Exploring Headaches in Pediatric Behçet Disease: Prevalence, Clinical Impact, and Management.

Behçet's Disease (BD), also recognized as Behçet Syndrome, manifests uniquely in pediatric populations as Pediatric Behçet's Disease (PBD), characterized by multisystemic inflammatory symptoms including recurrent oral and genital aphthae, and diverse ocular, vascular, and neurological involvements. This review elucidates the prevalence, burden, and management strategies of headaches in children with PBD, focusing on both primary headaches, such as migraine and tension-type headaches, and secondary headaches linked to systemic disease manifestations. It explores the pathophysiological underpinnings specific to PBD-related headaches and discusses the intricate relationship between systemic inflammatory processes and neurological symptoms. By examining the literature from 2004 to 2024, this study highlights the high frequency of headache in PBD patients, underscoring its diagnostic and clinical significance. We aim to provide a detailed understanding of headache management in PBD, emphasizing tailored therapeutic strategies that address the unique challenges faced by this patient population. This review also underscores the importance of comprehensive clinical evaluations to optimize outcomes and mitigate long-term sequelae, proposing that awareness and understanding of headache in PBD can significantly enhance both diagnosis and management.

Pediatric Migraine and Visual Cortical Excitability: A Prospective Observational Study with Sound-Induced Flash Illusions.

The pathophysiological mechanisms underlying migraine are more difficult to investigate in children than in the adult population. Abnormal cortical excitability turns out to be one of the most peculiar aspects of migraine, accounting for the manifestations of migraine attacks. Recently, visual cortical excitability has been explored effectively in adult migraineurs with a technique based on cross-modal audio-visual illusions (with sound-induced flash illusions (SIFIs) being reduced in migraineurs compared to non-migraineur subjects). On such a basis, in this study, we investigated visual cortical excitability in children with migraine using SIFIs using combinations of visual and sound stimuli presented randomly. We evaluated 26 children with migraine without aura and 16 healthy children. Migraineurs did not differ from the age-matched healthy subjects regarding fission or fusion illusions but perceived more flashes in trials of multiple flashes with or without beeps. The higher number of SIFIs in migraineur children compared to adults may be due to a greater propensity of visual stimulation to be driven by auditory stimuli (i.e., acoustic dominance). The increased ability to perceive flashes reveals a hyperfunctional visual cortex, demonstrating that the use of SIFIs is a valid tool for assessing visual cortical responsiveness even in pediatric migraine.

Orofacial Migraine and Other Idiopathic Non-Dental Facial Pain Syndromes: A Clinical Survey of a Social Orofacial Patient Group.

Background: Orofacial pain syndromes (OFPs) are a heterogeneous group of syndromes mainly characterized by painful attacks localized in facial and oral structures. According to the International Classification of Orofacial Pain (ICOP), the last three groups (non-dental facial pain, NDFP) are cranial neuralgias, facial pain syndromes resembling primary headache syndromes, and idiopathic orofacial pain. These are often clinical challenges because the symptoms may be similar or common among different disorders. The diagnostic efforts often induce a complex diagnostic algorithm and lead to several imaging studies or specialized tests, which are not always necessary. The aim of this study was to describe the encountered difficulties by these patients during the diagnostic-therapeutic course. Methods: This study was based on the responses to a survey questionnaire, administered to an Italian Facebook Orofacial Patient Group, searching for pain characteristics and diagnostic-therapeutic care courses. The questionnaire was filled out by patients affected by orofacial pain, who were 18 years and older, using a free online tool available on tablets, smartphones, and computers. Results: The sample was composed of 320 subjects (244F/76M), subdivided by age range (18-35 ys: 17.2%; 36-55 ys: 55.0%; >55 ys 27.8%). Most of the patients were affected by OFP for more than 3 years The sample presented one OFP diagnosis in 60% of cases, more than one in 36.2% of cases, and 3.8% not classified. Trigeminal neuralgia is more represented, followed by cluster headaches and migraines. About 70% had no pain remission, showing persisting background pain (VAS median = 7); autonomic cranial signs during a pain attack ranged between 45 and 65%. About 70% of the subjects consulted at least two different specialists. Almost all received drug treatment, about 25% received four to nine drug treatments, 40% remained unsatisfied, and almost 50% received no pharmacological treatment, together with drug therapy. Conclusion: To the authors' knowledge, this is the first study on an OFP population not selected by a third-level specialized center. The authors believe this represents a realistic perspective of what orofacial pain subjects suffer during their diagnostic-therapeutic course and the medical approach often results in unsatisfactory outcomes.

