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The aim of the study was to retrospectively evaluate the consistency of longitudinal findings on intellectual functioning in DMD boys and their relationship to behavioral and neuropsychiatric difficulties. The cohort included 70 patients of age 3 to 17 years with at least two assessments using the Wechsler scales. CBCL and clinical observation of behavior were also performed. Changes in total intelligence quotient were interpreted as stable or not stable using the reliable-change method. On the first assessment 43/70 had normal quotients, 18 borderline, 5 mild, and 4 moderate intellectual disability, while 27/70 had no behavioral disorders, 17 had abnormal CBCL, and 26 patients had clear signs of attention deficits despite normal CBCL. The remaining seven were untestable. The mean total intelligence quotient change in the cohort was −2.99 points (SD: 12.29). Stable results on TIQ were found in 63% of the paired assessments. A third of the consecutive cognitive assessments showed a difference of more than 11 points with changes up to 42 points. Boys with no behavioral/attention disorder had smaller changes than those with attention (p = 0.007) and behavioral disorders (p = 0.002). Changes in IQ may occur in Duchenne and are likely to be associated with behavioral or attention deficits.

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.

Objective To investigate ultrasound features of diaphragm motion and function in type 1 spinal muscular atrophy (SMA-1) patients. Design Prospective study. Patients The study cohort included SMA-1 children younger than 18-year-old. Control subjects included type 2 and type 3 SMA and other neuromuscular disorders younger than 18-year-old. Methodology Diaphragm ultrasound evaluating diaphragmatic excursion, speed of diaphragmatic contraction, duration of the respiratory cycle, inspiratory/expiratory relationship, end-inspiratory and -expiratory thickness, thickening fraction, and pattern of contractility. The interrater reliability for each variable was established by calculation of Cohen's k coefficient. Results Twenty-three SMA-1 patients and 12 controls were evaluated. Diaphragm ultrasound values were within normal ranges in all study cohort patients and no difference was found with controls. There was a gradient of diaphragm function with SMA 1.9 subgroup having the best and SMA 1.1 having the worst parameters, particularly in end-inspiratory thickness and diaphragmatic excursion (P = .031 and P = .041, respectively). Seventy-four percent of SMA-1 patients had a dysmotility pattern of diaphragm contraction, mostly represented in SMA 1.9 subgroup (P = .001). This pattern was observed in 92.8% of children on noninvasive ventilation (NIV) for less than 16 hours/d of and in 20% patients with invasive ventilation or NIV for more than 16 hours/d (P = .027). The dysmotility pattern was never observed in the control group. The levels of interobserver agreement were high for "diaphragm irregularities," "inspiratory/expiratory relationship," and "diaphragm thickness," and good for the other variables. Conclusions Ultrasound can be used to evaluate diaphragm function and contractility in SMA-1 children, providing additional information to the clinical examination and functional respiratory tests, describing a characteristic contractility pattern in these patients. Longitudinal studies are needed to understand the impact of diaphragm dysmotility and other parameters on long-term outcome in SMA-1 patients.

IntroductionThe aim of the study was to longitudinally assess swallowing abilities in nusinersen-treated patients with type 1 spinal muscular atrophy.MethodsTwenty infants with type 1 SMA (11 female and 9 male) treated with nusinersen between 3 weeks and 15 months of age, were assessed using the Oral and Swallowing Abilities Tool (OrSAT). The duration of the follow-up after treatment ranged between 12 months and 62 months.ResultsTwelve of the 20 infants had normal swallowing and there was no need for tube feeding at the time treatment started. Ten of the 12 had consistently normal swallowing with no need for tube feeding on follow-up. The other two required tube feeding but they regained the ability to eat some food by mouth.The remaining 8 infants already had tube feeding inserted at the time treatment started: 4 of them also had tracheostomy and they showed no changes on the OrSAT Scale. The other 4 who had tube feeding but no tracheostomy had partial functional improvement.ConclusionOur results suggest that the degree of functional impairment at the time treatment is started can help to predict the progression of swallowing abilities. The use of a structured assessment also helped to detect partial improvements.

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.

We describe the development of a new tool specifically designed to record oral abilities, swallowing and, more generally, feeding in young type 1 SMA patients, to be used during the first 24 months of life. The tool is composed by a checklist and a separate section summarizing the functional abilities into levels of feeding/swallowing impairment. The checklist includes 12 questions assessing aspects thought to be clinically meaningful for a type 1 SMA population and developmentally appropriate for infants during the first months of life. Each item is graded with a score of 0 or 1, depending on the child’s ability to perform the activity. As some items are age-dependent, the number of items to be used, and therefore the maximum score, changes with increasing age. The levels of feeding/swallowing impairment include four levels that can be identified using easily identifiable clinical criteria. In an attempt to validate the tool in an untreated population we applied it to 24 type 1 SMA patients (age range: 2.3–24.1 months, mean: 10.8) in whom the same information collected by the new tool had been previously recorded using a less-structured format. When patients were classified in three groups according to the Dubowitz decimal classification, there was a significant difference both at baseline and at follow-up (p

Background: Swallowing is one of the most important aspects in the care of type 1 spinal muscular atrophy. Main text:The aim of this paper is to describe the development of a new tool specifically designed to record different aspects related to oral abilities, swallowing and feeding in young type1 SMA patients. We also report its application to a cohort of type 1 infants to identify possible changes during the first 24 months of life. The new tool includes a checklist with 12 questions for carers and a classification of levels of impairment.The scale was retrospectively used in 24 type 1 patients (8 females and 16 males,age range from2.3 to 24.1 months (average age: 10.8 months), classified according to the Dubowitz's decimal classification into 1.1 (n=8); 1.5 (n=8); 1.9 (n=8). There was a significant difference among the 3 subtypes both at baseline and at follow up (pConclusion: Our results suggest that the new tool may help to routinely capture changes over time in type 1 infants and that the trajectories of progression reflect the overall severity of the disease. The items assessing fatigue during the nursing sessions were the most frequently impaired even in infants who did not have any other obvious clinical sign of swallowing difficulties.

