Longitudinal data of neuropsychological profile in a cohort of Duchenne muscular dystrophy boys without cognitive impairment.

The aim of the study was to re-assess neuropsychological profile in a group of boys with Duchenne muscular dystrophy without intellectual disability and neuropsychiatric disorder three years apart from a previous evaluation, to establish possible changes over time. We were also interested in defining more in detail correlation between genotype and neuropsychological phenotype. Thirty-three of the previous 40 subjects (mean age at follow up: 10 years and 7 months) agreed to participate in the follow up study and to perform the new assessment. The results confirm a typical neuropsychological profile, with difficulty in the manipulation of stored information, poor abstract reasoning and planning capacity and impulsiveness, supporting the involvement of a cerebellar striatal cortical network for these children. The more detailed description of subgroups of subjects, according to the real expression of Dp140, let to reveal possible genotype-neuropsychological phenotype correlations, and a more general neuropsychological impairment emerged in boys without Dp140 expression.

Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions.

The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy.

A comparison between linguistic skills and socio-communicative abilities in Williams syndrome.

BACKGROUND: Individuals with Williams syndrome (WS) show a disharmonic linguistic profile with a clear pattern of strengths and weaknesses. Despite their sociable nature, atypical socio-communicative abilities and deficits in communication and relationship with others have been found. AIM: The aim of the present study was to investigate whether linguistic skills (LS) were in line with the pragmatic and social use of language and the cognitive development of 32 individuals with WS (18 boys and 14 girls) with a mean chronological age of 12.3 (±4.4) years. To examine the relationship between language and mental age (MA) at different ages, the issue was investigated in children and adolescents/young adults with WS. METHOD: Measures of LS, including lexical and morphosyntactic competences, and adaptive socio-communicative abilities (ASCA), pertaining to the use of language in daily living social context, were compared with the MA of participants. In a second step, participants with WS were split into two subgroups based on age, and the relationship between LS, ASCA and MA was studied. RESULTS: Although expressive and receptive LS were generally found to be in line with or better than would be expected for MA, specific deficits in receptive ASCA were documented. LS and ASCA appeared to have a different evolution during the different time windows considered. CONCLUSIONS: Our results underlined the importance of assessing linguistic abilities in the context of adaptive functioning, to guide educational and rehabilitative strategies for individuals with WS.

Visual perception skills: a comparison between patients with Noonan syndrome and 22q11.2 deletion syndrome.

Ventral and dorsal streams are visual pathways deputed to transmit information from the photoreceptors of the retina to the lateral geniculate nucleus and then to the primary visual cortex (V1). Several studies investigated whether one pathway is more vulnerable than the other during development, and whether these streams develop at different rates. The results are still discordant. The aim of the present study was to understand the functionality of the dorsal and the ventral streams in two populations affected by different genetic disorders, Noonan syndrome (NS) and 22q11.2 deletion syndrome (22q11.2DS), and explore the possible genotype-phenotype relationships. 'Form coherence' abilities for the ventral stream and 'motion coherence' abilities for the dorsal stream were evaluated in 19 participants with NS and 20 participants with 22q11.2DS. Collected data were compared with 55 age-matched controls. Participants with NS and 22q11.2DS did not differ in the form coherence task, and their performance was significantly lower than that of controls. However, in the motion coherence task, the group with NS and controls did not differ, and both obtained significantly higher scores than the group with 22q11.2DS. Our findings indicate that deficits in the dorsal stream are related to the specific genotype, and that in our syndromic groups the ventral stream is more vulnerable than the dorsal stream.

Mutations in the IRBIT domain of ITPR1 are a frequent cause of autosomal dominant nonprogressive congenital ataxia.

Congenital ataxias are nonprogressive neurological disorders characterized by neonatal hypotonia, developmental delay and ataxia, variably associated with intellectual disability and other neurological or extraneurological features. We performed trio-based whole-exome sequencing of 12 families with congenital cerebellar and/or vermis atrophy in parallel with targeted next-generation sequencing of known ataxia genes (CACNA1A, ITPR1, KCNC3, ATP2B3 and GRM1) in 12 additional patients with a similar phenotype. Novel pathological mutations of ITPR1 (inositol 1,4,5-trisphosphate receptor, type 1) were found in seven patients from four families (4/24, ∼16.8%) all localized in the IRBIT (inositol triphosphate receptor binding protein) domain which plays an essential role in the regulation of neuronal plasticity and development. Our study expands the mutational spectrum of ITPR1-related congenital ataxia and indicates that ITPR1 gene screening should be implemented in this subgroup of ataxias.

