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Background: Multiple sclerosis (MS) is increasing in the pediatric population and, as in adults, symptoms vary among patients. In children the first manifestations can sometimes overlap with acute neurological symptoms. Urological symptoms have not been much studied in childhood. We shared our experience with MS urological manifestation in children., Methods: This article is a retrospective evaluation of all children with MS, according to the Krupp criteria, who also present with urological symptoms. We collected demographic and clinical history, the MR localization of demyelinating lesions, urological symptoms, and exams., Results: We report on six MS pediatric cases with urological manifestation. Urinary symptoms, characterized by urinary incontinence in five patients and urinary retention in one patient, appeared in a different time frame from MS diagnosis. Urodynamic exams showed both overactive and underactive bladder patterns. Treatment was defined according to lower urinary tract dysfunction, using clean intermittent catheterization, oxybutynin, and intradetrusor Onabotulinum Toxin-A injection. A low acceptance rate of invasive evaluation and urological management was observed., Conclusions: The MS diagnosis was traumatic for all our patients. We believe it is important to address urological care in young people from the time of diagnosis for prompt management; it could be useful to include a pediatric urologist in multidisciplinary teams.

Multiple sclerosis (MS) is primarily a disease diagnosed in young and middle-aged adults. Although MS is a rare condition in pediatric age, an increasing rate of patients is diagnosed under the age of 18. The disabling nature of the disease cannot be reduced only to physical symptoms. Several additional symptoms such as cognitive impairment, fatigue, and psychological symptoms are common features of pediatric MS. The reviewed literature suggests that, despite the lower physical disability, children and adolescents diagnosed with MS are vulnerable to cognitive impairment even in the early stage of the disease. The neuropsychological profile of pediatric MS may resemble that of adult MS, including an impairment in attention/information processing speed, learning, verbal, and visuospatial memory. However, cognitive difficulties in children and adolescents are more likely to involve also general intelligence and linguistic abilities, presumably due to patients' younger age and cognitive growth stage. Cognitive difficulties, beyond physical disability and relapses, may have a considerable impact on learning and school achievement. Depression and fatigue are other highly prevalent disturbances in pediatric MS and may contribute to patients' low functional outcomes. Overall, these manifestations may cause considerable functional impairment on daily activities and quality of life that may require individualized rehabilitative treatment and extensive psychosocial care. Additional neuropsychological research evaluating larger samples, using more homogenous methods, and exploring the role of MS treatment on cognitive and psychological development is required., (© 2023. The Author(s).)

Background: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders., Methods: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation., Results: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05)., Conclusions: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities., (© 2024. The Author(s).)

Multiple sclerosis (MS) is a chronic and unpredictable inflammatory disease impacting the central nervous system. The disabling nature of this disease is not limited to only physical symptoms. MS, even at a pediatric age, often includes cognitive impairment, fatigue, and psychological issues, affecting education and social life, causing emotional distress, and reducing quality of life. Despite the paucity of quantitative data in the existing literature, our review demonstrates that the impact of pediatric MS extends beyond the patients themselves, affecting their parents as well. There is evidence suggesting that having a child with MS may be associated with a reduction in the parental quality of life, even in families of MS patients with low or no disability and without clinical relapses. Moreover, an increased risk of parents' mental illness has been described, particularly in mothers, leading to a heightened utilization of mental health services. Research data show that inadequate information about MS may impact parents' anxiety and their sense of competence. Since parents' involvement has been found to also play a role in their child's adherence to treatment, special attention should be paid to parental psychological health. Additional research exploring family adaptation to their children's illness is required.