We report the clinical case of a nine-year-old girl who presented with progressive motor neuropathy, revealed via the detection of a higher delay in F-wave recording using digitalized nerve conduction/electromyography. Since the lupus anticoagulant (LAC) positivity, detected using diluted Russell viper venom time (dRVVT), switched to persistent serological anticardiolipin immunoglobulin G (IgG) positivity, a possible non-thrombotic antiphospholipid antibody (aPL)-related clinical manifestation was suspected, and intravenous immunoglobulin treatment (IVIG) was started. The IVIG treatment was well tolerated and the complete resolution of motor impairment was obtained after the third IVIG infusion. Our findings suggest that it could be useful to check for antiphospholipid antibodies in children with a rapid onset of progressive neurological signs in order to provide the beneficial use of IVIG in the treatment of pediatric aPL neurological conditions.

ObjectiveTo report the long-term progression in a cohort of patients with type II spinal muscular atrophy (SMA) assessed with the Hammersmith Functional Motor Scale–Expanded.MethodsSeventy-three patients (age 2.6–25 years) were included in the study. Twenty-eight of the 73 were first assessed before the age of 5 years and had been followed up for ≈5 years or longer. We observed an overall progression that was not linear. A piecewise regression analysis showed an improvement of scores in the younger patients with a point of slope change at ≈5 years of age, a decline between 5 and 13 years of age, and stability/slower decline after that.ResultsPatients with the lowest scores at baseline had the earliest onset of scoliosis and a higher need for noninvasive ventilation compared to those with higher scores. Our results confirm that on the long-term follow-up all patients with type II SMA show a clear and progressive decline.ConclusionThe severity of functional impairment at baseline can help to predict the magnitude of changes over time and the overall progression, including onset of scoliosis and need for noninvasive ventilation.

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.

ObjectiveTo report cross-sectional clinical findings in a large cohort of patients affected by type 1 spinal muscular atrophy.MethodsWe included 122 patients, of age ranging between 3 months and 22 years, 1 month. More than 70% (85/122) were older than 2 years and 25% (31/122) older than 10 years. Patients were classified according to the severity of phenotype and to the number of SMN2 copies.ResultsPatients with the more common and the most severe phenotype older than 2 years were, with few exceptions, on noninvasive ventilation and, with increasing age, more often had tracheostomy or >16-hour ventilation and a gastrostomy inserted. In contrast, 25 of the 28 patients with the mildest phenotype older than 2 years had no need for tracheostomy or other ventilatory or nutritional support. In patients older than 2 years, the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were generally lower compared to those found in younger patients and showed distinct levels of functional abilities according to the severity of the phenotype. Similar findings were also observed on the Hammersmith Infant Neurological Examination.ConclusionsOur findings confirm that, after the age of 2 years, patients with type 1 spinal muscular atrophy generally survive only if they have gastrostomy and tracheostomy or noninvasive ventilation >16 hours and have low scores on the functional scales. More variability, however, can be expected in those with the mildest phenotype, who achieve head control. These data provide important baseline information at the time treatments are becoming available.

The aim of the study was to evaluate the spectrum of upper limb functional activities and imaging finding in a cohort of patients affected by Duchenne muscular dystrophy. Thirty-one patients of age between 5 and 29 years were included in the study (17 ambulant and 14 non-ambulant). They were all assessed using the Performance of Upper Limb (PUL) test and muscle MRI of shoulder, arm and forearm in order to establish if the functional scores obtained at shoulder, mid and distal level related to specific patterns of involvement in each upper limb segment on muscle MRI. At shoulder level, latissimus dorsi, serratus anterior, infraspinatus and subscapularis were always involved, even in patients with full functional scores at shoulder level. Diffuse and severe involvement of all muscles was found in the patients with a PUL shoulder functional score of ≤ 5. At arm level biceps brachii, brachialis and triceps were generally concordantly involved or spared. Some degree of involvement could already be detected in patients with reduced scores on the PUL mid domain. They were generally severely involved in patients with functional scores less than 6 at mid-level. At distal level supinator and pronator muscles were often involved, followed by brachioradialis and, less frequently, by the muscles of the flexor compartment. The extensor muscles were generally completely spared. A diffuse and severe involvement was found only in patients who had very low scores (8 or below) on the PUL distal domain. The integrated use of functional scales and imaging allowed to establish patterns of involvement at each level, and the functional scores that were more frequently associated with diffuse and severe involvement.

A group of differently substituted acetoxy- and methoxystilbenes were synthesised via Heck reaction. A comparison between the use--as coupling reagents--of iodobenzene derivatives and diazonium salts was performed. A successful microwave-assisted demethylation by pyridine hydrochloride of some methoxystilbenes was carried out.