Headache attributed to aeroplane travel: the first multicentric survey in a paediatric population affected by primary headaches.

BACKGROUND: This multicentric survey investigates the prevalence and characteristics of Airplane Headache in children affected by primary headaches. METHODS: Patients with symptoms of Airplane Headache were recruited from nine Italian Pediatric Headache Centres. Each patient was handed a structured questionnaire which met the ICHD-III criteria. RESULTS: Among 320 children suffering from primary headaches who had flights during their lifetime, 15 (4.7%) had Airplane Headache, with mean age of 12.4 years. Most of the patients were females (80%). The headache was predominantly bilateral (80%) and localized to the frontal area (60%); it was mainly pulsating, and lasted less than 30 min in all cases. Accompanying symptoms were tearing, photophobia, phonophobia in most of the cases (73.3%). More than 30% of patients used medications to treat the attacks, with good results. CONCLUSION: Our study shows that Airplane Headache is not a rare disorder in children affected by primary headaches and highlights that its features in children are peculiar and differ from those described in adults. In children Airplane Headache prevails in females, is more often bilateral, has frequently accompanying symptoms and occurs at any time during the flight. Further studies are needed to confirm the actual frequency of Airplane Headache in the general pediatric population not selected from specialized Headache Centres, with and without other concomitant headache condition, and to better clarify the clinical characteristics, pathophysiology and potential therapies.

Visual and vestibular functioning, and age and surgery effects on postural control in healthy children with vertical strabismus.

PURPOSE: To describe visual and vestibular functioning and the effects of age and surgery effects on postural control in healthy children with vertical strabismus. DESIGN: This is a comparative case series. METHODS: We evaluated participants at the Scientific Institute Eugenio Medea during routine clinical activities. We enrolled 30 consecutive children/adolescents (age range 4-13 years) with isolated vertical strabismus, with and without corrective surgery. Participants were split into four subgroups according to age (4-8 years versus 9-13 years) and ocular surgery (surgery versus no surgery). The clinical protocol included ophthalmological, orthoptic, neurological, physiatrical, otolaryngological, and vestibular evaluations, and the instrumental protocol included ocular cyclotorsions assessment, posturography, and vestibular myogenic-evoked potentials. Main outcome measures of the study were the prevalence of study-relevant orthopedic, ocular, vestibular, and posturographic abnormalities. RESULTS: Among the overall largely variable findings across patients' groups, we found some interesting trends: larger binocular vision and convergence disorders in younger children, smaller prevalence of asymmetric vestibular-evoked potentials in operated children, less posturographic abnormalities in younger children. No clear-cut beneficial effect of surgery was found on all clinical and instrumental parameters considered, despite good re-alignment of the eyes. CONCLUSION: The pathophysiology of postural control in vertical strabismus is extremely complex and above the potential of this study design and should be specifically addressed in deeper experimental studies.

High frequency oscillations after median nerve stimulations in healthy children and adolescents.

The aim of the present research was to address somatosensory high frequency oscillations (400-800Hz) in healthy children and adolescents in comparison with healthy adults. We recorded somatosensory evoked potentials following median nerve stimulation in nineteen resting healthy children/adolescents and in nineteen resting healthy adults with eyes closed. We administered six consecutive stimulation blocks (500 sweeps each). The presynaptic component of high frequency oscillations amplitudes was smaller in healthy children/adolescents than in healthy adults (no difference between groups was found as far as the postsynaptic component was concerned). Healthy children/adolescents had smaller presynaptic component than the postsynaptic one (the postsynaptic component amplitude was 145% of the presynaptic one), while healthy adults showed the opposite (reduction of the postsynaptic component to 80% of the presynaptic one). No habituation phenomena concerning high frequency oscillation amplitudes were registered in neither healthy children/adolescents nor healthy adults. These findings suggest that healthy children/adolescents present with significantly different pattern of somatosensory high frequency oscillations compared with healthy adults' ones. This different pattern is reasonably expression of higher cortical excitability of the developing brain cortex.

Cortical hyper-excitability in healthy children: evidence from habituation and recovery cycle phenomena of somatosensory evoked potentials.

