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Spatially fractionated ultra-high-dose-rate beams used during microbeam radiation therapy (MRT) have been shown to increase the differential response between normal and tumour tissue. Quality assurance of MRT requires a dosimeter that possesses tissue equivalence, high radiation tolerance and spatial resolution. This is currently an unsolved challenge. This work explored the use of a 500 nm thick organic semiconductor for MRT dosimetry on the Imaging and Medical Beamline at the Australian Synchrotron. Three beam filters were used to irradiate the device with peak energies of 48, 76 and 88 keV with respective dose rates of 3668, 500 and 209 Gy s−1. The response of the device stabilized to 30% efficiency after an irradiation dose of 30 kGy, with a 0.5% variation at doses of 35 kGy and higher. The calibration factor after pre-irradiation was determined to be 1.02 ± 0.005 µGy per count across all three X-ray energy spectra, demonstrating the unique advantage of using tissue-equivalent materials for dosimetry. The percentage depth dose curve was within ±5% of the PTW microDiamond detector. The broad beam was fractionated into 50 microbeams (50 µm FHWM and 400 µm centre-to-centre distance). For each beam filter, the FWHMs of all 50 microbeams were measured to be 51 ± 1.4, 53 ± 1.4 and 69 ± 1.9 µm, for the highest to lowest dose rate, respectively. The variation in response suggested the photodetector possessed dose-rate dependence. However, its ability to reconstruct the microbeam profile was affected by the presence of additional dose peaks adjacent to the one generated by the X-ray microbeam. Geant4 simulations proved that the additional peaks were due to optical photons generated in the barrier film coupled to the sensitive volume. The simulations also confirmed that the amplitude of the additional peak in comparison with the microbeam decreased for spectra with lower peak energies, as observed in the experimental data. The material packaging can be optimized during fabrication by solution processing onto a flexible substrate with a non-fluorescent barrier film. With these improvements, organic photodetectors show promising prospects as a cost-effective high spatial resolution tissue-equivalent flexible dosimeter for synchrotron radiation fields.

Background It has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children. Methods We analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another—comparable—group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma. Results The gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features, and appeared to be linked by a complex network of inter-correlations involving the Aryl Hydrocarbon Receptor signaling pathway. In addition, when the study of inter-correlations within the expression pattern of these molecules was extended to include the healthy subjects, the intrinsic physiological relationships of the inflammatory/oxidative stress network emerged. Plasma levels of Prx2 and Prx5 were remarkably increased in ASD compared to healthy controls, while no significant differences were found in red cell Prx levels. Conclusions Previous findings reported elevated inflammatory cytokines in the plasma of ASD children, without clearly pointing to the presence of neuro-inflammation. On the other hand, the finding of microglia activation in autoptic specimens was clearly suggesting the presence of neuro-inflammation in ASD. Given the role of peroxiredoxins in the protection of brain cells against oxidative stress, the whole of our results, using peripheral data collected in living patients, support the involvement of neuro-inflammation in ASD, and generate a rational for neuro-inflammation as a possible therapeutic target and for plasma Prx5 as a novel indicator of ASD severity.

A new printable organic semiconducting material combination as a tissue equivalent photodetector for indirect X-ray detection is demonstrated in this work. The device exhibits a higher optical-to-electrical conversion efficiency than any other reported printable organic systems for X-ray photodetection while also operating efficiently with zero applied bias. Complete X-ray detectors fabricated by coupling the photodiode with a plastic scintillator are among the first flexible and fully tissue equivalent X-ray detectors capable of operating without external bias. The response to X-rays is energy independent between 50 keV and 1.2 MeV, with a detection sensitivity equivalent to inorganic direct X-ray detectors and one of the fastest temporal responses ever reported for organic X-ray detectors. The materials can be printed into arrays with a pixel pitch of 120 μm, providing 2D spatial detection. The devices are found to be highly stable with respect to time, mechanical flexing, and large (5 kGy) radiation doses. The new materials and fully tissue equivalent X-ray detectors reported here provide stable, printable, flexible, and tissue equivalent detectors with a high radiolucency that are ideally suited for wearable applications, where simultaneous monitoring and high transmission of the X-ray absorbed dose into the human body is required.

[Non applicable]

There is growing interest in the development of novel materials and devices capable of ionizing radiation detection for medical applications. Organic semiconductors are promising candidates to meet the demands of modern detectors, such as low manufacturing costs, mechanical flexibility, and a response to radiation equivalent to human tissue. However, organic semiconductors have typically been employed in applications that convert low energy photons into high current densities, for example, solar cells and LEDs, and thus existing design rules must be re-explored for ionizing radiation detection where high energy photons are converted into typically much lower current densities. In this work, we report the optoelectronic and X-ray dosimetric response of a tissue equivalent organic photodetector fabricated with solution-based inks prepared from polymer donor poly(3-hexylthiophene) (P3HT) blended with either a non-fullerene acceptor (5Z,5'Z)-5,5'-((7,7'-(4,4,9,9-tetraoctyl-4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis(benzo[c][1,2,5]thiadiazole-7,4-diyl))bis(methanylylidene))bis(3-ethyl-2-thioxothiazolidin-4-one) (o-IDTBR) or a fullerene acceptor, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). Indirect detection of X-rays was achieved via coupling of organic photodiodes with a plastic scintillator. Both detectors displayed an excellent response linearity with dose, with sensitivities to 6 MV photons of 263.4 ± 0.6 and 114.2 ± 0.7 pC/cGy recorded for P3HT:PCBM and P3HT:o-IDTBR detectors, respectively. Both detectors also exhibited a fast temporal response, able to resolve individual 3.6 μs pulses from the linear accelerator. Energy dependence measurements highlighted that the photodetectors were highly tissue equivalent, though an under-response in devices compared to water by up to a factor of 2.3 was found for photon energies of 30-200 keV due to the response of the plastic scintillator. The P3HT:o-IDTBR device exhibited a higher stability to radiation, showing just an 18.4% reduction in performance when exposed to radiation doses of up to 10 kGy. The reported devices provide a successful demonstration of stable, printable, flexible, and tissue-equivalent radiation detectors with energy dependence similar to other scintillator-based detectors used in radiotherapy.

