Early onset absence epilepsy of childhood: Epidemiologic data, treatment and outcome in a sample of 56 patients born between 2000 and 2018.

PURPOSE: The aim of our work is to describe the characteristics of Early Onset Absence Epilepsy (EOAE) and to observe whether specific anamnestic, clinical or electroencephalographic characteristics can influence the drug sensitivity of this pathology. METHODS: We carried out a retrospective study of patients affected by absence epilepsy with onset under four years of age, born between January 1st 2000 and December 31st 2018, who were reffered to the Regional Epilepsy Center of Spedali Civili of Brescia. We then divided the sample into three groups based on the age of onset. RESULTS: Our sample is composed of 56 patients. Among the children with epilepsy onset under two years of age (11), all were still on therapy after three and six years of follow-up, and 64 % of them required polytherapy. Among patients with epilepsy onset between two and three years of age (24), 87 % were still on therapy after three years of follow-up and 68 % after six years of follow-up; 46 % of these subjects required polytherapy. Among patients with epilepsy onset between three and four years of age (21), 89 % were still on therapy after three years of follow-up and 38 % after six years of follow-up; 38 % of them required polytherapy. CONCLUSIONS: We observe that patients with an earlier epilepsy onset have a worse outcome and a lower drug sensitivity. This may allow to predict in which cases it would be appropriate to maintain antiseizure therapy for a prolonged period.

Health and welfare assessment of beef cattle during the adaptation period in a specialized commercial fattening unit.

Beef cattle welfare and health status are influenced by housing and management systems. The present study aimed to assess the welfare and health status in the first 15 days after arrival of Limousine bulls imported from France and fattened in a commercial fattening unit in Italy. A total of 264 bulls were included in the study. Welfare, biosecurity, and major hazard and warning system were assessed on days 2 (T1) and 15 (T2) after arrival to the unit. At T1 and T2 an inspective clinical examination was performed on all bulls. At T1 and T2 blood samples were collected from 88 bulls for haematological analysis. Both at T1 and T2, the welfare, biosecurity, and major hazards and warning systems were classified with a general score of medium but with a decrease on animal-based measurements in T2. At T1 and T2 the clinical examination revealed a significant increase (p-value≤0.05) of skin lesions and lameness in T2. A high incidence of respiratory disease was noticed in both assessed times. Leucocytes and all differentials count, and platelets were significantly increased (p-value≤0.05) at T2, while the fibrinogen was significantly decreased. The haematological changes suggest that the bulls were under higher stress in T2 when compared with T1 linked with a difficult adaptation response to the fattening unit. A multi-factorial approach that integrates the indicators of the checklist and the clinical and haematological findings of animals can be a useful method to deepen the assessment of welfare in beef cattle.

Calving time identified by the automatic detection of tail movements and rumination time, and observation of cow behavioural changes.

The use of electronic devices to improve animal health, welfare and farm efficiency in precision livestock farming is a developing area of great scientific and commercial interest. In particular, the use of on-site dairy farm instruments to detect calving is a tool in reproduction livestock farming. The primary aim of this study was to validate the ability of the Moocall device (MD) to detect calving cows. In addition, behavioural changes in parturient dairy cows were evaluated using video-based observations. The MD was applied approximately 9 days before cow delivery. Observational sessions were conducted three times a day for each cow from the day before MD application to calving time. The sensitivity (Se) and specificity (Sp) at 3 and 24 h before calving were measured to test the effectiveness of the MD. In addition, behavioural changes were investigated before and after the MD application as well as before and during calving time. The 3 h Se and the 3 h Sp obtained were 95.2 and 71.4%, respectively. No false negatives were observed in the 24 h before delivery (24 h Se=100%) while the 3 h Se was 95.2%. The MD was well tolerated by the dairy cows since no change in behaviours was observed in this study among the cows with or without the MD, except for an increase in eating behaviour in the animals with the MD. As regards, the behavioural pattern during calving time (8 h before calving) in comparison with the previous phases, a significant increase in tail contraction frequency and raised tail position, and a decrease in eating behaviour and rumination time were observed. The first principal component (PC) was primarily explained by these variables, and calving cows best contributed to this PC. According to the results of the present study, the use of the MD can be a useful tool in detecting the moment of calving.