AIM: To compare neurophysiological parameters of central nervous system excitability in healthy children/adolescents with those of healthy adults. METHOD: Two experimental protocols were used in 19 healthy children/adolescents (10 males and 9 females, mean age 9y 11mo [SD 2y 9mo], range 5-15y) and 19 healthy adults (8 males and 11 females, mean age 36y 6mo [SD 7y 9mo], range 27-51y). First, we administered repetitive trains of innocuous electrical stimulation of the median nerve and analysed habituation (progressive attenuation) of the cervical and cortical responses. Second, we administered several blocks of two closely timed electrical innocuous stimuli of the median nerve (with interstimulus intervals set at 5, 10, and 20ms in each block) and analysed the recovery index (the percentage of the response to the second stimulus with respect to that to the first). RESULTS: Clear-cut neurophysiological signs of cortical hyper-excitability were found in children/adolescents but not in adults. In contrast with the adults, the children/adolescents did not attenuate cortical responses to repetitive stimulation, and presented with extremely shortened recovery cycle. At baseline, both groups presented with comparable cortical responses. INTERPRETATION: Healthy children/adolescents present cortical hyper-excitability compared with healthy adults. These findings agree with previous findings that show an overall imbalance of excitatory and inhibitory neuronal and neurochemical mechanisms in favour of excitatory ones, in the healthy developing cerebral cortex.

Neuropsychological assessment of children with epilepsy and average intelligence using NEPSY II.

INTRODUCTION: Many studies have shown altered neuropsychological functioning of children with epilepsy even in the absence of intellectual disability, with notable concerns for both patients and their families. Although studies have described the cognitive profiles associated with specific epilepsy syndromes, there is incomplete agreement on the relation between spared and impaired abilities in different cognitive domains and on how deficits in one neuropsychological ability can secondarily affect performance in other cognitive domains. The aim of this study was to investigate the neuropsychological profile and vulnerabilities of children with epilepsy without intellectual disability or borderline intellectual functioning. METHOD: 23 children aged 7-15 years, with a diagnosis of epilepsy of genetic or unknown cause and average intellectual functioning (IQ >85), were administered all age-appropriate tests of the Italian-language version (Urgesi, Campanella, & Fabbro, 2011) of a comprehensive neuropsychological battery (NEPSY-II: A Developmental Neuropsychological Assessment, Second Edition; Korkman, Kirk, & Kemp, 2007). Their performance was compared with that of a control group matched for gender, age, handedness and education. RESULTS: Children with epilepsy showed significant impairments as compared to the control group in tests of attention and executive functions and sensorimotor skills. Notably, particular difficulties were observed also in social perception tasks that require affect recognition, an ability that has been so far poorly considered in children with epilepsy. CONCLUSIONS: The results highlight the importance of performing extensive evaluation of cognitive functions, including social cognition processes, in children with epilepsy with average intelligence in order to design appropriate interventions aimed at minimizing long-term consequences on educational and behavioral outcome.

A new patient with a terminal de novo 2p25.3 deletion of 1.9 Mb associated with early-onset of obesity, intellectual disabilities and hyperkinetic disorder.

Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH analysis, have been reported in about 18 patients sharing common clinical features represented by early-onset obesity/ overweightness associated with intellectual disabilities (ID) and behavioural troubles. This observations led to hypothesize that 2p subtelomeric deletion should be associated with syndromic obesity and MYT1L became the main candidate gene for ID and obesity since it is deleted or disrupted in all hitherto published cases. Here we described a 2p25.3 de novo terminal deletion of 1.9 Mb, of paternal origin, detected by array-CGH analysis in a girl of 4.4 years with a distinctive phenotype consisting of early-onset of obesity associated with moderate ID, and hyperkinetic disorder. The deletion disrupted MYT1L and encompassed five other OMIM genes, ACP1, TMEM18, SNTG2, TPO, and PXDN. Here, we discuss the combined functional effects of additional haploinsufficient genes, that may concur with heterozygous deletion of MYT1L, in the aetiology for syndromic obesity associated with 2p25.5 subtelomeric deletion.

Patterns of habituation and clinical fluctuations in migraine.

BACKGROUND: Habituation deficit, suggesting a deregulation of cortical excitability, represents a typical hallmark of interictal stages of migraine. We previously demonstrated that several neurophysiological markers of altered cortical excitability are significantly correlated to spontaneous clinical fluctuations of migraine. We therefore aimed at verifying whether clinical fluctuations are correlated to specific patterns of somatosensory evoked potential (SEP) habituation. METHODS: We analyzed habituation after median nerve stimulation of both high-frequency oscillations (HFOs) and N20 SEP in 25 migraine patients and 18 healthy volunteers. Subjects underwent six consecutive series of 500 stimuli. RESULTS: Migraine patients as a whole showed a significant habituation deficit of the N20 response. Moreover, spontaneously worsening patients show a clear potentiation of this wave in the last block of stimuli, whereas in spontaneously improving patients the N20 amplitude remained stable. Presynaptic HFOs were smaller in worsening patients and larger in improving ones, but they did not undergo habituation in patients as well as in healthy subjects. CONCLUSIONS: Potentiation of the N20 response in spontaneously worsening migraineurs confirms that the reduction of the thalamocortical drive plays a major role in migraine pathogenesis. Moreover, the stable pattern we observed in spontaneously improving patients suggests that compensatory mechanisms can also play an important role. The normal response to repeated stimuli of HFOs in migraineurs might indicate that, although its initial amount depends on clinical conditions, high-frequency thalamocortical drive remains stable during the stimulation and probably reflects the activity of a buffer mechanism.