Obesity has been suggested as an environmental risk factor for multiple sclerosis (MS) and may negatively effect the progression of the disease. The aim of this study is to determine any correlation between overweight/obesity and the clinical and neuroradiological features at the onset of pediatric onset multiple sclerosis (POMS). Were included patients referred to the POMS Unit of the Bambino Gesù Children's Hospital between June 2012 and June 2021. The diagnosis of MS with an onset of less than 18 years was required. For all included subjects, we considered for the analysis the following data at the onset of symptoms: general data (age, sex, functional system compromised by neurological signs, weight and height), brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid exams. We identified 55 pediatric cases of POMS and divided them into two groups according to the body mass index (BMI): 60% were healthy weight (HW) and 40% were overweight/obese (OW/O). OW/O patients experienced a two-year age difference in disease onset compared to the HW patients (12.7 ± 3.8 years vs. 14.6 ± 4.1 years; p < 0.05). Onset of polyfocal symptoms was seen more frequently in OW/O patients than in HW (72.7% vs. 21.2%; p < 0.05). The pyramidal functions were involved more frequently in the OW/O group than in the HW group (50% vs. 25%; p < 0.005). Black holes were detected more frequently in OW/O patients in onset MRI scans compared to the HW group (50% vs. 15.5%; p < 0.05). Our findings suggest that being overweight/obese affects the risk of developing MS at an earlier age and is associated with an unfavorable clinical-radiological features at onset. Weight control can be considered as a preventive/therapeutic treatment.

Background: The use of OnabotulinumtoxinA (OBT-A) for the treatment of chronic migraine (CM) in adults represents a therapy with the greatest efficacy and safety data. However, we have little evidence on the use of OBT-A in children or adolescents. The present study aims to describe the experience with OBT-A in the treatment of CM in adolescents in an Italian third-level headache center., Methods: The analysis included all patients under the age of 18 treated with OBT-A for CM at the Bambino Gesù Children's Hospital. All patients received OBT-A following the PREEMPT protocol. Subjects were classified as good responders if a greater than 50% reduction in the monthly frequency of attacks was observed, partial responders if the reduction was between 30 and 50%, and non-responders if it was <30%., Results: The treated population consisted of 37 females and 9 males with a mean age of 14.7 years. Before starting OBT-A, 58.7% of the subjects had attempted prophylactic therapy with other drugs. From OBT-A initiation to the last clinical observation, the mean duration of follow-up was 17.6 ± 13.7 SD (range: 1-48) months. The number of OBT-A injections were 3.4 ± 3 SD. Sixty eight percent of the subjects responded to treatment within the first three administrations of OBT-A. Proceeding with the number of administrations, a progressive improvement in frequency was further observed., Conclusions: The use of OBT-A in pediatric age can have benefits in terms of reduction in the frequency and intensity of headache episodes. Furthermore, treatment with OBT-A has an excellent safety profile. These data support the use of OBT-A in the treatment of childhood migraine.

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor DL declared a shared parent affiliation with some of the authors RM, PP at the time of review., (Copyright © 2023 Monte, Papetti, Ferilli, Ursitti, Moavero, Sforza, Panella, Tarantino, Checchi, Vigevano, Palma and Valeriani.)

Background and Objectives: We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD)., Methods: In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with follow-up >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up., Results: Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) ( p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) ( p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) ( p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03-0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03-0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01-0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) ( p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33-33.26, p = 0.021)., Discussion: At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1)., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment., Methods: Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP)., Results: A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians., Conclusion: In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Papetti, Tarantino, Ursitti, Moavero, Proietti, Sforza, Monte, Ferilli, Balestri, Vigevano and Valeriani.)