Thewithdrawal of consent to haematopoietic stem cells (HSC) donation: The complicated balance between donor's rights and patient's protection.

Hematopoietic stem cells donation is an essential prerequisite of allogeneic transplantation. Both family donors and matched unrelated donors should have a conscious involvement in every phase of the overall path, from selection to HSC collection. Donors also should be informed about the right to withdraw at any time as well as the extreme risk for recipient's life coming from the decision of interrupting, if the donation is not carried out once the patient's preparative regimen has commenced. We report our challenging experience about a donor who withdraws her consent to HSC donation after 3 days of mobilization with G-CSF. The possibility of withdrawal protects the donor but it also puts at risk both a chance for a transplant and the patient's life if preparative regimen has started. Can the donor really be free to withdraw the consent to HSC donation at any time even when this endangers the life of a recipient? Is this ethical? However, if the donor decides to withdraw, would we really be ready to manage promptly all the consequences coming from the consent revocation? At the moment there is not a well-defined "plan B" in case of impossibility to proceed with the transplant when conditioning has already started or has even been completed. In our opinion, because of this hard balance and such a high risk, it would be necessary to plan every time an alternative strategy which may be different according to different circumstances.

Manipulation, and cryopreservation of autologous peripheral blood stem cell products in Italy: A survey by GITMO, SIDEM and GIIMA societies.

There is considerable heterogeneity in manipulation and cryopreservation of hematopoietic stem cells (HSC) for autologous HSC transplantation across Europe and Italy. To better address this point, three Italian Scientific Societies (GITMO- Gruppo Italiano per il Trapianto di Midollo Osseo; SIDEM- Società Italiana Emaferesi e Manipolazione Cellulare; and GIIMA- Gruppo Italiano Interdisciplinare Manipolazione e Aferesi per Terapie Cellulari), in collaboration with the Competent Authority "National Transplant Center" (CNT) sent to 85 Italian transplant centers (TC) a survey, which included 12 questions related to the most critical elements in graft processing. Fifty-nine centers (70 %) responded to the questionnaire. Overall, this survey demonstrates that the majority (>90 %) of responding TC used standardized procedures for HSC processing; however, an intercenter heterogeneity was clearly documented in several standard operating procedures adopted by different TC. These results seem to suggest that further standardization and efforts are needed to provide recommendations and guidelines on HSC manipulation, cryopreservation and functional assessment of cryopreserved material for autologous HSCT.

Gut microbiome structure and adrenocortical activity in dogs with aggressive and phobic behavioral disorders.

Accompanying human beings since the Paleolithic period, dogs has been recently regarded as a reliable model for the study of the gut microbiome connections with health and disease. In order to provide some glimpses on the connections between the gut microbiome layout and host behavior, we profiled the phylogenetic composition and structure of the canine gut microbiome of dogs with aggressive (n = 11), phobic (n = 13) and normal behavior (n = 18). Hormones' determination was made through Radio Immuno-Assay (RIA), and next generation sequencing of the V3-V4 gene region of the bacterial 16S rRNA was employed to determine gut microbiome composition. Our results did not evidence any significant differences of hormonal levels between the three groups. According to our findings, aggressive behavioral disorder was found to be characterized by a peculiar gut microbiome structure, with high biodiversity and enrichment in generally subdominant bacterial genera (i.e. Catenibacterium and Megamonas). On the other hand, phobic dogs were enriched in Lactobacillus, a bacterial genus with known probiotic and psychobiotic properties. Although further studies are needed to validate our findings, our work supports the intriguing opportunity that different behavioral phenotypes in dogs may be associated with peculiar gut microbiome layouts, suggesting possible connections between the gut microbiome and the central nervous system and indicating the possible adoption of probiotic interventions aimed at restoring a balanced host-symbiont interplay for mitigating behavioral disorders.

Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of 159 patients.

OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the clinical manifestations of patients with complicated cryoglobulinemic vasculitis (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22 Italian Centers who underwent at least one AT session between 2005 and 2015. The response to AT was evaluated on the basis of a defined grading system. RESULTS: Peripheral neuropathy was the most frequent clinical condition leading to AT. Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not assessable in 36. Life-threatening CV-related emergencies and renal impairment independently correlated with failure to respond to AT. The independent variables associated with an increased risk of death were age at the time of the first AT session, multi-organ life-threatening CV, the presence of renal impairment and failure to respond to AT. The time-dependent probability of surviving until CV-related death in the second year was 84%, with an AHR in patients with absent/not assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to be a safe procedure in patients with CV. Early AT should be considered in patients with severe CV, especially in cases with impending renal involvement, in order to prevent irreversible kidney damage. Although its efficacy in patients with multi-organ failure is limited, AT is the only treatment that can rapidly remove circulating cryoglobulins, and should be considered an emergency treatment.

Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).

OBJECTIVE: To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. MATERIAL AND METHODS: The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. RESULTS: Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. CONCLUSIONS: Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Secondary solid cancer following hematopoietic cell transplantation in patients with thalassemia major.

Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSCs). The aim of this retrospective study was to compare the incidence of SSC in a monocentric cohort of thalassemia major (TM) patients (n=122) who received HCT versus an hematopoietic cell donor monocentric cohort (n=122) and versus a large multicenter cohort of age- and sex-matched TM patients (n=244) who received conventional therapy. With a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC at a median of 18 years after HCT and at a median age of 33 years. Three patients died of cancer progression and 5 are living after a follow-up ranging from 10 months to 16 years after SSC diagnosis. The 30-year cumulative incidence of developing SSC was 13.24%. The occurrence of solid cancers in the hematopoietic cell donor cohort was limited to only one case for a significantly lower cumulative incidence (3.23%, P=0.02) and to 3 cases in the cohort of nontransplant patients for a significantly lower cumulative incidence (1.32%, P=0.005). This study shows that the magnitude of increased risk of SST is fourfold to sixfold for patients treated with HCT as compared with hematopoietic cell donors and nontransplant patients.

Did you know that your animals have consciousness?

Consciousness is the greatest enigma in human history. For centuries scientists and researchers have tried to describe it without coming to conclusions. In the last years with the neurosciences development, consciousness has become the common goal of numerous studies. But consciousness has always been studied only in humans, but after "Cambridge Declaration on Consciousness" in 2012, even non-human animalsthey feel possessed of the consciousness. According to "theory Orch-OR" of Hameroff and Penrose we have conducted a study on Alaskan malamute and German shepherd to analysed a triplet of platelet fatty acids (linoleic acid; palmitic acid; arachidonic acid). Through these analysis and the relative mapping of subjects within a SOM it was possible to make an assessment of the possible onset of mood disorders in the dogs. A critical analysis of the results obtained shows that animals have molecular analogies with humans compared to mood disorders. The German shepherd and Alaskan malamute, indeed, have, in the case of major depression, a bio-chemical profile, the most similar to man.

MR Imaging Diagnosis of Diencephalic-Mesencephalic Junction Dysplasia in Fetuses with Developmental Ventriculomegaly.

Diencephalic-mesencephalic junction dysplasia is a rare malformation characterized by a poorly defined junction between the diencephalon and the mesencephalon, associated with a characteristic butterfly-like contour of the midbrain (butterfly sign). This condition may be variably associated with other brain malformations, including callosal abnormalities and supratentorial ventricular dilation, and is a potential cause of developmental hydrocephalus. Here, we have reported 13 fetuses with second-trimester obstructive ventriculomegaly and MR features of diencephalic-mesencephalic junction dysplasia, correlating the fetal imaging with available pathology and/or postnatal data. The butterfly sign can be clearly detected on axial images on fetal MR imaging, thus allowing for the prenatal diagnosis of diencephalic-mesencephalic junction dysplasia, with possible implications for the surgical management of hydrocephalus and parental counseling.

Overstocking dairy cows during the dry period affects dehydroepiandrosterone and cortisol secretion.

