Non-Pharmacological Treatments in Paediatric Migraine.

Psychological, social, and biological aspects contribute synergistically to the maintenance and chronicity of pain in primary headaches. An integrated intervention seems to be the most appropriate in the management of these conditions, taking advantage not only of pharmacological strategies, but also of different approaches according to the global assessment and patient necessities. In this perspective, non-pharmacological treatments are becoming increasingly used to overcome these issues also in paediatric migraine treatment. Particularly, nutraceuticals, non-invasive neuromodulation, and behavioural approaches are well tolerated and of potential interest. This paper aims to present the main approaches reported in the literature in the management of migraine in children and adolescents presenting an up-to-date review of the current literature. We therefore performed a narrative presentation for each of these three categories: nutraceuticals (riboflavin; magnesium; melatonin; vitamin D; coenzyme Q10; and polyunsaturated fatty acid); non-invasive neuromodulation (trigeminal nerve stimulator; non-invasive vagal nerve stimulation; transcranial magnetic stimulation; and remote electrical neuromodulation), and behavioural therapies (biofeedback; cognitive behavioural therapy; and mindfulness-based therapy). These approaches are increasingly seen as a valid treatment option in primary headache management also in paediatrics, avoiding medication overuse and drug treatment contraindications.

Prolonged Social Withdrawal During Adolescence: Transdiagnostic Syndrome or a New Psychiatric Entity?

The Japanese term Hikikomori is used to describe a clinical condition in which young people present a prolonged social withdrawal and isolation. Hikikomori syndrome represents an emergent worldwide phenomenon but is still poorly reported and often misdiagnosed. This study investigates and describes an Italian hikikomori adolescent group. Socio-demographic and psychopathological profiles and the relationship between hikikomori and psychopathological conditions were analyzed. No gender difference, a medium-high intellectual level, and no correlation with socioeconomic status were highlighted among the clinical group. The relationship between social withdrawal and social anxiety was significant while no correlation was found with depressive symptoms. The presence of Hikikomori syndrome was also significant in Italian adolescents, suggesting that hikikomori is not a culture-bound syndrome related to the Japanese cultural context, but rather a syndrome occurring in the upper-medium class.

Tension-Type Headache in Children and Adolescents.

In pediatric neurology, tension-type headache (TTH) represents a very common type of primary headache during the pediatric age. Despite the high prevalence of TTH, this diagnosis is often underestimated in childhood, with relevant difficulties in the differential diagnosis of TTH from secondary and primary headache manifestations. Even among primary headaches, a clinical overlap is not so infrequent in children: migraine attacks could present tension headache-like features while tension-type headaches may display migraine-like symptoms as well. Several variables play a role in the complex trajectory of headache evolution, such as hormonal changes during adolescence, triggers and genetic and epigenetic factors. The trajectories and outcomes of juvenile migraine and TTH, as well as the transition of one form to the other, have been investigated in several long-term prospective studies. Thus, the aim of this paper is to review the current literature on the differential diagnosis workout of TTH in pediatrics, the possible outcomes during the developmental age and the appropriate therapeutic strategies. Indeed, TTH represents a challenging diagnostic entity in pediatrics, both from a clinical and a therapeutic point of view, in which early diagnosis and appropriate treatment are recommended.

Special Issue "Migraine and Headache in Children and Adolescents".

Migraine in developmental age is a common pathology [...].

Link Between Topographic Memory and the Combined Presentation of ADHD (ADHD-C): A Pilot Study.

Background: Topographic memory is the ability to reach various places by recognizing spatial layouts and getting oriented in familiar environments. It involves several different cognitive abilities, in particular executive functions (EF), such as attention, working memory, and planning. Children with attention deficit hyperactivity disorder (ADHD) show impairments in inhibitory control, regulation of attention, planning, and working memory. Aim: The aim of this study was to evaluate the topographic memory in children with ADHD-combined subtype (ADHD-C). Method: Fifteen children (8-10 years) with a diagnosis of ADHD-C (DSM-5) (ADHD-C group) were compared to 15 children with typical development (TD group) of the same age. All children performed Raven's colored progressive matrices (CPM) test to obtain a measure related with cognitive functioning. The walking Corsi test (WalCT), a large-scale version of the Corsi block-tapping test, was used to assess topographic memory in experimental environment. Results: A higher impairment was observed in ADHD-C than TD with significant differences in the WalCT, in particular on the topographic short-term memory (TSTM) task, on the topographic learning (TL) task, and on the repetition number (RN) task during the TL task. Perseverative errors were reported in performing the square-sequence in the WalCT. Zero-order correlations showed a positive correlation between TSTM and auditory attention, and memory of design of NEPSY-II and digit span of WISC-IV. No statistically significant differences were found between the ADHD-C group and TD group in the TL task in the WalCT condition. Conclusion: In ADHD-C, initial topographic learning was compromised whereas the long-term retention of learned topographical material seemed to not be impaired. In particular, these impairments seem to be linked with difficulties in sustained attention, in spatial memory for novel visual materials, in a poor working memory, and in perseverative behaviors.