Primary headache is a very common and disabling disease. The burden of pain and recurrent attacks may lead to a poor quality of life, anxiety and depression. An increased risk of low functioning and curricular performances in young patients with primary headache has been described. The mechanisms underlying the relationship between migraine and poor school achievement may be various and could be a reflection of weak cognitive skills. Data concerning the cognitive functioning in the free pain interval in pediatric age are under-investigated and results are far from conclusive. The present review article suggests that, though considered a benign disease, pediatric migraine may be associated to altered neuropsychological functioning in the interictal phase. Although children and adolescents with migraine generally have a normal intelligence, they may show a not homogeneous cognitive profile, characterized by possible difficulties in verbal skills, in particular comprehension abilities. Pediatric primary headache may present altered neuropsychological functioning involving attentional resources, processing speed and memory, particularly verbal memory. Given the impact that this disease can have on school performance and the tendency to persist from childhood to adulthood, a cognitive screening in young patients affected by primary headache is pivotal. Additional neuropsychological research using more homogenous methods is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tarantino, Proietti Checchi, Papetti, Ursitti, Sforza, Ferilli, Moavero, Monte, Capitello, Vigevano and Valeriani.)

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome characterized by the predominant involvement of the pons, the cerebellum and the spinal cord with a distinct corticosteroid responsiveness. To date, several cases of neurological disorders with a CLIPPERS-like phenotype have been described, including patients with Immunoglobulin G (IgG) antibodies binding to myelin oligodendrocyte glycoprotein (MOG). We herein report the case of a man with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) fulfilling the diagnostic criteria for probable CLIPPERS and a literature review of CLIPPERS-mimicking patients with MOG-IgG., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose of Review: To analyze systematically the evidence currently available from the literature regarding the diagnosis, clinical characteristics, treatment and outcome of new daily persistent headache (NDPH)., Recent Findings: NDPH is a primary headache characterized by an abrupt onset with continuous daily pain that can persist for many months. Although self-limiting forms have been described, NDPH is frequently associated with high disability even in children and adolescents. For this reason, it is very important to recognize it from a diagnostic point of view and to treat it. We found little specific data on NDPH in developmental age. Most of the therapy studies have been conducted on adults with conflicting data. Currently, pediatric NDPH therapy is based on experiences in adult patients and in individuals with other forms of primary chronic headache, hence the need for more pediatric studies to fill this information gap., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray matter. The aquaporin-4 antibody (AQP4-IgG) is specific for NMOSD. Recently, myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been found in a group of AQP4-IgG negative patients. NMOSD is rare among children and adolescents, but early diagnosis is important to start adequate therapy. In this report, we present cases of seven pediatric patients with NMOSD and we review the clinical and neuroimaging characteristics, diagnosis, and treatment of NMOSD in children.

Sleep disorders and primary headaches are frequent health problems in childhood, and they are often comorbid in an individual, linked by a mutual and complex relationship. This comorbidity is frequent and well-documented, but the available literature is usually biased in favor of one aspect or another, mainly depending on the expertise of the authors. The aim of this paper is to review existing literature on the diagnostic assessment of comorbid primary headaches and sleep disorders, so as to propose practical suggestions to accurately investigate the presence of comorbid conditions in children evaluated for primary headaches or for sleep disorders.

Migraine is the first in order of frequency of the neurological disorders, affecting both adult and paediatric populations. It is also the first cause of primary headaches in children. Migraine equivalents are periodic disorders that can be associated with migraine or considered as prognostic features of a future migraine manifestation. Despite the mechanisms underlying migraine and its equivalents are not entirely clear, several elements support the hypothesis of common pathophysiological patterns shared by these conditions. The aim of this review is thus to analyze the literature in order to highlight which currently known mechanisms may be common between migraine and its equivalents.

Anti- N -methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a rare autoimmune illness characterized by a constellation of often severe, but treatable, psychiatric and neurological symptoms. Whereas symptoms such as psychosis and bizarre and abnormal motor behavior are common in adults, pediatric patients typically present with behavioral changes, irritability and sleep dysfunction. The recovery phase is usually slow and may be associated with longstanding adaptive, behavioral and neuropsychological problems. Very few studies explored the cognitive and adaptive sequelae in children with anti-NMDAR encephalitis. The present review article suggests that, although most children and adolescents return to their daily life and previous activities, they may have a low quality of life and show neuropsychological sequelae involving language, memory, especially verbal memory, and attentional resources, even after several months from the hospital discharge. In particular, the available results reveal difficulties in cognitive skills involving executive functions. This impairment is considered the "core" of the cognitive profile of young patients with anti-NMDAR encephalitis. On the other hand, some cognitive skills, such as general intelligence, show good overall recovery over time. Additional neuropsychological research evaluating larger samples, more homogenous methods and longitudinal studies is required.

