Unsatisfactory response to acute medications does not affect the medication overuse headache development in pediatric chronic migraine.

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.

Cluster Headache: Diagnosis, Management, and Treatment in Pediatric Headache.

Despite its rarity, cluster headache can affect children. Patients with cluster headaches often experience symptoms in their adolescence, but the time it takes for a correct diagnosis can be very long. Cluster headache can be mistaken for other pathologies, which can result in patients being diagnosed and treated incorrectly. CH therapy often represents a challenge in pediatric age as there are no studies dedicated to this age category and the therapy strategy is generally based on data from adult experience. The aim of this review is to provide a summary of the current literature on cluster headache in children and adolescents.

Childhood primary stabbing headache: A double center study.

BACKGROUND: Primary stabbing headache (PSH) is an idiopathic headache disorder characterized by head pain occurring as a transient and localized single stab or a series of stabs. The present study aimed to examine the characteristics of childhood PSH and whether they fit the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria. We also investigated the association with migraine and episodic syndromes. METHODS: In this retrospective study, we included 60 patients seen at two headache clinics (Rome and Bari) between 2016 and 2022. A headache-focused history was obtained. All patients had normal neurological examination. PSH was defined according to ICHD-3 criteria. RESULTS: Twenty-three patients were male (38%) and median (range) age at disease onset was 8 (3-17) years. Stabs recurred with irregular frequency and their duration varied from a few seconds up to 30 minutes. Stabs were located in different head regions. Twenty-five patients (42%) underwent neuroimaging exams. Five children reported a limitation of daily activities and none had a chronic pattern. Forty-seven patients (78%) reported a family history of primary headache, especially migraine, and forty-three had episodic syndromes (i.e. infantile colic, benign paroxysmal vertigo, motion sickness, recurrent abdominal pain, cyclic vomiting). Twenty patients had an associated primary headache: 16 suffered from migraine and four suffered from tension type-headache. According to ICHD-3 criteria, thirty-one patients had a diagnosis of probable PSH as a result of a duration of stabs longer than a few seconds (>3 seconds). CONCLUSIONS: Features of childhood PSH can vary widely. As seen in previous studies, several patients reported a stab duration longer than a few seconds and this might suggest that current ICHD-3 criteria may need adjustments to be suitable for children. High frequency of associated migraine and episodic syndromes could suggest a common pathophysiological mechanism between PSH and migraine. We can hypothesize that PSH and migraine attacks may be part of a spectrum of the same disease, although further evidence is needed. Larger studies with long-term follow-up are needed to improve understanding of this condition.

Visual Disturbances Spectrum in Pediatric Migraine.

Migraine is a complex neurological disorder with partially unknown pathophysiological mechanisms. The prevalence in childhood ranges from 7.7% to 17.8%, thus representing the most frequent primary headache. In half of the cases, migraine is accompanied or preceded by various neurological disturbances, among which the visual aura is the best known. In literature, other conditions, such as Alice in Wonderland Syndrome and Visual Snow syndrome, are characterized by visual manifestations and are often associated with migraine. The aim of this narrative review is to describe the spectrum of visual disturbances in pediatric migraine and their pathophysiological mechanisms.

Real Life Data on OnabotulinumtoxinA for Treatment of Chronic Migraine in Pediatric Age.

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.

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.

Migraine in childhood: Gender differences.

Migraine is a common neurological disorder in developmental age, involving up to 20% of children and adolescents. Although gender differences in migraine epidemiology and clinical characteristics have been largely investigated in adulthood, this issue is considerably less known in pediatric patients. We aim at providing an overview of gender differences in pediatric migraine. The most recent literature was reviewed taking into account the epidemiological, pathophysiological, and clinical differences between boys and girls with migraine. Although many aspects need to undergo further investigation, we conclude that different aspects of childhood migraine syndrome may vary depending on the gender and age, especially with regard to pubertal development.

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.

Interictal Cognitive Performance in Children and Adolescents With Primary Headache: A Narrative Review.

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.

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.

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.

The Enigma of New Daily Persistent Headache: What Solutions for Pediatric Age?

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.

How to Assess the Headache-Sleep Disorders Comorbidity in Children and Adolescents.

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 and Its Equivalents: What Do They Share? A Narrative Review on Common Pathophysiological Patterns.

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.

Neuropsychological Sequelae, Quality of Life and Adaptive Behavior in Children and Adolescents with Anti-NMDAR Encephalitis: A Narrative Review.

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.

Opsoclonus-Myoclonus Syndrome in Children and Adolescents: A Therapeutic Challenge.

Opsoclonus-myoclonus syndrome (OMS) is a neurological non-fatal disease that usually responds to immunotherapies. However, the real challenge is to counteract the high frequency of relapses and long-term developmental sequelae. Since the OMS is extremely rare, a common consensus regarding therapeutic guidelines is still lacking. The goals of this study were to test whether ACTH was superior to other immunotherapies and to investigate whether an early treatment could improve the outcome. Sixteen children affected by OMS were retrospectively reviewed. Eight children had a neuroblastic tumor. The other eight patients were affected by non-paraneoplastic OMS. Overall, the most commonly used treatment was corticotherapy (n = 11). However, ACTH (n = 10), rituximab (n = 7), immunoglobulins (n = 4), cyclophosphamide (n = 3), and mycophenolate (n = 2) were also administered. ACTH was associated with a high percentage of patients who healed (80%) and, as a first-line therapy, was associated with a lower incidence of relapses. An early treatment was associated with a favorable long-term outcome. Long-term sequelae occurred in 42% of patients who were treated early and in all of those who were treated late. It is advisable for the affected children to be identified at an early time, as they may benefit from an early treatment. ACTH represents an effective treatment with a high probability of recovery and low rate of relapses.

Case Report: Migralepsy: The Two-Faced Janus of Neurology.

We report three cases of pediatric patients suffering from migraine aura triggered seizures. This entity, also called migralepsy, still does not have a unique definition today. Migraine and epilepsy are both episodic neurological disorders with periods of interictal well-being; this is indicative of similar pathophysiological mechanisms, such as increased neuronal excitation and ion channel dysfunction. The purpose of this paper is to discuss the clinical and instrumental features of migralepsy through the description of three clinical cases in which the symptoms of the usual migraine aura developed into a generalized tonic-clonic or focal seizure.

Truths and Myths in Pediatric Migraine and Nutrition.

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.