I stay at home with headache. A survey to investigate how the lockdown for COVID-19 impacted on headache in Italian children.

OBJECTIVE: The present Italian multicenter study aimed at investigating whether the course of primary headache disorders in children and adolescents was changed during the lockdown necessary to contain the COVID-19 emergency in Italy. METHODS: During the lockdown, we submitted an online questionnaire to patients already diagnosed with primary headache disorders. Questions explored the course of headache, daily habits, psychological factors related to COVID-19, general mood and school stress. Answers were transformed into data for statistical analysis. Through a bivariate analysis, the main variables affecting the subjective trend of headache, and intensity and frequency of the attacks were selected. The significant variables were then used for the multivariate analysis. RESULTS: We collected the answers of 707 patients. In the multivariate analysis, we found that reduction of school effort and anxiety was the main factor explaining the improvement in the subjective trend of headache and the intensity and frequency of the attacks (p < 0.001). The greater the severity of headache, the larger was the clinical improvement (p < 0.001). Disease duration was negatively associated with the improvement (p < 0.001). It is noteworthy that clinical improvement was independent of prophylaxis (p > 0.05), presence of chronic headache disorders (p > 0.05) and geographical area (p > 0.05). CONCLUSIONS: Our study showed that lifestyle modification represents the main factor impacting the course of primary headache disorders in children and adolescents. In particular, reduction in school-related stress during the lockdown was the main factor explaining the general headache improvement in our population.

Acceptability of the Transitional Wearable Companion "+me" in Children With Autism Spectrum Disorder: A Comparative Pilot Study.

+me is an experimental interactive soft toy, looking like a panda, developed for young children. When touched on the paws or head (inputs), the toy can emit attractive responses such as colored lights and amusing sounds (outputs). +me is wirelessly connected to a control tablet through which an adult caregiver can modify its input-output contingencies so as to produce different, rewarding response patterns using the same device. Given these features, we propose +me as a potential novel tool to support the therapy of Autism Spectrum Disorder (ASD). The allure of the device could be exploited to capture the attention and encourage the social interaction of toddlers during play activities with therapists. In this pilot study, +me was tested on two small groups of children aged 30-48 months, one group diagnosed with ASD and the second with Communication Disorder, a condition that often presents-especially at an early age-overlapping symptoms with ASD. The proposed play activities aimed to foster simple imitative behaviors and stimulate the engagement of the children. The results were compared with those of a previous test run on Typically Developed children. Preliminary observations, based on the analysis of video recordings, suggest that, on average, +me is able to encourage a positive engagement and that different groups tend to manifest some different behaviors.

The Relationship Between Parental Care and Pain in Children With Headache: A Narrative Review.

PURPOSE: In migraine or primary headache in children, parents play a fundamental role in pain management. For this narrative review, PubMed, Google Scholar, and Psych Info were searched using the terms "parent headache", "mother/father headache", "parental impact headache", "alexithymia parents headache", "catastrophizing parent headache", "family headache", "children parent headache", and "quality of life family headache". Articles were chosen for inclusion based on their relevance in to the topic. OVERVIEW: Several parental and psychological characteristics can influence in children and adolescent headache, such as parental attitudes as oppressive or overprotective; punitive parenting styles; familial psychological symptoms, especially anxiety and depression; catastrophizing about their child's pain or excessive worry about their child's headache; inability to express emotions; and feelings that may lead to somatization problems. DISCUSSION: Parents' attitudes and behaviors toward their child's headache have a strong relation with the severity of headache attacks. Mothers seem to have more influence than fathers on children's pain and emotional regulation. We suggest that the presence of caregiver-child transmission of maladaptive coping strategies, arising from difficulties expressing emotion, may lead to incorrect management of headache pain, further facilitating headache chronification.