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.

Familial hemiplegic migraine in pediatric patients: A genetic, clinical, and follow-up study.

OBJECTIVE: The aim of this study was to describe a cohort of pediatric patients with genetically confirmed familial hemiplegic migraine (FHM). The knowledge of genotype-phenotype correlations may suggest prognostic factors associated with severe phenotypes. BACKGROUND: Hemiplegic migraine is a rare disease and data concerning the pediatric population are even more rare as they are often extrapolated from mixed cohorts. METHODS: We selected patients who met International Classification of Headache Disorders, third edition criteria for FHM, who had a molecular diagnosis, and whose first attack occurred under the age of 18 years. RESULTS: We enrolled nine patients (seven males and two females) first referred to our three centers. Three of the nine (33%) patients had calcium voltage-gated channel subunit alpha1 A (CACNA1A) mutations, five (55%) had ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2) mutations, and one had both genetic mutations. The patients experienced at least one aura feature other than hemiplegia during the first attack. The mean (SD) duration of HM attacks in the sample was 11.3 (17.1) h; 3.8 (6.1) h in the ATP1A2 group, and 24.3 (23.5) h in the CACNA1A group. The mean (SD, range) duration of follow-up was 7.4 (2.2, 3-10) years. During the first year from the disorder's onset, only four patients had additional attacks. Over the course of follow-up, the attack frequency overall was 0.4 attacks/year without a difference between the two groups (CACNA1A and ATP1A2). CONCLUSION: The study data show that most of our patients with early-onset FHM experienced infrequent and non-severe attacks, which improved over time. Furthermore, the clinical course revealed neither the appearance of novel neurological disorders or a deterioration of basic neurological or cognitive functioning.

A Narrative Review of Visual Hallucinations in Migraine and Epilepsy: Similarities and Differences in Children and Adolescents.

Since the earliest descriptions of the simple visual hallucinations in migraine patients and in subjects suffering from occipital lobe epilepsy, several important issues have arisen in recognizing epileptic seizures of the occipital lobe, which often present with symptoms mimicking migraine. A detailed quantitative and qualitative clinical scrutiny of timing and characteristics of visual impairment can contribute to avoiding mistakes. Differential diagnosis, in children, might be challenging because of the partial clinical, therapeutic, and pathophysiological overlaps between the two diseases that often coexist. Ictal elementary visual hallucinations are defined by color, shape, size, location, movement, speed of appearance and duration, frequency, and associated symptoms and their progression. The evaluation of the distinctive clinical features of visual aura in migraine and visual hallucinations in occipital epilepsy could contribute to understanding the pathogenetic mechanisms of these two conditions. This paper aims to critically review the available scientific evidence on the main clinical criteria that address diagnosis, as well as similarities and differences in the pathophysiological mechanisms underlying the visual impairment in epilepsy and migraine.

Idiopathic Non-Dental Facial Pain Syndromes in Italian Children: A Clinical Case Series.

BACKGROUND: The orofacial pain syndromes (OFPs) are a heterogeneous group of syndromes characterized by painful attacks involving the orofacial structures. They may be summarily subdivided into two great categories: (1) orofacial pain mainly attributed to dental disorders such as dentoalveolar and myofascial orofacial pain or temporomandibular joint (TM) pain; (2) orofacial pain mainly attributed to non-dental pain as neuralgias, facial localization of primary headaches or idiopathic orofacial pain. The second group is uncommon, often described by single case reports, can often show overlapping symptoms with the first group, and represents a clinical challenge, carrying the risk of undervaluation and possibly invasive odontoiatric treatment. We aimed to describe a clinical pediatric series of non-dental orofacial pain and better to underline some topographic and clinical features associated with them. We retrospectively collected the data of children admitted to our headache centers (Bari, Palermo, Torino) from 2017 to 2021. Our inclusion criterion was the presence of non-dental orofacial pain following the topographic criteria of 3° International Classification of Headache Disorders (ICHD-3), and exclusion criteria included the pain syndromes attributed to the dental disorders and pain syndromes due to the secondary etiologies Results. Our sample comprised 43 subjects (23/20 M/F, in the range of ages 5-17). We classified them int: 23 primary headaches involving the facial territory during attacks, 2 facial trigeminal autonomic cephalalgias, 1 facial primary stabbing headache, 1 facial linear headache, 6 trochlear migraines, 1 orbital migraine 3 red ear syndrome and 6 atypical facial pain. All patients described debilitating pain for intensity (moderate/severe), 31 children had episodic attacks, and 12 had continuous pain. Almost all received drugs for acute treatment (less than 50% were satisfied), and some received non-pharmacological treatment associated with drug therapy Conclusion. Although rare OFP can occur in pediatric age, it can be debilitating if unrecognized and untreated, affecting the psychophysical well-being of young patients. We highlight the specific characteristics of the disorder for a more correct and earlier identification during the diagnostic process, already difficult in pediatric age, and to define the approach and possible treatment to prevent negative outcomes in adulthood.

Evolution of Pediatric Migraine Patients Admitted at an Emergency Department after a 10-Year Follow-Up.

BACKGROUND: Despite its high prevalence, the clinical course of pediatric migraine has not been fully understood, and previous studies present conflicting results. We present here the findings of a 10-year follow-up study involving children with severe migraine pain admitted to our emergency department. Furthermore, all studies were carried out on selected outpatient clinical case studies. Our aim was to evaluate a population of migraine children admitted to an emergency department because of increased severity or frequency of pain or even because of very anxious parents concerning their child's headache in order to describe their long-term outcomes, whether it differed from that of outpatient populations and to identify possible predictors of prognosis. METHODS: We recruited 80 subjects with migraine headaches (mean age 8 years with a range of 4-14 years, 50% females), attending the baseline examination of a population admitted for a headache to the Emergency Department in the first half year of 2012. Of the 80 subjects, 48 (60%) were eligible for follow-up in 2022. We included in our study only patients diagnosed with migraine, according to the diagnostic criteria of the International Classification of Headache Disorders. All were contacted by telephone, and a semi-structured questionnaire was provided to them by email. The association between several possible prognostic factors (gender, familiar neurologic disorders, prenatal and perinatal disorders, social activities, sleep disorders, etc.) and the long-term persistence of migraine headaches were explored using logistic regression analysis. RESULTS: Of 48 subjects with migraine headaches at baseline, 31 (65%) had persistent migraine, and 17 (35%) experienced remission. The preliminary results showed that the presence of neurologic disorders in parents (p < 0.01-odds ratio 9.34 (2.53-41.64) and sleep disorders (p < 0.01-odds ratio 13.18 (2.25-252.74) significantly predicted the 10-year persistence of migraine headaches, while the other considered predictors were found not to influence prognosis. CONCLUSIONS: To our knowledge, this was the first study conducted on a selected pediatric population upon admission to the emergency room. Our study suggests that a population of pediatric migraine selected for admission to the emergency department also shows a favorable long-term prognosis, like the studies conducted in the outpatient sample. Familial neurological comorbidity and sleep disorders were unfavorable factors for predicting good outcomes.

New-onset headache following COVID-19: An Italian multicentre case series.