We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these results we discuss the role that brain MRI may play in the diagnostic procedure of ASD.

Sleep disorders are one of the most frequent comorbidities in children with autism spectrum disorder (ASD). Heterogeneous sleep problems in children with ASD have been reported, and insomnia has a prevalence in children with ASD ranging from 60% to 86%. Poor sleep can cause harmful effects on cognitive functions, fostering the appearance of aggression, irritability, inattention, and hyperactivity in children with ASD. Sleep disorders can also be related to the severity of the core symptoms of ASD, including social cognition and communication, stereotypic behavior, and hypersensitivity to the environment. The etiology of sleep disorders in children with ASD is multifactorial, related to complex interactions between biological factors and psychological, socio-environmental, and family factors. From the therapeutic perspective, interventions should only be considered after any medical conditions potentially contributing to sleep disorders have been carefully evaluated. [ Pediatr Ann. 2020;49(6):e278–e282.]

Multiple complex developmental disorder is characterized by early-onset combined impairment in the regulation of affective states, in the social behavior, and in the thought processes. First described in the Eighties, so far multiple complex developmental disorder has so far not found recognition as an autonomous nosographic entity in international classifiers. In the past, the most common diagnosis for patients presenting with this clinical picture was that of 'pervasive developmental disorder not otherwise specified,' due to the early-onset impairment in various development areas, including the social functioning, with pervasive characteristics. Over recent years, based on literature data, the interest in multiple complex developmental disorder has seemed to decline. Yet, several clinical and neurobiological findings emerging from the literature seem to support the nosographic autonomy of multiple complex developmental disorder. The correct recognition of this clinical picture appears to be of considerable importance because children who are affected seem to be predisposed to develop a schizophrenia spectrum disorder during their lifetime. Multiple complex developmental disorder could be a very interesting entity, being a possible kind of "bridge" condition between autism spectrum disorder and childhood-onset schizophrenia. However, there is a lack of findings of the real recurrence, neurobiologic background, and course of this clinical picture.Çoklu karmaşık gelişimsel bozukluk, duygulanım halleri, sosyal davranış ve düşünme süreçlerinin düzenlenmesinde erken başlangıçlı bozuklukla belirgindir. İlk olarak 1980’li yıllarda tarif edilmiş olan çoklu karmaşık gelişimsel bozukluk, bugüne kadar uluslararası sınıflandırıcılar tarafından özerk bir nozografik antite olarak tanınmamıştır. Geçmişte, bu klinik tablo ile başvuran hastalar için en sık konulan tanı, sosyal işlevsellik gibi çeşitli gelişim alanlarında yaygın özellikler gösteren erken başlangıçlı bozukluğa bağlı olarak ‘yaygın gelişimsel bozukluk, başka yerde tanımlanmamış’ olmuştur. Son yıllar içinde, dizin verilerine göre, çoklu karmaşık gelişimsel bozukluğa ilgi azalmış görünmektedir. Ancak, dizinden ortaya çıkan bazı klinik ve nörobiyolojik bulgular, çoklu karmaşık gelişimsel bozukluğun nozografik özerkliğini destekliyor görünmektedir. Bu klinik tablonun doğu olarak tanınması dikkate değer derecede önem taşımaktadır, çünkü etkilenen çocuklar yaşam boyu şizofreni spektrum bozukluğu geliştirmeye yatkın görünmektedirler. Çoklu Karmaşık Gelişimsel Bozukluk, otizm spektrum bozukluğu ile çocukluk dönemi başlangıçlı şizofreni arasında muhtemel bir “köprü” durumu olarak çok ilginç bir antite olabilir. Ancak, bu klinik tablonun gerçek nüksü, nörobiyolojik zemini ve seyri ile ilgili bulgular yeterli değildir.

Purpose: The development of novel detectors for dosimetry in advanced radiotherapy modalities requires materials that have a water equivalent response to ionizing radiation such that characterization of radiation beams can be performed without the need for complex calibration procedures and correction factors. Organic semiconductors are potentially an ideal technology in fabricating devices for dosimetry due to tissue equivalence, mechanical flexibility, and relatively cheap manufacturing cost. The response of a commercial organic photodetector (OPD), coupled to a plastic scintillator, to ionizing radiation from a linear accelerator and orthovoltage x-ray tube has been characterized to assess its potential as a dosimeter for radiotherapy. The radiation hardness of the OPD has also been investigated to demonstrate its longevity for such applications. Methods: Radiation hardness measurements were achieved by observing the response of the OPD to the visible spectrum and 70keV x rays after pre-exposure to 40kGy of ionizing radiation. The response of a preirradiated OPD to 6-MV photons from a linear accelerator in reference conditions was compared to a nonirradiated OPD with respect to direct and indirect (RP400 plastic scintillator) detection mechanisms. Dose rate dependence of the OPD was measured by varying the surface-to-source distance between 90 and 300cm. Energy dependence was characterized from 29.5 to 129keV with an x-ray tube. The percentage depth dose (PDD) curves were measured from 0.5 to 20cm and compared to an ionization chamber. Results: The OPD sensitivity to visible light showed substantial degradation of the broad 450 to 600nm peak from the donor after irradiation to 40kGy. After irradiation, the spectral shape has a dominant absorbance peak at 370nm, as the acceptor better withstood radiation damage. Its response to x rays stabilized to 30% after 35kGy, with a 0.5% difference between 770Gy increments. The OPD exhibited reproducible detection of ionizing radiation when coupled with a scintillator. Indirect detection showed a linear response from 25 to 500cGy and constant response to dose rates from 0.31Gy/pulse to 3.4×10−4Gy/pulse. However, without the scintillator, response increased by 100% at low dose rates. Energy independence between 100keV and 1.2MeV advocates their use as a dosimeter without beam correction factors. A dependence on the scintillator thickness used during a comparison of the PDD to the ionizing chamber was identified. A 1-mm-thick scintillator coupled with the OPD demonstrated the best agreement of±3%. Conclusions: The response of OPDs to ionizing radiation has been characterized, showing promising use as a dosimeter when coupled with a plastic scintillator. The mechanisms of charge transport and trapping within organic materials varies for visible and ionizing radiation, due to differing properties for direct and indirect detection mechanisms and observing a substantial decrease in sensitivity to the visible spectrum after 40kGy. This study proved that OPDs produce a stable response to 6-MV photons, and with a deeper understanding of the charge transport mechanisms due to exposure to ionizing radiation, they are promising candidates as the first flexible, water equivalent, real-time dosimeter.

