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Abstract Background and aim Migraine is a common disabling conditions which, globally, affects 15.2% of the population. It is the second cause of health loss in terms of years lived with disability, the first among women. Despite being so common, it is poorly recognised and too often undertreated. Specialty centres and neurologists with specific expertise on headache disorders have the knowledge to provide specific care: however, those who do not regularly treat patients with migraine will benefit from a synopsis on the most relevant and updated information about this condition. This paper presents a comprehensive view on the hallmarks of migraine, from genetics and diagnostic markers, up to treatments and societal impact, and reports the elements that identify migraine specific features. Main results The most relevant hallmark of migraine is that it has common and individual features together. Besides the known clinical manifestations, migraine presentation is heterogeneous with regard to frequency of attacks, presence of aura, response to therapy, associated comorbidities or other symptoms, which likely reflect migraine heterogeneous genetic and molecular basis. The amount of therapies for acute and for prophylactic treatment is really wide, and one of the difficulties is with finding the best treatment for the single patient. In addition to this, patients carry out different daily life activities, and might show lifestyle habits which are not entirely adequate to manage migraine day by day. Education will be more and more important as a strategy of brain health promotion, because this will enable reducing the amount of subjects needing specialty care, thus leaving it to those who require it in reason of refractory condition or presence of comorbidities. Conclusions Recognizing the hallmarks of migraine and the features of single patients enables prescribing specific pharmacological and non-pharmacological treatments. Medical research on headaches today particularly suffers from the syndrome of single-disease approach, but it is important to have a cross-sectional and joint vision with other close specialties, in order to treat our patients with a comprehensive approach that a heterogeneous condition like migraine requires.

Abstract Background Recently, there has been increasing interest in the possible role of the gut microbiota (GM) in the onset of migraine. Our aim was to verify whether bacterial populations associated with intestinal dysbiosis are found in pediatric patients with migraine. We looked for which metabolic pathways, these bacteria were involved and whether they might be associated with gut inflammation and increased intestinal permeability. Methods Patients aged between 6 and 17 years were recruited. The GM profiling was performed by the 16S rRNA metataxonomics of faecal samples from 98 patients with migraine and 98 healthy subjects. Alpha and beta diversity analyses and multivariate and univariate analyses were applied to compare the gut microbiota profiles between the two group. To predict functional metabolic pathways, we used phylogenetic analysis of communities. The level of indican in urine was analyzed to investigate the presence of metabolic dysbiosis. To assess gut inflammation, increased intestinal permeability and the mucosal immune activation, we measured the plasmatic levels of lipopolysaccharide, occludin and IgA, respectively. Results The α-diversity analysis revealed a significant increase of bacterial richness in the migraine group. The β-diversity analysis showed significant differences between the two groups indicating gut dysbiosis in patients with migraine. Thirty-seven metabolic pathways were increased in the migraine group, which includes changes in tryptophan and phenylalanine metabolism. The presence of metabolic dysbiosis was confirmed by the increased level of indican in urine. Increased levels of plasmatic occludin and IgA indicated the presence of intestinal permeability and mucosal immune activation. The plasmatic LPS levels showed a low intestinal inflammation in patients with migraine. Conclusions Pediatric patients with migraine present GM profiles different from healthy subjects, associated with metabolic pathways important in migraine.

Abstract 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

Abstract Introduction Thirty years ago, the first migraine-specific drugs (triptans) appeared. Today two new categories (gepants and ditans) are marketed for acute migraine treatment. That said, is there still a role for conventional therapy? The aim of the present narrative review is to provide an expert overview examining the possible role of the combination paracetamol/caffeine in treatment of acute migraine pain. Methods To understand possible settings for more appropriate use of paracetamol/caffeine (1000 mg/130 mg) in treatment of acute migraine, a structured literature search was performed using the PubMed database by a panel of experts from major Italian headache centers; articles not referring to migraine pain were excluded from this review; review articles were prioritized. Results Overall response, even to newer specific and selective trigeminal targeted drugs (TTTs), is not over 60%; thus, there is still room for conventional therapies in acute migraine treatment. The panel identified settings in which the use of paracetamol/caffeine combination to treat acute migraine attacks might offer benefit considering the consolidated use through years, despite the lack of studies directly addressing the efficacy of paracetamol/caffeine in the identified populations: subjects > 65 years of age; presence of cardiovascular (CV) comorbidities; TTTs non-responders; pregnancy and breastfeeding; subjects

