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Aim: To develop a short version of the original Hammersmith Infant Neurological Examination (HINE) to be used as a screening tool (Brief-HINE) and to establish if the short examination maintains good accuracy and predictive power for detecting infants with cerebral palsy (CP). Method: Eleven items were selected from the original HINE (‘visual response’; ‘trunk posture’; ‘movement quantity’; ‘movement quality’; ‘scarf sign’; ‘hip adductor angles’; ‘popliteal angle’; ‘pull to sit’; ‘lateral tilting’; ‘forward parachute reaction’; ‘tendon reflexes’) identifying those items previously found to be more predictive of CP in both low- and high-risk infants. In order to establish the sensitivity of the new module, the selected items were applied to existing data, previously obtained using the full HINE at 3, 6, 9, and 12 months, in 228 infants with typical development at 2 years and in 82 infants who developed CP. Results: Brief-HINE scores showed good sensitivity and specificity, at each age of assessment, for detecting infants with CP. At 3 months, a score of less than 22 was associated with CP with a sensitivity of 0.88 and a specificity of 0.92; at 6, 9, and 12 months, the cut-off scores were less than 25 (sensitivity 0.93; specificity 0.87), less than 27 (sensitivity 0.95; specificity 0.81), and less than 27 (sensitivity 1; specificity 0.86) respectively. The presence of more than one warning sign, or items that are not optimal for the age of assessment, imply the need for a full examination reassessment. Interpretation: These findings support the validity of the Brief-HINE as a routine screening method and the possibility of its use in clinical practice.

Duchenne muscular dystrophy (DMD) is a neuromuscular condition characterized by muscle weakness. The Performance of upper limb (PUL) test is designed to evaluate upper limb function in DMD patients across three domains. The aim of this study is to identify frequently lost or gained PUL 2.0 abilities at distinct functional stages in DMD patients. This retrospective study analyzed prospectively collected data on 24-month PUL 2.0 changes related to ambulatory function. Ambulant patients were categorized based on initial 6MWT distance, non-ambulant patients by time since ambulation loss. Each PUL 2.0 item was classified as shift up, no change, or shift down. The study's cohort incuded 274 patients, with 626 paired evaluations at the 24-month mark. Among these, 55.1 % had activity loss, while 29.1 % had gains. Ambulant patients showed the lowest loss rates, mainly in the shoulder domain. The highest loss rate was in the shoulder domain in the transitioning subgroup and in elbow and distal domains in the non-ambulant patients. Younger ambulant patients demonstrated multiple gains, whereas in the other functional subgroups there were fewer gains, mostly tied to singular activities. Our findings highlight divergent upper limb domain progression, partly linked to functional status and baseline function.

BACKGROUND: The precision and accuracy of mass spectrometry (MS) made it a fundamental tool in anti-doping analysis. High-resolution (HR) mass spectrometers significantly improved compound identification. This study systematically analyzes data from an athlete (Subject 1) who tested positive for meldonium and compares it with data from a healthy volunteer (Subject 2) to examine the correctness of the doping verdict. CASE PRESENTATION: The documentation related to Subject 1 was thoroughly processed and analyzed. A study involving a volunteer (Subject 2) replicated Subject 1 regimen and urine sample collection for data alignment with anti-doping results, with Subject 2 reporting not using meldonium. The anti-doping agency’s analysis of Subject 1 showed the presence of meldonium at a concentration close to the established cut-off level. However, a closer examination revealed that one specific ion, crucial for meldonium identification, was absent from the mass spectra. Analyzing Subject 2 data, using the same methodology, the absence of the specific ion was confirmed, even though the volunteer did not consume meldonium. The European directive and the method that was validated and cited by the anti-doping agency identified meldonium on at least four specific ions, whereas the anti-doping analysis used only three ions. This discrepancy compromises the specificity of meldonium identification. CONCLUSIONS: To enhance the analytical methodology, two strategic interventions are suggested: adjusting the meldonium cut-off value and expanding the analysis to include meldonium metabolites. By addressing these avenues, the precision of meldonium detection and doping verdicts can be improved. In conclusion, this study challenges the anti-doping agency’s verdict and prompts a reevaluation of meldonium detection methodologies in anti-doping measures.