We describe a girl with syndromic autism spectrum disorder (ASD), who at the end of the medical workup proved affected by a succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare autosomal-recessive disorder of degradation of the γ-aminobutyric acid (GABA), that is, the most important central nervous system inhibitory neurotransmitter. The diagnosis of SSADH deficiency was made using a next-generation sequencing (NGS) multigene panel for neurological disorders and was confirmed by urinary organic acid analysis. Compared to the classic description of SSADH deficiency, our patient presented a less severe picture. In fact, she had no epilepsy, and her neuromotor signs were soft, and over time they became less evident. This case report emphasizes the importance of considering in a patient with syndromic ASD, the possible diagnosis of SSADH deficiency, even when all its typical signs are not present. Nowadays, the use of NGS multigene panels could facilitate the etiological diagnosis in individuals with syndromic ASD.

The Solute Carrier Family 6 Member 1 (SLC6A1) gene encodes the gamma-aminobutyric acid (GABA) transporter 1, which is one of the main GABA transporters. The clinical picture of SLC6A1 gene mutations is characterized by a broader spectrum including a mild-to-moderate intellectual disability, speech difficulties, behavioral problems, epilepsy (often with myoclonic-atonic and atypical absence seizures, characterizing a myoclonic-atonic epilepsy), and neurological signs. We describe a boy with an SLC6A1 mutation and a milder phenotype, characterized by a learning disorder without intellectual disability, nonspecific dysmorphisms, and an electroencephalogram picture closely resembling that of myoclonic-atonic epilepsy with brief absence seizures that have appeared during the follow-up, responsive to valproic acid.

Purpose: The aim of the study was to examine the discontinuation rate of hormonal contraception with estradiol valerate (E2V) and dienogest (DNG). Patients and methods: We collected data at the Family Planning Clinics of the Departments of Obstetrics and Gynecology of Pisa and Cagliari. We included in the analysis 354 consecutive women using oral contraceptive pills containing E2V and DNG. We analyzed the rate and the reason for discontinuation, classifying the reasons in 5 categories: 1) minor side effects, 2) adverse events, 3) other events not directly caused by the drug or conditions for which the pill could represent a risk factor, 4) no compliance with the method and 5) no further need. Results: Of the 354 women examined, 50.8% had discontinued E2V/DNG pill. Excluding women who stopped the pill because of no further need (10.5%), 27.4% discontinued because of minor side effects, 1.7% discontinued for adverse events, 9.9% because of other events not directly caused by the drug or conditions for which the pill could represent a risk factor and 1.4% because of difficulties with compliance. Irregular bleedings were the main reasons reported for discontinuation. The time to discontinuation for irregular bleedings was significantly (p

Today, a significant role of genetic factors is widely accepted also in non-syndromic autism spectrum disorder (ASD), that is ASD not secondary to a well-known genetic condition. Modern genetic techniques, such as microarray and whole-genome sequencing, showed the involvement of a large number of genes in ASD etiopathogenesis. However, the dramatic increase of ASD prevalence during the last decades suggests that environmental factors also play an important role. The pre-, peri-, and postnatal exposure to many heterogeneous environmental factors have been hypothesized to be involved, such as air pollutants, pesticides, and other endocrine-disrupting chemicals. Further research is needed to understand the subtle interactions between genetic and environmental factors in the etiopathogenesis of ASD, considering also the concept of epigenetics, which is a very important gene regulation mechanism based on chemical modifications of DNA and histone proteins, without altering the DNA sequence. Moreover, an increasing amount of literature data suggest that epigenetic mechanisms could be the mediators of effects deriving from environmental factors both in ASD and in other neurodevelopmental disorders.

Background Autism spectrum disorder is characterized by impairment in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests and activities. It is important to detect this condition as soon as possible and promptly begin targeted treatments. This study aimed to report on age at onset, early signs, and mode at onset in 105 Italian patients with autism spectrum disorder, searching for correlations with a series of clinical and instrumental variables. Methods This retrospective cross-sectional study considered the following five categories of symptoms at onset: language, social interaction and relationships, stereotyped behavior and activities, motor skills, and regulation. Three modes of presentation were considered: a delay, a stagnation, or a regression of development, which were defined modes of onset of autism spectrum disorder. The age at onset, the category of clinical features, and the mode at onset were considered in the entire sample and statistically analyzed for several clinical variables. Statistical analysis was performed utilizing Fisher Exact test and Chi Square test. Results The first symptoms between 7 and 12 months were evident in 41.9% of cases, and between 13 and 24 months in 27.6%; no significant differences for the age at onset related to diagnosis, etiopathogenesis, early onset epilepsy, and intelligence quotient level emerged. Social interaction and relationships (93.3%) and language (92.4%) were the categories of early signs more represented in our sample. Delay in spoken language (to be understood as both verbal production and verbal comprehension) was one of the most common (even though not specific) symptoms prompting initial medical consultation for a possible diagnosis of autism spectrum disorder. At onset, patients without intellectual disability manifested stagnation more often than delay or regression of development; patients with a severe/profound intellectual disability more frequently showed delay or regression of development. Language signs at onset were less frequent in cases with regression, whereas motor skill disorders prevailed in cases with delay at onset. Feeding problems were more numerous in cases with delay and stagnation of development. Conclusions These data contribute to identifying an early trend of autism spectrum disorder, useful also for pediatricians.