BackgroundSotos syndrome (SoS) is a rare overgrowth genetic disease caused by intragenic mutations or microdeletions of the NSD1 gene located on chromosome 5q35. SoS population might present cognitive impairment and a spectrum of behavioral characteristics, with a worse profile in patients with microdeletion. Although patients with SoS are known to have impaired sleep habits, very little data are available. The present study aimed to assess the prevalence of sleep disorders (SDs) in a pediatric cohort of patients with SoS and their correlation with neuropsychiatric profiles.MethodsWe included patients with a SoS diagnosis and age

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 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.

Ischemic stroke (IS) can be caused by perturbations of the gut–brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk factors and can influence the brain through the production of different metabolites, such as short-chain fatty acids (SCFAs), indole and derivatives. This study examines ecological changes in the GM and its metabolic activities after stroke. Fecal samples of 10 IS patients were compared to 21 healthy controls (CTRLs). GM ecological profiles were generated via 16S rRNA taxonomy as functional profiles using metabolomics analysis performed with a gas chromatograph coupled to a mass spectrometer (GC-MS). Additionally fecal zonulin, a marker of gut permeability, was measured using an enzyme-linked immuno assay (ELISA). Data were analyzed using univariate and multivariate statistical analyses and correlated with clinical features and biochemical variables using correlation and nonparametric tests. Metabolomic analyses, carried out on a subject subgroup, revealed a high concentration of fecal metabolites, such as SCFAs, in the GM of IS patients, which was corroborated by the enrichment of SCFA-producing bacterial genera such as Bacteroides, Christensellaceae, Alistipes and Akkermansia. Conversely, indole and 3-methyl indole (skatole) decreased compared to a subset of six CTRLs. This study illustrates how IS might affect the gut microbial milieu and may suggest potential microbial and metabolic biomarkers of IS. Expanded populations of Akkermansia and enrichment of acetic acid could be considered potential disease phenotype signatures.

IntroductionSince 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 presentationWe 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.ConclusionThis 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.

IntroductionConcern 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 methodsPatients 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.ResultsWe 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.DiscussionCOVID-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.

Abstract Background Migraine is the most common neurological disease, with high social-economical burden. Although there is growing evidence of brain structural and functional abnormalities in patients with migraine, few studies have been conducted on children and no studies investigating cortical gyrification have been conducted on pediatric patients affected by migraine without aura. Methods Seventy-two pediatric patients affected by migraine without aura and eighty-two controls aged between 6 and 18 were retrospectively recruited with the following inclusion criteria: MRI exam showing no morphological or signal abnormalities, no systemic comorbidities, no abnormal neurological examination. Cortical thickness (CT) and local gyrification index (LGI) were obtained through a dedicated algorithm, consisting of a combination of voxel-based and surface-based morphometric techniques. The statistical analysis was performed separately on CT and LGI between: patients and controls; subgroups of controls and subgroups of patients. Results Patients showed a decreased LGI in the left superior parietal lobule and in the supramarginal gyrus, compared to controls. Female patients presented a decreased LGI in the right superior, middle and transverse temporal gyri, right postcentral gyrus and supramarginal gyrus compared to male patients. Compared to migraine patients younger than 12 years, the ≥ 12-year-old subjects showed a decreased CT in the superior and middle frontal gyri, pre- and post-central cortex, paracentral lobule, superior and transverse temporal gyri, supramarginal gyrus and posterior insula. Migraine patients experiencing nausea and/or vomiting during headache attacks presented an increased CT in the pars opercularis of the left inferior frontal gyrus. Conclusions Differences in CT and LGI in patients affected by migraine without aura may suggest the presence of congenital and acquired abnormalities in migraine and that migraine might represent a vast spectrum of different entities. In particular, ≥ 12-year-old pediatric patients showed a decreased CT in areas related to the executive function and nociceptive networks compared to younger patients, while female patients compared to males showed a decreased CT of the auditory cortex compared to males. Therefore, early and tailored therapies are paramount to obtain migraine control, prevent cerebral reduction of cortical thickness and preserve executive function and nociception networks to ensure a high quality of life.

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.

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.

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.