OBJECTIVE: To describe the characteristics of patients with new-onset headache following SARS-CoV-2 infection. BACKGROUND: SARS-CoV-2 infection leads to several neurological manifestations, and headache is a frequent and disabling symptom, both exacerbating pre-existing headache syndromes and causing new-onset ones. METHODS: Patients with new-onset headache after SARS-CoV-2 infection with consent to participate were included, while those ones with previous headaches were excluded. The temporal latency of headache after infection, pain characteristics, and concomitant symptoms were analysed. Moreover, the efficacy of acute and preventive medications was explored. RESULTS: Eleven females (median age 37.0 [10.0-60.0] years old) were included. In most cases, headache onset occurred with the infection, the location of pain varied, and the quality was either pulsating or tightening. Headache was persistent and daily in 8 patients (72.7%), while it occurred in episodes in the remaining subjects. Baseline diagnoses were new daily persistent headache (36.4%), probable new daily persistent headache (36.4%), probable migraine (9.1%), and migraine-like headache secondary to COVID-19 (18.2%). Ten patients received one or more preventive treatments and six of them showed an improvement. CONCLUSION: New-onset headache following COVID-19 is a heterogenous condition with uncertain pathogenesis. This type of headache can become persistent and severe, with a wide spectrum of manifestations (new daily persistent headache being the most represented one) and variable response to treatment.

Pediatric Migraine: Diagnosis and Management.

The WHO recognizes migraine as one of the most disabling diseases [...].

Cranial Autonomic Symptoms and Migraine: What Relationship and What Meaning? A Review.

Cranial autonomic symptoms (CAS) have been usually associated with trigeminal autonomic cephalalgias (TAC's), however in the last few years several reports in adult and pediatric population have reported important presence of the CAS in migraine. Also several evidences experimentally show that the increased parasympathetic outflow can enhance the sensitization of nociceptive receptors involved in migraine. The presence of CAS suggests an activation of the trigeminal-autonomic reflex, probably related to an over-activation of the trigeminal afferent arm. For these reasons identifing and understanding of these symptoms in migraine may be important to help in the diagnosis and effective management. The purpose of this review is, analyzing the literature data, to discuss the prevalence of these CAS in migraine, the pathophysiological meaning in the pathogenesis of migraine and whether their presence influences the prognosis and therapy of migraine in adult and pediatric age.

Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP).

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

The Pediatric Trochlear Migraine: Diagnostic and Therapeutic Implications.

Trochlear Migraine has been recently described as the concurrence of strictly unilateral migraine and ipsilateral trochleodynia with relief of migraine after successful treatment of trochleodynia. This disorder has been interpreted as "cluster-tic syndrome" or "seizure-triggered migraine". Trochlear Migraine is unrecognized and rarely described in childhood. The aim of this study is to review the few cases of Trochlear Migraine reported in the literature in addition to the cases observed in our clinical experience. In particular, our cases showed recurrent attacks of severe and pulsating headache associated with nausea, vomiting, phonophobia, photophobia, and strict trochlear localization of pain. They often presented with alternating side attacks. Therefore, we suggest that the term "Trochlear Migraine" should be reserved for clinical migraine attacks strictly localized in the trochlear region, and we assume that the excessive increase in descriptions of new primary headache syndromes, according to the International Classification of Headache Disorders, can be probably be ascribed to the common physiopathological mechanisms characterizing these forms of migraine.

Study on "Atypical" Migraine Auras in the Pediatric Age: The Role of Cortical Spreading Depression and the Physiopathogenetic Hypothesis Arising from Our Clinical Cases.

Migraine is a complex neurologic disorder by which several systems of the central nervous system (autonomous system, affective, cognitive, sensory and motor system) may be affected on different levels. About a fourth of migraine patients have migraine auras. The most common aura is the visual aura followed by the sensorial aura but motor deficits, as well as deficits of higher cortical centers (disorders of thinking, orientation, coherence, or concentration), may occur as well. In analogy with a headache diary, an aura diary can deliver important help in the diagnostic process of rare migraine manifestations and prevent the under-diagnosis of unusual migraine manifestations. Complex migraine manifestations are a diagnosis of exclusion, and a broad diagnostic work-up is necessary in order to exclude dangerous neurologic pathologies. In addition, here, we discuss the atypical clinical presentation and possible physio-pathogenetic related aspects of these atypical migraine aura features in the developmental age. In addition, we wanted to stress and analyze the clinical aspects of our children/adolescents with atypical auras, which seem to be more difficult to frame with the mechanisms originally proposed to explain the physio-pathogenetic relationship between CSD and aura. Finally, we discuss in detail the complex aspects of this topic on the basis of available data and propose new terminology: "Multiple, Synchronous and Asynchronous, Cortical and Subcortical Spreading Depression".

The association between gastro-oesophageal reflux and migraine in the paediatric population: a multicentre case-control study.

Infantile regurgitation is one of the most common discomforts in the first months of life. Infantile colic and, in older children, functional dyspepsia have been linked to migraine. To date, this is the first study to investigate a possible association between infantile regurgitation and primary headaches in children. This is a case-control study of 195 children aged 6-17 years, with primary headache (migraine, or tension type headache) in 5 European paediatric hospitals. The control group is composed of 240 same-aged children attending with minor injuries during the same period - February 1st 2020 to December 1st 2020. A structured questionnaire identified a history of infantile regurgitation and other functional gastrointestinal disorders for case and control participants. The outcome was the difference in the prevalence of infantile regurgitation among children with or without a diagnosis of primary headache. The analysis showed a significant association between infantile regurgitation and migraine (OR = 1.88, CI 95 = 1.01-3.4, p = 0.04). No association was found between infantile regurgitation and tension type headache (p = 0.33). Subgroup analysis confirmed that the association was only significant for migraine without aura (OR = 2.3, CI 95 = 1.2-4.4, p = 0.01). In a further subgroup analysis, the presence of functional dyspepsia, irritable bowel syndrome and abdominal migraine was associated with migraine without aura. CONCLUSION: The presence of migraine among children aged 6-17 was associated with a history of infantile regurgitation. Additional longitudinal studies are required to confirm whether infantile regurgitation could be considered as a precursor of migraine. WHAT IS KNOWN: • Children suffering from functional gastrointestinal disorders are more likely to be suffering from migraine and tension-type headache as well. • Children suffering from primary headache are more likely to have had infantile colic in their first six month of life. WHAT IS NEW: • It is the first study to find an association between migraine and infantile regurgitation in children. • These findings could have an impact on the diagnosis and therapeutics of both migraine and infantile regurgitation.

ADEM post-Sars-CoV-2 infection in a pediatric patient with Fisher-Evans syndrome.

INTRODUCTION: Sars-CoV-2 is a single-strained RNA virus belonging to Coronaviridae's family. In pediatric age, the majority of patients is asymptomatic; however, several neurological manifestations associated with Sars-CoV-2 infection have been detected in a percentage of cases ranging from 17.3 to 36.4%. Acute disseminated encephalomyelitis (ADEM) has been recently included among the potential complications of Sars-Cov2 infection. The available data regarding pediatric patient show only one case. CASE REPORT: We present a case regarding a 6-year-old patient suffering from Fisher-Evans syndrome who was given sirolimus and thalidomide therapy. After 10 days since the first positive nasopharyngeal swab for Sars-CoV-2, in which he had no symptoms, he presented an episode of generalized tonic-clonic seizure with spontaneous resolution. The patient underwent MRI which showed the typical picture of acute disseminated encephalomyelitis. His clinical course was favorable, with a good response to cortisone therapy and a progressive improvement of the neuroradiological and electroencephalographic picture. CONCLUSIONS: According to our knowledge, this is the second case of an acute disseminated encephalomyelitis following SARS-CoV-2 infection in a pediatric patient, characterized by monosymptomatic onset, in which the immunosuppressive therapy practiced for the Fisher-Evans syndrome has probably contributed to a favorable evolution of ADEM, in contrast to other case described in the literature.

Migraine and handedness.

Migraine is a typically unilateral disorder in adulthood; however, the reasons for painful lateralization have been little investigated. The possible influence of manual dominance was suggested. We aimed to investigate the localization of pain in migraine attacks in right-handed and left-handed subjects. The retrospective study collected 546 patients with migraine aged between 16 and 65 years, reporting the manual dominance to the Edinburgh test. We included 466 right-handed and 80 left-handed subjects with migraine. We registered 4215 unilateral painful attacks. The right-handers had 3412 unilateral episodes; 62.8% of the attacks were characterized by pain on the right side and 37.2% by pain on the left. The left-handed subjects reported 803 unilateral pain with 63.5% of unilateral pain episodes on the left side and 36.5% of attacks with lateralized pain on the right (p < 0.001). Our data suggest that manual dominance may influence the side of pain lateralization in migraine.

