Biomedical subjects

Eugenio Mercuri

Publications and source records attributed to Eugenio Mercuri.

At least 19 recordsLinked to original sources

PubMed2006

Visual development in infants with prenatal post-haemorrhagic ventricular dilatation.

OBJECTIVE: The aim of this study was to assess visual function in 13 infants with evidence of prenatal post haemorrhagic ventricular dilatation. DESIGN: Infants were assessed at 5, 12 and 24 months using a battery of tests specifically designed to assess various aspects of visual function in infancy. Visual findings were correlated with several variables, including extent of the lesion and presence of epilepsy. RESULTS AND CONCLUSIONS: Abnormalities of visual function were frequent (over 60%) in our cohort at age 2 years, ranging from isolated abnormal ocular movements to severe abnormalities of all the aspects of visual function assessed. The most severe and persistent abnormalities of visual function were found in infants with grade IV intraventricular haemorrhage and shunted hydrocephalus who also had epilepsy in the first year.

Cerebral Hemorrhage↗

PubMed2006

Feeding problems and weight gain in Duchenne muscular dystrophy.

The aim of the study was to conduct a survey using a dedicated questionnaire to estimate feeding difficulties, gastrointestinal involvement and weight gain in a population of 118 Duchenne muscular dystrophy (DMD) patients (age range 13.80-35.8 years). All the answers were entered in a database and the data analysed subdividing the cohort into age groups (3-9, 9-13, 13-18, 18-24, 24-30, 30-36 years). The results indicate that chewing difficulties are frequent and become increasingly present with age, associated with a progressive increase of the duration of meals. Episodes of choking or other clinical signs of swallowing difficulties are in contrast much less frequent even after age 18. Aspiration pneumonia were also not very frequent and only occurred in 7/118. Clinical signs of gastroesophageal reflux requiring treatment were only found in 5 while 43/118 complained of constipation requiring treatment. Very few of our patients had their weight above 2 SD (n = 4) and this was always found in patients between 9 and 18 years while after this age there was an increasing number of patients with weight below 2 SD. The results of our survey suggest that although choking is one of the most feared complications in patients with DMD, clinical signs of swallowing abnormalities are infrequent when collecting clinical information retrospectively. Further studies using an objective evaluation such as videofluoroscopy are needed to identify minor signs that may not be obvious on clinical examination.

Adolescent↗

PubMed2006

Thalamic atrophy in infants with PVL and cerebral visual impairment.

The aim of this retrospective study was to establish the presence and severity of cerebral visual impairment in preterm infants with PVL. We also wished to establish whether abnormalities of visual function are related to brain MRI findings and more specifically not only to the involvement of optic radiations and occipital cortex but also to changes in the thalami, that are often affected in infants with PVL. Twelve infants with cystic PVL were assessed at 1 year (+2) corrected age with a battery of tests specifically designed to assess various aspects of visual function in infancy, such as ocular movements, visual acuity, visual fields and fixation shift. All infants also had a brain MRI. Eleven of the 12 had involvement of the optic radiations: all had some abnormalities of visual function and visual impairment was more severe in infants with more extensive involvement of the optic radiations. The child with normal optic radiations had normal visual function. Six of the 12 infants also had obvious signs of atrophy of the thalami and all had severe and wide-ranging abnormalities of visual function in all testing domains. Two children had equivocal atrophy of the thalami, both had some abnormalities of visual function. Four children had normal thalami and had normal visual function or only minor abnormalities on one of the visual tests. Our results suggest that the atrophy of the thalami may play an additional role in the abnormal development of visual function in infants with PVL and abnormal optic radiations.

Atrophy↗

PubMed2006

Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations.

OBJECTIVES: To report the spectrum of brain magnetic resonance imaging findings in 13 patients with congenital muscular dystrophy and FKRP gene mutations and to explore possible genotype-phenotype correlations. DESIGN: We retrospectively reviewed brain magnetic resonance imaging in patients with congenital muscular dystrophy and FKRP gene mutations. PATIENTS: Thirteen patients with congenital muscular dystrophy and mutations in the FKRP gene. RESULTS: Five of the 13 patients had the typical phenotype originally described for congenital muscular dystrophy (MDC1C) with normal intelligence and normal brain magnetic resonance imaging while 3 other patients had isolated cerebellar cysts and mental retardation without any other sign of posterior fossa of supratentorial abnormalities. In the remaining 5 patients cerebellar cysts were associated with structural brain changes involving the posterior fossa and the cortex, ranging from focal unilateral periventricular nodular heterotopia to marked cerebellar dysplasia and pontine hypoplasia. In 2 of these 5 patients the severity and distribution of changes resembled muscle-eye-brain disease in 1 patient who had mild Walker-Warburg syndrome. The distribution of FKRP gene mutations identified in this group of patients did not reveal any obvious association with the severity of central nervous system involvement. CONCLUSIONS: The severity of central nervous system involvement observed in our patients in contrast broadly reflected the severity of the disruption of alpha-dystroglycan glycosylation. In particular, dystroglycan expression was almost absent in the patients with muscle-eye-brain diseaselike phenotype and less severely reduced in the patients with congenital muscular dystrophy (MDC1C) with or without cerebellar cysts. This study further highlights the central role that dystroglycan has in neuronal migration.