Aim: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify cognitive performance delay at 2 years in a large cohort of infants born at term. Method: We conducted a retrospective study of infants born at term at risk of neurodevelopmental impairments assessed using the HINE between 3 and 12 months post-term age and compared them with a cohort of typically developing infants born at term. All infants performed a neurodevelopmental assessment at 2 years of age using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, Second Edition; the presence of cerebral palsy (CP) was also reported. The infants were classified as being cognitively normal/mildly delayed or significantly delayed (MDI < 70). The predictive validity of HINE scores for significantly delayed cognitive performance, in infants with and without CP, was calculated using specific cut-off scores according to age at assessment. Results: A total of 446 at-risk and 235 typically developing infants (345 males, 336 females; mean [SD] gestational age 38.7 weeks [1.4], range 25–36 weeks) were included. Of the at-risk infants, 408 did not have CP at 2 years; 243 had a normal/mild delayed MDI and 165 had an MDI less than 70. Of the at-risk infants, 38 developed CP. HINE scores showed a good sensitivity and specificity, mainly after 3 months, for identifying significantly delayed cognitive performance in infants without CP. In those with CP, the score was associated with their cognitive performance. The comparison group had the highest HINE scores. Interpretation: The HINE provides evidence about the risk of delayed cognitive performance at age 2 years in infants born at term with and without CP.

Specific Learning Disorder (SLD) is a neurodevelopmental disorder characterized by difficulties in perceiving and processing verbal and non-verbal information. It is usually accompanied by impaired academic skills leading to school dropout and emotional disturbances, resulting in significant distress and behavioral problems. Methods: A cognitive, academic, and emotional-behavioral assessment was performed at T0 and T1 in children and adolescents with SLD. Participants received psychotherapy and speech therapy treatment from T0 to T1. Results: In SLD,the most compromised cognitive functions were working memory and writing skills. An impact on academic abilities was found. Children and adolescents with SLD experience greater anxiety and depression levels compared to their control peers. Conclusions: SLD may adversely influence psychological well-being. To counteract such a consequence, more specific cognitive and academic skill-oriented strategies should be taken into consideration.

Introduction: The Performance of Upper Limb version 2.0 (PUL 2.0) is increasingly used in Duchenne Muscular Dystrophy (DMD) to study longitudinal functional changes of motor upper limb function in ambulant and non-ambulant patients. The aim of this study was to evaluate changes in upper limb functions in patients carrying mutations amenable to skipping exons 44, 45, 51 and 53. Methods: All DMD patients were assessed using the PUL 2.0 for at least 2 years, focusing on 24-month paired visits in those with mutations eligible for skipping exons 44, 45, 51 and 53. Results: 285 paired assessments were available. The mean total PUL 2.0 12-month change was -0.67 (2.80), -1.15 (3.98), -1.46 (3.37) and -1.95 (4.04) in patients carrying mutations amenable to skipping exon 44, 45, 51 and 53, respectively. The mean total PUL 2.0 24-month change was -1.47 (3.73), -2.78 (5.86), -2.95 (4.56) and -4.53 (6.13) in patients amenable to skipping exon 44, 45, 51 and 53, respectively. The difference in PUL 2.0 mean changes among the type of exon skip class for the total score was not significant at 12 months but was significant at 24 months for the total score (p < 0.001), the shoulder (p = 0.01) and the elbow domain (p < 0.001), with patients amenable to skipping exon 44 having smaller changes compared to those amenable to skipping exon 53. There was no difference within ambulant or non-ambulant cohorts when subdivided by exon skip class for the total and subdomains score (p > 0.05). Conclusions: Our results expand the information on upper limb function changes detected by the PUL 2.0 in a relatively large group of DMD patients with distinct exon-skipping classes. This information can be of help when designing clinical trials or in the interpretation of the real world data including non-ambulant patients.

Autism spectrum disorder (ASD) and joint hypermobility (JH) are considered two different etiological and clinical entities that most often appear in childhood. Despite growing increased research showing a co-occurrence for both conditions, a link between them is rarely established in clinical settings, and the relationship between ASD and JH has not so far been completely investigated in all age groups of ASD children. This preliminary study examined a cohort of 67 non-syndromic ASD children aged 2–18 years (sex ratio M:F = 12:1) showing different degrees of cognitive impairment and autism severity, using the Beighton scale and its revised version. A total of 63% of ASD patients aged 2–4 years and 73% of ASD patients aged ≥5 years presented significant scores of hypermobility. No significant correlation was found comparing total laxity score and cognitive assessments and severity of autistic symptomatology (p > 0.05). The results suggest that JH could be considered as a clinical characteristic of ASD patients and it needs to be assessed in order to schedule a better rehabilitation program.