Predictive validity for the clinical diagnosis of a new parent questionnaire, the CABI, compared with CBCL.

BACKGROUND: The questionnaires completed by the parents give a first general information on the behavioral problems of the child-adolescent, as a useful orientation to the clinical evaluation. The Child and Adolescent Behavior Inventory (CABI) is a 75-item parent questionnaire, which explores a large number of problem areas. The study of its predictive validity for the clinical diagnosis, in comparison with the Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scales of the Child Behavior Checklist (CBCL), can assess whether its use may be advantageous. MATERIAL AND METHODS: Parents/caregivers of 462 children and adolescents responded to both CABI and CBCL as a preliminary routine investigation. The results were compared with those of diagnoses obtained after the completion of the usual clinical procedure. RESULTS: Accuracy values (probability of correct classification) resulted high for both instruments and significantly better for CABI anxiety and attention-deficit hyperactivity disorder (ADHD) scales, and for CBCL oppositional defiant disorder (ODD) and conduct disorder (CD) scales; no significant difference was found for depression scales. All the areas under the curve (AUC) of the receiver operating characteristic analysis reached excellent values, suggesting a very good predictive ability of the five scales of the two instruments. The comparison of AUC showed the CABI's anxiety and ADHD scales to give significantly higher values than those of CBCL, indicating that these two scales have a better predictive ability. CONCLUSION: The study indicates a very good comparative (vs CBCL) and predictive validity of the CABI, suggesting an advantage in the use of this shorter questionnaire, available for free use both for clinical practice and supposedly for screening and epidemiological evaluations.

ADHD Is Comorbid to Migraine in Childhood: A Population-Based Study.

Objective: Recurrent headaches and ADHD are prevalent in the pediatric population. Herein, we assess if ADHD is comorbid to headaches overall, to headache subtypes (e.g., migraine), and to headache frequency. Method: Informed consent and analyzable data were obtained for 5,671 children aged 5 to 12 years (65.9% of the target sample). Parents and teachers were interviewed using validated questionnaires based on the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). Relative risks were modeled using univariate and multivariate analyses. Results: As contrasted to nonheadache controls, the prevalence of ADHD was significantly higher in children with migraine (p < .001) but not in those with tension-type headaches. In children with migraine, risk of ADHD increased as a function of headache frequency (p < .05). Conclusion: Migraine and frequent migraine are comorbid to ADHD. Future studies should focus on the impact of the association on the burden to the children and their families.

Alexithymia, Metacognition, and Theory of Mind in Children and Preadolescents With Migraine Without Aura (MWoA): A Case-Control Study.

Background: Some studies have demonstrated the high impact of headache and migraine in several areas of children and adolescents' life. In recent years, there has been an increase in scientific interest in the relationship between migraine and emotional regulation, investigating the possible consequences of emotional dysregulation on physical and mental health. While some studies have been carried out on the relationship between alexithymia and headache or migraine (especially in adults), no data exist on relationship between Theory of Mind (TOM), metacognition, and alexithymia in children and adolescents with migraine. Methods: Children with diagnosis of migraine without aura (MWoA) (36 males and 34 females) were compared to a healthy control group (31 males and 39 females). The age range was from 8 to 13 years in both groups. All children completed the Alexithymia Questionnaire for Children (AQC) for the assessment of alexithymia levels and the Domain of Social Perception included in the NEPSY-II to evaluate levels of TOM. Metacognitive development was evaluated with Io e La Mia Mente for children aged between 8 and 10 years and with Metacognitions Questionnaire for Children (MCQ-C) for children from 11 to 13. Results: There were no differences between children with MWoA and the control group in metacognitive abilities; only in the subscale "Negative Meta Worrying" of MCQ-C girls scored higher than boys, regardless of the group they were part of. Also, in the NEPSY-II subscale there were no statistically significant differences between the two groups. Children with MWoA scored higher in the AQC subscales "Difficulty Identifying Feelings" and "Difficulty Describing Feelings" than controls. Moreover, children between 8 and 10 years statistically differed from older children in "Difficulty Identifying Feelings" and in Total Score. Conclusion: Our data suggest that children with MWoA have no metacognitive and TOM problems compared to a healthy group. The experimental group showed higher traits of alexithymia, confirming what suggested by other studies in the literature. Future research will have to focus on migraine with aura and tension-type headache to evaluate any differences with children with MWoA.