Volar fixation of distal radial fracture using compression plate: clinical and radiographic evaluation of 20 patients.

Distal radius fractures can be treated with different methods, depending on the type of fracture and, on our experience, according to the Fernandez algorithm. The report presents our experience treating distal radius fractures using a volar plate. We reviewed retrospectively 20 patients treated, during a period of 3 years (May 2008-May 2011) at our center, for unstable distal radius fractures using a volar plate. All patients were reviewed by thorough clinical examination and standard radiographs of the operated wrist. For the clinical evaluation, we used Mayo Wrist Score and DASH Score. At review, the injured wrist had recovered an average range of motion in flexion-extension of 120°, and the grip strength was an average of 50% compared to contralateral side. Overall, results at Mayo Wrist Score were good to excellent in 30%, satisfactory in 55%, and poor in 15%; results at DASH Score were good to excellent in 90%, satisfactory in 10% with no poor case. The majority of patients were fully satisfied with the results (65%), 20% of patients were partially satisfied, 5% were poorly satisfied, and 10% were not satisfied. At review, 4 patients reported the presence of transient paresthesia localized to the first three rays of the hand. At radiographic evaluation, the majority of patients had a radial tilt between 20 and 23, ulnar variance between 0 and 3, and dorsal tilt between 9 and 14. The treatment of unstable distal radius fractures with a volar plate provided stable internal fixation and allowed early function and was associated with a low complication rate.

Enhanced human brain associative plasticity in Costello syndrome.

Costello syndrome (CS) is a rare multiple congenital anomaly disorder which is caused by germline mutations in the v-Ha-ras Harvey rat sarcoma viral oncogene homologue (HRAS) proto-oncogene. Experimental data suggest perturbing effects of the mutated protein on the functional and structural organization of networks of cerebral cortex and on the activity-dependent strengthening of synaptic transmission known as long term potentiation (LTP). In five patients with molecularly proven diagnosis of CS and in a group of 13 age-matched control subjects we investigated activity-dependent synaptic plasticity. To this end, we used a paired associative stimulation (PAS) protocol, in which left ulnar nerve stimuli were followed by transcranial magnetic stimulation (TMS) pulses to right cortical hand area, and recorded motor evoked potentials (MEPs) by single pulse TMS from left first dorsal interosseus (FDI) muscle before and after PAS. In 4 out of 5 CS patients and in a subgroup of nine control subjects we also evaluated the time course and the topographical specificity of PAS after-effects. In these two subgroups, MEPs were measured before, immediately after and 30 min after PAS in the left FDI and left abductor pollicis brevis (APB). While the PAS protocol led to a 65% increase of the FDI MEP amplitude in controls, the LTP-like phenomenon was significantly more pronounced in CS patients, with motor responses increased by 230%. In addition, CS patients showed a similar MEP increase in both muscles while control subjects showed a slight increase in APB and only immediately after PAS. We hypothesize that the extremely enhanced PAS after-effects could be due to the influence of HRAS activity on the susceptibility of synapses to undergo LTP.

Infecciones intrahospitalarias en una unidad de cuidados intensivos pediátricos: análisis de tres años de vigilancia (2006-2008) / Nosocomial infections in the intensive care unit

Objetivos: Determinar las tasas de infecciones intrahospitalarias por egresos y procedimientos invasivos; edad, localización, microorganismos aislados y letalidad de pacientes con IIH. Material y Métodos. Estudio descriptivo, retrospectivo, realizado desde el año 2006 al 2008, de pacientes con IIH, internados en la Unidad de Terapia Intensiva Pediátrica. Se utilizó un sistema de vigilancia activa, global, selectiva por indicadores, con definiciones del Programa Nacional de Control de IIH y del NNIS. Resultados: Fueron notificados 104 episodios de IIH. Predominaron los menores de 1 año (48%), neonatos (36%). La tasa de IIH fue: 8% (28/359) en el año 2006, 12% (45/363) en el año 2007 y 10% (31/310) en el año 2008. Bacteremias (46%), infección urinaria (23%) y sepsis clínica (16%) han sido demostradas como las principales localizaciones. La tasa global de infección del tracto urinario (ITU) asociada a catéter urinario permanente (CUP) fue: 17,9 por 1.000 días CUP (27/1.508), la tasa global de infección del torrente sanguíneo (ITS) asociada a catéter venoso central (CVC) fue: 6,1 por 1.000 días CVC (41/6.668) y la tasa global de neumonía asociada a asistencia respiratoria mecánica (ARM) fue: 2 por 1.000 días ARM (8/3.830). En 84% (87/104) se obtuvo retorno bacteriológico. En ITU/CUP predominaron: Candida sp. (82%, 22/27), seguido de K. pneumoniae BLEE (11%, 3/27)y P. aeruginosa (7%, 2/27). En ITS/CVC fueron aislados:Estafilococo coagulasa negativo meticilinoresistente (33%, 13/41), K.pneumoniae BLEE (24%, 10/41), Candida sp (15%, 6/41). La letalidad registrada fue del 20% (21/104). Conclusiones: La Tasa de IIH osciló entre 8-12%. Los lactantes y neonatos fueron los más afectados. ITU/CUP fue el procedimiento más riesgoso. La letalidad fue elevada.