Eteplirsen is FDA-approved for the treatment of Duchenne muscular dystrophy (DMD) in exon 51 skip-amenable patients. Previous studies in boys > 4 years of age indicate eteplirsen is well tolerated and attenuates pulmonary and ambulatory decline compared with matched natural history cohorts. Here the safety, tolerability and pharmacokinetics of eteplirsen in boys aged 6–48 months is evaluated. In this open-label, multicenter, dose-escalation study (NCT03218995), boys with a confirmed mutation of the DMD gene amenable to exon 51 skipping (Cohort 1: aged 24–48 months, n = 9; Cohort 2: aged 6 to < 24 months, n = 6) received ascending doses (2, 4, 10, 20, 30 mg/kg) of once-weekly eteplirsen intravenously over 10 weeks, continuing at 30 mg/kg up to 96 weeks. Endpoints included safety (primary) and pharmacokinetics (secondary). All 15 participants completed the study. Eteplirsen was well tolerated with no treatment-related discontinuations, deaths or evidence of kidney toxicity. Most treatment-emergent adverse events were mild; most common were pyrexia, cough, nasopharyngitis, vomiting, and diarrhea. Eteplirsen pharmacokinetics were consistent between both cohorts and with previous clinical experience in boys with DMD > 4 years of age. These data support the safety and tolerability of eteplirsen at the approved 30-mg/kg dose in boys as young as 6 months old.

The increasing pressure to include non ambulant Duchenne muscular dystrophy (DMD) boys in clinical trials has highlighted the need for outcome measures that could address the impact of upper limb function on activities of daily living. The aim of the present study was to establish the correlation between the recently developed Patient Reported Outcome Measure for the upper limb (PROM UL) and the observer rated functional scale Performance of Upper Limb (PUL 2.0) in a large cohort of DMD boys and young adults. As part of a larger natural history study, non ambulant DMD patients were assessed using PUL2.0 and PROM UL. One hundred and twenty-five concurrent PUL 2.0 and PROM UL evaluations from 60 non ambulant DMD boys were taken into consideration. The total PROM UL scores showed a strong correlation with both PUL 2.0 total scores and with PUL 2.0 entry item score. The strong correlation between the two tools confirms the clinical meaningfulness of the PUL2.0 and that the PROM UL can help to detect the gradient of progression of upper limb involvement.

Despite the early onset of clinical signs suggestive of Duchenne muscular dystrophy (DMD), a diagnosis is often not made until four years of age or older, with a diagnostic delay of up to two years from the appearance of the first symptoms. As disease-modifying therapies for DMD become available that are ideally started early before irreversible muscle damage occurs, the importance of avoiding diagnostic delay increases. Shortening the time to a definite diagnosis in DMD allows timely genetic counseling and assessment of carrier status, initiation of multidisciplinary standard care, timely initiation of appropriate treatments, and precise genetic mutation characterization to assess suitability for access to drugs targeted at specific mutations while reducing the emotional and psychological family burden of the disease. This comprehensive literature review describes the early signs of impairment in DMD and highlights the bottlenecks related to the different diagnostic steps. In summary, the evidence suggests that the best mitigation strategy for improving the age at diagnosis is to increase awareness of the early symptoms of DMD and encourage early clinical screening with an inexpensive and sensitive serum creatine kinase test in all boys who present signs of developmental delay and specific motor test abnormality at routine pediatrician visits.

Background and Objectives: The aim of this study was to evaluate longitudinal changes using both upper limb muscle Magnetic Resonance Imaging (MRI) at shoulder, arm and forearm levels and Performance of upper limb (PUL) in ambulant and non-ambulant Duchenne Muscular Dystrophy (DMD) patients. We also wished to define whether baseline muscle MRI could help to predict functional changes after one year. Materials and Methods: Twenty-seven patients had both baseline and 12month muscle MRI and PUL assessments one year later. Results: Ten were ambulant (age range 5-16 years), and 17 non ambulant (age range 10-30 years). Increased abnormalities equal or more than 1.5 point on muscle MRI at follow up were found on all domains: at shoulder level 12/27 patients (44%), at arm level 4/27 (15%) and at forearm level 6/27 (22%). Lower follow up PUL score were found in 8/27 patients (30%) at shoulder level, in 9/27 patients (33%) at mid-level whereas no functional changes were found at distal level. There was no constant association between baseline MRI scores and follow up PUL scores at arm and forearm levels but at shoulder level patients with moderate impairment on the baseline MRI scores between 16 and 34 had the highest risk of decreased function on PUL over a year. Conclusions: Our results confirmed that the integrated use of functional scales and imaging can help to monitor functional and MRI changes over time.

