Association Between Migraine and Atopic Diseases in Childhood: A Potential Protective Role of Anti-Allergic Drugs.

BACKGROUND: Migraine is a common cause of headache in childhood. Several studies have investigated the association between migraine and atopic diseases, mostly in the adult population. OBJECTIVE: This study aimed to investigate this association in children. METHODS: A case-control study was conducted across 3 European tertiary care hospitals between June 2014 and August 2014. Cases (n = 229) were children aged 6-18 years consulting for a migraine episode. Controls in the same age range (n = 406) were consulting for a minor injury and did not have a history of recurrent headache. Logistic regression analyses tested the effect of atopic diseases and anti-allergic therapies on occurrence of migraine. RESULTS: Children with migraine were more likely to have persistent asthma compared to absence of asthma (odds ratio [OR]: 4.57, 95% confidence interval [CI]: 2.04-10.24) and less likely to have been treated by inhaled or nasal corticosteroid (OR: 0.34, 95% CI: 0.15-0.76) or antihistamine therapy (OR: 0.33, 95% CI: 0.18-0.60). The median number of monthly migraine episodes was higher in children with persistent asthma (3; interquartile [IQR]: 1-4; range: 0.5-10) compared to children with intermittent asthma (2; IQR: 1-3; range: 0.1-4) or non-asthmatic children (2; IQR: 1-3; range: 0.1-12) (P < .01). CONCLUSION: Persistent childhood asthma was associated with increased risk of migraine and higher frequency of migraine attacks. History of anti-asthmatic or anti-allergic therapies was associated with decreased risk of migraine in children and adolescents. The role of these therapies on the pathogenesis and occurrence of migraine needs to be further elucidated because of the huge potential impact in terms of public health.

Triage of children with headache at the ED: a guideline implementation study.

UNLABELLED: We present a multicenter validation of a modified Manchester Triage System (MTS) flowchart for pediatric patients who present with headache to the emergency department. A prospective observational study was conducted across 5 European pediatric emergency departments. The standard MTS headache flowchart and a modified MTS headache flowchart were tested in the participating centers, and results were compared with triage categories identified by either the physician at the end of the clinical examination or the reference classification matrix (RCM). Fifty-three patients were enrolled in the preimplementation phase and 112 in the postimplementation phase. When compared with physician's triage and RCM, the modified MTS flowchart demonstrated good sensitivity (79% and 70%, respectively), specificity (77% and 76%, respectively), and a high positive likelihood ratio (9.14 and 16.75, respectively) for the identification of low-risk children. CONCLUSIONS: Our modified headache flowchart is safe and reliable in pediatric emergency settings, especially for lower classes of urgency.

Association between childhood migraine and history of infantile colic.

IMPORTANCE: Infantile colic is a common cause of inconsolable crying during the first months of life and has been thought to be a pain syndrome. Migraine is a common cause of headache pain in childhood. Whether there is an association between these 2 types of pain in unknown. OBJECTIVE: To investigate a possible association between infantile colic and migraines in childhood. DESIGN, SETTING, AND PARTICIPANTS: A case-control study of 208 consecutive children aged 6 to 18 years presenting to the emergency department and diagnosed as having migraines in 3 European tertiary care hospitals between April 2012 and June 2012. The control group was composed of 471 children in the same age range who visited the emergency department of each participating center for minor trauma during the same period. A structured questionnaire identified personal history of infantile colic for case and control participants, confirmed by health booklets. A second study of 120 children diagnosed with tension-type headaches was done to test the specificity of the association. MAIN OUTCOMES AND MEASURES: Difference in the prevalence of infantile colic between children with and without a diagnosis of migraine. RESULTS: Children with migraine were more likely to have experienced infantile colic than those without migraine (72.6% vs 26.5%; odds ratio [OR], 6.61 [95% CI, 4.38-10.00]; P < .001), either migraine without aura (n = 142; 73.9% vs 26.5%; OR, 7.01 [95% CI, 4.43-11.09]; P < .001), or migraine with aura (n = 66; 69.7% vs 26.5%; OR, 5.73 [95% CI, 3.07-10.73]; P < .001). This association was not found for children with tension-type headache (35% vs 26.5%; OR, 1.46 [95% CI, 0.92-2.32]; P = .10). CONCLUSION AND RELEVANCE: The presence of migraine in children and adolescents aged 6 to 18 years was associated with a history of infantile colic. Additional longitudinal studies are required.

Type 1 diabetes onset in Lombardy region, Italy, during the COVID-19 pandemic: The double-wave occurrence.

BACKGROUND: The Italian Lombardy region has been the epicenter of COVID-19 since February 2020. This study analyses the epidemiology of pediatric type 1 diabetes (T1D) onset during the first two pandemic waves and three previous years. METHODS: All the 13 pediatric diabetes centers in Lombardy prospectively evaluated charts of children at T1D onset (0-17 years), during year 2020. After calculating the annual incidence, the data were compared with those of the 3 previous years, using generalized linear models, adjusted for age and sex. Monthly T1D new onsets and diabetic ketoacidosis (DKA) were investigated yearly from 2017 to 2020. Data were extracted from outpatients charts of the pediatric diabetes centers and from the database of the national institute of statistics. FINDINGS: The estimated incidence proportion of T1D was 16/100·000 in 2020, compared to 14, 11 and 12 in 2019, 2018 and 2017, respectively. When adjusting for age and gender, the incidence was significantly lower in 2018 and 2017 compared to 2020 (adjusted incidence ratio: 0.73 and 0.77 respectively, with 95% CI: 0.63 to 0.84, and 0.67 to 0.83; p = 0·002 and p = 0·01), but no difference was found between the years 2020 and 2019. A reduction trend in the percentage of T1D diagnosis during the first wave (March-April) over the total year diagnoses was observed compared to previous years (11·7% in 2020, 17·7% in 2019, 14·1% in 2018 and 14·4% 2017). No difference was observed during the second wave (October-December) (32·8% in 2020, 33·8% in 2019, 34% in 2018, 30·7% in 2017). The proportion of DKA over the total T1D diagnoses during the second wave had higher trend than the first one (41·7% vs 33·3%), while severe DKA over the total DKA appeared higher during the first wave (60% vs 37·1%). INTERPRETATION: The study suggests an increase in the incidence of pediatric T1D in Lombardy throughout the past five years. Pandemic waves may have affected the clinical presentation at onset. FUNDING: None.

Association between functional gastrointestinal disorders and migraine in children and adolescents: a case-control study.

BACKGROUND: Functional gastrointestinal disorders and migraine are both common causes of medical attention. We have previously shown an association between migraine and infant colic. In this case-control study, we aimed to establish whether there is an association between migraine and other functional gastrointestinal disorders in children and adolescents. METHODS: We included children and adolescents aged 6-17 years presenting to the emergency department of four tertiary hospitals in France and Italy. Patients diagnosed with either migraine or tension-type headache by the hospital's paediatric neurologist were enrolled as cases. Patients presenting to the emergency department with minor trauma and no history of recurrent headache were enrolled as controls. Investigators masked to a patient's group allocation diagnosed functional gastrointestinal disorders using the Rome III diagnostic criteria. Univariable and multivariable analyses were done to identify specific disorders and baseline factors associated with migraines and tension-type headache. FINDINGS: Between Nov 1, 2014, and Jan 31, 2015, we enrolled 648 controls and 424 cases (257 patients with migraine and 167 with tension-type headache). 83 (32%) children and adolescents in the migraine group were diagnosed with functional gastrointestinal disorders compared with 118 (18%) in the control group (p<0·0001). Multivariable logistic regression showed a significant association between migraine and three gastrointestinal disorders: functional dyspepsia (odds ratio 10·76, 95% CI 3·52-32·85; p<0·0001), irritable bowel syndrome (3·47, 1·81-6·62; p=0·0002), and abdominal migraine (5·87, 1·95-17·69; p=0·002). By contrast, there was an inverse association between migraine and functional constipation (0·34, 0·14-0·84, p=0·02). 41 (25%) participants with tension-type headache had functional gastrointestinal disorders, which did not significantly differ from the prevalence of these disorders in the control group (p=0·07); no significant association was noted between any functional gastrointestinal disease and tension-type headaches. INTERPRETATION: Three abdominal-pain-related functional gastrointestinal disorders were associated with migraine in children and adolescents. These findings are of value to the diagnosis and management of these common diseases. Future studies should investigate whether antimigraine drugs are of benefit in functional gastrointestinal disorders. FUNDING: None.

Recovery position significantly associated with a reduced admission rate of children with loss of consciousness.

BACKGROUND: Loss of consciousness (LOC) is often seen in children. The response of caregivers to a child with LOC has been poorly investigated. Potential caregivers (parents, teachers) seem to have a poor knowledge of the recovery position (RP)-that is, the position into which an unconscious child should be placed in order to protect the airway. OBJECTIVES: To report the management and diagnoses of LOC in childhood, and to evaluate variables associated with an increased hospital admission rate. METHODS: We conducted a prospective cohort study of consecutive children aged between 0 and 18 years diagnosed with LOC at 11 paediatric emergency departments (PEDs) of 6 European countries. The enrolment period was 3 months. Data were obtained from parental interviews, PED reports and clinical examination. RESULTS: 553 children were enrolled. The most frequent final diagnoses causing LOC were seizures (n=278, 50.3%), and vasovagal syncope (n=124, 22.4%). Caregivers put the child in the RP in 145 cases (26.2%). The RP was independently associated with a significant decrease in the admission rate (aOR=0.28; 95% CI 0.17 to 0.48; p<0.0001). CONCLUSIONS: Our study demonstrates for the first time that the RP may reduce the admission rate of infants with LOC. Caregivers often perform inadequate manoeuvres when a child becomes unconscious. Campaigns aiming at increasing knowledge of the RP should be promoted.

Pediatric migraine and episodic syndromes that may be associated with migraine.

IMPORTANCE: Migraine is a common disorder and a frequent cause of medical consultation in children. Many childhood episodic syndromes have been described as common precursors of migraine. OBJECTIVE: To review current knowledge on migraine and childhood episodic syndromes, and to discuss future directions for research and clinical practice. FINDINGS: For most children it is difficult to describe a headache and fully verbalize symptoms such as photophobia and phonophobia that must be inferred from behaviour. Classical migraine features are rare before the age of 6 years, but some migraine-related syndromes have been described. Benign paroxysmal torticollis of infancy, benign paroxysmal vertigo of childhood, cyclic vomiting syndrome and abdominal migraine are currently classified as childhood episodic syndromes, and therefore common precursors of migraine. A strong association between infantile colic and migraine has recently been reported. There are similarities between children with episodic syndromes and children with migraine, regarding social and demographic factors, precipitating and relieving factors, and accompanying gastrointestinal, neurologic, and vasomotor features. The real pathophysiological mechanisms of migraine are not fully understood. Current data obtained through molecular and functional studies provide a complex model in which vascular and neurologic events cooperate in the pathogenesis of migraine attacks. Genetic factors causing disturbances in neuronal ion channels, make a migraineur more sensitive to multiple trigger factors that activate the nociception cascade. The expanding knowledge on migraine genetics and pathophysiology may be applicable to childhood episodic syndromes. Migraine preventive strategies are particularly important in children, and could be beneficial in childhood episodic syndromes. Nonspecific analgesics like ibuprofen and acetaminophen are widely used in pediatrics to control pain and have been found to be effective also in the treatment of acute migraine attacks. Triptans are the specific fist-line drugs for acute migraine treatment. CONCLUSIONS AND RELEVANCE: Migraine phenotype differs somewhat in the developing brain, and childhood episodic syndromes may arise before typical migraine headache. Diagnosing pediatric migraine may be difficult because of children's language and cognitive abilities. The risk of underestimating migraine in pediatric age is high. An adequate diagnosis is important to maintain a good quality of life and to avoid inappropriate therapy.

Status epilepticus as manifestation of posterior reversible encephalopathy syndrome in a healthy child.

Posterior reversible encephalopathy syndrome is a recently described cliniconeuroradiological syndrome reported in children with several predisposing conditions such as transplantation, autoimmune, hematological, infectious, renal, and neoplastic diseases or administration of chemotherapeutic immunosuppressive drugs. Seizures are one of the most frequent manifestations of posterior reversible encephalopathy syndrome; status epilepticus has been described more frequently in adults but rarely in children. We report on the case of a 6-year-old healthy boy who presented status epilepticus as the main manifestation of posterior reversible encephalopathy syndrome in the absence of other underlying conditions. This is the first report of posterior reversible encephalopathy syndrome in a previously healthy child. Our case reminds us that pathogenesis of this condition is far from being completely understood and may include both genetic and environmental factors. Moreover, posterior reversible encephalopathy syndrome should always be suspected by clinicians in cases of status epilepticus with a prolonged neurological failure.

Lowering postprandial glycemia in children with type 1 diabetes after Italian pizza "margherita" (TyBoDi2 Study).

BACKGROUND: Continuous subcutaneous insulin infusion is considered a safe and effective way to administer insulin in pediatric patients with type 1 diabetes, but achieving satisfactory and stable glycemic control is difficult. Several factors contribute to control, including fine-tuning the basal infusion rate and bolus type and timing. We evaluated the most effective type and timing of a pump-delivered, preprandial bolus in children with type 1 diabetes for a pizza "margherita" meal. SUBJECTS AND METHODS: We assessed the response of 38 children with type 1 diabetes to a meal based on pizza "margherita" (with mozzarella cheese and tomato sauce) after different types and timings of a bolus dose. RESULTS: The glucose levels for 6 h after the meal were lower (i.e., closer to the therapeutic target of <140 mg/dL) when the bolus doses were administered as a simple bolus 15 min before the meal (area under the curve [AUC] 0-6 h, 6.9 ± 14.9 mg/dL/min) versus a simple bolus administered immediately before the meal (AUC 0-6 h, 4.2 ± 25.9 mg/dL/min) (P = not significant) versus a double-wave bolus 30/70 extended over a 6-h period administered 15 min before the meal (AUC 0-6 h, 1.9 ± 21.3 mg/dL/min) (P = not significant) versus a double-wave bolus 30/70 extended over a 6-h period administered immediately before the meal (AUC 0-6 h, 13.3 ± 15.6 mg/dL/min) (P = 0.01). CONCLUSIONS: In the case of a pizza "margherita," our data support the injection of the simple bolus 15 min before a meal, rather than immediately before or delivered as a double-wave bolus, to control the glycemic rise usually observed.

Headache in children and adolescents aged 6-18 years in northern Italy: prevalence and risk factors.

OBJECTIVE: Aim of this study is to examine the epidemiology of paediatric headache and periodic syndromes in a school population and to evaluate the co-existence of environmental predisposing conditions. DESIGN AND METHODS: A 60-item questionnaire was completed by a school-based sample (n = 1536, ages 6-18 years). Diagnostic assessment of primary headache and periodic syndromes was established in first section; predisposing conditions in the second section; while the third section quantified the frequency of self medication and identified drugs most frequently used. RESULTS: Headache was reported by 62.1% of subjects. Socioeconomic status, composition of family unit and nutrition habits in the first year of life did not appear significantly different in subjects with headache compared to healthy controls. A good sleep quality was found in 95.2% of healthy controls, in 89.4% of children with occasional headache. Recurrent abdominal pain, motor weakness and car sickness was significantly higher in primary headache group compared to occasional headache. Depressive/anxious traits were significantly higher in primary headache and occasional headache groups than in healthy controls. The frequency of aggressive traits was also higher in children with primary headache compared to occasional headache and healthy control subjects. 72.5% of subjects with primary headache and 58.4% of children with occasional headache assumed medicines to relieve pain. Paracetamol was the most frequently assumed drug. CONCLUSIONS: Our data show a more frequent occurrence of anxious/depressive profile in children suffering from primary headache. In agreement with literature data, this research points out that self-treatment is a relevant problem in paediatric headache.

Timing of bolus in children with type 1 diabetes using continuous subcutaneous insulin infusion (TiBoDi Study).

BACKGROUND: Continuous subcutaneous insulin infusion is considered a safe and effective way to administer insulin in pediatric patients with type 1 diabetes, but achieving satisfactory and stable glycemic control is difficult. Several factors contribute to control, including fine-tuning the basal infusion rate and bolus timing. We evaluated the most effective timing of a pump-delivered, preprandial bolus in children with type 1 diabetes. METHODS: We assessed the response of 30 children with type 1 diabetes to a standard meal after different timing of a bolus dose. RESULTS: The glucose levels for 3 h after the meal were lower (i.e., closer to the therapeutic target of <140 mg/dL) when the bolus doses were administered 15 min or immediately before the meal, rather than after the meal. However, these differences were not statistically significant, except at the 1-h postprandial time point: bolus just after meal, 177 +/- 71 mg/dL (9.83 +/- 3.94 mmol/L); 15 min before meal, 136 +/- 52 mg/dL (7.55 +/- 2.89 mmol/L) (P = 0.044); and just before meal, 130 +/- 54 mg/dL (7.22 +/- 3.00 mmol/L) (P = 0.024). The area under the curve (AUC) (in mg/min) did not differ significantly with different bolus times, but the SD of the AUC was the lowest with the bolus given 15 min before the meal. CONCLUSIONS: These data support injection of the bolus before, rather than after, eating, even if the patient is hypoglycemic before meals.

Insulin pump therapy for type 1 diabetes treatment in a girl with Down's syndrome.

We present the case of a 29.5-year-old girl with Down's syndrome, type 1 diabetes mellitus (DMT1), autoimmune thyroiditis and celiac disease starting on insulin pump therapy. After 22-month follow-up hemoglobin A1c dropped from 9% to 6.8%, even with a lower insulin requirement and no change in BMI.