Behavioral therapies in headache: focus on mindfulness and cognitive behavioral therapy in children and adolescents.

Introduction: A wide proportion of children and adolescents with headache tends not to respond to various pharmacological treatments in use. The failure to respond to symptomatic treatment and prophylaxis is often due to the presence of a comorbid psychopathology undiagnosed or not properly treated. For these reasons and for the negative impact of headache on the quality of life of the patients and on the costs for the public health system, the adoption of an integrated multi-disciplinary perspective in the diagnosis and treatment of headache is needed.Areas covered: Several researchers have shown that behavioral treatment is effective as pharmacological treatment, not only for headache management but also to maintain a lifetime response to the headache treatment. In particular, Cognitive Behavioral Therapy (CBT) and Mindfulness have proven to be very resolutive both in the management of pain and in the management of stressful situations that can trigger the headache in children and adolescents with headache.Expert opinion: Although studies on behavioral treatments on children and adolescents with primary headaches are still few but a combined approach seems to be very useful in improving the quality of life of these subjects, especially in those who have internalizing disorders in comorbidities.

Improved Efficacy of Pregabalin by Restoring Plasma Vitamin D Levels in Migraine: a Case Report.

Migraine appears to be the most common neurological syndrome in primary care. Pain in migraine is mediated by the release of inflammatory mediators at the level of nerves and blood vessels. The antioxidant and neuroprotective effects of vitamin D in the central nervous system suggest that deficiency of this vitamin can be involved in migraine. Moreover, low serum levels of vitamin D correlates with a higher incidence of chronic pain, including migraine and in co-administered with anti-migraine treatment reduces the frequency of migraine attacks. We report a 46-year old woman affected by migraine, anxiety and mild depressive mood (MSQ score: 24; BDI score: 34; VAS score: 8) that partially improved with pregabalin treatment (VAS: 5). Laboratory findings documented low serum levels of vitamin D (25-hydroxy-vitamin D: 12 ng/mL; normal range: 20-100 ng/mL; 1-25 di-hydroxy-vitamin D: 19 ng/mL, normal range: 25-66 ng/mL). The treatment with 10,000 UI vitamin D during pregabalin therapy induced an improvement of clinical symptoms (pain, anxiety and depression) and of the quality of life. This case report suggest that in chronic migraine patient with anxiety and mild mood depression in treatment with pregabalin a supplementation of vitamin D improvement the clinical symptoms of migraine and a modulation of inhibitoy synaptic neurotransmission may explain this effect in our migraine patient.

Intellectual functioning and executive functions in children and adolescents with attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD).

Several studies have shown neuropsychological deficits across multiple domains in attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD), but differences and similarities between these disorders have been little considered. We were interested in analyzing the intellectual and executive profiles in a sample of children and adolescents, divided according to the diagnosis into the ADHD group and the SLD group, and in identifying the differences and similarities between these disorders. The sample included two clinical groups: the first included 36 children and adolescents with a diagnosis of ADHD (5-15 years; mean = 9.42; SD = 2.22) while the second included 36 children and adolescents with a diagnosis of SLD (7-15 years; mean = 9.43; SD = 2.25). The WISC-IV was used to measure intellectual ability and the NEPSY-II was employed to measure executive functions. The results showed that the SLD group had significantly higher scores than the ADHD group on the NEPSY-II in the inhibition, cognitive flexibility, short-term verbal memory and verbal working memory domains. The ANCOVA showed differences regarding the FSIQ of WISC-IV, in that the SLD group obtaining higher scores than ADHD group. Findings showed that ADHD children are more impaired than SLD children, in particular in cognitive inhibition, cognitive flexibility, verbal memory, working memory and intellectual functioning. The recognition of the strengths and weaknesses of children and adolescents with ADHD and SLD allows to outline an educational and clinical intervention focused on their specific executive and intellectual functioning.

Hsa-miR-34a-5p and hsa-miR-375 as Biomarkers for Monitoring the Effects of Drug Treatment for Migraine Pain in Children and Adolescents: A Pilot Study.