Assessing and improving walking abilities is considered one of the most important functional goals of physical therapy in children with cerebral palsy. However, there is still a gap in knowledge regarding the efficacy of treatment targeting the walking capacity of children with CP, as well as their responsiveness to the treatment. The 6 min walk test (6MWT) is a reliable tool to measure this function in children with CP, although less has been known about its potential efficacy to assess changes in the walking abilities associated with interventions. The aim of the present narrative review is to increase the amount of knowledge regarding the use of the 6MWT as a reliable measure to evaluate the effect of interventions on walking capacity in children with CP.

Background: the present study aims to assess language in preschool-aged Duchenne muscular dystrophy (DMD) boys with normal cognitive quotients, and to establish whether language difficulties are related to attentional aspects or to the involvement of brain dystrophin isoforms. Methods: 20 children aged between 48 and 72 months were assessed with language and attention assessments for preschool children. Nine had a mutation upstream of exon 44, five between 44 and 51, four between 51 and 63, and two after exon 63. A control group comprising 20 age-matched boys with a speech language disorder and normal IQ were also used. Results: lexical and syntactic comprehension and denomination were normal in 90% of the boys with Duchenne, while the articulation and repetition of long words, and sentence repetition frequently showed abnormal results (80%). Abnormal results were also found in tests assessing selective and sustained auditory attention. Language difficulties were less frequent in patients with mutations not involving isoforms Dp140 and Dp71. The profile in Duchenne boys was different form the one observed in SLI with no cognitive impairment. Conclusion: The results of our observational cross-sectional study suggest that early language abilities are frequently abnormal in preschool Duchenne boys and should be assessed regardless of their global neurodevelopmental quotient.

No abstract available

In the last years, new evidence has increased the attention on sex differences in the development of children with cerebral palsy (CP). Males seem to present with a higher risk for severe motor impairment and in the response to chirurgical and rehabilitative interventions. The published data confirmed a higher incidence of CP in males than in females. The aim of this literature review was to evaluate the impact of the sex on the most important areas that characterized CP: motor function, comorbidities (pain, cognitive impairment, communications skills, epilepsy, sleep, and behavior), and the different kind of interventions.

Aim: To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. Method: The HINE was performed at 3, 6, 9, and 12 months’ corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. Results: A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23–31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. Interpretation: Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.

Objectives: (i) to assess the presence of sleep disorders in a population of very preterm children (ie, with a gestational age [GA] ≤ 31 weeks) of preschool age with no history of neurological disabilities using a questionnaire standardized for this age group and (ii) to identify possible differences in a control group of term-born children. Methods: A total of 146 low-risk preterm children (mean gestational age 28 weeks; range: 25–30), were assessed at a preschool age (mean age 3.8 years; range 3–6 years) using the sleep disturbance scale for children (SDSC) to assess sleep problems. As controls, 146 typically developing children matched for age and gender were also evaluated using the SDSC. Results: An abnormal total sleep score (>70) was found in 7% of preterm children, while 21% had an abnormal score on at least one SDSC factor. No significant differences were reported according to the age of assessment or gestational age. The preterm group reported higher significant median scores on SDSC total, sleep-disordered breathing, sleep hyperhidrosis and difficulty in initiating and maintaining sleep factors. Conclusions: Low-risk very preterm children showed only a slightly higher incidence of sleep disorders than term-born peers at preschool age, with higher scores in specific sleep factors. These data could be useful to clinicians for screening those preterm children at risk for sleep disorders who need a more detailed assessment for a conclusive diagnosis and treatment.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of alpha motor neurons, clinically associated with muscle weakness, hypotonia and muscle atrophy. The weakness is predominant in the proximal muscles, with lower limbs often more involved than upper limbs with a typical distribution [1]. In the most severe cases the involvement is more diffuse affecting both proximal and distal muscles with very limited movements of hands and feet. The predominant proximal involvement has also been observed on muscle Magnetic Resonance Imaging (MRI) [2,3].