In most cases, autism spectrum disorder is a life-long condition, often severely affecting the quality of life of the patient and his/her family, but nowadays this diagnosis should not be considered a final sentence without appeal. Although even today the recovery from the autism spectrum is an unlikely possibility, a timely psycho-educational intervention can significantly improve the level of autonomy reached by the individual and therefore favorably modify the outcome. Some predictors of long-term outcome are known, primarily childhood intelligence quotient and early language/communication ability, but today this issue is still open. The lack of studies evaluating the long-term effects of the most important intervention programmes should be filled with adequate research. Community support and social integration may be very important in improving outcomes for individuals with autism spectrum disorder. But a real social integration involves a work activity and this is still a great problem today. An adequate and timely preparation of the working career of these individuals is fundamental for their future, and it should be done by choosing, as far as possible, suitable activities for them. Finally, in creating a dignified future for people with autism, we must never forget to listen to their point of view, whenever possible, in order to meet their particular needs.Otizm spektrum bozukluğu, çoğu olguda yaşam boyu devam eden bir durumdur ve sıklıkla hastanın ve ailesinin yaşam kalitesini ciddi derecede etkiler. Ancak, günümüzde bu tanı itirazsız son tanı olarak kabul edilmemelidir. Günümüzde, otizm spektrumunun düzelmesi, uzak bir olasılık olmasına rağmen, zamanında yapılacak bir psiko-eğitim müdahalesi, kişinin ulaşacağı otonomi düzeyini önemli derecede artırabilir ve bu nedenle, seyri olumlu şekilde değiştirebilir. Uzun vadeli sonuçların bazı öngöstergeleri bilinmektedir (öncelikle çocukluk çağı zeka katsayısı ve erken dil/iletişim becerisi), ama günümüzde bu konu halen karara bağlanmamıştır. En önemli müdahale programlarının uzun vadedeki etkilerini değerlendiren çalışmaların eksikliği, uygun araştırmalarla doldurulmalıdır. Toplum desteği ve sosyal entegrasyon, otizm spektrum bozukluğu olan kişiler için sonuçların iyileştirilmesi açısından çok önemli olabilir. Ancak, gerçek bir sosyal entegrasyon, çalışma faaliyetini içerir ve bu konu halen büyük bir sorundur. İş kariyeri için uygun ve zamanında hazırlık yapılması, bu kişilerin geleceği için esastır ve bu hazırlık, mümkün olduğu kadar kişiye uygun aktivitelerin seçilmesi şeklinde yapılmalıdır. Son olarak, otizmi olan kişiler için saygın bir gelecek yaratırken, onların özel gereksinimlerini karşılayabilmek üzere, kendi bakış açılarının dinlenmesi asla unutulmamalıdır.

Highlights • Degradation of light sensitivity stabilized to 65% after exposure to 40 kGy. • Uniform dose rate dependence for indirect detection of ionising radiation. • Percentage depth dose curves within ±3% in comparison to an Ionisation Chamber. • Response to keV energies is only dependent on the coupled plastic scintillator., Background and purpose Measurement of dose delivery is essential to guarantee the safety of patients undergoing medical radiation imaging or treatment procedures. This study aimed to evaluate the ability of organic semiconductors, coupled with a plastic scintillator, to measure photon dose in clinically relevant conditions, and establish its radiation hardness. Thereby, proving organic devices are capable of being a water-equivalent, mechanically flexible, real-time dosimeter. Materials and methods The shelf-life of an organic photodiode was analyzed to 40 kGy by comparison of the charge-collection-efficiency of a 520 nm light emitting diode. A non-irradiated and pre-irradiated photodiode was coupled to a plastic scintillator and their response to 6 MV photons was investigated. The dose linearity, dose-per-pulse dependence and energy dependence was characterized. Finally, the percentage depth dose (PDD) between 0.5 and 20 cm was compared with ionization chamber measurements. Results Sensitivity to 6 MV photons was (190 ± 0.28) pC/cGy and (170 ± 0.11) pC/cGy for the non-irradiated and pre-irradiated photodiode biased at −2 V. The response was independent of the dose-per-pulse between 0.031 and 0.34 mGy/pulse. An energy dependence was found for low keV energies, explained by the energy dependence of the scintillator which plateaued between 70 keV and 1.2 MeV. The PDD was within ±3% of the ionization chamber. Conclusion Coupling an organic photodiode with a plastic scintillator provided reliable measurement of a range of photon energies. Dose-per-pulse and energy independence advocate their use as a dosimeter, specifically image-guided treatment without beam-quality correction factors. Degradation effects of organic semiconducting materials deteriorate sensor response but can be stabilized.

The deployment of organic semiconducting materials for radiation detection is an emerging and highly attractive area of materials science research. These organic materials offer the enticing vision of technologies created from low cost materials that can be printed on-demand with a range of different tailored optoelectronic functionalities. An explosion in the number of available materials, improved functionality of materials, and sophistication of solution-based device fabrication techniques for organic semiconductors in recent years has led to considerable opportunities for the utilization of organic materials in the detection of ionizing radiation. Whilst the potential of organic semiconducting materials for low cost radiation detection is clear, transitioning these printable materials through to a commercial reality presents a significant scientific challenge. In this work we provide a comprehensive analysis of the use of organic semiconductors for radiation detection. We discuss the fundamental physics of these materials and how their conduction mechanisms, including charge generation and charge transport, differ significantly from established inorganic semiconductors. Various strategies employed to control the nanostructure in organic semiconductors in order to optimize charge generation and transport for radiation detection are discussed. We provide insights into the strategies employed to fabricate organic semiconducting devices at industrially relevant scales using roll-to-roll solution processing, and finally discuss existing examples of organic semiconducting materials utilized in the radiation detection arena.