Different levels of cortical excitability reflect clinical fluctuations in migraine.

BACKGROUND: In a previous study we demonstrated that high-frequency oscillations (HFOs) elicited by median nerve stimulation are significantly correlated to clinical fluctuations of migraine. We aimed at verifying whether clinical fluctuations and HFO changes are correlated to N20 somatosensory evoked potential (SEP) recovery cycle, which is likely to reflect the functional refractoriness of primary somatosensory cortex neurons. METHODS: We analysed both HFOs and N20 SEP recovery cycle to paired stimulation in 21 migraine patients and 18 healthy volunteers. RESULTS: Shortened recovery cycle correlated with low-amplitude HFOs as well as with clinical worsening. By contrast, prolonged recovery cycle correlated with enhanced HFOs, as well as with spontaneous clinical improvement. CONCLUSIONS: In our migraine patients the strict relationship between presynaptic HFO amplitude and N20 recovery function suggests that changes of both parameters might be caused by modifications of the thalamo-cortical drive. Our findings suggest that the thalamo-cortical drive during interictal stages could fluctuate from abnormally high to abnormally low levels, depending on mechanisms which reduce cortical excitability in spontaneously improving patients, and increase cortical excitability in spontaneously worsening ones.

Somatosensory High Frequency Oscillations reflect clinical fluctuations in migraine.

OBJECTIVE: It has been demonstrated that the early part of 600 Hz High Frequency Oscillations (HFOs), probably generated in the terminal part of thalamo-cortical somatosensory radiations, are abnormally reduced between attacks in migraineurs. We aimed at verifying whether spontaneous clinical fluctuations in migraine are correlated to HFO changes. METHODS: We recorded somatosensory evoked potentials in 28 migraine patients. Clinical fluctuations (number of attacks in the 6 months preceding and following the test) were correlated to the HFOs' amplitudes. Moreover, eight out of 28 patients underwent a longer follow-up, including HFO control and clinical observation during the 12 months following the baseline recording. RESULTS: The amplitude of early presynaptic HFOs was significantly correlated to the clinical evolution, since spontaneous worsening was associated with reduced presynaptic HFOs, whereas spontaneous improvement was associated with enhanced presynaptic HFOs (correlation test, p<0.05). No correlation was found between the amplitude of postsynaptic HFOs and clinical fluctuations. Patients undergoing longer follow-up showed substantially unchanged HFOs, accordingly with their stable clinical condition. CONCLUSIONS: HFOs' enhancement in spontaneously improved patients can reflect the increased activity of brainstem arousal related structures, which in turn increases the thalamo-cortical drive and the cortical lateral inhibition mediated by GABAergic interneurons. SIGNIFICANCE: HFOs' recording could represent a useful tool in the functional assessment of migraine.

Pediatric biobanking: a pilot qualitative survey of practices, rules, and researcher opinions in ten European countries.

Ethical, legal, and social issues related to the collection, storage, and use of biospecimens and data derived from children raise critical concerns in the international debate. So far, a number of studies have considered a variety of the individual issues crucial to pediatric biobanking such as decision making, privacy protection, minor recontact, and research withdrawal by focusing on theoretical or empirical perspectives. Our research attempted to analyze such issues in a comprehensive manner by exploring practices, rules, and researcher opinions regarding proxy consent, minor assent, specimens and data handling, and return of results as faced in 10 European countries. Because of the lack of comparative analyses of these topics, a pilot study was designed. Following a qualitative methodology, a questionnaire draft mostly including open-ended queries was developed, tested, and sent by e-mail to a selected group of researchers dealing with pediatric biobanking (n=57). Returned questionnaires (n=31) highlighted that the collection, storage, distribution, and use of biospecimens and data from children were widely practiced in the contacted laboratories. In most cases, pediatric biobanking was subjected to national or local regulations covering adult biobanks (n=26). Informed consent was generally given by parents or legal representatives (n=17). Children's opinions were frequently sought and taken into account (n=16). However, minors were usually not recontacted at the age of maturity to express their own choices (n=26). Based on the collected data, dedicated recommendations are needed to govern unique ethical and regulatory issues surrounding pediatric biobanking.