Stressful situations trigger several changes such as the secretion of cortisol and dehydroepiandrosterone (DHEA) from the adrenal cortex, in response to ACTH. The aim of this study was to verify whether overstocking during the dry period (from 21±3 d to the expected calving until calving) affects DHEA and cortisol secretion and behavior in Holstein Friesian cows. Twenty-eight cows were randomly divided into 2 groups (14 animals each), balanced for the number of lactations, body condition score, and expected date of calving. Cows in the far-off phase of the dry period (from 60 to 21 d before the expected calving date) were housed together in a bedded pack. Then, animals from 21±3 d before the expected calving until calving were housed in pens with the same size but under different crowding conditions due to the introduction of heifers (interference animals) into the pen. The control condition (CTR) had 2 animals per pen with 12.0m2 each, whereas the overstocked condition (OS) had 3 interference animals in the same pen with 4.8m2 for each animal. On d -30±3, -21±3, -15±3, -10±3, and -5±3 before and 10, 20, and 30 after calving, blood samples were collected from each cow for the determination of plasma DHEA and cortisol concentrations by RIA. Rumination time (min/d), activity (steps/h), lying time (min/d), and lying bouts (bouts/d) were individually recorded daily. In both groups, DHEA increased before calving and the concentration declined rapidly after parturition. Overstocking significantly increased DHEA concentration compared with the CTR group at d -10 (1.79±0.09 vs. 1.24±0.14 pmol/mL), whereas an increase of cortisol was observed at d -15 (3.64±0.52 vs. 1.64±0.46ng/mL). The OS group showed significantly higher activity (steps/h) compared with the CTR group. Daily lying bouts tended to be higher for the OS group compared with CTR group in the first week of treatment. The overall results of this study documented that overstocking during the dry period was associated with a short-term changes in DHEA and cortisol but these hormonal modifications did not influence cow behavior.

Neurodevelopmental profile in Angelman syndrome: more than low intelligence quotient.

BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopment disorder resulting from deficient expression or function of the maternally inherited allele of UBE3A gene. The aim of the study is to attempt at providing a detailed definition of neurodevelopmental profile in AS, with particular regard to motor, cognitive, communicative, behavioural and neurovisual, features by using standardized instruments. METHOD: A total of ten subjects aged from 5 to 11 years (4 males and 6 females) with molecular confirmed diagnosis of AS (7 15q11.2-q13 deletion and 3 UBE3A mutation) were enrolled in our study. All of them underwent an assessment protocol including neurological and neurovisual examination and the evaluation of motor (Gross Motor Function Measure Scale), cognitive (Griffiths Mental Development Scale and Uzgiris-Hunt Scale); adaptive (Vineland Adaptive Behavioural Scale); communication (MacArthur-Bates Communicative Development Inventory and video-recordings children's verbal expression), behavioural aspects (IPDDAG Scale) and neurovisual aspects. RESULTS: All children presented motor function involvement. A severe cognitive impairment was detected with different profiles according to the test applied. In all cases, communicative disability (phonemic inventory, word/gesture comprehension and production) and symptoms of inattention disorder were revealed. Neurovisual impairment was characterized by refractive errors, fundus oculi anomalies, strabismus and/or oculomotor dysfunction. CONCLUSION: AS presents a complex neurodevelopmental profile in which several aspects play a negative role in global development leading to a severe functional impairment. Intellectual disability is not the only component because neurovisual functions and behavioural disorders may worsen the global function and are needed of specific rehabilitation programs.

Hyperventilation and seizures in an adolescent female.