An early diagnosis of autism spectrum disorder, leading to a timely enabling intervention, is associated with a better long-term prognosis and allows the early detection of any medical comorbidities that are sometimes found in individuals with autism. It is, therefore, an important challenge to begin the diagnostic procedure of these children as soon as possible. Nowadays, much progress has been made in this respect compared with the past, but considerable work remains. A fundamental role in starting a correct and timely diagnostic procedure is obviously played by the pediatrician. Today, many tools are available for the early screening of autism in the general population, but unfortunately, their real effectiveness has yet to be established. In this narrative review, we address the topic of the early diagnosis of autism spectrum disorder, emphasizing, in particular, those that are now considered the first warning signs. We list a few of the most important signs to consider when a child aged around 18 months presents to a pediatrician, subdivided into three subgroups: social-communication skills; patterns of behavior, interests, or activities; and sensory behaviors and reactivity/temperament. We deal separately with the possible presence of slight motor signs, which can also go unnoticed, but probably they should be considered as very early signs appearing even before social-communication deficits.Otizm spektrum bozukluğunun zamanında müdahaleye olanak tanıyan erken tanısı, uzun vadede daha iyi bir prognozla ilişkili olup, bazen otizmli kişilerde bulunan komorbiditelerin erken saptanmasına da olanak tanır. Bu nedenle, bu çocuklarda tanısal prosedürün mümkün olduğu kadar erken başlatılması önemli bir sorundur. Geçmişle kıyaslandığında, günümüzde bu açıdan oldukça fazla ilerleme kaydedilmiştir, ama bu konuda halen önemli ölçüde çaba sarfetmek gerekmektedir. Tanısal prosedürün doğru şekilde ve zamanında başlatılması açısından temel rol açık bir şekilde pediatristlere düşmektedir. Günümüzde, genel popülasyonda otizmin erken taraması için birçok araç vardır, ama maalesef bunların gerçek etkinliği henüz belirlenmemiştir. Bu anlatısal derlemede, otizm spektrum bozukluğunun erken tanısı konusunu ele almaktayız ve özellikle ilk uyarı işaretleri olarak kabul edilen bulgulara odaklanmaktayız. Yaşı 18 ay civarında olan bir çocuk pediatriste muayeneye geldiğinde göz önüne alınması gereken en önemli bulgulardan bazılarını üç alt grup şeklinde sıralıyoruz: sosyal-iletişim becerileri; davranış modelleri, ilgi ya da aktiviteler; ve duyusal davranışlar ve tepkisellik/mizaç. Gözden kaçabilecek olan hafif motor bulguların olası varlığı konusunu ayrıca ele alıyoruz. Ancak, bu bulgular muhtemelen sosyal-iletişim kusurlarından bile önce ortaya çıkan çok erken bulgular olarak kabul edilmelidir.

Background The aim of this study is to compare robotic single-site hysterectomy (RSSH) and robotic multiport hysterectomy (RMPH) for endometrial cancer (EC) in obese patients in terms of surgical outcomes. Methods This retrospective study compares RSSH with RMPH in obese patients with EC and FIGO stages I to II divided in three classes according to their body mass index (BMI): class A (30-34.9 kg/m2 ), class B (35-39.9 kg/m2 ), and class C (>40 kg/m2 ). Results We included 225 patients (RSSH: 76; RMPH: 149). The operative time and estimated blood loss (EBL) were lower in the A class of the RSSH group. The EBL and the conversion rate increased when the BMI increased in the RSSH group. The hospital stay was higher in the A class of the RMPH group. Conclusions The advantages of RSSH in terms of reduced invasiveness remain true only in the first BMI class, whereas they are lost when the BMI increased.

Pseudohypoparathyroidism (PHP) is a rare heterogeneous genetic disease characterized by end-organ resistance to parathyroid hormone. In adulthood, heterogeneous neurological and psychiatric disorders have been reported which are associated with hypoparathyroidism in general and with PHP in particular, while for childhood, data are scanty. We report a case of a boy with PHP type 1b, in whom neurological signs at the onset prevailed, characterized by tic-like dyskinesias associated with a series of heterogeneous not well-defined neurological and behavioral features, describing the diagnostic work-up performed and the follow-up. We suggest that the diagnostic hypothesis of PHP might be considered when dealing with a child with tic-like dyskinesias, especially if associated with a series of heterogeneous not well-defined neurological and behavioral features. In these cases, treatment with calcitriol and calcium has to be started as soon as possible to achieve a prompt and persistent clinical improvement.

There are many variables that can affect the clinical picture of a person with autism spectrum disorder (ASD), leading to the great clinical heterogeneity of ASD. We show our proposal for a simple tool to describe patients with ASD, in order to favor a subdivision into groups that are as homogeneous as possible.

Objective: The clinical picture of children with autism spectrum disorder is characterized by deficits of social interaction and communication, as well as by repetitive interests and activities. Sensory abnormalities are a very frequent feature that often go unnoticed due to the communication difficulties of these patients. This narrative review summarizes the main features of sensory abnormalities and the respective implications for the interpretation of several signs and symptoms of autism spectrum disorder, and therefore for its management. Sources: A search was performed in PubMed (United States National Library of Medicine) about the sensory abnormalities in subjects (particularly children) with autism spectrum disorder. Summary of the findings: Sensory symptoms are common and often disabling in children with autism spectrum disorder, but are not specific for autism, being a feature frequently described also in subjects with intellectual disability. Three main sensory patterns have been described in autism spectrum disorder: hypo-responsiveness, hyper-responsiveness, and sensory seeking; to these, some authors have added a fourth pattern: enhanced perception. Sensory abnormalities may negatively impact the life of these individuals and their families. An impairment not only of unisensory modalities but also of multisensory integration is hypothesized. Conclusions: Atypical sensory reactivity of subjects with autism spectrum disorder may be the key to understand many of their abnormal behaviors, and thus it is a relevant aspect to be taken into account in their daily management in all the contexts in which they live. A formal evaluation of sensory function should be always performed in these children. Resumo: Objetivo: O quadro clínico de crianças com transtorno do espectro do autismo é caracterizado por déficits de interação social e comunicação, bem como por interesses e atividades repetitivos. As alterações sensoriais são uma característica muito frequente que geralmente não é percebida devido às dificuldades de comunicação desses pacientes. Nesta análise narrativa, resumimos as principais características de alterações sensoriais e as respectivas implicações para a interpretação de vários sinais e sintomas do transtorno do espectro do autismo e, portanto, para seu manejo. Fontes: Realizamos uma busca no PubMed (Biblioteca Nacional de Medicina dos Estados Unidos) sobre as alterações sensoriais em indivíduos (principalmente crianças) com transtorno do espectro do autismo. Resumo dos achados: As alterações sensoriais são comuns e geralmente invalidam as crianças com transtorno do espectro do autismo, porém não são específicas do autismo, sendo uma característica frequentemente descrita também em indivíduos com deficiência intelectual. Três principais padrões sensoriais foram descritos no transtorno do espectro do autismo: hiporreatividade, hiperreatividade e busca sensorial; a eles, alguns autores acrescentaram um quarto padrão: percepção aprimorada. As alterações sensoriais podem afetar negativamente a vida desses indivíduos e de suas famílias. Hipotetizamos uma deficiência não apenas das modalidades não sensoriais, mas também da integração multissensorial. Conclusões: A reatividade sensorial atípica de indivíduos com transtorno do espectro do autismo pode ser a chave para entender muitos de seus comportamentos anormais e, portanto, é um aspecto relevante para ser considerado em seu manejo diário em todos os contextos nos quais eles vivem. Sempre se deve fazer uma avaliação formal da função sensorial nessas crianças. Keywords: Autism spectrum disorder, Sensory reactivity, Sensory abnormalities, Sensory seeking, Palavras-chave: Transtorno do espectro autista, Reatividade sensorial, Alterações sensoriais, Busca sensorial

In the chapter dedicated to the Pervasive Developmental Disorders in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), which was published in 1994, various nosographic entities born in the scientific context of Mitteleuropa found recognition, even though with a delay of several decades. In 2013, the DSM-5 erased all five mentioned diagnostic subcategories of the DSM-IV, proposing a single, all-embracing category of Autism Spectrum Disorder, subdivided into 3 severity degrees. In our opinion, this subdivision does not reflect the great clinical heterogeneity of the disorder, and therefore the DSM-5 autism classification requires improvements.

Introduction/Background The majority of women who undergo radical hysterectomy for endometrial cancer (EC) are obese and they may benefit from robotic surgery. The aim of this study is to compare robotic single-site hysterectomies (RSSH) and robotic multiport hysterectomies (RMPH) for EC in obese patients. Methodology This study compares RSSH with RMPH in obese patients with EC and FIGO stage I or II. Data were collected from July 2010 to October 2018 in four Italian institutes: Regina Elena National Cancer Institute of Rome, Fondazione Policlinico San Matteo and University of Pavia, Santa Chiara Hospital of Trento and University of Pisa. According to their BMI, patients were divided in 3 classes: A from 30 to 34.9 kg/m2, B from 35 to 39.9 kg/m2 and C 40 kg/m2 or higher. Results We included 225 patients: 76 in the RSSH group divided, respectively, in 53, 18 and 5 in the A, B and C classes; 149 in the RMPH group divided, respectively, in 76, 37 and 36 in the A, B and C classes. In the RSSH group, the median operation time (OT) and blood loss (BL) were, respectively, 139 min and 50 ml in the A class, 142.5 min and 50 ml in the B class and 165 min and 100 ml in the class C. In the RMPH group, the median OT and the median BL were, respectively, 195 min and 100 ml in the class A, 170 min and 50 ml in the class B and 122.5 min and 75 ml in the class C. The conversion rate increased in the 3 classes, especially in the RSSH group (in the A, B and C classes, respectively, 1.8%, 5.5% and 60%). Conclusion Technical difficulties in single-site surgery increase with the patients‘ BMI and when the BMI is 40 kg/m2 or higher this technique is most of the times unfeasible. Disclosure Nothing to disclose.

One of the most commonly used complementary and alternative practices in children with autism spectrum disorder (ASD) is the supplementation of omega-3. We describe the case of a child with ASD who seemed to respond to omega-3 supplementation in a relevant and lasting manner. So far, based on the results of randomized clinical trials, evidence-based medicine negates the effectiveness of omega-3 in ASD children. Nevertheless, considering anecdotal experiences, including that of our patient, and nonrandomized trials, the presence of a subgroup of ASD patients who are really responders to omega-3 cannot be excluded. These responders might not appear when evaluating the omega-3 effects in a sample taken as a whole. Studies that check for the possible presence of this subgroup of ASD individuals responders to omega-3 are necessary.

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Two experiments were performed to evaluate the reproductive performance of zebu beef cows treated with different doses of eCG at the end of a progesterone (P4)/estrogen based protocol for timed artificial insemination (TAI). In Experiment 1, suckling Bos indicus Nelore cows (n = 261) received, on day 0, a progesterone (P4) intravaginal device (PD) and an injection of 1 mg estradiol benzoate (EB). On day 8, the PD was removed, 500 μg of cloprostenol was injected, and cows were assigned to one of the following groups: Control (no treatment), 300 (300 IU of eCG), 600 (600 IU of eCG), and 900 (900 IU of eCG). On day 9, all cows received 1 mg EB and TAI performed 54-56 h after cloprostenol injection. A pregnancy diagnosis was done by ultrasound scanning 40 days after TAI, and the number of fetuses and calves was recorded at pregnancy diagnosis and at birth. More cows treated with eCG displayed estrus within 48 h after removal of the PD (42.3% vs. 11.6%, P 0.01), and ovulated more than one follicle (42%, 58/138 vs. 1.8%, 1/54; P 0.01). This effect on ovulation rate was dose dependent (P 0.05). The pregnancy rate was affected only by cow parity (primiparous, 25.3% vs. multiparous, 48.9%; P 0.01). Twin pregnancy was higher (P 0.01) in cows treated with eCG (42%, 58/138) than controls (0%, 0/54). However, few cows (33.3%) were able to keep both fetuses intact until birth. For evaluation of ovarian characteristics by B-mode and Doppler ultrasonography, 43 Nelore cows were submitted In Experiment 2 to the same four groups described in Experiment 1. Although no difference (P 0.1) was observed for size and blood perfusion in the pre-ovulatory follicles, corpus luteum was larger and with greater blood perfusion (P 0.05) in eCG-treated cows. In conclusion, eCG increased the number of double/multiple ovulations in a dose-dependent manner, induced larger and more vascularized corpora lutea, but did not affect the fertility of cyclic or anestrous cows. Although eCG results in twin pregnancies, most of cows underwet embryo/fetus loss and birth a single calf.

The phenotype of cyclin-dependent kinase-like 5 (CDKL5) syndrome includes Rett syndrome variant with early onset seizures, early onset epileptic encephalopathy; and severe developmental delay. Autistic features have often been reported in literature, but detailed reports of the behavior of these individuals are lacking. We describe the clinical picture of a girl aged 15 years 9 months affected by CDKL5 syndrome, with special attention to the neurobehavioral phenotype. The evaluation showed, apart from a profound intellectual disability, the presence of atypical features of behavior, mainly in relating to people, in imitation, and in verbal and nonverbal communication, thus justifying the diagnosis of comorbid autism spectrum disorder. A formal assessment of the behavior, through appropriate tools, is necessary to choose the most appropriate rehabilitative intervention and to characterize in more detail the CDKL5 syndrome phenotype. We propose a testing protocol for the neurobehavioral assessment of these patients.

The fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5) introduced significant changes in the classification of autism spectrum disorders (ASD), including the abolition of the diagnostic subcategories proposed by DSM-IV-Text Revision. DSM-5 describes three levels of increasing severity of ASD. The authors report two explanatory cases with ASD (verbal boys, aged about 7 and a half years, without intellectual disability). According to DSM-5, both cases fall into the lowest severity level of ASD. However, their neuropsychological and neurobehavioral profile varies significantly. While the first boy showed a prevalent impairment of visuoconstructional and visuoperceptual abilities, the second one presented a predominant involvement of verbal functions, with qualitative impairments in communication. A further step forward in the definition and classification of ASD, taking into account both intensity and quality of symptoms, is recommended in order to formulate a reliable prognosis, plan an individualized treatment and monitor the clinical course over time.

Background Epilepsy is drug resistant in 30–40% of cases. We studied, retrospectively, the prognostic factors of drug resistance (DR) during a 15 year period, in an Italian sample of patients with childhood epilepsy. Methods A total of 117 patients were divided into two groups: one with DR, and the other without DR. The two groups were compared at the following time points: epilepsy onset (T0), and at 2, 5, 8 and 10 years after seizure onset (T2, T5, T8 and T10, respectively) using Fisher's exact test and randomization test. Multiple logistic regression analysis was then used to identify the most reliable predictive model of DR. Results Positive neurological examination at onset, symptomatic/probable symptomatic etiology, lack of response to the first drug, seizure clustering during follow up, intelligence quotient ≤ 70, altered neuropsychological examination at onset, and presence of cerebral lesions were predominant in cases of DR. The most reliable combinations of predictors of DR included partial or no response to the first drug, presence of seizure clustering during follow up, altered neurological examination at onset, and long latency between epilepsy onset and first drug at T2; partial or absent response to the first drug and positive magnetic resonance imaging (MRI) at T5; positive MRI and absence of generalized seizures at T8; and positive MRI at T10. DR also sometimes appeared after discontinuation of an effective therapy. Conclusions Predictive factors of DR can be recognized in a large number of patients with epilepsy at disease onset, although the current possibility of predicting epilepsy outcome remains limited. In the long term, evidence of cerebral lesions appears to become the most significant prognostic factor.

The use of complementary and alternative medicine is widespread among children with autism spectrum disorder (ASD), but methodologically rigorous studies are still necessary to establish its effects. In this article, we address the role of omega-3 in the treatment of ASD, reviewing the relevant literature highlighted by searches of PubMed from 1949 to the present. According to the criteria of evidence-based medicine (ie, randomized clinical trials), the data do not support the effectiveness of omega-3 treatment in children with ASD. However, based on anecdotal experiences and on nonrandomized trials, we cannot exclude that there might be a subset of people with ASD who do respond to this type of approach. We propose a series of questions to be answered by future studies to clarify the possible role of omega-3 in the treatment of ASD. [ Pediatr Ann . 2016;45(3):e103–e107.]

The glucose transport protein type 1 (GLUT1) deficit causes a chronic brain energy failure. The classic phenotype of GLUT1 deficiency syndrome is characterized by: Mild to severe motor delay and mental retardation; infantile-onset epilepsy; head growth deceleration; movement disorders (ataxia, dystonia, spasticity); and non-epileptic paroxysmal events (intermittent ataxia, periodic confusion, recurrent headaches). During last years the classic phenotype of this syndrome, as originally reported, has expanded. We report the atypical phenotype of a boy with GLUT1 deficiency syndrome, characterized by mild mental retardation and drug-resistant absence seizures with onset at the age of 6 years, without movement disorders nor decrease of head circumference. A prompt diagnosis of this disorder is mandatory since the ketogenic diet might represent an effective treatment.

Background Headache and epilepsy are two relatively common neurological disorders and their relationship is still a matter of debate. Our aim was to estimate the prevalence and clinical features of inter-ictal (inter-IH) and peri-ictal headache (peri-IH) in patients with epilepsy. Methods All patients aged ≥ 17 years referring to our tertiary Epilepsy Centre were consecutively recruited from March to May 2011 and from March to July 2012. They underwent a semi-structured interview including the International Classification Headache Disorders (ICHD-II) criteria to diagnose the lifetime occurrence of headache.χ2-test, t-test and Mann–Whitney test were used to compare clinical variables in patients with and without inter-IH and peri-IH. Results Out of 388 enrolled patients 48.5 % had inter-IH: migraine in 26.3 %, tension-type headache (TTH) in 19.1 %, other primary headaches in 3.1 %. Peri-IH was observed in 23.7 %: pre-ictally in 6.7 %, ictally in 0.8 % and post-ictally in 19.1 %. Comparing patients with inter-ictal migraine (102), inter-ictal TTH (74) and without inter-IH (200), we found that pre-ictal headache (pre-IH) was significantly represented only in migraineurs (OR 3.54, 95 % CI 1.88-6.66, P

Summary Purpose Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by prominent auditory or aphasic symptoms. Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE patients. Methods Twenty-four ADLTE families and 140 sporadic LTE patients with no evidence of point mutations in LGI1 were screened for copy number alterations using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained familial and sporadic LTE patients were clinically investigated, and interictal EEG and MRI findings were obtained; probands were tested for LGI1 mutations by direct exon sequencing or denaturing high performance liquid chromatography. Results We identified a novel microdeletion spanning LGI1 exon 2 in a family with two affected members, both presenting focal seizures with visual symptoms. Also, we identified a novel LGI1 missense mutation (c.1118T>C; p.L373S) in a newly ascertained family with focal seizures with prominent visual auras, and another missense mutation (c.856T>C; p.C286R) in a sporadic patient with auditory seizures. Conclusions We describe two novel ADLTE families with predominant visual auras segregating pathogenic LGI1 mutations. These findings support the notion that, in addition to auditory symptoms, other types of auras can be found in patients carrying LGI1 mutations. The identification of a novel microdeletion in LGI1 , the second so far identified, suggests that LGI1 microrearrangements may not be exceptional.

