No abstract

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.

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<0.001). The mean intensity of the attacks dropped from 1.67 ± 0.6 (T0) to 1.16 ± 0.5 (T1) (p<0.001), and the percentage of patients with severe attacks decreased after treatment (from 8.2% to 1.6%; p<0.05). The monthly assumptions of drugs for the attack reduced from 9.5 ± 4.4 to 4.9 ± 2.5 (p<0.001). Only one patient developed mild side effects (nausea and floating). Conclusions. Our preliminary data show that umPEA administered for three month reduces pain intensity and the number of attacks per month in pediatric patients with migraine. Although the small number of patients and the lack of control group do not allow us to consider these initial results as definitely reliable, they encourage us to expand the sample.

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.

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

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

The pathophysiological mechanisms underlying normal aging and neurodegenerative disorders represent the focus of a bulk of recent research. Physiological brain aging is characterized by a progressive dysfunction and loss of synaptic contacts and neuronal abnormal apoptosis. Neural and synaptic redundancy as well as functional and structural plastic remodeling of brain networking promote maintenance of brain activity in healthy elderly for everyday life but are not sufficient to face the pathologic scenario of excessive synaptic/ neuronal loss as in dementias. It is, then, important to implement techniques that are able to measure changes in normal aging brain and to discriminate the threshold from neurodegenerative processes. Rhythmic electromagnetic brain oscillatory activity is a hallmark of neuronal function and it contains relevant traces of neuronal assemblies cooperation across different brain functions; an integrated approach utilizing modern neurophysiological techniques, including electroencephalography (EEG), event-related potentials (ERPs), and transcranial magnetic stimulation (TMS), together with biological markers and structural and functional imaging is promising for largescale, affordable, and non-invasive intercept of at-risk populations both at a group and probably also at a single-subject level. This approach might also guarantee the possibility of studying drug-induced changes in the electrical properties of the human cortex, developing and testing models of brain connectivity and treating neuropsychiatric diseases. In this paper some neurophysiological cutting-edge techniques will be presented that provide innovative information and deal with the broad issue of the role of neurophysiology for the assessment of patho-physiological aging and dementia also providing new insight to the actions of central nervous system drugs at the cortical level.

This case expands the spectrum of paraneoplastic AQP4 autoimmunity highlighting the importance of considering an oncological screening in patients with late-onset NMOSD.