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.

Spontaneous Breathing Pattern as Respiratory Functional Outcome in Children with Spinal Muscular Atrophy (SMA).

INTRODUCTION: SMA is characterised by progressive motor and respiratory muscle weakness. We aimed to verify if in SMA children 1)each form is characterized by specific ventilatory and thoraco-abdominal pattern(VTAp) during quiet breathing(QB); 2)VTAp is affected by salbutamol therapy, currently suggested as standard treatment, or by the natural history(NH) of SMA; 3)the severity of global motor impairment linearly correlates with VTAp. MATERIALS AND METHODS: VTAp was analysed on 32 SMA type I (SMA1,the most severe form), 51 type II (SMA2,the moderate), 8 type III (SMA3,the mildest) and 20 healthy (HC) using opto-electronic plethysmography. Spirometry, cough and motor function were measured in a subgroup of patients. RESULTS: In SMA1, a normal ventilation is obtained in supine position by rapid and shallow breathing with paradoxical ribcage motion. In SMA2, ventilation is within a normal range in seated position due to an increased respiratory rate(p<0.05) with reduced tidal volume(p<0.05) secondary to a poor contribution of pulmonary ribcage(%ΔVRC,P, p<0.001). Salbutamol therapy had no effect on VTAp during QB(p>0.05) while tachypnea occurred in type I NH. A linear correlation(p<0.001) was found between motor function scales and VTAp. CONCLUSION: A negative or reduced %ΔVRC,P, indicative of ribcage muscle weakness, is a distinctive feature of SMA1 and SMA2 since infancy. Its quantitative assessment represents a non-invasive, non-volitional index that can be obtained in all children, even uncollaborative, and provides useful information on the action of ribcage muscles that are known to be affected by the disease.Low values of motor function scales indicate impairment of motor but also of respiratory function.

Early development of epileptic infants with pre- or perinatal brain injuries: role of the epileptic disorder.

To try to understand the causative role of epilepsy PER SE in the developmental deterioration of brain injured infants, twenty-eight infants affected with early acquired, pre- and perinatal brain injuries were enrolled and divided into three groups, a) those with West syndrome, b) those with other non-West epilepsies, and c) those without epilepsy. Developmental monitoring consisted of a full clinical assessment, including examination of visual function, Griffiths developmental scales, standard EEG, long-term monitoring when necessary, and MRI, from the seizure onset or the first observation to the end of follow-up. Patients with epilepsy showed at study onset abnormal clinical features (neurological and developmental) distinct from those of non-epileptic patients, partially due to the varying severity of their brain injuries. A definite differentiation between groups was observed in the clinical evolution that showed among the epileptic patients, mostly in West syndrome, a significant deterioration. Moreover, impaired visual function at seizure onset was possibly associated with a bad developmental evolution. A developmental deterioration, mostly in West syndrome, accounts for a causative role of the epileptic disorder PER SE, but in few cases it was also observed in infants with only a brain injury, suggesting other aetiopathogenic mechanisms. The predictive value of early visual function seems to be confirmed.

Longitudinal assessment of visual development in non-syndromic craniosynostosis: a 1-year pre- and post-surgical study.

OBJECTIVE: to investigate visual function pre- and post surgery in children with single-suture non-syndromic craniosynostosis DESIGN: Twenty-nine infants (12 with sagittal synostosis, 10 with trigonocephaly and 7 with anterior plagiocephaly) were longitudinally evaluated using a battery of tests assessing various aspects of visual function, including ocular behaviour, acuity, visual fields and fixation shift. All infants were assessed before surgery and 2, 6 and 12 months after surgery. RESULTS: Before surgery only 16% of infants had completely normal visual function, while on the assessment performed 12 months after surgery, the number with normal results on all the tests increased to 65%. The only abnormalities found 12 months after surgical correction were mainly found on abnormal oculomotor behaviour in infants with plagiocephaly. CONCLUSION: Abnormalities of visual function were not frequent in infants with non-syndromic craniosynostosis who underwent surgical correction. Approximately half of the patients had some visual abnormalities before surgery, which subsequently improved, showing a delayed visual maturation rather than persistent abnormalities.

Antenatal post-hemorrhagic ventriculomegaly: a prospective follow-up study.