Abstract Background Post-Infectious Neurological Syndromes (PINS) are heterogeneous neurological disorders with post or para-infectious onset. PINS diagnosis is complex, mainly related to the absence of any recognized guidelines and a univocal definition. Aim of the study To elaborate a diagnostic guide for PINS. Materials and methods We retrospectively analysed patients younger than 14 years old admitted to Bambino Gesù Children’s Hospital in Rome for PINS from December 2005 to March 2018. Scientific literature using PubMed as research platform was analysed: the key words “Post-Infectious Neurological Syndromes” were used. Results A polysymptomatic presentation occurred in a percentage of 88% of the children. Motor signs and visual disturbances the most observed symptoms/signs were the most detached, followed by fever, speech disturbances, sleepiness, headache and bradipsychism. Blood investigations are compatible with inflammation, as a prodromal illnesses was documented in most cases. Normal cerebral spinal fluid (CSF) characteristics has been found in the majority of the study population. Magnetic resonance imaging (MRI) was positive for demyelinating lesions. Antibiotics, acyclovir and steroids have been given as treatment. Discussion We suggest diagnostic criteria for diagnosis of PINS, considering the following parameters: neurological symptoms, timing of disease onset, blood and CSF laboratory tests, MRI imaging. Conclusions We propose criteria to guide clinician to diagnose PINS as definitive, probable or possible. Further studies are required to validate diagnostic criteria.

Introduction. Although laser stimuli activate both Ad- and C-fibres, the corresponding laser evoked potentials (LEPs) remain restricted to the Ad-fibers input, while the C-fibers related potential is hardly detectable. Aims. To evaluate multichannel ultralate LEPs (U-LEPs) by using Nd : Yap laser pulses in healthy volunteers to stimulation of face and lower and upper limbs, in order to estimate the reliability of C-LEPs elicited from both trigeminal and somatic sites. Methods. Twenty healthy volunteers participated in two stimulation sessions to record Aδ-LEPs and C-LEPs. We used a Nd : YAP Laser and 62 EEG recording electrodes. Stimuli parameters were set to activate either small myelinated (Aδ), eliciting purely warmth sensations, or unmyelinated (C) afferents, and eliciting pinprick sensations. Results. At the trigeminal level, we obtained a negative-positive complex in a time interval compatible with the C fibers activation. In the somatic districts, the averaged responses consisted of an earlier negative-positive complex, followed by a later one. Single trials analysis of U-LEPs showed a maximal positive peak in a time interval in the range of C fibers. Topographical analysis of U-LEPs resembled that of LEPs. All subjects exhibited readable U-LEPs in at least 2 stimulated sites. Discussion. A purely warmth sensation seems to correspond to Aδ and C-fibers coactivation, at least in the somatic districts. While the related cortical waves seem hardly readable, their total absence could be a sign of systemic involvement of warm related C-fibers in specific clinical conditions.

Objective: The objective of this study is to present the rare case of a young girl with idiopathic intracranial hypertension secondary to hypoparathyroidism.Background: Idiopathic intracranial hypertension is a neurological syndrome characterized by elevated intracranial pressure (> 25 cmH2O) in the absence of intracerebral abnormalities or hydrocephalus. The pathophysiology of idiopathic intracranial hypertension is unknown, and rare cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. It is supposed that hypocalcemia causes decrease in the absorption of cerebrospinal fluid in arachnoidal granulations.Methods: The workup of the girl with idiopathic intracranial hypertension and hypoparathyroidism included physical examination, blood tests, diagnostic imaging, and lumbar puncture.Results: We present a 9-year-old female patient who was hospitalized for headache associated with nausea and vomiting for 3 weeks. She underwent an ophthalmologic examination that revealed papilledema. Lumbar puncture revealed an opening pressure of 65 cm H2O; cerebrospinal fluid analysis and brain computed tomography scan were normal. The patient started taking acetazolamide. Blood tests revealed hypocalcemia associated with high phosphorus level and undetectable PTH hormone, which led us to suspect hypoparathyroidism. She had never had cramps, paraesthesias, or tetany. Chvostek's and Trousseau's signs were positive. In the neck ultrasonography, parathyroids were not visible. Oral supplementation with calcitriol and calcium was started. Headache, nausea, and vomiting immediately disappeared after the lumbar puncture, and the papilledema improved gradually.Conclusions: Several anecdotal cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. However, our case report is of particular interest, since the child did not present with typical neurological hypoparathyroidism symptoms. Therefore, we recommend that hypoparathyroidism should be included in diagnostic investigations on children with clinical findings of idiopathic intracranial hypertension, because clinical manifestations of hypoparathyroidism are variable and may involve almost all organ systems.

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.

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.

Narcolepsy, a neurologic disorder that leads to excessive daytime sleepiness, may represent a rare consequence of neoplastic lesions involving the sellar/parasellar and hypothalamic regions, the anatomical areas responsible for wakefulness. Optic pathway gliomas represent the most common neoplasm of these regions and present an excellent overall survival, while long-term neurologic impairments, such as visual loss, endocrinopathies, or sleep disorders, are the principal causes of morbidity. In this case report, we describe a non-NF1 patient suffering from a very extensive optical pathway glioma, who several years after the diagnosis in a radiological condition of stable disease, presented with severe narcolepsy, a rare complication, that led to the death of the patient.

Abstract Neuromyelitis optica is an immune‐mediated disease characterized by a relapsing course, resulting in progressive disability. In children, given the long life expectancy, a disease‐modifying treatment could be particularly desirable. Unfortunately, the currently available treatment strategies with this potential are scarce. Very limited data are available about the use of allogeneic hematopoietic stem cell transplantation (HSCT) for autoimmune neurological diseases. In this report, we present a pediatric case successfully treated with allogeneic HSCT from an HLA‐haploidentical donor, after ex vivo TCR/CD19‐depletion of the graft. To the best of our knowledge, this is the first case of a pediatric patient to benefit from such a treatment.

The SARS-CoV-2 vaccine roll-out has been successful around the world. However, there are increasing concerns about adverse events. We report two pediatric cases of Multisystem-Inflammatory-Syndrome (MIS-C) with neurological involvement that occurred after SARS-CoV-2 vaccination and unknown recent SARS-CoV-2 infection. Brain magnetic resonance revealed mild-encephalopathy with reversible-splenial-lesion in both cases and complete resolution within 4 weeks. In conclusion, this report aims to describe rare emerging clinical entities that can help pediatricians to make an early diagnosis and to provide appropriate treatment. Multisystem-Inflammatory-Syndromes following COVID-19 vaccination remain rare events. When a history of a recent contact with SARS-CoV-2 is present, a careful evaluation by the clinicians in charge of immunization activities is suggested prior to proceeding with the vaccination.

The clinical effects of the Covid-19 pandemic are now the subject of numerous studies worldwide. But what are the effects of the quarantine imposed by the states that implemented the measures of lockdown? The present research aims to explore, in a preliminary way, the major stress-related symptoms during the lockdown, due to Covid-19, in the Italian population. Subjects were asked to fill out a survey, that traced a line identifying the most relevant psychophysiological symptoms that took into account factors such as perceived stress, body perception, perceived pain, quality of sleep, perceptive variations (i.e., olfactory, gustatory, visual, acoustic, and haptic perception). A network approach formulating a hypothesis-generating exploratory analysis was adopted. Main results of the network analysis showed that the beliefs of having had the Covid-19 was related to individual variables (i.e., gender, working in presence, sleep quality, anxiety symptoms), while the familiarity of Covid-19 disease was related to contextual factors (e.g., number of recorded cases in the Region, working in presence). The self-perception of olfactory and perceptive alterations highlighted a great sensorial cross-modality, additionally, the olfactory impairment was related to the belief of having had the Covid-19. Compared to general network data, BAI, perceived stress, anxiety and chronic pain were in relation to daily sleep disturbance. Main study's results show how the management of the Covid-19 stressful representation, in its cognitive aspects, can modulate the psychophysiological responses.

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.

Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy. Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CVS.

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

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.