Variability of the clinical phenotype in an Italian family with dementia associated with an intronic deletion in the GRN gene.

Mutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now and prominent phenotypic variability within and among affected kindreds has been described. We have studied an Italian family with clinical evidence of dementia, and here we report detailed clinical records, imaging, sequential neurological examinations, cognitive assessments, and genetic analysis of three affected members of the same generation. Genetic analysis revealed the presence of the null mutation IVS6 + 5_8delGTGA in GRN, leading to haploinsufficiency, as documented by mRNA analysis. The mutation is associated with wide variation of the clinical phenotype, ranging from FTD to Alzheimer's disease and to a rapidly-progressive dementia. In summary, the patients of this kindred showed highly variable clinical features that do not have a close correspondence with the pattern of the cerebral atrophy. Our data extend the phenotypic spectrum and the complexity of neurodegenerative diseases linked to GRN mutations.

Primary progressive aphasia in a bilingual speaker: a single-case study.

We report on the case of an elderly bilingual woman presenting with a diagnosis of primary progressive aphasia. The participant's native language was Friulian (L1), a predominantly oral Romance language, and her second language was Italian (L2), formally learned at primary school in oral and written forms. We investigated her linguistic abilities by means of the Bilingual Aphasia Test ( Paradis, M., & Libben, G. (1987). The assessment of bilingual aphasia. Hillsdale, NJ: Lawrence Erlbaum Associates), which is specifically devised for studying language levels and skills in bilingual/polyglot individuals with aphasia. Specifically, we focused on different tasks extracted from the Bilingual Aphasia Test, targeting phonology, morphology, syntax and lexical semantics. Results show that both languages were affected to a clinically significant degree, but with different profiles in terms of linguistic levels, suggesting the presence of greater phonological, morphological, grammatical and syntactic impairments in L2. Results are discussed in terms of possible dissociations both within the language system of each language and between languages, within the Procedural/Declarative theoretical framework of language acquisition in bilinguals.

Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study.

BACKGROUND: A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. METHODS: Twenty children with autism (mean age= 7 ± 2.75 years old; age range: 4-14; 2 girls) and 22 matched normally developing children (mean age = 7.68 ± 2.03 years old; age range: 4-11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the ADC values. RESULTS: Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. CONCLUSIONS: These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits.

High-frequency oscillations after median-nerve stimulation do not undergo habituation: a new insight on their functional meaning?

OBJECTIVE: Amplitude decrease of cortical responses after repeated stimuli ('habituation') is a well-known phenomenon, the functional meaning of which is to prevent sensory overflow and to save resources for meaningful and novel stimuli. It is known that the primary low-frequency N20 somatosensory evoked potential (SEP) undergoes habituation in healthy subjects. By contrast, the presence of this phenomenon has never been tested in High Frequency Oscillations (HFOs), which probably reflect the activity of a somatosensory arousal system. METHODS: We recorded SEPs after right median nerve stimulation in 19 healthy volunteers. Six consecutive series of 500 sweeps were collected and averaged at a repetition rate of 5 Hz. SEPs were recorded by means of Erb'point-to-Fz, Cv6-to-AC and P3-to-F3 arrays. P3-to-F3 recording further underwent narrow-bandpass (400-800 Hz) digital filtering to selectively analyse high-frequency components. RESULTS: Statistical analysis revealed a significant amplitude decrease of the primary N20 LF-SEP between the first and sixth block of stimuli. By contrast, HFO amplitudes remained substantially unchanged throughout the whole procedure. CONCLUSIONS: Differently from the N20 LF-SEP, scalp-recorded HFOs do not undergo habituation. SIGNIFICANCE: Our findings reinforce the view that HFOs reflect the activity of an arousal somatosensory system, which is able to signal novel stimuli, the relevance of which points out high synaptic efficacy.

Palatal expansion and maxillary protaction: case report / Disjunção palatal e protração maxilar: relato de caso clínico

Early Class III malocclusion correction is an important factor for the patient, whereas it can avoid later surgical procedures. This malocclusion causes esthetic and functional damage; as well it can cause disturbances in patient's social life and psychological problems. This paper presents a clinical case report of palatal expansion followed by maxillary protraction, occurred at University Paulista, Brasília-DF. It was used a hyrax expansor with vestibular hooks and PETIT´s facial mask. Clinical results were considered satisfatories.