Introduction: Nosocomial infections (NI) are a major cause of mortality and morbidity in patients treated in healthcare institutions, and treatment of these infections involves significant costs for both the patient and the healthcare system. Objectives: To determine the rate of nosocomial infections compared to discharged patients, invasive procedures performed, age, infection location, microorganism isolated, and mortality in patients with NI. Material and Methods: A descriptive, retrospective, study carried out between 2006 and 2008 among patients with NI hospitalized in the pediatric intensive therapy unit. We used an active and integrated system of selective internal monitoring of indicators defined by the National Nosocomial Infections Surveillance (NNIS) System. Results: Some 104 instances of NI were reported. Most commonly they were among infants under 1 year of age (48%) with neonates comprising 36%. The rate of NI was 8% (28/359) in the year 2006. 12% (45/363) in 2007 and 10% (31/310) in 2008. Infections were primarily localized as bacteremia (46%) urinary tract infection (23%) or clinical sepsis (16%). The rate of urinary tract infection (UTI) associated with use of an indwelling urinary catheter (IUC) was 17.9 per 1,000 IUC days (27/1,508), while bloodstream infection (BSI) associated with use of a central venous catheter (CVC) was 6.1 per 1,000 CVC days (41/6,668) and the rate of pneumonia associated with mechanically assisted ventilation (MAV) was 2 per 1,000 MAV days (8/3,830). In 84% (87/104) a bacteria was isolated. In UTI with IUC the dominant species were Candida sp. (82%, 22/27) followed by ESBL-producing K. pneumoniae , and P.aeruginosa (7%, 2/27%). In BSI with CVC, coagulase-negative methicillin-resistant staphylococci were isolated in 13/41 (33%), ESBL K.pneumoniae in 10/41 (24%), and Candida sp. in 6/41 (15%). Mortality recorded was 20% (21/104)...

Reliability of the North Star Ambulatory Assessment in a multicentric setting.

The aim of this study was to investigate the suitability of the North Star Ambulatory Assessment as a possible outcome measure in multicentric clinical trials. More specifically we wished to investigate the level of training needed for achieving a good interobserver reliability in a multicentric setting. The scale was specifically designed for ambulant children with Duchenne Muscular Dystrophy and includes 17 items that are relevant for this cohort. Thirteen Italian centers participated in the study. In the first phase of the study we provided two training videos and an example of the scale performed on a child. After the first session of training, all the 13 examiners were asked to send a video with an assessment performed in their centre and to score all the videos collected. There were no difficulties in performing the items and in obtaining adequate videos with a hand held camera but the results showed a poor interobserver reliability (<.5). After a second training session with review and discussion of the videos previously scored, the same examiners were asked to score three new videos. The results of this session had an excellent interobserver reliability (.995). The level of agreement was maintained even when the same videos were rescored after a month, showing a significant intra-observer reliability (.95). Our results suggest that the NSAA is a test that can be easily performed, completed in 10 min and can be used in a multicentric setting, providing that adequate training is administered.

Visual function in Noonan and LEOPARD syndrome.

