Children and adolescents with primary headaches exhibit altered sensory profiles - a multi-modal investigation.

BACKGROUND: Pediatric headache is an increasing medical problem that has adverse effects on children's quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains. METHODS: The study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache. RESULTS: Patients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache. CONCLUSIONS: Children with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification. TRIAL REGISTRATION: The study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

A Study on the Impact of the COVID-19 Pandemic on the Aetiology of Paediatric Olfactory Dysfunction.

INTRODUCTION: Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction. METHODS: Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset. RESULTS: A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets. CONCLUSION: The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium.

Olfactory function after mild traumatic brain injury in children-a longitudinal case control study.

The prevalence of posttraumatic olfactory dysfunction in children after mild traumatic brain injury ranges from 3 to 58%, with potential factors influencing this variation, including traumatic brain injury severity and assessment methods. This prospective longitudinal study examines the association between mild traumatic brain injury and olfactory dysfunction in children. Seventy-five pediatric patients with mild traumatic brain injury and an age-matched healthy control group were enrolled. Olfactory function was assessed using the Sniffin' Sticks battery, which focuses on olfactory threshold and odor identification. The study found that children with mild traumatic brain injury had impaired olfactory function compared with healthy controls, particularly in olfactory threshold scores. The prevalence of olfactory dysfunction in the patient group was 33% and persisted for 1 yr. No significant association was found between traumatic brain injury symptoms (e.g. amnesia, loss of consciousness) and olfactory dysfunction. The study highlights the importance of assessing olfactory function in children after mild traumatic brain injury, given its potential impact on daily life. Although most olfactory dysfunction appears transient, long-term follow-up is essential to fully understand the recovery process. The findings add valuable insights to the limited literature on this topic and urge the inclusion of olfactory assessments in the management of pediatric mild traumatic brain injury.

Smelling of the mothers' diet in amniotic fluid by adult noses.

In this study, the transfer of odorants, namely vanilla, and garlic, into the amniotic fluid (AF) during the second trimester was investigated by examination of collected AF samples through healthy adults. Eleven AF samples were collected from pregnant women (aged 32.9 ±â€…4.9 yr, 16-25 wk of gestation) undergoing diagnostic amniocentesis after eating garlic oil or vanilla powder in high-fat yogurt. The control group did not receive food before amniocentesis. Two vanilla, 3 garlic, and 6 control samples were collected through amniocentesis 60-120 min after ingestion. Samples were collected at -80 °C and carefully defrosted over 12 h at the same time point. Sixteen healthy volunteers (8 males, aged 26.5 ±â€…5.0 yr) were asked to judge AF samples with potential garlic or vanilla odors from controls in a 2-alternative forced choice (2AFC) paradigm. Judges were able to identify vanilla in the AF samples with an estimated probability of 50%, resulting in a significant P-value of < 0.001. In contrast, the identification of garlic was unsuccessful with a P-value of 0.86, and only 2 judges were able to identify both vanilla and garlic. According to the results of this study, the vanilla odor probably passes into the amniotic fluid.

Vanilla odor promotes oral feeding in premature infants-A randomized controlled trial.

PROPOSE: Introducing early oral feeding in premature infants is important because it supports intestinal maturation and helps prevent infections. In addition, early oral feeding is likely to contribute to improved neurocognitive outcomes in preterm infants. Several holistic therapeutic strategies have been developed to improve feeding skills, food tolerance, and the ability to drink independently, including practices such as early breastfeeding, oral stimulation, and subsequent olfactory stimulation. Based on several studies using olfactory stimulation with food odors (vanilla, breast milk) to promote oral feeding in preterm infants this study was conducted to test the following hypothesis: Does olfactory stimulation with vanilla or milk odor (breast milk or formula) lead to a reduction in the time required for nasogastric tube weaning in premature infants older than 26 + 6 weeks of gestational age? In addition, does it influence secondary outcomes such as length of hospital stay, weight development, and attainment of greater amounts of independently consumed food? METHODS: Premature with complete or partial feeding by gastric tube and without ventilation were included. For this study, 207 infants over 26 + 6 gestational weeks were randomized into three different study groups. Before each feeding, an olfactory presentation was made with milk odor, a vanilla Sniffin' Stick, or a control stick. In the final analysis, 165 infants were included (87 males, 78 females). At the time of randomization, infants were on average 12 ± 9.5 days old. RESULTS: While the influence of vanilla and milk odor did not provide a significant difference from the control for the primary outcome, a secondary analysis showed a significant group difference in the cumulative amount of independently drunk food consumed in the first ten days was the highest amount in the vanilla group. This time period was chosen due to the high dropout rate after the first ten days. In addition, there was a promising significance for earlier hospital discharge for prematurely below 32 weeks of gestation receiving vanilla odor stimulation in comparison to milk odor stimulation. CONCLUSION: Although the primary outcome of this study (gastric tube removal) did not provide significant results, a significant benefit of vanilla olfactory stimulation for preterm infants was demonstrated in subgroup analysis above milk odor stimulation. Younger preterm infants seem to benefit from the stimulation.

qU-Sniff - the development of a short version of the Universal "Sniffin' Sticks" test.