Red ear syndrome in children: Review of literature and report of three cases.

BACKGROUND: Red ear syndrome (RES) is a neurological syndrome that is characterized by attacks of redness and pain that is localized in the earlobe, accompanied by a burning sensation, swelling or otalgia. The exact pathophysiology of RES is not known. Several pediatric cases have been described. They show an extreme variability in clinical presentation and therapeutic response, and therefore there are numerous difficulties in the diagnostic-therapeutic approach and in the comprehension of the physiopathology. The goal of this report is to present three clinical cases of red ear syndrome in children. These cases show various characteristics that can give useful indications regarding the differential diagnosis and the pathogenetic mechanisms that are involved, particularly when they are compared with cases published in the literature. CASE-REPORTS: We report three pediatric RES cases: 1) a boy whose condition offered a typical example of the association that occurs between migraine and RES. 2) a girl with idiopathic RES. 3) a child who suffered RES attacks that showed many similarities with trigeminal autonomic cephalalgias. CONCLUSION: Our clinical series shows the different ways in which RES can be expressed and they support the reported scientific literature. We suggest that the different forms of RES have a common final autonomic pathogenetic mechanism that is activated by parasympathetic hyperactivity and sympathetic inhibition. The different temporal characteristics, frequency, etc. may depend on the activation of distinct physiopathological modules that are related to the pain circuits, as suggested by the modular theory which describes that groups of neurons are defined as a module, where each module is responsible for a symptom and the individual's headache is defined by the activated modules.

Broad neurodevelopmental features and cortical anomalies associated with a novel de novo KMT2A variant in Wiedemann-Steiner syndrome.

Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder including developmental delay/intellectual disability (DD/ID), hypertrichosis cubiti, short stature, and distinctive facial features, caused by mutation in KMT2A gene, which encodes a histone methyltransferase (H3K4) that regulates chromatin-mediated transcription. Different neurodevelopmental phenotypes have been described within the WDSTS spectrum, including a peculiar Autism Spectrum Disorder (ASDs) subtype in some affected individuals. Here, we report a 9-year-old Caucasian male found by next-generation panel sequencing to carry a novel heterozygous de novo KMT2A frameshift variant (NM_001197104.2:c.4433delG; p. Arg1478LeufsTer108). This boy presented a WDSTS phenotype associated with broad neurodevelopmental features, including an unusual speech difficulty (i.e., palilalia), and brain imaging studies revealed an array of cortical anomalies (e.g., frontal simplified gyration, focal frontal cortical dysplasia). These clinical and radiological observations expand the known WDSTS-related neurodevelopmental phenotypes and further strengthen the important role of KMT2A in brain function and cortical development.

Migraine in Children Under 7 Years of Age: a Review.

PURPOSE OF REVIEW: Despite the accumulation of a significant amount of data on pediatric headache, few studies have been conducted on its occurrence in children under 7 years of age. Within primary headaches in this age, migraine especially, turns out to be a disorder affecting up to 4% of the general population. An underestimate of its true prevalence can be due to lack of specific diagnostic markers, the frequent difficulty of describing pain in childhood, and the necessity of reliable parents' reports. Thus, migraine in children under 7 years of age represents an important challenge for clinicians. The objective of this manuscript is to provide a comprehensive review of epidemiologic, clinic, and therapeutic aspects of migraine in this age. RECENT FINDINGS: Current literature data show that migraine has some differences, especially in clinical and therapeutic terms, in this age group compared to subsequent ages. Furthermore, some evidences showing that an early onset of migraine may play an unfavorable role in its natural history, suggest an early identification and management of migraine in younger children. Moreover, we highlight the role that factors of prenatal and perinatal development can play in the predisposition and anticipation of migraine onset. Finally, open questions related to the several undefined features of migraine in this age are reported. Migraine in this pediatric population is absolutely not rare, represents an importan clinical challenge and probably has a negative predictive role.