There is a high comorbidity between migraine and sleep disorders (SD), with a mutual dependence between sleep and headache. This study aimed to analyze the relationship between headache features (migraine frequency and severity, migraine equivalents, use and efficacy of treatments) and sleep in pediatric migraine. Parents of children and adolescents with migraine completed the Children's Sleep Habits Questionnaire (CSHQ) and the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) and answered questions about headache characteristics. The presence of SD was defined according to CSHQ score. SD were detected in 72.9% of 140 subjects, but only 5.0% already received a diagnosis. Patients with SD presented statistically significant higher headache frequency ( p = 0.031) and higher prevalence of migraine equivalents ( p = 0.007). A higher CSHQ total score was associated with higher frequency of severe attacks ( p = 0.012) and lower acute drug efficacy ( p = 0.003). Significant positive correlations of sleep onset delay, sleep duration and nightwakings subscales with migraine frequency emerged. Our findings indicate that SD are highly prevalent in pediatric migraine and frequently associated with a higher headache severity and lower response to acute therapy, but often remain underdiagnosed. Improving sleep quality could help to reduce migraine intensity and disability and vice versa.

The link between migraine and nutrition can be explored from several points of view. Lifestyle and, in particular, aspects of nutrition can have a significant impact on the course of pediatric migraine. In addition, some dietary treatments, such as the ketogenic diet, and some active ingredients present in foods (nutraceuticals) may have a therapeutic effect on migraine. A diet that can control weight gain and obesity has beneficial effects on migraine severity. On the other hand, when we talk about the link between nutrition and headaches, it is also necessary to point out that some public information is actually fake news that has no scientific basis. The purpose of this review is to provide an update on the salient points linking pediatric migraine to nutritional principles, focusing on the relationship between weight and headaches, the therapeutic effect of food for medical purposes, the ketogenic diet as a migraine treatment, and the relationship between migraine and dietary habits.

Background Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been recently reevaluated as a biomarker of acquired demyelinating syndromes (ADS) of the central nervous system (CNS). Here, we describe the clinical and neuroimaging features, and the long-term outcome of children with ADS of the CNS associated with MOG-IgG. Methods All patients underwent brain and spinal cord magnetic resonance imaging (MRI), lumbar puncture for cerebrospinal fluid (CSF) analysis and MOG-IgG and aquaporin-4 IgG (AQP4-IgG) testing. Results Forty-eight pediatric patients were recruited. MOG-IgG were detected in 11/48 (25%) patients with the following clinical presentations: encephalomyelitis (EM), 8/11 (73%); optic neuritis (ON), 2/11 (18%); transverse myelitis (TM), 1/11 (9%). Patients negative for MOG-IgG were diagnosed with Multiple Sclerosis (MS) (n=15), EM (n=7), ON (n=7), neuromyelitis optica spectrum disorders (NMOSD) (n=5), TM (n=2) and encephalitis (n=1). MOG-IgG positive patients were younger at disease onset and they more frequently experienced encephalopathy and epileptic seizures compared with negative patients. EM and inflammatory lesions involving optic nerves on MRI imaging were more frequent in MOG-IgG positive patients. None of the patients with MOG-IgG became persistently seronegative during the follow-up, although a decrease in MOG-IgG titer was observed. Patients with MOG-IgG showed a good response to therapy and only two patients presented relapses during follow-up. Conclusion This study supports the distinction of MOG autoimmune oligodendrocytopathy as a unique disease entity, with clinical features different from those of MS and AQP4-IgG-positive NMOSD., (Copyright © 2021. Published by Elsevier B.V.)

