Migraine, Allergy, and Histamine: Is There a Link?

The relationship between migraines and allergies is controversial. Though they are epidemiologically linked, the underlying pathophysiological connection between them remains unclear. Migraines and allergic disorders have various underlying genetic and biological causes. As per the literature, these conditions are epidemiologically linked, and some common pathophysiological pathways have been hypothesized. The histaminergic system may be the clue to understanding the correlation among these diseases. As a neurotransmitter in the central nervous system with a vasodilatory effect, histamine has a well-documented influence on the allergic response and could be involved in the pathophysiology of migraines. Histamine may influence hypothalamic activity, which may play a major role in migraines or may simply influence their severity. In both cases, antihistamine drugs could prove useful. This review examines whether the histaminergic system, particularly H3 and H4 receptors, may provide a mechanistic link between the pathophysiology of migraines and allergic disorders, two common and debilitating conditions. Identifying their connection could help identify novel therapeutic strategies.

Short lingual frenulum as a risk factor for sleep-disordered breathing in school-age children.

BACKGROUND: Recent evidence has emphasized the role of a short lingual frenulum in the pathogenesis of sleep-disordered breathing (SDB) in childhood. The oral dysfunction induced by a short frenulum may promote oral-facial dysmorphism, decreasing the size of upper airway lumen and increasing the risk of upper airway collapsibility during sleep. The aim of this study was to evaluate the presence of a short lingual frenulum as risk factor for SDB in children of school age, with and without snoring, who were recruited from the community. METHODS: Children aged 6-14 years were recruited from a school in Rome. For all participants, the previously described Sleep Clinical Record (SCR) was completed, and orthodontic evaluation and measurement of lingual frenulum were performed. Tongue strength and endurance were evaluated in all participants using the Iowa Oral Performance Instrument (IOPI). SDB was defined as positive SCR (≥6.5). RESULTS: We assessed 504 children with mean age of 9.6 ± 2.3 years, and in 114 of them (22.6%) a short frenulum was identified. Children with a short lingual frenulum were at significantly higher risk for a positive SCR compared to those with a frenulum of normal length (odds ratio = 2.980, 95% confidence interval = 1.260-6.997). Participants with positive or negative SCR did not differ in tongue strength or endurance. CONCLUSION: Short lingual frenulum is a risk factor for SDB. An early multidisciplinary approach and screening for SDB are indicated when this anatomical abnormality is recognized.

Comparison of two exhaled biomarkers in children with and without sleep disordered breathing.

OBJECTIVE: Airway oxidative stress and inflammation are likely to be involved in sleep disordered breathing (SDB) in children. We aimed to measure concentrations of 8-isoprostane (8-IsoP) in the exhaled breath condensate (EBC) and exhaled nitric oxide (FENO) in patients with SBD and healthy children, in order to assess the relationship between these two biomarkers, disease severity, and overnight changes. METHODS: Patients with SDB (n = 46) and healthy controls (n = 20) aged 4.5-15.1 years (M/F: 36/30) underwent exhaled measurements. Patients with SDB underwent standard polysomnography to define primary snoring (PS: AHI < 1) and obstructive sleep apnea (OSA). Upon awakening the following morning, FENO was measured and EBC was collected for the measurement of EBC 8-IsoP. RESULTS: OSA patients yielded higher awakening levels of 8-IsoP in EBC than PS patients and control subjects. The 8-IsoP levels, though not FENO, correlated with AHI (r = 0.40, p = 0.003) and SaO2 (r = -0.50, p = 0.001). Cut-off levels of 8-IsoP predicted OSA with a high AUC value (0.84, p = 0.000). Sensitivity and specificity for 8-IsoP levels above the percentile 50 (33.3 pg/mL) were 76.5% and 78.1%, respectively. 8-IsoP levels did not change from the evening to morning session, whereas morning FENO levels rose significantly only in patients with mild OSA (p = 0.03). CONCLUSION: Levels of 8-IsoP, though not FENO, distinguish children with OSA from those with PS or healthy, correlate with disease severity and closely predict OSA in the whole sample.

Sleep clinical record: what differences in school and preschool children?

The sleep clinical record (SCR) may be a valid method for detecting children with obstructive sleep apnoea (OSA). This study aimed to evaluate whether there were differences in SCR depending on age and to identify the possible risk factors for OSA development. We enrolled children with sleep disordered breathing between 2013 and 2015, and divided them according to age into preschool- and school-age groups. All patients underwent SCR and polysomnography. OSA was detected in 81.1% and 83.6% of preschool- and school-age groups, respectively. Obesity, malocclusions, nasal septal deviation and inferior turbinate hypertrophy were significantly more prevalent in school-age children (p<0.05); however, only tonsillar hypertrophy had significant hazard ratio (2.3) for OSA development. Saddle nose, nasal hypotonia, oral breathing and tonsillar hypertrophy were significantly more prevalent for development of OSA in preschoolers (p<0.03). The SCR score was significantly higher among preschool children than in school-age children (8.4±2.22 versus 7.9±2.6; p=0.044). Further, SCR score >6.5 had a sensitivity of 74% in predicting OSA in preschool children with positive predictive value of 86% (p=0.0001). Our study confirms the validity of the SCR as a screening tool for patient candidates for a PSG study for suspected OSA, in both school and preschool children.

Rapid maxillary expansion outcomes in treatment of obstructive sleep apnea in children.

OBJECTIVES: The objectives of this study were to confirm the efficacy of rapid maxillary expansion in children with moderate adenotonsillar hypertrophy in a larger sample and to evaluate retrospectively its long-term benefits in a group of children who underwent orthodontic treatment 10 years ago. METHODS: After general clinical examination and overnight polysomnography, all eligible children underwent cephalometric evaluation and started 12 months of therapy with rapid maxillary expansion. A new polysomnography was performed at the end of treatment (T1). Fourteen children underwent clinical evaluation and Brouilette questionnaire, 10 years after the end of treatment (T2). RESULTS: Forty patients were eligible for recruitment. At T1, 34/40 (85%) patients showed a decrease of apnea-hypopnea index (AHI) greater than 20% (ΔAHI 67.45% ± 25.73%) and were defined responders. Only 6/40 (15%) showed a decrease <20% of AHI at T1 and were defined as non-responders (ΔAHI -53.47% ± 61.57%). Moreover, 57.5% of patients presented residual OSA (AHI > 1 ev/h) after treatment. Disease duration was significantly lower (2.5 ± 1.4 years vs 4.8 ± 1.9 years, p <0.005) and age at disease onset was higher in responder patients compared to non-responders (3.8 ± 1.5 years vs 2.3 ± 1.9 years, p <0.05). Cephalometric variables showed an increase of cranial base angle in non-responder patients (p <0.05). Fourteen children (mean age 17.0 ± 1.9 years) who ended orthodontic treatment 10 years previously showed improvement of Brouilette score. CONCLUSION: Starting an orthodontic treatment as early as symptoms appear is important in order to increase the efficacy of treatment. An integrated therapy is needed.

Adenotonsillectomy and orthodontic therapy in pediatric obstructive sleep apnea.

PURPOSE: Rapid maxillary expansion (RME) is an additional treatment in pediatric obstructive sleep apnea (OSA). The aim of this study was to present data about the outcome of adenotonsillectomy (AT) and of RME in a clinical sample of pediatric OSA. METHODS: We consecutively enrolled children with OSA to undergo RME or AT. The age and the severity of OSA are the main factors involved in the choice of treatment. A polysomnography was performed at the baseline (i.e., before treatment, T0) and 1 year after treatment (T1). RESULTS: A total of 52 subjects fulfilled the inclusion criteria. Twenty-five children underwent AT (group 1) and 22 children underwent RME (group 2). Five children underwent both treatments (group 3). Children in group 2 were older, had a longer disease duration, a higher body mass index (BMI), a lower apnea-hypopnea index (AHI), and a lower arousal index at T0 than children in group 1. After 1 year, BMI percentile and overnight mean saturation increased in group 1 while AHI and arousal index decreased. In group 2, mean overnight saturation increased while AHI decreased. Children in group 3 displayed a significant decrease in AHI from T0 to T1. CONCLUSIONS: Our data demonstrate that both treatments help to improve OSA, and a multidisciplinary approach to treatment is suggested.

Reduced NREM sleep instability in benign childhood epilepsy with centro-temporal spikes.

OBJECTIVE: To analyze sleep architecture and NREM sleep instability by means of the cyclic alternating pattern (CAP) in children with benign epilepsy with rolandic spikes (BERS). METHODS: Ten children with BERS, drug free at the time of the study and 10 age-matched normal controls were included in this study. Sleep was visually scored for sleep architecture and CAP using standard criteria. RESULTS: Sleep architecture in BERS showed only few significant differences vs. controls with a reduction of total sleep time, sleep efficiency, and REM sleep percentage. CAP analysis revealed several significant differences: reduced total CAP rate, mainly in sleep stage 2, and reduced EEG slow oscillations and arousals during stages N1 and N2. CONCLUSIONS: Sleep architecture is not importantly affected in BERS but CAP analysis reveals a decrease of NREM instability, mainly in sleep stage 2. Since there is a spindle-related spike activation in BERS, we speculate that the decrease of CAP and of EEG slow oscillations and arousals might be linked with the inhibitory action of spindling activity and spikes on arousals. SIGNIFICANCE: CAP analysis discloses sleep structure abnormalities in children with BERS not shown by the classical sleep scoring. Spike activity and CAP A1 subtypes seem to be mutually exclusive probably because centro-temporal spikes disturb the physiological synchronization mechanisms needed for the generation of slow-wave components of CAP.

Ictal video-polysomnography and EEG spectral analysis in a child with severe Panayiotopoulos syndrome.

OBJECTIVE: To describe the ictal polysomnographic features of a patient with Panayiotopoulos syndrome, a peculiar epileptic syndrome characterized by infrequent, often single, prolonged, nocturnal, focal seizures comprising an unusual constellation of autonomic symptoms (malaise, nausea, pallor, tachycardia, vomiting) and unilateral deviation of the eyes at the onset of seizures. These clinical, ictal manifestations are rarely followed by post-ictal headache. In the literature, there is little information on the ictal EEG characteristics of Panayiotopoulos syndrome and, in particular, on certain autonomic manifestations, such as tachycardia, as the sole ictal phenomena at the onset of seizures. METHODS AND RESULTS: One, all-night videopolysomnography, during which one seizure was recorded. Video-EEG data were evaluated visually and by means of quantitative spectral analysis. The spectral analysis of the recorded seizure showed a complex ictal pattern of cortical involvement with focal onset in the right occipital area followed by the recruitment of widespread extra-occipital cortical regions. CONCLUSIONS: This is the first such analysis of this peculiar epileptic condition. Most of the symptoms were consistent with a diagnosis of severe Panayiotopoulos syndrome, although the patient also presented "atypical findings": a relatively high frequency of seizures, post-ictal headache, no spontaneous remission of seizures with age, and late onset of visual hallucinations; this last finding is more frequent in "Gastaut-type childhood occipital epilepsy", in which onset typically occurs later than in Panayiotopoulos syndrome. [Published with video sequences].