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Chronic migraine (CM) in childhood and adolescence is associated with a high disease burden, including impaired quality of life, school absenteeism, and reduced daily functioning. OnabotulinumtoxinA (ONA) is approved for prophylactic treatment of CM in adults, but its use in pediatric patients remains off-label, with evidence still limited. This narrative review summarizes current data on the efficacy, safety, and tolerability of ONA in pediatric CM, drawing from randomized controlled trials, prospective cohorts, and retrospective series. In addition to summarizing efficacy and safety data, our review aims to focus on potential practical clinical implications and on discussion points and research questions that remain open.

•We explored the role of somatosensory system in coding visual self-identity.•RTs and SEPs to tactile stimuli are modulated by the self-hand image presentation.•Coding of visual self-identity entails primary and secondary somatosensory cortices.•Somatosensory, and not visual, activity vary as a function of bodily self-identity.•Visuo-tactile associations promotes the coding of visual self-identity. How does the brain process our bodily identity? This question has long fascinated scientists because of its potential implications for the study of self-awareness. Here, to test the idea that the somatosensory system is directly involved in coding bodily self-identity even when conveyed through vision, we probed the somatosensory system with tactile stimuli while participants observed hand images, either belonging to them (self-hand) or to another person (other-hand). In three psychophysical experiments (discovery, replicating and control samples), we found faster reaction times to tactile stimuli when paired with the self- than the other-hand image. To explore the neural basis of this effect, we conducted two electrophysiological experiments (discovery and replicating samples), and we observed that visual activity did not vary as a function of bodily identity, whereas the activity of the primary (at around 40 ms) and secondary (from 100 ms) somatosensory cortices did vary, as revealed by significantly higher somatosensory responses to tactile probes when presenting the self- than the other-hand image. We propose that this somatosensory coding of visual self-identity may be the result of associative learning mechanisms, through which individuals learn that the association between visual and somatosensory input only pertains to the own body, thus representing a possible prerequisite for establishing self-awareness.

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.

Background Chronic postoperative pain affects approximately 20% of patients with knee osteoarthritis after total knee replacement. Circulating microRNAs can be found in serum and might act as biomarkers in a variety of diseases. The current study aimed to investigate the preoperative expression of circulating microRNAs as potential predictive biomarkers for the development of chronic postoperative pain in the year following total knee replacement. Methods Serum samples, collected preoperatively from 136 knee osteoarthritis patients, were analyzed for 21 circulatory microRNAs. Pain intensity was assessed using a visual analog scale before and one year after total knee replacement. Patients were divided into a low-pain relief group (pain relief percentage <30%) and a high-pain relief group (pain relief percentage >30%) based on their pain relief one year after total knee replacement, and differences in microRNAs expression were analyzed between the two groups. Results We found that three microRNAs were preoperatively dysregulated in serum in the low-pain relief group compared with the high-pain relief group. MicroRNAs hsa-miR-146a-5p, -145-5p, and -130 b-3p exhibited fold changes of 1.50, 1.55, and 1.61, respectively, between the groups (all P values < 0.05). Hsa-miR-146a-5p and preoperative pain intensity correlated positively with postoperative pain relief (respectively, R = 0.300, P = 0.006; R = 0.500, P < 0.001). Discussion This study showed that patients with a low postoperative pain relief present a dysregulation of circulating microRNAs. Altered circulatory microRNAs expression correlated with postoperative pain relief, indicating that microRNAs can serve as predictive biomarkers of pain outcome after surgery and hence may foster new strategies for preventing chronic postoperative pain after total knee replacement (TKR).

BackgroundMigraine 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.MethodsSeventy-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.ResultsPatients 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.ConclusionsDifferences 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.

Treatment for pediatric-onset multiple sclerosis (POMS) currently reflects treatment for adult-onset MS, despite some differences in its clinical course. First-choice treatment of POMS generally consists of interferon β-1a or glatiramer acetate, with therapies such as natalizumab or fingolimod reserved for second-choice treatment. In cases of severe disease, both fingolimod and natalizumab can be considered first-choice therapy. This paper presents three case histories of patients with POMS and highlights the different uses of fingolimod within the POMS treatment algorithm. The first and third cases are examples of escalation therapy, both in females aged 16 to 17 years, with fingolimod administering as second choice following disease progression. The second case is an example of using fingolimod as first-choice therapy, given to a 12-year-old male with severe disease. In all three cases, over a period of approximately 1 year after the initiation of fingolimod treatment, there was no further disease progression and no adverse events were recorded.

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.

Phantom limb pain (PLP) is a disabling and intractable sensation arising in about 80% of patients after amputation. The aim of this study was to evaluate the possibility to modulate nociceptive processing and pain perception with cerebellar transcranial direct current stimulation (ctDCS) in patients suffering from painful and non-painful phantom limb sensations. Fourteen upper limb amputees underwent ctDCS (anodal or sham, 2.0 mA, 20 min per day, 5 days a week). Clinical scores and electrophysiological parameters were assessed before tDCS, at the end of the 5-day treatment, 2 and 4 weeks later. Laser-evoked potentials (LEPs) were obtained from the stump using a Nd:YAP laser by pulses with short duration (5 ms) and small diameter spots (5 mm). Changes in visual analogue scores (VAS) were evaluated (chronic pain, paroxysmal pain, stump pain, phantom movements, phantom sensations). Anodal polarization significantly dampened LEP amplitudes (N1, p = 0.021 and N2/P2, p = 0.0034), whereas sham intervention left them unchanged. Anodal ctDCS significantly reduced paroxysmal pain (p < 0.0001), non-painful phantom limb sensations (p < 0.0001) and phantom limb movements (p = 0.0003), whereas phantom limb and stump pain did not change compared to the sham condition. Anodal ctDCS significantly improves both paroxysmal pain and non-painful phantom limb sensations, which are likely induced by maladaptive changes in the sensorimotor network and posterior parietal cortex respectively.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

Objective Several studies examined stress factors in both adult and pediatric patients with migraine, but few of them have analyzed coping strategies adopted to deal with stressful events in pediatric age. In particular, some of these studies have focused on specific migraine populations or have not employed standardized instruments. Our study used a standardized tool to investigate the coping strategies adopted by patients with primary migraine in dealing with stressful events. We aimed at exploring: 1) Coping responses to stressful events and their possible association with migraine characteristics such as headache frequency, pain intensity and use of prophylactic treatment; (2) Potential differences in anxiety and depression symptoms based on migraine characteristics, and (3) Association between migraine characteristics, coping strategies, and psychological aspects. Methods We studied 81 adolescents (mean age 13.8 ± 1.6 years; 18 M and 63 F). They were divided into: (1) high frequency (weekly to daily episodes) and low frequency (≤ 4 episodes per month); (2) mild and severe pain; (3) need for prophylactic treatment or not. To evaluate patients’ anxiety, depression and coping strategies we used respectively SAFA-A, SAFA-D and CRI-Y questionnaires. Results School and socialization represent the most commonly reported stressful events among our patients with migraine. Patients with high frequency of headache tend to adopt maladaptive coping strategies in “Logical Analysis” ( p  = 0.012), “Positive Reappraisal” ( p  = 0.002) and “Total Approach” ( p  = < 0.001). Moreover, patients with a high frequency of headache showed higher anxiety and depression scores ( p  = < 0.050). On the other hand, lower scores in some subscales of anxiety and depression emerged in high frequency patients who used “Logical Analysis” maladaptively ( p  = < 0.050). Conclusion Adolescents with a more disabling migraine pattern tend to employ maladaptive coping strategies focused on active behavioral responses to the stressful events.