OBJECTIVE: The aim of this study was to evaluate the presence and the severity of neurological and cognitive impairment at 2 years of age in 16 infants (9 term born, 7 preterm of mean gestation 33.6 weeks) with cerebral ventriculomegaly of antenatal onset associated with intraventricular haemorrhage. METHODS: Ventricular dilatation, with or without associated lesions, was, with one exception, not identified on the antenatal routine scan at approximately 22 weeks but was obvious on the scans performed between weeks 27 and 33. In 8 of the 16 cases there were signs of parenchymal involvement or of abnormalities of the corpus callosum or cerebellum. In all patients the diagnosis of antenatal IVH was confirmed by early neonatal imaging. Outcome was measured using the Hammersmith infant neurological examination and the Griffiths developmental scales at 2 years. RESULTS AND CONCLUSIONS: At 2 years, 8 infants had normal motor outcome and 8 had cerebral palsy. The presence and severity of cerebral palsy or neurodevelopmental delay was not always related to the magnitude or symmetry of the ventricular dilatation per se. The presence of associated lesions was a negative prognostic marker. The early development of epilepsy was also associated with an abnormal outcome.

Visual function in infants with non-syndromic craniosynostosis.

The aim of this study was to assess various aspects of visual function in children with single-suture, non-syndromic craniosynostosis. Thirty-eight infants (28 males, 10 females; age range 3.5-13mo, mean age 7mo, 11 with plagiocephaly, 12 with trigonocephaly, and 15 with scaphocephaly), were assessed with a battery of tests specifically designed to assess various aspects of visual function in infancy. Thirty-two of the 38 infants had at least one abnormality on one of the aspects of visual function assessed. Abnormal eye movements were found in eight infants of the whole cohort and were mainly found in infants with plagiocephaly (6/11), who also had frequent visual field abnormalities (5/11). In contrast, fixation shift, an aspect of visual function related to the integrity of parietal lobes, was more frequently abnormal in patients with scaphocephaly. Our results suggest that the presence and severity of visual impairment is related to the type of craniosynostosis. Follow-up studies after surgical correction are needed to evaluate the possible beneficial effects of reconstructive surgery on visual function.

Neurological examination at 6 to 9 months in infants with cystic periventricular leukomalacia.

The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL.

Auditory attention at the onset of West syndrome: correlation with EEG patterns and visual function.

At the onset of West syndrome a specific impairment of visual function has been clearly demonstrated, while other aspects of sensorial development, and in particular of the auditory function, have been less studied. The aim of this study was to evaluate auditory function and orienting responses at the onset of West syndrome, and to relate the results with EEG patterns, visual function and neurodevelopmental competence. A prospective multicentric study was performed on 25 successively enrolled infants with West syndrome; all the patients underwent a full clinical assessment, including MRI and video-EEG, visual function and auditory orienting responses (AORs) as well as Griffiths' developmental scales. The whole assessment performed at the onset of spasms (T0) was repeated after two months (T1). AORs resulted significantly impaired both at T0 and T1. At the onset of spasms a highly significant relationship of auditory attention with visual function and neurodevelopmental competence was shown in both cryptogenic and symptomatic forms, but it was no longer present after two months. Our results may suggest a possible pervasive effect of the epileptic disorder on sensory processing, associated to a deficit of neurodevelopment. Although we failed to show a significant correlation between auditory orienting responses and EEG patterns, some evidence seems to support at least partially an influence of the epileptic disorder per se on the genesis of the sensorial impairment. A longer follow up and a larger cohort will be useful for a better clarification of these findings.

Severe abnormalities of the pons in two infants with goldenhar syndrome.

We describe 2 cases of Goldenhar syndrome with severe abnormalities of the pons. The first case is a 10-month-old Caucasian female infant. At birth the girl showed polydactyly, labiopalatoschisis, right ear agenesis, left eye coloboma and vertebral anomalies. She also had marked hypotonia, severely reduced movements and respiratory and feeding abnormalities. She required gastrostomy at 5 months and tracheostomy at 7 months. Brain MRI scans showed moderate cerebellar hypoplasia and severe abnormalities of the pons with a congenital cleft. The child died at age 12 months. Case 2 is a Caucasian boy. Clinical signs and presentation were similar to case 1. The child also had severely reduced lacrimation, sweating, with thermoregulation abnormalities. He also underwent gastrostomy at 18 months. The child is now 3 years old and is able to sit only with support. Brain MRI was similar to case 1. The association of Goldenhar syndrome and pons abnormalities in 2 subjects suggests that this is more than a mere coincidence. Further studies and characterization of the genes involved in Goldenhar syndrome are needed to establish an adequate genotype-phenotype correlation.