Background and Objectives: The aim of this study was to evaluate longitudinal changes using both upper limb muscle Magnetic Resonance Imaging (MRI) at shoulder, arm and forearm levels and Performance of upper limb (PUL) in ambulant and non-ambulant Duchenne Muscular Dystrophy (DMD) patients. We also wished to define whether baseline muscle MRI could help to predict functional changes after one year. Materials and Methods: Twenty-seven patients had both baseline and 12month muscle MRI and PUL assessments one year later. Results: Ten were ambulant (age range 5–16 years), and 17 non ambulant (age range 10–30 years). Increased abnormalities equal or more than 1.5 point on muscle MRI at follow up were found on all domains: at shoulder level 12/27 patients (44%), at arm level 4/27 (15%) and at forearm level 6/27 (22%). Lower follow up PUL score were found in 8/27 patients (30%) at shoulder level, in 9/27 patients (33%) at mid-level whereas no functional changes were found at distal level. There was no constant association between baseline MRI scores and follow up PUL scores at arm and forearm levels but at shoulder level patients with moderate impairment on the baseline MRI scores between 16 and 34 had the highest risk of decreased function on PUL over a year. Conclusions: Our results confirmed that the integrated use of functional scales and imaging can help to monitor functional and MRI changes over time.

Background: Over the last few years there has been increasing attention to detect early signs of impairment in young Duchenne muscular dystrophy boys but less has been reported on whether the delay may also affect the very early aspects of motor development, such as gross motor milestones. Objective: The aim of this study was to retrospectively assess the age when early motor milestones were achieved in Duchenne muscular dystrophy. Methods: The study is a retrospective analysis of data collected as part of a larger natural history project. Information on past medical history, collected at the time the boys were seen for the first time, were recorded and re available on clinical notes and on electronic CRF. Results: Data were collected in 134 DMD boys. Sitting was achieved at 7.04 months. The % of DMD boys not achieving sitting by 9.4 months was 10%, ranging from 2% in the boys with mutations before exon 44 to 33% in those beyond exon 63. Walking was achieved at a mean age of 16.35 months. The % of DMD boys not achieving independent walking by 18 months was 17%, ranging from 9% in the boys with mutations between 44 and 51 to 42% in those beyond exon 63. Conclusions: Our results showed that the risk of a delay in sitting and walking was increasingly high in patients with mutations predictive of the involvement of different brain dystrophin isoforms.

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.

Introduction The aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. Materials and methods We included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52. Results The difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (p≤0.001). Discussion Mutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up. Conclusion Our results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.

Background and Objectives: Sleep disorders are common in children with Autism Spectrum Disorder (ASD). The aims of this study were to describe the incidence and characteristics of sleep disorders using a questionnaire completed by the caregiver in a sample of preschool-aged children with ASD and to identify possible differences in a control group of peers. Materials and Methods: Sleep disorders were investigated with the Sleep Disturbance Scale for Children (SDSC) in a population of pre-school-aged (3–5 years) ASD children and in a control group. The Autism Diagnostic Observation Schedule—second ed. (ADOS-2) was further used to assess autism symptom severity. A total of 84 children (69 males; mean age 3.9 ± 0.8 years) with a diagnosis of ASD and 84 healthy controls (65 males; mean age of 3.7 ± 0.8 years) that were matched for age and sex were enrolled. Results: ASD children reported significantly higher (pathological) scores than the control group on the SDSC total scores and in some of the factor scores, such as Difficulty in Initiating and Maintaining Sleep (DIMS), disorders of excessive somnolence (DOES), and sleep hyperhidrosis. A total of 18% of ASD children had a pathological SDSC total T-score, and 46% had an abnormal score on at least one sleep factor; DIMS, parasomnias, and DOES showed the highest rates among the sleep factors. Younger children (3 years) reported higher scores in DIMS and sleep hyperhidrosis than older ones (4 and 5 years). No specific correlation was found between ADOS-2 and SDSC scores. Conclusions: Pre-school children with ASD showed a high incidence of sleep disorders with different distributions of specific sleep factors according to their age. We suggest a screening assessment of sleep disorders using the SDSC in these children with a more in-depth evaluation for those reporting pathological scores on the questionnaire.

Objectives: The aim of the present study is to assess the psychometric properties of the Sleep Disturbance Scale for Children (SDSC) in an Italian population of infants and toddlers. Methods: The SDSC was distributed to the primary caregivers of infants aged 6–36 months recruited via nurseries in the urban area of Rome. Reliability analysis for evaluating internal consistency and item–total correlation coefficients, and factor analysis were performed. Results: During a 12-months study period, a total of 193 healthy infants (aged 6–36 months) were evaluated using a 22-item version of the SDSC for Italian infants and toddlers. Three of the 22 original items displayed a low item–total correlation (<30) and a low frequency and were eventually removed, resulting in a 19 items questionnaire. Six factors were derived from the factor analysis using the principal component method of extraction and rotated with the varimax method: Difficulty in initiating sleep, Difficulty in maintaining sleep, Sleep breathing disorders, Parasomnias, Disorders of excessive somnolence and Sleep hyperhidrosis. The SDSC adapted for infants and toddlers showed a good level of internal consistency (Cronbach's alpha: 0.83). Conclusions: The statistical analysis, the internal consistency and the factor analysis encourage the use of SDSC as an evaluation tool even at this age. The six factors extracted represent the most common areas of sleep disorders at this age and could therefore help clinicians to detect the areas that need a deeper investigation.