Background and Aim: Tuberous sclerosis complex (TSC) is associated with a high rate of attention deficit-hyperactivity disorder (ADHD), usually with more severe symptoms than in idiopathic cases. Event-related potentials have been used in idiopathic ADHD, and they have been proposed as a possible biomarker of symptoms severity. Aim of this study was to investigate event-related potential (ERP) characteristics in patients with ADHD secondary to TSC, compared to patients with drug-naive idiopathic ADHD and healthy controls (HCs), to investigate whether (1) distinct clinical features can be due to different pathophysiological mechanisms, and (2) ERPs may reliably predict ADHD symptoms severity in TSC.Materials and Methods: We enrolled 13 patients with idiopathic ADHD (iADHD), 6 patients with ADHD associated with TSC (tscADHD), and 14 age-matched HCs (7–17 years). All of them underwent ERP recording, with mismatch negativity (MMN) preceding the P300 recording. All patients underwent neurocognitive evaluations.Results: Mismatch negativity latency was shorter in iADHD (P = 0.04) and tscADHD (P = 0.06) than in HC, with no difference between patients' groups. Mismatch negativity amplitude was significantly higher in patients (both iADHD and tscADHD) than in HC. The P300 amplitude was significantly lower in iADHD patients than in both tscADHD patients (P = 0.03) and HCs (P < 0.001). No difference was found between tscADHD patients and HCs (P = 0.2).Conclusion: While patients with iADHD present lower P300 amplitude than HC, in tscADHD patients P300 amplitude was not different from that in HC, suggesting that in TSC P300 amplitude does not really reflect symptom severity.

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 T1 decreased significantly compared with the baseline assessment (from 13.9 ± 7.5 SD of T0 to 6.5 ± 5.9 SD of T1; p

High Intellectual Potential (HIP) and High Functioning Autism (HFA) are two different conditions sharing some clinical and neurobiological features. The aim of the present study was to characterize a sample of HIP children (n: 16; M/F: 14/2; median age: 10 years) in comparison to those with HFA (n: 17; M/F: 16/1; median age: 13 years) and to neurotypically developed (NTD) children (n: 10; M/F: 4/6; median age: 11 years) from a clinical and neurophysiological perspective. Specifically, a standardized clinical assessment of cognitive and adaptive skills, autistic symptoms, executive functions and behavioral features was performed. Moreover, event-related potentials (ERPs) were recorded, referring specifically to the mismatch negativity (MMN) and P300 paradigm. Our data highlighted the presence of similarities between the intellectually gifted individuals and the ones with autism (i.e., a nonhomogeneous intellective profile, an adaptive skills impairment, subthreshold autistic symptoms and increased perfectionism). Interestingly, a distinct neurophysiological characterization between groups came out, with evidence of a reduced MMN amplitude only in the HFA group. Furthermore, no differences within groups in the P300 component emerged. Therefore, our results start to provide a more informative characterization of the HIP phenotype in comparison to those of HFA and NTD, highlighting the potential role of the MMN amplitude index in helping clinicians and researchers to distinguish between HIP and HFA. Nevertheless, further research on the topic is strongly needed.

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.

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.

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 (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.

Abstract Background The 2013 International Classification of Headache Disorders-3 (ICHD-3) was published in a beta version to allow the clinicians to confirm the validity of the criteria or to suggest improvements based on field studies. The aim of this work was to review the Primary Headache Disorders Section of ICHD-3 beta data on children and adolescents (age 0-18 years), and to suggest changes, additions, and amendments. Methods Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the literature available on pediatric headache, they made observations and proposed suggestions for the primary headache disorders section of ICHD-3 beta data on children and adolescents. Results Some headache disorders in children have specific features which are different from those seen in adults and which should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psycho-social basis in children and adolescents making primary headache disorders in children distinct from those in adults. Conclusions Several recommendations are presented in order to make ICHD-3 more appropriate for use with children.

Abstract Background The 2013 International Classification of Headache Disorders-3 was published in a beta version to allow clinicians to confirm the validity of the criteria or suggest improvements based on field studies. The aim of this work was to review the Secondary Headache Disorders and Cranial Neuralgias and Other Headache Disorders sections of ICHD-3 beta data on children and adolescents (age 0–18 years) and to suggest changes, additions, and amendments. Methods Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the available literature on pediatric headache, they made observations and proposed suggestions for the mentioned headache disorders on children and adolescents. Results Some headache disorders in children have specific features, which are different from adults that should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psychosocial basis in children and adolescents making primary headache disorders in children distinct from those in adults. Conclusions Several recommendations are presented in order to make ICHD-3 more appropriate for use in children.