The aim of the study was to assess various aspects of visual and visuoperceptual function in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) with mutations affecting the PTPN11, SOS1 and RAF1 genes. Twenty-four patients were assessed with a battery of tests assessing visual function including ophthalmological and orthoptic evaluation and age appropriate behavioural visual tests, including measures of crowding acuity (Cambridge crowding cards), and stereopsis (TNO test). Twenty-one subjects were also assessed with the visuo-motor integration (VMI) test. Twenty of the 24 patients (83%) had abnormalities of visual function on at least one of the tests used to assess visual function or on ophthalmological examination, and 7 of 21 (33%) also had abnormalities on VMI. Ocular movements and stereopsis were most frequently abnormal (50% and 79%, respectively). Our results suggest that visual and visuoperceptual abilities are commonly impaired in patients with Noonan and LEOPARD syndrome and they are probably related to a multifactorial etiology.

The Hammersmith functional score correlates with the SMN2 copy number: a multicentric study.

Previous studies showed that SMN2 copy number correlates inversely with the disease severity. Our aim was to evaluate SMN2 copy numbers and the Hammersmith functional motor scale in 87 patients with SMA II in order to establish whether, within SMAII, the number of copies correlates with the severity of functional impairment. Our results showed a relative variability of functional scores, but a significant correlation between the number of SMN2 genes and the level of function.

[Echography, computerized tomography and retrograde cholangiopancreatography for the diagnosis of focal pathology of the exocrine pancreas]. / L'ecografia, la tomografia computerizzata e la colangiopancreatografia retrograda nella diagnostica della patologia focale del pancreas esocrino.

In spite of the improved imaging techniques currently available, mortality for pancreatic cancer is still high, and pancreatitis is often diagnosed only in its advanced stages. The authors investigated the value of different imaging techniques--i.e., US, CT, and ERCP--for an early diagnosis, when a more effective (curative?) treatment can be suggested. Fifty-six cases of pancreatic cancer and 36 cases of chronic pancreatitis were evaluated. The results indicate that ERCP, with the help of statistical methods, is superior to US and CT not only in evaluating early neoplastic or inflammatory lesions, but also for their differential diagnosis. In the latter case, ERCP can sometimes be used as a valid alternative to fine-needle aspiration biopsy.

[Waist to hip ratio and the distribution of adipose tissue]. / WHR e distribuzione del tessuto adiposo.

The aim of the study was to assess the relation between the waist to hips ratio (WHR) and the distribution of adipose tissue in visceral or subcutaneous site through the use of CAT. Results are expressed as the ratio of visceral to subcutaneous adipose tissue area (VSR). A total of 61 patients were randomly selected for inclusion in the study. Contrary to normal weight subjects, obese patients did not reveal significant correlations between the two ratios. Following multi-variant analysis in normal weight subjects, WHR appeared to be influenced by sex, BMI and VSR. In patients with prevalently visceral adiposity WHR was determined by sex and VSR, whereas in patients with prevalently subcutaneous adiposity it was influenced by BMI alone. In conclusion, the significant correlations between WHR and tomographic indices of adipose tissue distribution reported in the literature are not present in all types of patient, and in particular are not found in obese patients and normal weight subjects with prevalently subcutaneous adiposity.

A study of the development of fracture callus in the presence of an experimentally induced osteosarcoma.

The results of two experiments are reported in which the formation of an osteosarcoma was induced in mice by the intraosseous injection of Moloney's virus. In the first group of fifty mice, a complete diaphyseal fracture was carried out nine days later at the site of the tumour. In the second group of 200 mice, a partial fracture was produced at the time of injection so that immobilisation was assured. The effects of cyclophosphamide and calcitonin administration were also studied in this group. The course of the repair processes of the bone was studied in both groups, and showed that, even in the presence of an osteosarcoma, these begin and can reach completion, though obstructed and delayed by the tumour.

Treatment of self-injurious behavior by a combination of reinforcement for incompatible behavior and overcorrection.

In two related studies, a combination of reinforcement for incompatible behavior and positive practice overcorrection was applied to the elimination of head-slapping and head-banging behavior exhibited, respectively, by two profoundly retarded boys. The design for both studies also included a period in which only reinforcement for incompatible behavior was applied. The results from Study 1 indicated that, while reinforcement had little effect in reducing the frequency of the learner's head slapping, the combination of reinforcement and overcorrection had an immediate effect in significantly reducing and eventually eliminating that behavior. A 4-month follow-up indicated no significant recurrence of the behavior. In Study 2, on the other hand, both reinforcement and the combination of reinforcement and overcorrection resulted in a significant increase in the frequency of the learner's head-banging behavior. Discussion centered on several research questions left unanswered by the differing effects of the procedures applied in both studies.