The partial trisomy 13q encompasses an extensive variability of phenotypic and radiolog-ical findings including leukoencephalopathy and brain malformations such as holoprosencephaly, callosal dysgenesis, hippocampal hypoplasia, olfactory hypoplasia, and vermian hypoplasia. We report for the first time a case of a 23-year-old patient affected by de novo partial 13q22.1q34 trisomy (41.7 Mb, 72,365,975-114,077,122x3) presenting with hemiparesis related to both ischemic and haem-orrhagic cerebral lesions compatible with cerebral vasculitis due to a possible combination of genetic and immunological interaction.

The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7-15.8 years), and 90 non-ambulant (age range: 9.08-24.78). The total scores changed significantly over time (p<0.001). Non-ambulant patients had lower total scores at baseline (mean 19.7) when compared to the ambulant ones (mean 38.4). They also had also a bigger decrease in total scores over 24 months compared to the ambulant boys (4.36 vs 2.07 points). Multivariate model analysis showed that the Performance of Upper Limb changes reflected the entry level and ambulation status, that were independently associated to the slope of Performance of Upper Limb changes. This information will be of help both in clinical practice and at the time of designing clinical trials.

No abstract available.

BACKGROUND: Heterogeneity in the phenotypic presentation of autism spectrum disorder (ASD) is apparent in the profile and the severity of sensory features. Here, we applied factor mixture modelling (FMM) to test a multidimensional factor model of sensory processing in ASD. We aimed to identify homogeneous sensory subgroups in ASD that differ intrinsically in their severity along continuous factor scores. We also investigated sensory subgroups in relation to clinical variables: sex, age, IQ, social-communication symptoms, restricted and repetitive behaviours, adaptive functioning and symptoms of anxiety and attention-deficit/hyperactivity disorder. METHODS: Three hundred thirty-two children and adults with ASD between the ages of 6 and 30 years with IQs varying between 40 and 148 were included. First, three different confirmatory factor models were fit to the 38 items of the Short Sensory Profile (SSP). Then, latent class models (with two-to-six subgroups) were evaluated. The best performing factor model, the 7-factor structure, was subsequently used in two FMMs that varied in the number of subgroups: a two-subgroup, seven-factor model and a three-subgroup and seven-factor model. RESULTS: The 'three-subgroup/seven-factor' FMM was superior to all other models based on different fit criteria. Identified subgroups differed in sensory severity from severe, moderate to low. Accounting for the potential confounding effects of age and IQ, participants in these sensory subgroups had different levels of social-communicative symptoms, restricted and repetitive behaviours, adaptive functioning skills and symptoms of inattention and anxiety. LIMITATIONS: Results were derived using a single parent-report measure of sensory features, the SSP, which limits the generalisability of findings. CONCLUSION: Sensory features can be best described by three homogeneous sensory subgroups that differ in sensory severity gradients along seven continuous factor scores. Identified sensory subgro

Objective. The aim of this study was to use a structured questionnaire in a large cohort of Duchenne Muscular Dystrophy (DMD) patients to assess caregivers and patients views on respiratory function and to establish if their responses were related to the patients' age or level of functional impairment. Methods. Questionnaires were administered to caregivers in 205 DMD patients of age between 3 and 36 years (115 ambulant, 90 non-ambulant), and to 64 DMD patients (3 ambulant, 61 non-ambulant) older than 18 years, subdivided into groups according to age, FVC, ambulatory and ventilatory status. Results. Some differences were found in relation to FVC % values (p = 0.014), ambulatory (p = 0.043) and ventilatory status (p = 0.014). Nearly half of the caregivers expected deterioration over the next years, with the perspective of deterioration more often reported by caregivers of non-ambulant (p = 0.018) and ventilated patients (p = 0.004). Caregivers appeared to be aware of the relevance of respiratory function on quality of life (84%) showing willingness to enter possible clinical trials if these were aiming to stabilize the progression of respiratory function with a very high number of positive responses across the spectrum of age, FVC, ambulatory and ventilatory status. The boys older than 18 years showed similar results. Conclusions. Our study showed that the concern for respiratory function increases with age and with the reduction of FVC or the need for ventilation, but the need for intervention was acknowledged across the whole spectrum of age and functional status.