Background: Data on clinical presentation of Hemiplegic Migraine (HM) are quite limited in the literature, particularly in the pediatric age. The aim of the present study is to describe in detail the phenotypic features at onset and during the first years of disease of sporadic (SHM) and familial (FHM) pediatric hemiplegic migraine and to review the pertinent literature.Results: Retrospective study of a cohort of children and adolescents diagnosed with hemiplegic migraine, recruited from 11 Italian specialized Juvenile Headache Centers. Forty-six cases (24 females) were collected and divided in two subgroups: 32 SHM (16 females), 14 FHM (8 females). Mean age at onset was 10.5 ± 3.8 y (range: 2–16 y). Mean duration of motor aura was 3.5 h (range: 5 min−48 h). SHM cases experienced more prolonged attacks than FHM cases, with significantly longer duration of both motor aura and of total HM attack. Sensory (65%) and basilar-type auras (63%) were frequently associated to the motor aura, without significant differences between SHM and FHM. At follow-up (mean duration 4.4 years) the mean frequency of attacks was 2.2 per year in the first year after disease onset, higher in FHM than in SHM cases (3.9 vs. 1.5 per year, respectively). A literature review retrieved seven studies, all but one were based on mixed adults and children cohorts.Conclusions: This study represents the first Italian pediatric series of HM ever reported, including both FHM and SHM patients. Our cohort highlights that in the pediatric HM has an heterogeneous clinical onset. Children present fewer non-motor auras as compared to adults and in some cases the first attack is preceded by transient neurological signs and symptoms in early childhood. In SHM cases, attacks were less frequent but more severe and prolonged, while FHM patients had less intense but more frequent attacks and a longer phase of active disease. Differently from previous studies, the majority of our cases, even with early onset and severe attacks, had a favorable clinical evolution.

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.

Introduction: Chronic headaches are not a rare condition in children and adolescents with negative effects on their quality of life. Our aims were to investigate the clinical features of chronic headache and usefulness of the International Classification of Headache Disorders 3rd edition (ICHD 3) criteria for the diagnosis in a cohort of pediatric patients.Methods: We retrospectively reviewed the charts of patients attending the Headache Center of Bambino Gesù Children and Insubria University Hospital during the 2010–2016 time interval. Statistical analysis was conducted to study possible correlations between: (a) chronic primary headache (CPH) and demographic data (age and sex), (b) CPH and headache qualitative features, (c) CPH and risk of medication overuse headache (MOH), and (d) CPH and response to prophylactic therapies. Moreover, we compared the diagnosis obtained by ICHD 3 vs. ICHD 2 criteriaResults: We included 377 patients with CPH (66.4% females, 33.6% males, under 18 years of age). CPH was less frequent under 6 years of age (0.8%; p < 0.05) and there was no correlation between age/sex and different CPH types. The risk to develop MOH was higher after 15 years of age (p < 0.05). When we compared the diagnosis obtained by ICHD 2 and ICHD 3 criteria we found a significant difference for the undefined diagnosis (2.6% vs. 7.9%; p < 0.05), while the diagnosis of probable chronic migraine was only possible by using the ICHD2 criteria (11.9% of patients; p < 0.05). The main criterion which was not satisfied for a definitive diagnosis was the duration of the attacks less than 2 h (70% of patients younger than 6 years; p < 0.005). Amitriptyline and topiramate were the most effective drugs (p < 0.05), although no significant difference was found between them (p > 0.05).Conclusion: The ICHD 3 criteria show limitations when applied to children under 6 years of age. The risk of developing MOH increases with age. Although our “real word” study shows that amitriptyline and topiramate are the most effective drugs regardless of the CPH type, the lack of placebo-controlled data and the limited follow-up results did not allow us to conclude about the drug efficacy.