OBJECTIVES: Extensive olfactory testing is sparsely applied in pediatric patients in clinical routine especially because of its time taking nature. Therefore a 5-item odor identification test (quick "U-Sniff", "qU-Sniff") from the 12-item "U-Sniff" test was developed. METHODS: A total of 724 normosmic children between 6 and 17 years of age, divided in four age groups, were included in this retrospective study. Additionally, 17 children with congenital anosmia in the same age range were included. To calculate test-retest reliability 90 participants from the healthy group were tested twice. RESULTS: The five most correctly identified odors from the 12-item "U-Sniff" test were: coffee (98 %), peach (95 %), flower (90 %), fish (88 %) and onion (84 %). Normosmic participants scored 4.71 ± 0.62 points on the "qU-Sniff" test. A significant correlation between results of the 12-item and 5-item test (n = 724; rs = 0.580; p < 0.001) and a significant test-retest reliability (rs = 0.626, p < 0.001) were shown. For "qU-Sniff" validation a ROC analysis to distinguish between anosmic patients and healthy controls was conducted for each age group separately. AUCs were as followed: i) 0.963 ± 0.018, p < 0,001; ii) 0.978 ± 0.013, p < 0.001; iii) 0.992 ± 0.006, p < 0.001; iv) 0.994 ± 0.005, p < 0.001. The cut-off value to determine anosmic and normosmic participants was <4 points. CONCLUSION: With the "qU-Sniff" test, we present a short screening tool for clinical routine with <4 points as cut-off to initiate more detailed olfactory testing.

Olfactory training effects in children after mild traumatic brain injury.

OBJECTIVE: Mild traumatic brain injury (mTBI) might impair the sense of smell and cognitive functioning. Repeated, systematic exposure to odors, i.e., olfactory training (OT) has been proposed for treatment of olfactory dysfunctions, including post-traumatic smell loss. Additionally, OT has been shown to mitigate cognitive deterioration in older population and enhance selected cognitive functions in adults. We aimed to investigate olfactory and cognitive effects of OT in the pediatric population after mTBI, likely to exhibit cognitive and olfactory deficits. METHODS: Our study comprised 159 children after mTBI and healthy controls aged 6-16 years (M = 9.68 ± 2.78 years, 107 males), who performed 6-months-long OT with a set of 4 either high- or low-concentrated odors. Before and after OT we assessed olfactory functions, fluid intelligence, and executive functions. RESULTS: OT with low-concentrated odors increased olfactory sensitivity in children after mTBI. Regardless of health status, children who underwent OT with low-concentrated odors had higher fluid intelligence scores at post-training measurement, whereas scores of children performing OT with high-concentrated odors did not change. CONCLUSION: Our study suggests that OT with low-concentrated odors might accelerate rehabilitation of olfactory sensitivity in children after mTBI and support cognitive functions in the area of fluid intelligence regardless of head trauma.

Genetics of congenital olfactory dysfunction: a systematic review of the literature.

Olfaction, as one of our 5 senses, plays an important role in our daily lives. It is connected to proper nutrition, social interaction, and protection mechanisms. Disorders affecting this sense consequently also affect the patients' general quality of life. Because the underlying genetics of congenital olfactory disorders (COD) have not been thoroughly investigated yet, this systematic review aimed at providing information on genes that have previously been reported to be mutated in patients suffering from COD. This was achieved by systematically reviewing existing literature on 3 databases, namely PubMed, Ovid Medline, and ISI Web of Science. Genes and the type of disorder, that is, isolated and/or syndromic COD were included in this study, as were the patients' associated abnormal features, which were categorized according to the affected organ(-system). Our research yielded 82 candidate genes/chromosome loci for isolated and/or syndromic COD. Our results revealed that the majority of these are implicated in syndromic COD, a few accounted for syndromic and isolated COD, and the least underly isolated COD. Most commonly, structures of the central nervous system displayed abnormalities. This study is meant to assist clinicians in determining the type of COD and detecting potentially abnormal features in patients with confirmed genetic variations. Future research will hopefully expand this list and thereby further improve our understanding of COD.

Assessment of Olfactory Function in Children and Adolescents: An Overview.