Aim: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify typical and delayed cognitive performance in a large population of infants born preterm, both with and without cerebral palsy (CP). Method: We conducted a retrospective study of infants born preterm who had repeated HINEs between 3 and 12 months corrected age. At 2 years, cognition was assessed using the Mental Development Index (MDI; from the Bayley Scales of Infant Development, Second Edition) and the presence and severity of CP was determined. All children were classified as cognitively typical/mildly delayed or significantly delayed (MDI <70) and CP. The predictive validity of HINE scores for significantly delayed cognitive performance, in children with and without CP, was calculated using specific cut-off scores according to age at assessment. Results: Of 1229 eligible infants (gestational age 25–36wks, mean [SD] 34.9 [2.3]; 646 males, 583 females), 1108 did not develop CP, 891 had an MDI that was typical/mildly delayed, and 217 had an MDI less than 70. Of the 121 infants who developed CP, the MDI was typical in 28, mildly delayed in 27, and less than 70 in 66. HINE scores showed a good sensitivity and specificity, especially after 3 months, for detecting significantly delayed cognitive performance in infants without CP. In those who developed CP, the score was associated with their cognitive level. Interpretation: The HINE provides information about the risk of delayed cognitive performance in infants born preterm with and without CP.

Costello syndrome (CS), a rare syndrome with multisystemic involvement inherited as a dominant trait, is characterized by developmental delay, coarse facial appearance, cardiac defects including hypertrophic cardiomyopathy, skin abnormalities, brain complications, and a predisposition to certain malignancies. The musculoskeletal system is particularly affected in CS, with peculiar orthopedic anomalies that impact posture and gait. Dystonia has been recently documented to contribute to abnormal postures and musculoskeletal anomalies characterizing CS, suggesting the possible use of pharmacological treatments to treat these complications. We report the case of a child affected by CS displaying a particularly severe musculoskeletal involvement with dystonic posture especially in the arms and legs. The Movement Disorder‐Childhood Rating Scale (MD‐CRS) and a gait analysis were used to assess clinical patterns of hyperkinetic movement disorder and dystonia. The child was further treated with trihexyphenidyl for six months with a final dosage of 14 mg. MD‐CRS and gait analysis assessments provided evidence for a significant improvement of posture and the related musculoskeletal problems with no side effects. Our preliminary study report provides first evidence that pharmacological anti‐dystonia treatment significantly improves movement and posture disorders in patients with CS. Further studies enrolling larger cohorts of patients should be performed to validate these preliminary observations.

Only few studies have reported muscle involvement in spinal muscular atrophy using muscle MRI but this has not been systematically investigated in a large cohort of both pediatric and adult patients with type 2 and type 3 spinal muscular atrophy. The aim of the present study was to define possible patterns of muscle involvement on MRI, assessing both fatty replacement and muscle atrophy, in a cohort of type 2 and type 3 spinal muscular atrophy children and adults (age range 2–45 years), including both ambulant and non-ambulant patients. Muscle MRI protocol consisted in T1-weighted sequences acquired on axial plane covering the pelvis, the thigh, and the leg with contiguous slices. Each muscle was examined through its whole extension using a grading system that allows a semiquantitative evaluation of fatty infiltration. Thigh muscles were also grouped in anterior, posterior, and medial compartment for classification of global atrophy. The results showed a large variability in both type 2 and type 3 spinal muscular atrophy, with a various degree of proximal to distal gradient. Some muscles, such us the adductor longus and gracilis were always selectively spared. In all patients, the involvement was a combination of muscle atrophy and muscle infiltration. The variability observed may help to better understand both natural history and response to new treatments.