Treatment for pediatric-onset multiple sclerosis (POMS) currently reflects treatment for adult-onset MS, despite some differences in its clinical course. First-choice treatment of POMS generally consists of interferon β-1a or glatiramer acetate, with therapies such as natalizumab or fingolimod reserved for second-choice treatment. In cases of severe disease, both fingolimod and natalizumab can be considered first-choice therapy. This paper presents three case histories of patients with POMS and highlights the different uses of fingolimod within the POMS treatment algorithm. The first and third cases are examples of escalation therapy, both in females aged 16 to 17 years, with fingolimod administering as second choice following disease progression. The second case is an example of using fingolimod as first-choice therapy, given to a 12-year-old male with severe disease. In all three cases, over a period of approximately 1 year after the initiation of fingolimod treatment, there was no further disease progression and no adverse events were recorded.

Introduction: Our aim was to investigate the clinical features of primary new daily persistent headache (NDPH) in a cohort of paediatric patients., Methods: We reviewed the data of patients with persistent daily headache, attending the Headache Centre of Bambino Gesù Children from the January 2009. The ICHD-III criteria were used for diagnosis. Statistical analysis was conducted to study possible correlations between NDPH and population features (age and sex), NDPH and headache qualitative features, and NDPH and response to pharmacological therapies., Results: We included 46 subjects with NDPH. The features of pain more closely resembled those of migraine than to those of tension-type headache (62 vs. 38%). The NDPH patients showed nausea and vomiting less frequently than migraine ones (28.6 vs. 48.2%, p < 0.01). A total of 75% of NDPH patients experienced an onset of the symptoms in the winter months (November to February) ( p < 0.01). NDPH was less common in very young children under 10 years of age. Almost 58% of NDPH patients received pharmacological therapy and the most used drug was amitriptyline. A reduction of attacks by at least 50% in a month was detected in 30.6% of patients., Conclusions: NDPH can be very disabling and correlates with seasonal factors. Although long term pharmacological therapy is recommended, considering the long duration that this headache can have, there are no data supporting the treatment choice.

Backgrounds: To investigate the clinical and instrumental features at the onset addressing to the diagnosis of anti-NMDAR encephalitis., Methods: Twenty children (age: 15 months-17 years; 7 males, 13 females) with initial suspected diagnosis of autoimmune encephalitis, observed between January 2008 and March 2018, were included. The final diagnosis was anti-NMDAR encephalitis in 7 children, other/probable autoimmune encephalitis in 7 children, and primary psychosis in the remaining 6 children., Results: At the clinical onset, anxiety disorder was the main symptom that helped in distinguishing the group of psychotic children from children with non-infectious encephalitis (P = 0.05 OR = 0.001), while epileptic seizures strongly predicted anti-NMDAR encephalitis (P = 0.04 OR = 28.6). At the onset, anti-NMDAR encephalitis could be distinguished from other/probable autoimmune encephalitis for the presence of sleep/wake rhythm alteration (P = 0.05 OR = 15). Among the symptoms occurring during the hospitalization, movement disorders (P = 0.031 OR = 12) were predictive of non-infectious encephalitis rather than primary psychosis. More specifically, the occurrence of language impairment (P = 0.03 OR = 33), epileptic seizures (P = 0.04 OR = 28.6) and catatonia (P = 0.03, OR = 33), were predictive of anti-NMDAR encephalitis. Also at this stage, anxiety disorder (P = 0.03 OR = 0.033) was predictive of primary psychosis., Conclusion: Our findings suggest that at the clinical onset epileptic seizures and sleep/wake rhythm alteration represent the main features addressing to the diagnosis of anti-NMDAR encephalitis rather than primary psychosis and other/probable autoimmune encephalitis, while anxiety disorder could be a solid predictor of primary psychosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: There is a lack of studies that explore the possible association between body weight, psychological symptoms, and migraine severity in pediatric populations. The purpose of the study was to explore: (1) the association between body weight and the frequency of migraine attacks, (2) the possible differences in anxiety and depression symptoms according to the frequency of attacks and body weight, and (3) the possible mediating role of anxiety and/or depression in the association between body weight and frequency of migraine attacks in children. Methods: One hundred and eleven children/adolescents with migraine were included (47 boys and 64 girls; mean age 11.7; ±2.4 years). The patients were classified as: (1) high frequency patients, reporting from weekly to daily episodes and (2) low frequency patients, with ≤3 episodes per month. According to their body mass index percentiles, the patients were divided in "Normal weight" (from ≥5 to <85 percentile), "Overweight" (from ≥85 to <95 percentile), and "Obese" (≥95 percentile). Given the low number of obese patients, the overweight and obese groups were considered together in the "Overweight" group. Anxiety and depression symptoms were assessed by the Self-Administered Psychiatric Scales for Children and Adolescents (SAFA). Results: Fifty-four patients were normal in weight (49.6%), while 56 patients (50.4%) were overweight. The overweight patients showed a higher frequency of migraine attacks (64.7%; p < 0.05). Patients with a high frequency of attacks reported higher scores in all SAFA-Anxiety subscales (SAFA-A Tot: F = 15.107; p = 0.000). Overweight patients showed a significantly higher score in the "Separation anxiety" subscale ( F = 7.855; p = 0.006). We found a mediating role between the overweight and high frequency for total anxiety ( z = 2.11 ± 0.03; p < 0.05) and social anxiety ( z = 2.04 ± 0.03; p < 0.05). Conclusions: Our results suggest that, among the children suffering from migraine, the overweight status is associated with a higher frequency of attacks and separation anxiety symptoms. In particular, our study provides the first evidence of the role of anxiety in linking overweight and the frequency of migraine attacks in children and adolescents., (Copyright © 2020 Tarantino, Papetti, Di Stefano, Messina, Ursitti, Ferilli, Sforza, Moavero, Vigevano, Gentile and Valeriani.)

Background: MOH can be diagnosed in subjects with headache occurring 15 days/month in association with a regular medication overuse, but its existence is not universally accepted. ICHD-3 redefined criteria for MOH, removing the criterion associating drug suspension with headache course. The aim of our study was to compare the rate of patients diagnosed with medication overuse headache (MOH) according to ICHD-2 and ICHD-3 criteria, to verify the degree of concordance. The secondary aim was to verify if drug withdrawal was really associated with pain relief. Methods: In this cross-sectional study, we retrospectively analyzed a sample of 400 patients followed for primary chronic headache at the Headache Center of Bambino Gesù Children's Hospital. We then selected those presenting with a history of medication overuse, and we applied both ICHD-2 and ICHD-3 criteria to verify in which patients the criteria would identify a clinical diagnosis of MOH. Results: We identified 42 subjects (10.5%) with MOH; 23 of them (55%) presented a relief of headache withdrawing drug overuse. Regarding the applicability of the ICHD-2 criteria, 43% of patients (18/42) fulfilled all criteria, while all ICHD-3 diagnostic criteria were satisfied in 76% of patients (32/42). Eighteen patients (43%) satisfied both ICHD-2 and ICHD-3 criteria, while 10 patients (24%) did not satisfy either diagnostic criterion. Conclusions: Our study suggests that in children and adolescents, withdrawing medication overuse is not always associated with a clinical benefit. Therefore, though allowing a MOH diagnosis in a higher rate of patients as compared to ICHD-2, the application of ICHD-3 criteria does not guarantee a true a causal relationship between medication overuse and headache worsening., (Copyright © 2020 Moavero, Stornelli, Papetti, Ursitti, Ferilli, Balestri, Sforza, Tarantino, Vigevano and Valeriani.)