Epilepsy is common in chromosomal abnormalities, but systematic studies are scanty. We describe an Italian sample of patients with chromosomopathies to establish epilepsy occurrence and clinical electroencephalographic (EEG) features. Forty-five patients with different types of chromosomal abnormalities were analyzed to examine different variables in patients with epilepsy (group 1) and without (group 2) and to compare the types of epilepsy in our cases with respect to a nonselected sample of Italian people with epilepsy. Epilepsy occurred in 51.1% (group 1) of cases and prevailed in autosomal abnormalities but without a statistical significance ( P > .05). There was a prevalence of EEG paroxysmal abnormalities in group 1 ( P < .0001); continuous spike-waves during sleep were observed in three cases. Profound mental retardation prevailed in group 1 ( P < .001) and mild mental retardation in group 2 ( P < .05). Generalized epilepsies prevailed significantly ( P < .00001). A high-resolution karyotype should be undertaken in all patients with epilepsy presenting with mental retardation when an obvious etiology is not available. ( J Child Neurol 2005;20:419—423).

Objective: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. Methods: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. Results: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Conclusions: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.

Epilepsy with continuous spike-waves during slow-wave sleep (CSWS) is often characterized by a severe cognitive and behavioral impairment. Symptomatic cases also include patients with an early-onset hydrocephalus, but in literature detailed neuropsychological data on these subjects are not available. We describe the results of serial cognitive assessments in a girl with shunted early-onset hydrocephalus, followed by partial epilepsy complicated with CSWS at 4 years 10 months, in which a dramatic cognitive and behavioral deterioration occurred few months after CSWS onset. Adrenocorticotropic hormone treatment improved both clinical and electroencephalogram picture, but an impairment of visual perception, visual-motor coordination and executive functions persisted after CSWS disappearance. We hypothesize, in this case, an involvement of right occipital-parietal lobe and prefrontal lobe.

We describe 3 patients with different degrees of cerebellar hypoplasia and continuous spike-waves during sleep: the more extensive the cerebellar hypoplasia, the more compromised the neuropsychological abilities and behavior. Cerebellar hypoplasia is a risk factor for epilepsy and/or neuropsychological and psychiatric disorders. Epilepsy is also strongly associated with familial antecedents for seizures, as previously reported. The cerebellum is implicated in controlling epileptic seizures and in regulating motor, cognitive, and emotional functions with a topographic organization. The association between cerebellar hypoplasia and continuous spike-waves during sleep has never been reported. We suggest that continuous spike-waves during sleep may further compromise neuropsychological and behavioral features that are associated with cerebellar hypoplasia.

We describe a 11 year-old-boy with Sneddon syndrome, confirmed by skin biopsy, and MR evidence of diffuse cerebral hyperintensity of white matter; he also suffered from pre-perinatal hypoxic-ischemic distress. Arylsulfatase A activity was found reduced because of arylsulfatase A pseudodeficiency. We suggest that the association of pre-perinatal distress, Sneddon syndrome and arylsulfatase A pseudodeficiency is responsible for the diffuse impairment of cerebral white matter, never reported in Sneddon syndrome and similar to described cases of delayed posthypoxic demyelination and arylsulfatase A pseudodeficiency.

We describe the case of a 10-year-old girl with two epileptic seizures and subcontinuous spike-waves during sleep, who presented unusual side-effects related to clobazam (CLB) monotherapy. High plasma levels of N-desmethyl-clobazam (N-CLB), the major metabolite of CLB were detected. The patient and her parents underwent molecular analysis of the CYP2C19 gene, which may be implicated in the metabolism of this drug. Our patient presents one copy of the most common mutation (CYP2C19*2) affecting the activity of the isoenzyme and probably another rare or private mutation. CLB and N-CLB plasma level dosages and molecular analysis may be useful when a poor metabolic condition is suspected.

We report a clinically relevant suspected interaction between acyclovir and the antiepileptic drugs phenytoin (PHT) and valproic acid (VPA). In a child receiving PHT and VPA therapy, a 6-day acyclovir treatment reduced PHT and VPA plasma concentrations to subtherapeutic values. This probably worsened both clinical status and electroencephalographic recordings observed in this patient. We suggest that the interaction occurs at gastrointestinal level with a reduction of PHT and VPA oral bioavailability during antiviral treatment.

Introduction: Levetiracetam (LEV) is an effective antiepileptic drug also used in childhood and adolescence. Literature data regarding the long-term effects of LEV in childhood epilepsy and based on extensive neuropsychological evaluations using standardized tools are still scanty. Our study aimed to address this topic. Materials and Methods: We studied 10 patients with epilepsy characterized by focal or generalized seizures (4 boys, 6 girls; mean age: 10 years 8 months; range: 6 years 2 months - 16 years 2 months), treated with adjunctive LEV during a follow-up of 12 months. In 6 patients electroencephalogram (EEG) showed continuous spike and waves during sleep. Using standardized tools, we performed seriated assessments of cognitive and behavioral functioning in relation to seizure and EEG outcome. Results: Six patients completed the trial after 12 months of treatment; 1 patient dropped out of the study after 9 months, 3 patients after 6 months. Adjunctive LEV was effective on seizures in 3/10 patients and on EEG in 2/10 patients, and was well tolerated in all examined cases. Overall, no worsening of cognitive or behavioral functions has been detected during the period of the study; even at 6 and 12 months from baseline, an improvement in patients’ abstract reasoning has been found, that was not related to seizure or EEG outcome. Conclusions: In our population of children and adolescents, LEV had no adverse cognitive or behavioral effects, short- or long-term. We found an improvement of abstract reasoning, regardless of seizure and EEG outcome.