The aim of this prospective multicentric study was to document disease progression in young boys affected by Duchenne muscular dystrophy (DMD) between age 3 and 6 years (±3 months) using the North Star Ambulatory Assessment scale. One hundred fifty-three DMD boys (573 assessments) younger than 6 years (mean: 4.68, SD: 0.84) with a genetically proven DMD diagnoses were included. Our results showed North Star Ambulatory Assessment scores progressively increased with age. The largest increase was observed between age 3 and 4 years but further increase was steadily observed until age of 6 years. Using a multiple linear regression analysis, we found that both the use of corticosteroids and the site of mutation significantly contributed to the North Star Ambulatory Assessment changes (p < 0.001). At each age point, boys on corticosteroid treatment had higher scores than corticosteroid naïve ones (p < 0.001). Similarly, patients with mutations downstream exon 44, had lower baseline scores and lower magnitude of changes compared to those with mutations located at the 5′ end of the gene (p < 0,001). Very few boys achieved the age appropriate maximum score. These results provide useful information for the assessment and counselling of young DMD boys and for the design of clinical trials in this age group.

OBJECTIVE: To assess whether structured reports (SRs) of MRI in patients with inherited neuromuscular disorders (IND) provide more clinically relevant information than non-structured reports (NSRs) and whether neuroradiologists' expertise affects completeness of reports. MATERIAL AND METHODS: Lower limbs' MRI reports of patients with IND produced by neuroradiologists with different level of expertise (> 15 years vs. < 15 years of experience in reading IND-MRI) before and after implementation of a SR template were included. Reports were assessed for the presence of 9 key features relevant for IND management. Reports and images were evaluated by neurologists who assessed: disease-specific muscular involvement pattern; presence of sufficient information to order the appropriate genetic/diagnostic tests; presence of sufficient information to make therapeutic decision/perform biopsy and necessity to review MRI images. Mann-Whitney and Fisher's exact tests were used to compare the number of key features for NSR and SR and neurologists' answers for reports produced by neuroradiologists with different experience. RESULTS: Thirty-one SRs and 101 NSRs were reviewed. A median of 8 and 6 key features was present in SR and NSR, respectively (p value < 0.0001). When reports were produced by less expert neuroradiologists, neurologists recognized muscular involvement pattern, had sufficient information for clinical decision-making/perform biopsy more often with SR than NSR (p values: < 0.0001), and needed to evaluate images less often with SR (p value: 0.0001). When reports produced by expert neuroradiologists were evaluated, no significant difference in neurologists' answers was observed. CONCLUSION: SR of IND-MRI contained more often clinically relevant information considered important for disease management than NSR. Radiologist's expertise affects completeness of NSR reports.

There is an error in affiliation 9 for author Angela Berardinelli. The correct affiliation is: IRCCS Mondino Foundation, Pavia, Italy.

Introduction The aim of this international collaborative effort was to report 36-month longitudinal changes using the 6MWT in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. Materials and methods Of the 92 patients included in the study, 24 had deletions amenable to skip exon 44, 27 exon 45, 18 exon 51, and 28 exon 53. Five patients with a single deletion of exon 52 were counted in both subgroups skipping exon 51 and 53. Results The difference between subgroups amenable to skip different exons was not significant at 12 months but became significant at both 24 (p0.05) and 36 months (p0.01). Discussion Mutations amenable to skip exon 53 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had better results both at baseline and at follow up. Deletions amenable to skip exon 45 were associated with a more variable pattern of progression. Single exon deletions were more often associated with less drastic changes but this was not always true in individual cases. Conclusion Our results confirm that the progression of disease can differ between patients with different deletions, although the changes only become significant from 24 months onwards. This information is relevant because there are current clinical trials specifically targeting patients with these subgroups of mutations.

Objective: To evaluate the prevalence of joint laxity in children born preterm assessed in the first 2 years, the relationship between joint laxity and motor performance at preschool age, and possible changes over time in a subgroup of children followed longitudinally. Study design: The revised scale of Beighton Score was used to evaluate joint laxity in a population of 132 preschool children born preterm between 24 and 32 weeks of gestational age. All were assessed for joint laxity between 12 and 24 months of age. Children also performed the Movement Assessment Battery for Children-Second Edition between the age of 3 years and 6 months and 4 years; the age at onset of independent walking also was recorded. Results: The total Beighton Score ranged between 0 and 8. Twenty percent of the cohort showed joint laxity. No differences related to sex or gestational age were observed. Children born preterm with joint laxity achieved later independent walking and achieved lower scores on Movement Assessment Battery for Children-Second Edition than those without joint laxity. In 76 children born preterm, an assessment for joint laxity was repeated once between 25 and 36 months and again after >36 months. No statistically significant difference was observed between the 3 assessments. Conclusions: The Beighton Score can be used to assess generalized joint laxity in children born preterm. As the presence of joint laxity influenced motor competences, the possibility to early identify these infants in the first 2 years is of interest to benefit from early intervention and potentially improve gross motor skills and coordination.