MicroRNAs (miRs) have emerged as biomarkers of migraine disease in both adults and children. In this study we evaluated the expression of hsa-miR-34a-5p and hsa-miR-375 in serum and saliva of young subjects (age 11 ± 3.467 years) with migraine without aura (MWA), while some underwent pharmacological treatment, and healthy young subjects were used as controls. miRs were determined using the qRT-PCR method, and gene targets of hsa-miR-34a-5p and hsa-miR-375 linked to pain-migraine were found by in silico analysis. qRT-PCR revealed comparable levels of hsa-miRs in both blood and saliva. Higher expression of hsa-miR-34a-5p and hsa-miR-375 was detected in saliva of untreated MWAs compared to healthy subjects (hsa-miR-34a-5p: p < 0.05; hsa-miR-375 p < 0.01). Furthermore, in MWA treated subjects, a significant decrease of hsa-miR-34a-5p and of hsa-miR-375 was documented in saliva and blood compared to MWA untreated ones. Altogether, these findings suggested thathsa-miR-34a-5p and hsa-miR-375 are expressed equally in blood and saliva and that they could be a useful biomarker of disease and of drug efficacy in patients with MWA.

Migraine in childhood: an organic, biobehavioral, or psychosomatic disorder?

Migraine is one of the most frequent complaints in children and adolescents and it can have a significant impact on quality of life. There are several factors underlying the onset and the maintenance of this disorder and there is still no a clear etiopathogenesis common to all subjects suffering from migraine. Psychological factors such as individual characteristics, psychiatric comorbidities, and temperament are strictly related to psychosomatic disorders and to migraine. Also, the environmental influence is very relevant and studied: socio-economic status, family dysfunctions, attachment style, or psychiatric disease in parents can influence the onset of migraine in children. Finally, many studies are trying to find out any alteration in genetics or in cerebral areas or networks that can explain migraine vulnerability. In this review, we analyze the most recent findings on neurological, psychological, and environmental factors that may potentially cause migraine.

Acceptability of the Transitional Wearable Companion "+me" in Typical Children: A Pilot Study.

This work presents the results of the first experimentation of +me-the first prototype of Transitional Wearable Companion-run on 15 typically developed (TD) children with ages between 8 and 34 months. +me is an interactive device that looks like a teddy bear that can be worn around the neck, has touch sensors, can emit appealing lights and sounds, and has input-output contingencies that can be regulated with a tablet via Bluetooth. The participants were engaged in social play activities involving both the device and an adult experimenter. +me was designed with the objective of exploiting its intrinsic allure as an attractive toy to stimulate social interactions (e.g., eye contact, turn taking, imitation, social smiles), an aspect potentially helpful in the therapy of Autism Spectrum Disorders (ASD) and other Pervasive Developmental Disorders (PDD). The main purpose of this preliminary study is to evaluate the general acceptability of the toy by TD children, observing the elicited behaviors in preparation for future experiments involving children with ASD and other PDD. First observations, based on video recording and scoring, show that +me stimulates good social engagement in TD children, especially when their age is higher than 24 months.

Effects of Add-On Ultramicronized N-Palmitol Ethanol Amide in Patients Suffering of Migraine With Aura: A Pilot Study.

Background: Palmitoyl ethanol amide (PEA) is an endogenously produced substance showing anti-nociceptive effect through both receptor and non-receptor mediated effects at the level of different cellular and tissue sites. This study showed the results of a single blind study that was conducted to evaluate both the safety and the efficacy of ultramicronized PEA (umPEA; 1,200 mg/day) for up 90 days in patients suffering of Migraine with Aura (MA) treated with NSAIDs. Methods: A total of 20 patients, 8 male (33-56-years, average 41.4 ± 7.8) and 12 female (19-61-years, average 38.5 ± 11.9) with MA were admitted to our observation and diagnosed according to ICHD-3 criteria, they received umPEA (1,200 mg/day) in combination with NSAIDs for up to 90 days. They were revaluated at 30, 60, and 90 days after treatment. Results: umPEA administration induced a statistically significant and time dependent pain relief. In particular, these effects were evident at 60 days (male P = 0.01189; female P = <0.01) and they lasted until the end of the study (male P = 0.0066; female P = 0.01473). Conclusion: Although further studies are needed, our findings indicate that in patients suffering of MA treatment with umPEA had good efficacy and safety which candidate this compound as a therapeutic tool in pain migraine management.