Restless legs syndrome (RLS) is characterized by unpleasant sensations generally localized to legs, associated with an urge to move. A likely pathogenetic mechanism is a central dopaminergic dysfunction. The exact role of pain system is unclear. The purpose of the study was to investigate the nociceptive pathways in idiopathic RLS patients. We enrolled 11 patients (mean age 53.2 ± 19.7 years; 7 men) suffering from severe, primary RLS. We recorded scalp laser-evoked potentials (LEPs) to stimulation of different sites (hands and feet) and during two different time conditions (daytime and nighttime). Finally, we compared the results with a matched control group of healthy subjects. The Aδ responses obtained from patients did not differ from those recorded from control subjects. However, the N1 and the N2-P2 amplitudes’ night/day ratios after foot stimulation were increased in patients, as compared to controls (N1: patients: 133.91 ± 50.42%; controls: 83.74 ± 34.45%; p=0.016; Aδ-N2-P2: patients: 119.15 ± 15.56%; controls: 88.42 ± 23.41%; p=0.003). These results suggest that RLS patients present circadian modifications in the pain system, which are not present in healthy controls. Both sensory-discriminative and affective-emotional components of pain experience show parallel changes. This study confirms the structural integrity of Aδ nociceptive system in idiopathic RLS, but it also suggests that RLS patients present circadian modifications in the pain system. These findings could potentially help clinicians and contribute to identify new therapeutic approaches.

Background/Objective: The aim of the study was to estimate the rate of evolution or for multiple sclerosis (MS), after a first acute demyelinating event (ADE) in pediatric patients, and to investigate the variables that predict this evolution.Methods: We retrospectively evaluated the clinical and neuroradiological features of children who presented a first ADE between January 2005 and April 2017. All patients included underwent a baseline MRI, a cerebrospinal fluid and blood analysis, including virological examinations. The evolution into MS was determined by the 2013 International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria. Clinical and radiological features predictive of MS were determined using multivariate analyses.Results: Ninety-one patients were selected (mean age at onset: 10.11 ± 4.6). After a mean follow-up of 5.6 ± 2.3 years, 35% of patients' conditions evolved to MS. In the logistic multivariate analysis of clinical and laboratory data, the best predictors of evolution into MS were: the presence of oligoclonal bands in CSF (p < 0.001), past infection with EBV (p < 0.001), periventricular lesions (p < 0.001), hypointense lesions on T1 (p < 0.001), and lesions of the corpus callosum (p < 0.001) including Dawson fingers (p < 0.001).Conclusion: Our findings suggest that a pattern of neuroimaging and laboratory findings may help to distinguish between, at clinical onset, children with a monophasic syndrome (clinically isolated syndrome or acute disseminated encephalomyelitis) from those who will develop MS.

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.

The PLP1 gene, located on chromosome Xq22, encodes the proteolipid protein 1 and its isoform DM20. Mutations in PLP1 cause a spectrum of white matter disorders of variable severity. Here we report on four additional HEMS patients from three families harboring three novel PLP1 mutations in exon 3B detected by targeted next-generation sequencing. Patients experienced psychomotor delay or nystagmus in the first year of age and then developed ataxic–spastic or ataxic syndrome, compatible with a phenotype of intermediate severity in the spectrum of PLP1-related disorders. Regression occurred at the beginning of the third decade of the eldest patient. Extrapyramidal involvement was rarely observed. Brain MRI confirmed the involvement of structures that physiologically myelinate early, although the pattern of abnormalities may differ depending on the age at which the study is performed. These new cases contribute to expanding the phenotypic and genotypic spectrum of HEMS. Additional studies, especially enriched by systematic functional evaluations and long-term follow-up, are welcome to better delineate the natural history of this rare hypomyelinating leukodystrophy.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique of cortical stimulation. Although the exact mechanism of action is not clearly understood, it has been postulated that rTMS action on pain depends most on stimulation sites and stimulation parameters. Most studies concern high-frequency rTMS of the primary motor cortex (M1). High-frequency rTMS over motor cortex seems to induce an analgesic effect while contrasting results were reported after low-frequency rTMS. The aim of the current study was to investigate the effects of 1 Hz rTMS stimulation over the left primary motor cortex on subjective laser pain rating and laser evoked potential (LEP) amplitudes in healthy subjects. Subjects underwent two different sessions (real and sham rTMS) according to a cross-sectional design. In each session, LEPs and laser-pain rating to stimulation of both right and left hand dorsum were collected before 1 Hz rTMS over the left M1 area (baseline), which lasted 20 min. Then, LEPs and laser-pain rating were measured immediately after rTMS (T0), after 20 min from T0 (T0+20), and after 40 min from T0 (T0+40). We could not find any modification of both laser-pain rating and LEP parameters (latencies and amplitudes) following 1 Hz rTMS. Therefore, our results show that the low-frequency rTMS of the M1 area does not change the response of the cerebral cortex to pain.