Valid and reliable tools for assessing olfactory function are necessary for the diagnosis of olfactory dysfunction. Olfactory testing can be challenging in a pediatric population due to shorter attention span, linguistic development, and lower olfactory experience in this age group. The aim of this article is to present an overview about olfactory tests that are suitable for a pediatric population. Publications were included when reporting new developed methods of psychophysical olfactory testing in children or adaptation and applications of existing olfactory tests for a pediatric population. Olfactory tests for all 3 major aspects of olfactory function-olfactory threshold, odor discrimination, and odor identification-were included. Olfactory tests were evaluated regarding test validity, test reliability, normative data, and test availability. The current literature shows that several tests are available to assess olfactory function in children. Especially odor identification abilities in a pediatric population are well examined and understood. Tests for olfactory threshold and odor discrimination are less frequently used. In terms of the abovementioned evaluation criteria, only a few tests met all or 3 of these 4 criteria. Based on the current literature the following tests can be recommended for valid and reliable olfactory testing in children: "U-Sniff" odor identification test, the "Sniffin' Sticks" olfactory threshold test, pBOT-6 olfactory threshold and odor identification test, NIH-Toolbox, and Smell Wheel. Age has to be considered when evaluating olfactory function in children.

Central Nervous System Processing of Floral Odor and Mother's Milk Odor in Infants.

Newborns have a functioning sense of smell at birth, which appears to be highly significant for feeding and bonding. Still, little is known about the cerebral odor processing in this age group. Studies of olfactory function relied mostly on behavioral, autonomic, and facial responses of infants. The aim of the present study was to investigate central odor processing in infants focusing on electroencephalography (EEG)-derived responses to biologically significant odors, namely a food and a non-food odor. A total of 21 term-born, healthy infants participated (11 boys and 10 girls; age range 2-9 months, mean 5.3 ± 2.2 months). Odor stimuli were presented using a computer-controlled olfactometer. Breast milk was used as food odor. Farnesol was presented as a non-food odor. In addition, odorless air was used as a control stimulus. Each stimulus was presented 30 times for 1 s with an interstimulus interval of 20 s. EEG was recorded from 9 electrodes and analyzed in the frequency domain. EEG amplitudes in the delta frequency band differed significantly after presentation of food (breast milk) odor in comparison to the control condition and the non-food odor (farnesol). These changes were observed at the frontal recording positions. The present study indicates that central odor processing differs between a food and a non-food odor in infants. Results are interpreted in terms of focused attention towards a physiologically relevant odor (breast milk), suggesting that olfactory stimuli are of specific significance in this age group.

Odor identification performance in children using the "U-Sniff" test - Administered by an untrained person.

OBJECTIVE: The examination of olfactory function of patients with psychophysical olfactory tests such as the "Sniffin' Stick" test is a central component of any olfactory clinical diagnostics and clinical trials. Because olfactory disorders can also occur in childhood, reliable, valid and time-efficient olfactory tests are important. With the "U-Sniff", a child-friendly odor identification test that has already been sufficiently validated is available The aim of this study was to investigate whether untrained persons (e.g. parents with their children) are able to administer the "U-Sniff" odor identification test with appropriate guidance. METHOD: A total of 80 kindergarten children, aged 6 years, underwent an odor identification test. Half of the children were tested by their parents and the other half by a trained examiner. In addition, the examiner performed a concentration test (Kaseler Konzentrationsaufgaben). The results of the two groups were compared. RESULTS: All children completed the rapid testing protocol. No significant differences between the results of the two testing procedures occurred. On average an odor identification score of 9.68 ± 2.02 points (mean ± SD) was reached in the examiner's group while 9.65 ± 2.38 points were observed in the parents' group. CONCLUSION: It can be concluded that this study presents a new testing procedure using the "U-Sniff" odor identification test for children by untrained persons. Further validation of this test procedure examining olfactory impaired children should follow.

Human olfactory dysfunction: causes and consequences.

The sense of smell essentially contributes to social communication, guides nutrition behaviour and elicits avoidance towards environmental hazards. Olfactory smell impairment may hence entail severe consequences for affected individuals. Compared with sensory loss in other modalities, reduced olfactory function is often unnoticed by those affected and diagnosed late. Those patients seeking help frequently suffer from long-term impairments resulting in reduced well-being and quality of life. The current review provides an overview of aetiology, prevalence and specifics of diagnostics in acquired and congenital olfactory loss and focusses on short- and long-term consequences. Compensation strategies are elaborated, and treatment options are mentioned. Individual characteristics associated with the development of serious mental health impairment are discussed in order to help practitioners identifying populations at risk.

The Influence of Cognitive Parameters on Olfactory Assessment in Healthy Children and Adolescents.