A correção precoce da Classe III é de suma importância, uma vez que previne futura correção cirúrgica. Esta maloclusão acarreta prejuízos estéticos e funcionais ao paciente, levando a problemas de ordem psicológica, podendo gerar o aparecimento de transtornos nas relações interpessoais e no convívio social. Este trabalho relata um caso clínico de disjunção palatal seguida de protração maxilar, ocorrido na Clínica de Ortodontia/Odontopediatria da Universidade Paulista, Brasília-DF. Foram utilizados um expansor Hyrax com ganchos vestibulares e máscara facial de PETIT. Os resultados clínicos obtidos foram considerados satisfatórios.

Spontaneous language production in bilingual Parkinson's disease patients: Evidence of greater phonological, morphological and syntactic impairments in native language.

Nine early non-demented bilingual (L1 - Friulian, L2 - Italian) patients with Parkinson's disease and nine normal controls matched for age, sex and years of education were studied on a spontaneous language production task. All subjects had acquired L1 from birth in a home environment and L2 at the age of six at school formally. Patients with PD evidenced more phonological, morphological and syntactic errors in L1 than in L2. The opposite pattern was observed in normal controls as far as grammar was concerned. These findings suggest that implicit language processing is more impaired than explicit language processing in Parkinson's disease.

Somatosensory mismatch negativity in healthy children.

AIM: Event-related potentials (ERPs) obtained when focused attention is kept away from the stimulus (unnoticed stimulation) are possibly linked to automatic mismatch-detection mechanisms, and could be a useful tool to investigate sensory discrimination ability. By considering the high impact of impaired somatosensory integration on many neurological disturbances in children, we aimed to verify whether mismatch-related responses to somatosensory stimulation could be obtained in healthy children. METHOD: Eleven healthy participants (age range 6-11y, mean 8y 2mo, SD 1y 7mo; seven males, four females) underwent 'oddball' electrical stimulation of the right hand (80% frequent stimuli delivered to the thumb, 20% deviant stimuli delivered to the fifth finger). Data were compared with those obtained when the frequent stimuli to the thumb were omitted ('standard-omitted' protocol). ERPs were recorded at frontal, central, and parietal scalp locations. Children's overt attention was engaged by a demanding video game. RESULTS: In the oddball protocol, deviant stimulation elicited a left central negativity at about 160ms latency, followed by a left frontal negative response at about 220ms latency. Standard-omitted traces showed only a left parietal negative response spreading to right parietal regions. INTERPRETATION: Mismatch-related somatosensory responses can be reliably obtained in children, providing that appropriate technical contrivances are used. In clinical use, the frontal components, which are present only during the oddball protocol, could be a reliable and unequivocal neurophysiological marker of the automatic mismatch-detection mechanism.

Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson's disease: a pilot study.

Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson's disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson's disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.

Generalised script sequencing deficits following frontal lobe lesions.

Neuropsychological investigations have consistently shown that frontal cortices are relevant in processing temporal and sequential features of actions. However, one of the main theoretical issues that has been discussed in the last 25 years is whether these brain areas store some abstract representations of actions or, conversely, act upon action representations stored within other posterior associative cortices. We administered to 19 patients with frontal lobe lesions and 19 normal controls, script sequencing and generating tasks concerning actions, natural events and "époques" (ordered events such as the days of the week). The main findings from frontal lobe patients were a generalised sequencing deficit concerning actions and natural phenomena (and not what we labelled "époques") with almost intact ability to verbally generate, from the long-term memory, scripts' sequences. These findings are discussed within two of the main theoretical frameworks on frontal lobes: the "processing" perspective of the Supervisory Attentional System, SAS (Norman and Shallice, 1986) and the "representational" one represented by the Structure Event Complex (SEC) theory (Grafman, 2002).

Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence.

Human anterior cingulate function has been explained primarily within a cognitive framework. We used functional MRI experiments with simultaneous electrocardiography to examine regional brain activity associated with autonomic cardiovascular control during performance of cognitive and motor tasks. Using indices of heart rate variability, and high- and low-frequency power in the cardiac rhythm, we observed activity in the dorsal anterior cingulate cortex (ACC) related to sympathetic modulation of heart rate that was dissociable from cognitive and motor-related activity. The findings predict that during effortful cognitive and motor behaviour the dorsal ACC supports the generation of associated autonomic states of cardiovascular arousal. We subsequently tested this prediction by studying three patients with focal damage involving the ACC while they performed effortful cognitive and motor tests. Each showed abnormalities in autonomic cardiovascular responses with blunted autonomic arousal to mental stress when compared with 147 normal subjects tested in identical fashion. Thus, converging neuroimaging and clinical findings suggest that ACC function mediates context-driven modulation of bodily arousal states.