Idiopathic intracranial hypertension (IIH) is characterized by intracranial pressure >28 cmH2O in the absence of identifiable causes. Aim of this paper is to describe the clinical phenotype of pediatric IIH and to analyze the applicability of ICHD-3 criteria in comparison to the ICHD-2. We conducted a retrospective analysis of full clinical data of pediatric patients diagnosed with IIH between January 2007 and June 2018. Diagnostic evaluation included neuroimaging (all patients) and ultrasound-based optic nerve sheath diameter measurement (9 patients). Diagnosis of IIH was verified according to both ICHD-2 and ICHD-3 criteria for headache attributed to IIH, to verify the degree of concordance. We identified 41 subjects with suspected IIH; 14 were excluded due a diagnosis of secondary IH or lack of data. We therefore selected 27 subjects (age 4–15 years, mean 11). All patients presented with headache and bilateral papilloedema. Headache was daily in 22% cases, with diffuse gravative pain in 41%. In 4%, pain was exacerbated by cough, stress or tension. The most common presentation symptoms, in addition to headache, were blurred vision or diplopia (70%), vomiting (33%), and dizziness (15%). Twenty patients (74%) were obese. In 6 patients (22%) neuroimaging showed empty sella. Optic nerve sheath distension was detected in 6 out of 9 patients. Regarding the applicability of the ICHD-2 criteria, 18/27 (71%) patients have criterion A; 24/27 (89%) criterion B; 27/27 (100%) criterion C; 27/27 (100%) criterion D. When the ICHD-3 criteria were used, 27/27 (100%) fitted criterion A; 24/27 (89%) criterion B; 27/27 (100%) criterion C; and 27/27 (100%) criterion D. Our study suggests that, as compared with the ICHD-2, the new ICHD-3 criteria for headache attributed to IIH are better satisfied by pediatric patients with IIH. This is mainly due to the fact that qualitative headache characteristics are no longer considered in ICHD-3. Although the risk of under-rating the symptom of headache in IIH should not be disregarded, in pediatric population headache characteristics are usually less defined than in adults and obtaining a precise description of them is often very difficult.

IntroductionA growing body of literature has shown an association between somatic symptoms and insecure “attachment style.” In a recent study, we found a relationship between migraine severity, ambivalent attachment style, and psychological symptoms in children/adolescents. There is evidence that caregivers’ attachment styles and their way of management/expression of emotions can influence children’s psychological profile and pain expression. To date, data dealing with headache are scarce. Our aim was to study the role of maternal alexithymia and attachment style on their children’s migraine severity, attachment style, and psychological profile.Materials and methodsWe enrolled 84 consecutive patients suffering from migraine without aura (female: 45, male: 39; mean age 11.8 ± 2.4 years). According to headache frequency, children/adolescents were divided into two groups: (1) high frequency (patients reporting from weekly to daily attacks), and (2) low frequency (patients having ≤3 episodes per month). We divided headache attacks intensity into two groups (mild and severe pain). SAFA “Anxiety,” “Depression,” and “Somatization” scales were used to explore children’s psychological profile. To evaluate attachment style, the semi-projective test SAT for patients and ASQ Questionnaire for mothers were employed. Maternal alexithymia traits were assessed by TAS-20.ResultsWe found a significant higher score in maternal alexithymia levels in children classified as “ambivalent,” compared to those classified as “avoiding” (Total scale: p = 0.011). A positive correlation has been identified between mother’s TAS-20 Total score and the children’s SAFA-A Total score (p = 0.026). In particular, positive correlations were found between maternal alexithymia and children’s “Separation anxiety” (p = 0.009) and “School anxiety” (p = 0.015) subscales. Maternal “Externally-oriented thinking” subscale correlated with children’s school anxiety (p = 0.050). Moreover, we found a correlation between TAS-20 Total score and SAFA-D “Feeling of guilt” subscale (p = 0.014). Our data showed no relationship between TAS-20 and ASQ questionnaires and children’s migraine intensity and frequency.ConclusionMaternal alexithymia and attachment style have no impact on children’s migraine severity. However, our results suggest that, although maternal alexithymic traits have no causative roles on children’s migraine severity, they show a relationship with patients’ attachment style and psychological symptoms, which in turn may impact on migraine severity.