A 16 year-old girl was admitted after suffering from recurrent episodes of dyspnea and stridor, cyanosis, loss of contact, stiffening of all four limbs, clenching of the jaw and eye retroversion that lasted for a few seconds to a minute, followed by slow recovery of consciousness without any loss of sphincter control. These symptoms began at the age of 11 and worsened over time. Prolonged rate corrected QT intervals was observed with an ECG. Two cardio-respiratory monitorings were performed (one during daytime hours while the patient was awake, and one at night time while the patient slept). Daytime recordings showed 17 central apnoeas and 97 central hypopneas, with an apnea-hypopnea index (AHI) of 13.2 events/hour, that were associated with severe oxyhemoglobin desaturation. In contrast, night time recordings were normal (AHI=1.1 events/hour). The patient underwent diurnal monitoring of transcutaneous pCO2(PtcCO2), transcutaneous O2(PtcO2), SpO2 and end tidal CO2 (PETCO2), with simultaneous monitoring of regional cerebral oxymetry (rSO2) which showed values of PtcCO2 between 8 and 15 mmHg, suggesting several episodes of marked hyperventilation. Twenty-nine episodes of severe arterial desaturation (SpO2<50%) were registered, all after the same number of apnea events, with ascent of PtcO2 up to 28 mmHg at the end of apnea. During the final phase of apnea, the patient showed cyanosis, contact disturbance, grimaces, oral movements of rhyme, and, on three occasions, partial seizures. A mask was packaged and applied daytime to the face of the patient during episodes of hyperventilation to prevent, together with a psychiatric follow up, rapid falls of PaCO2 levels determining central apnoeas.

Cortisol levels in cats' hair in presence or absence of Microsporum canis infection.

The purpose of this work was to perform a preliminary screening in the domestic cat to assess the concentration of cortisol in hairs by radioimmunoassay technique (RIA) in presence or absence of Microsporum canis infections. A total of 245 cats (7 with cutaneous lesions referable to dermatophytosis and 238 apparently healthy) coming from 14 shelters were examined. M. canis was isolated in 126 (51.4%) cats. The cortisol levels were significantly higher in cats with lesions or without lesions but with a high number of colonies in the plates (≥ 10 CFU) than in cats negative or with a lower number of colonies. The results obtained seem to highlight that chronic high levels of cortisol in cats could possibly promote the dermatophytes infections. Furthermore, in High-CFU asymptomatic cats, it could be present a state of infectious, and they, therefore, represents not a simple mechanical carrier.

Evaluation of hair cortisol in the diagnosis of hypercortisolism in dogs.

BACKGROUND: Measurement of hair cortisol is a noninvasive technique used for several purposes in humans and in animals. OBJECTIVES: To measure hair cortisol concentrations (HCC) in dogs with spontaneous hypercortisolism (HC) and determine whether it can represent a useful diagnostic test for this syndrome. ANIMALS: Twenty-two dogs with spontaneous HC before treatment, 28 sick control dogs (SCD), and 40 healthy dogs. METHODS: In this prospective, observational clinical study, the HCC was measured by an RIA assay after extraction in HC dogs, in dogs with other chronic diseases, and in healthy dogs. The diagnostic accuracy of HCC was evaluated by subjecting data from dogs with HC and dogs with other chronic diseases to receiver operating characteristic (ROC) curve analysis. RESULTS: Median (range) cortisol concentration in dogs with HC was 4.53 pg/mg (0.32-74.62 pg/mg) and was significantly higher than in SCD (1.49 pg/mg, 0.13-14.19 pg/mg) and healthy dogs (1.28 pg/mg, 0.34-5.38 pg/mg). Within the 3 groups, there was a large overlap of HCC. The area under the ROC curve was 0.80 (95% CI: 0.67-0.92). A cut-off value of HCC of 1.93 pg/mg revealed 91% sensitivity and 61% specificity to diagnose HC. CONCLUSIONS AND CLINICAL IMPORTANCE: Hair cortisol concentrations are higher in dogs with HC compared to SCD and healthy dogs. It is a noninvasive technique that should be further investigated as a possible diagnostic procedure for the diagnosis of HC in dogs.

Early-onset absence epilepsy: SLC2A1 gene analysis and treatment evolution.

BACKGROUND AND PURPOSES: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). METHODS: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. RESULTS: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). CONCLUSIONS: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

Familial Ohtahara syndrome due to a novel ARX gene mutation.

Recently, it has been reported that longer expansions of the polyalanine tract of the ARX gene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARX gene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARX is involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations.