associated with the improvement (p < 0.001). It is noteworthy that clinical improvement was independent of prophylaxis (p > 0.05), presence of chronic headache disorders (p > 0.05) and geographical area (p > 0.05). CONCLUSIONS: Our study showed that lifestyle modification represents the main factor impacting the course of primary headache disorders in children and adolescents. In particular, reduction in school-related stress during the lockdown was the main factor explaining the general headache improvement in our population.

Impact of COVID-19 pandemic on pediatric patients with epilepsy - The caregiver perspective.

The recent COVID-19 pandemic has disrupted care systems around the world. We assessed how the COVID-19 pandemic affected children with epilepsy in Italy, where lockdown measures were applied from March 8 to May 4, 2020. We compiled an Italian-language online survey on changes to healthcare and views on telehealth. Invitations were sent to 6631 contacts of all patients diagnosed with epilepsy within the last 5 years at the BambinoGesù Children's Hospital in Rome. Of the 3321 responses received, 55.6% of patients were seizure-free for at least 1 year before the COVID-19-related lockdown, 74.4% used anti-seizure medications (ASMs), and 59.7% had intellectual disability. Only 10 patients (0.4%) became infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Seizure frequency remained stable for most patients during the lockdown period (increased in 13.2%; decreased in 20.3%), and seizure duration, use of rescue medications, and adherence to treatment were unchanged. Comorbidities were more affected (behavioral problems worsened in 35.8%; sleep disorder worsened in 17.0%). Visits were canceled/postponed for 41.0%, but 25.1% had remote consultation during the lockdown period (93.9% were satisfied). Most responders (67.2%) considered continued remote consultations advantageous. Our responses support that patients/caregivers are willing to embrace telemedicine for some scenarios.