Lower Urinary Tract Dysfunction in Pediatric Patients with Multiple Sclerosis: Diagnostic and Management Concerns.

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.

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.

Parental Experiences in Pediatric Multiple Sclerosis: Insights from Quantitative Research.

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.

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.

Neuropsychological performances, quality of life, and psychological issues in pediatric onset multiple sclerosis: a narrative review.

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.

Pediatric Onset Multiple Sclerosis and Obesity: Defining the Silhouette of Disease Features in Overweight Patients.

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.

Clinical, neurophysiological and serological clues for the diagnosis of neuromyotonia and distinction from cramp-fasciculation syndrome.

Neuromyotonia and cramp-fasciculation syndrome diagnosis currently relies on neurophysiological examination. In this study we investigated the clinical features and neural antibody profile of patients with neuromyotonia and cramp-fasciculation syndrome to assess the diagnostic value of serological testing. Available sera from adult patients with electromyography-defined neuromyotonia and cramp-fasciculation syndrome were tested for neural antibodies by indirect immunofluorescence on mouse brain sections and live cell-based assays. Forty patients were included, 14 with neuromyotonia and 26 with cramp-fasciculation syndrome. Neural antibodies were detected in 10/10 neuromyotonia sera, most commonly against contactin-associated protein 2 (7/10, 70%), and in 1/20 (5%) cramp-fasciculation syndrome sera. Clinical myokymia, hyperhidrosis, and paresthesia or neuropathic pain were more common in neuromyotonia and mostly associated with contactin-associated protein 2 antibodies. Central nervous system involvement was present in 4/14 (29%) neuromyotonia patients. A tumor was detected in 13/14 (93%) neuromyotonia patients (thymoma, 13), and in 4/26 (15%) with cramp-fasciculation syndrome (thymoma, 1; other neoplasms, 3). Twenty-one/27 (78%) patients achieved a significant improvement or complete remission. Our findings highlight clinical, neurophysiological and serological clues that can be useful in the diagnosis of neuromyotonia and cramp-fasciculation syndrome. Antibody testing is valuable for neuromyotonia diagnosis, while its usefulness in cramp-fasciculation syndrome confirmation is limited.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

A Case Report of Pediatric Patient with Tuberous Sclerosis and Radiologically Isolated Syndrome.

INTRODUCTION: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease with central nervous system (CNS) involvement. Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS characterized by symptomatic episodes that occur months or years apart and affect different anatomic locations. In the absence of symptomatic episodes, radiologically isolated syndrome (RIS) could be diagnosed. Here, we report the case of a 10-year-old boy followed-up for TSC and diagnosed with RIS after a routine neuroimaging assessment. CASE DESCRIPTION: The patient was diagnosed with TSC after seizure onset at the age of 4 years. The follow-up magnetic resonance imaging (MRI) showed multiple asymptomatic demyelinating lesions. Brain and spinal cord MRI was performed after 2 months and showed additional lesions in the right frontal white matter and left cerebral peduncle, the latter with contrast enhancement. Therefore, he received a diagnosis of RIS. Visual evoked potentials were normal. Cerebrospinal fluid examination showed oligoclonal bands. The search for AQP4-IgG and MOG-IgG antibodies was negative. He was treated with interferon beta-1a. Six months later, follow-up MRI revealed no new demyelinating lesions and resolution of contrast enhancement. CONCLUSION: To the best of our knowledge, this is the third reported patient presenting a co-occurrence of TSC and demyelinating disease. Although we cannot state if the described comorbidity is casual or not, some clinical and preclinical data suggest that the mTOR complex might be the link between TSC and demyelinating disease.

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.

Case report: A case of acute disseminated encephalomyelitis after SARS-CoV-2 infection in pediatric patients.

Introduction: Since the beginning, there has been enough evidence about the multi-systematic involvement of the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent observations have revealed that, together with others, typical neurological manifestations are also associated with COVID-19 infection. In the first 2 years, children accounted for a few percent of cases, but with the emergence of the Omicron variant, the number of cases in the pediatric population has increased. It has been described that ~5% of the affected population suffered from severe neurological complications, such as seizure, coma, encephalitis, demyelinating disorders, and aseptic meningitis. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system. Typically, it presents in childhood and occurs 1 or 2 weeks after infection or vaccination. Case presentation: We present the case of a 12-year-old boy who developed ADEM, 10 days after an asymptomatic SARS-CoV-2 infection. Neurological symptoms began with headache, fever, irritability, paraplegia, and loss of sensitivity from the T1 level. The diagnosis of ADEM was confirmed by the typical signs found on brain MRI, whereas spinal cord MRI showed signs of transverse myelitis. The cerebrospinal fluid (CSF) testing excluded infections and did not reveal oligoclonal antibody bands (anti-MOG-negative and anti-AQP-negative). High-dose steroids (30 mg/kg/day) and IVIG (2 g/kg) were administered to the patient without any clinical improvement. The patient received a cycle of plasma exchange therapy, followed by rituximab infusion, with partial improvement. After 3 months, the magnetic resonance imaging (MRI) results demonstrated radiological improvement in accordance with the ADEM diagnosis. Conclusion: This clinical case confirms that SARS-CoV-2 infections are increasingly implicated in severe neurological consequences in both adult and pediatric patients. While the most frequent complications that were reported in children included headache, altered mental status, and encephalopathy, ~5% of the individuals suffered from severe neurological complications, leading to lifelong sequelae. All physicians must be aware of these data and detect neurological signs of severe (or not) complications that require a specific follow-up and treatment.