Background: Palmitoylethanolamide (PEA) is emerging as a new therapeutic approach in pain and inflammatory conditions, and it has been evaluated in studies on various painful diseases. The aim of this open-label study was to evaluate the efficacy of ultramicronized PEA (umPEA) in the prophylactic treatment of migraine., Methods: The study included 70 patients with mean age of 10.3 ± 2.7 (24.5% M and 75.5% F). All patients had a diagnosis of migraine without aura (ICHD 3 criteria) and received umPEA (600 mg/day orally) for three months. We compared the attack frequency (AF) and attack intensity at baseline and after three months. Patients were asked to classify the intensity of the attack with a value ranging from 1 to 3, where 1 means mild attack, 2 moderate, and 3 severe attack., Results: Nine patients discontinued treatment before the target time of 12 weeks. After 3 months of treatment with umPEA, the headache frequency was reduced by >50% per month in 63.9% patients. The number of monthly attacks at T 1 decreased significantly compared with the baseline assessment (from 13.9 ± 7.5 SD of T 0 to 6.5 ± 5.9 SD of T 1 ; p < 0.001). The mean intensity of the attacks dropped from 1.67 ± 0.6 ( T 0 ) to 1.16 ± 0.5 ( T 1 ) ( p < 0.001), and the percentage of patients with severe attacks decreased after treatment (from 8.2% to 1.6%; p < 0.05). The monthly assumptions of drugs for the attack reduced from 9.5 ± 4.4 to 4.9 ± 2.5 ( p < 0.001). Only one patient developed mild side effects (nausea and floating)., Conclusions: Our preliminary data show that umPEA administered for three month reduces pain intensity and the number of attacks per month in pediatric patients with migraine. Although the small number of patients and the lack of control group do not allow us to consider these initial results as definitely reliable, they encourage us to expand the sample., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2020 Laura Papetti et al.)

Competing Interests: None

Background and Aim: Episodic syndromes that may be associated with migraine are a group of disorders affecting patients with migraine or with an increased risk of presenting it, and likely represent an early life expression of migraine. Cyclic vomiting syndrome and benign paroxysmal torticollis are well characterized and represent a frequent cause of request for specialist consultations. The aim of this study is to longitudinally assess the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy, and to define the main clinical features of the disorder., Methods: We administered a questionnaire to the parents of all our pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis according to ICHD-3; questions were focused on the main clinical features of the disorder as well as the prognosis, with particular emphasis on the development of headache., Results: For the final analysis we considered 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis. Seventy-nine percent of patients with cyclic vomiting syndrome presented with headache during the follow-up, with a mean age at onset of 6 years; 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up, with a mean age at onset of 5 years., Discussion: Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. In both groups of patients, the vast majority presented with different episodic syndromes that may be associated with migraine at different ages, thus suggesting an age-dependent evolution of migraine-like symptoms before the onset of clear migrainous headache.

Migraine is a frequent and very disabling disease, especially at pediatric age. Despite this, there are few controlled data on the prophylactic treatment of primary headaches in this category of age. Given that the recently introduced calcitonin gene-related peptide (CGRP) inhibitors (CGRP-r) are still limited to adulthood, there is no drug with exclusive indication for migraine treatment in pediatric age. This raises several limitations in terms of adherence and effectiveness of the therapy. Moreover, the scenario is complicated by placebo response, which is larger in children and adolescents than in adults and often leads to an improvement in the attack frequency even in absence of any active pharmacological treatment. Our aim was to investigate the real evidence concerning the prophylactic therapy of pediatric migraine by reviewing the clinical studies published between 2010 and 2019.

Competing Interests: Competing interests: None declared.

Case Presentation: A 57-year-old man was referred to the ED for wake-up right-sided hemiparesis, hypoesthesia, dysarthria, and a National Institutes of Health Stroke Scale score of 7. Urgent CT brain scanning showed an ischemic lesion of the left temporal and insular lobes. The patient was admitted to the stroke unit, and acetylsalicylic acid 300 mg and low-molecular-weight heparin 6,000 IU were administered., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)