Olfactory threshold and odor identification tests are frequently used for assessment of olfactory function in children and adolescents. Whether olfactory test results are influenced by cognitive parameters or sex in children and adolescents is largely unknown. The aim of this study was to investigate the influence of cognition, age and sex on "Sniffin' Sticks" olfactory threshold and "U-Sniff" odor identification performance in a pediatric population. A total of 200 participants between age 6 and 17 years were included. Olfactory function (olfactory threshold and odor identification) was assessed using the "Sniffin' Sticks." In addition, age appropriate cognitive testing was applied. The results of this study indicate that odor identification test performance is positively correlated with age (r = 0.31) and verbal abilities of children (r = 0.24). Olfactory threshold results are only marginally influenced by age (r = 0.18) and are not associated with cognitive test performance. Olfactory assessment using olfactory threshold and "U-Sniff" odor identification testing is suitable for children and adolescents when considering age in the interpretation of test results.

Odor identification performance in children aged 3-6 years.

BACKGROUND: While valid and reliable olfactory tests have been developed for children aged >5 years, olfactory testing has not systematically been evaluated in younger children. The aim of this study was to evaluate the reliability and validity of the "U-Sniff" odor identification test in children aged 3-6 years. METHODS: We included 160 healthy children (age range 3-6 years) and 14 congenitally anosmic children. Participants were investigated in two identical sessions. The "U-Sniff" test was used to evaluate olfactory function. A picture identification test (PIT) and the Kasel-Concentration-Task (KKA) were administered to identify factors influencing odor identification performance. RESULTS: Age significantly influenced odor identification performance, with older children achieving higher scores. PIT and KKA scores correlated positively with odor identification scores. The "U-Sniff" test demonstrated a high test-retest reliability (r160 = 0.75, p < 0.001). It was possible to distinguish between healthy and anosmic children by means of "U-Sniff" scores starting at age 4 years with high sensitivity (79-93%) and specificity (88-95%). CONCLUSIONS: The "U-Sniff" test is feasible for children starting at age 3 years. In children aged ≥4 years, it is a reliable and valid method to distinguish between normal olfactory function and anosmia. IMPACT: Olfactory testing is reliable and valid starting at an age of 4 years. The study adds a systematic evaluation of olfactory testing in young children. Results of this study are especially interesting for clinicians in the diagnosis of olfactory dysfunction.

Decreasing prevalence of specific anosmia to non-steroid odorants from childhood to adolescence.

Specific anosmia is defined as the inability to detect a particular odorant, despite a normal olfactory function. Previous studies reported sex-related difference in detection threshold to steroid odorants, like androstenone or androstadienone during adolescence, and boys showed an increased detection threshold with age. However, such investigations have not been performed for non-steroid odorants. Hence, the current study investigated sex- and age-related effects on the prevalence of specific anosmia in children/adolescents aged 5-14 years (n = 800) to non-steroid odorants. The detection thresholds of three non-steroid odorants (bacdanol, methylsalicylate, and 3-hydrox-2-methyl-4-pyrone) with different molecular weights were measured. Results indicate that the rate of specific anosmia for all three odorants decreases from childhood to adolescence. This decrease is independent of sex and is most pronounced for odorants with higher molecular weight compared to the odorant with lower molecular weight. Thus, the development of basic olfactory functions for these three odorants continues until adolescence. The effect of molecular weight suggests that the locus of effect is at the periphery of the olfactory system, due to changes in either olfactory receptor expression patterns or perireceptor events.

Metal-containing Particulate Matter and Associated Reduced Olfactory Identification Ability in Children from an Area of High Atmospheric Exposure in Mexico City.

Air pollution has been linked to poor olfactory function in human adults. Among pollutants, particulate matter (PM) is especially relevant, as it may contain toxic metal ions that can reach the brain via olfactory pathways. Our purpose was to investigate the relation between atmospheric PM and olfactory identification performance in children. Using a validated method, we tested the olfactory identification performance of 120 children, 6-12 years old, from two locations in Mexico City: a focal group (n = 60) from a region with high PM levels and a control group of equal size and similar socioeconomic level from a region with markedly lower PM concentrations. Groups were matched for age and sex. Concentrations of manganese and lead in the hair of participants were determined as biomarkers of exposure. Daily outdoor PM levels were obtained from official records, and indoor PM levels were measured in the children's classrooms. Official records confirmed higher levels of outdoor PM in the focal region during the days of testing. We also found higher classroom PM concentrations at the focal site. Children from the focal site had on average significantly lower olfactory identification scores than controls, and hair analysis showed significantly higher levels of manganese for the focal children but no difference in lead. Children appear to be vulnerable to the effects of air pollution on olfactory identification performance, and metal-containing particles likely play a role in this. Olfactory tests provide a sensitive, noninvasive means to assess central nervous function in populations facing poor air quality.