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.

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.

Primary headache epidemiology in children and adolescents: a systematic review and meta-analysis.

INTRODUCTION: Headache is the most prevalent neurological manifestation in adults and one of the leading causes of disability worldwide. In children and adolescents, headaches are arguably responsible for a remarkable impact on physical and psychological issues, yet high-quality evidence is scarce. MATERIAL AND METHODS: We searched cross-sectional and cohort studies in Embase, Medline, Web of Science, and Cochrane databases from January 1988 to June 2022 to identify the prevalence of headaches in 8-18 years old individuals. The risk of bias was examined with the Joanna Briggs Institute (JBI) scale. A random-effects model was used to estimate the pooled prevalence of pediatric headache. Subgroup analyses based on headache subtypes were also conducted. RESULTS: Out of 5,486 papers retrieved electronically, we identified 48 studies that fulfilled our inclusion criteria. The pooled prevalence of primary headaches was 11% for migraine overall [95%CI: 9-14%], 8% for migraine without aura (MwoA) [95%CI: 5-12%], 3% for migraine with aura (MwA) [95%CI:2-4%] and 17% for tension-type headache (TTH) [95% CI: 12-23%]. The pooled prevalence of overall primary headache in children and adolescents was 62% [95% CI: 53-70%], with prevalence in females and males of 38% [95% CI: 16-66%] and 27% [95% CI: 11-53%] respectively. After the removal of studies ranked as low-quality according to the JBI scale, prevalence rates were not substantially different. Epidemiological data on less common primary headaches, such as trigeminal autonomic cephalalgias, were lacking. CONCLUSION: We found an overall remarkably high prevalence of primary headaches in children and adolescents, even if flawed by a high degree of heterogeneity. Further up-to-date studies are warranted to complete the picture of pediatric headache-related burden to enhance specific public interventions.

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.

Immunological response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis treated with Rituximab.

In this study we employed a comprehensive immune profiling approach to determine innate and adaptive immune response to SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis receiving rituximab. By multicolour cytometry, dendritic and natural killer cells, B- and T-cell subsets, including T-cells producing IFN-γ stimulated with SARS-CoV-2 peptides, were analysed after infection and mRNA vaccination. In the same conditions, anti-spike antibodies and cytokines' levels were measured in sera. Despite the impaired B cell and humoral response, rituximab patients showed an intact innate, CD8 T-cell and IFN-γ specific CD4+ and CD8+ T-cell response after infection and vaccination, comparable to controls. No signs of cytokine mediated inflammatory cascade was observed. Our study provides evidence of protective immune response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis on B cell depleting therapy and highlights the need for prospective studies with larger cohorts to clarify the role of B cells in SARS-CoV-2 immune response.

Efficacy and safety of rituximab in myelin oligodendrocyte glycoprotein antibody-associated disorders compared with neuromyelitis optica spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: Rituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears to be lower than in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSDs). The aim of this systematic review and meta-analysis is to assess the efficacy and safety profile of RTX in patients with MOGAD and to compare RTX efficacy between MOGAD and AQP4-IgG+NMOSD. METHODS: We searched original English-language articles published between 2012 and 2021 in MEDLINE, Cochrane, Central Register of Controlled Trials and clinicaltrials.gov, reporting data on RTX efficacy in patients with MOGAD. The main outcome measures were annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score mean differences (MDs) after RTX. The meta-analysis was performed with a random effects model. Covariates associated with the outcome measures were analysed with a linear meta-regression. RESULTS: The systematic review included 315 patients (138 women, mean onset age 26.8 years) from 32 studies. Nineteen studies (282 patients) were included in the meta-analysis. After RTX, a significant decrease of ARR was found (MD: -0.92, 95% CI -1.24 to -0.60, p<0.001), markedly different from the AQP4-IgG+NMOSD (MD: -1.73 vs MOGAD -0.92, subgroup difference testing: Q=9.09, p=0.002). However, when controlling for the mean ARR pre-RTX, this difference was not significant. After RTX, the EDSS score decreased significantly (MD: -0.84, 95% CI -1.41 to -0.26, p=0.004). The frequency of RTX-related adverse events was 18.8% (36/192) and overall RTX-related mortality 0.5% (1/192). CONCLUSIONS: RTX showed effective in MOGAD, although to a lesser extent than in AQP4-IgG+NMOSD, while the safety profile warrants some caution in its prescription. Randomised-controlled trials are needed to confirm these findings and provide robust evidence to improve treatment strategies in patients with MOGAD. PROSPERO REGISTRATION NUMBER: CRD42020175439.

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.