Brain↗

PubMed2005

The neurological examination of the newborn baby.

This paper provides an overview of the value of a structured neonatal neurological examination that may be performed in different settings, from routine examination to research settings. We will report how a structured neurological examination can help to identify infants with central and peripheral nervous system involvement. We also describe a short but structured proforma to be used for the routine examination of full-term infants. We will finally describe a quantitative assessment to be used in research settings.

Central Nervous System Diseases↗

PubMed2005

A homozygous COL6A2 intron mutation causes in-frame triple-helical deletion and nonsense-mediated mRNA decay in a patient with Ullrich congenital muscular dystrophy.

Ullrich congenital muscular dystrophy (UCMD) is a severe disorder caused, in most cases, by a deficiency in collagen VI microfibrils. Recessive mutations in two of the three collagen VI genes, COL6A2 and COL6A3, have been identified in eight of the nine UCMD patients reported thus far. A heterozygous COL6A1 gene deletion, resulting in a mutant protein that exerts a dominant negative effect, has recently been described in a severely affected UCMD patient. Here we describe a patient in whom reverse transcription-PCR analysis of fibroblast RNA suggested a heterozygous in-frame deletion of exon 13 in the triple-helical domain of COL6A2, which is predicted to be dominantly acting. However, a homozygous A --> G mutation at -10 of intron 12 was found in the genomic DNA. The intron mutation activated numerous cryptic splice acceptor sites, generating normal and exon 13-deleted COL6A2 mRNA, and multiple aberrant transcripts containing frameshifts that were degraded through a nonsense-mediated decay mechanism. Northern analysis indicated diminished COL6A2 mRNA expression as the primary pathogenic mechanism in this UCMD patient. Our results underscore the importance of multifaceted analyses in the accurate molecular diagnosis and interpretation of genotype-phenotype correlations of UCMD.

Base Sequence↗

PubMed2005

Prognostic value of EEG performed at term age in preterm infants.

RATIONALE: Electroencephalography (EEG) was performed at term age on 32 infants born prematurely (25-32 weeks). EEG was assessed looking for overall background activity and transients. METHODS: A quantitative analysis was performed, selecting 5-min epochs of "tracé alternant" free of artefacts during quiet sleep. EEG findings were compared with cranial ultrasound (US) findings at term age and with neurodevelopmental outcome at 2 years (Student's t-test). RESULTS: The overall EEG background activity was not always related to the outcome or to the severity of cranial US. Infants with normal US and normal outcome had longer synchrony percentage of bursts, longer maximum duration of bursts and shorter mean of abnormal transients per interbursts than children with major lesions and abnormal outcome. Infants with minor lesions, who all had normal outcome, also had better results than those with major lesions and abnormal outcome, but the range of the EEG findings was more variable. CONCLUSION: Our results suggest that the EEG performed at term age does not provide additional prognostic information compared to cranial US.

Brain Damage, Chronic↗

PubMed2005

The Dubowitz neurological examination of the full-term newborn.

In an ideal world, each neonate should have a comprehensive neurological examination but in practice this is often difficult. In this review we will describe what a routine neurological evaluation in the full-term neonate should consist of and how the Dubowitz examination is performed. The examination has been used for over 20 years and can be easily performed in a short time as the recording sheet provides simple instructions together with simple diagrams to make the recording and the scoring easier. We will also indicate how the examination can be used to identify infants with neurological abnormalities, describing clinical signs which can help to differentiate infants with peripheral neuromuscular disorders from those with central nervous system involvement. The correlation between clinical and imaging findings in infants with neonatal brain lesions will also be reported. Finally we will briefly describe how and when to apply an optimality scoring system in a research setting.

Humans↗

PubMed2005

Can clinical signs identify newborns with neuromuscular disorders?

OBJECTIVE: To evaluate retrospectively the prevalence of neuromuscular disorders in 83 newborns referred to a tertiary care center because of hypotonia and weakness and/or contractures, with a possible diagnosis of neuromuscular disorder. We also aimed to establish whether clinical signs could help to identify infants with neuromuscular disorders. STUDY DESIGN: Sixty-six of the 83 infants who fulfilled the inclusion criteria (79.5%) had an identifiable disorder, which was a neuromuscular disorder in 39 (46.9%). RESULTS: Absent or extremely reduced antigravity movements were mainly found in infants with neuromuscular disorders (sensitivity and specificity 97.4% and 75%), whereas partial range antigravity movements were more frequent in infants with other diagnosis. Contractures were mainly found in infants with peripheral nerve or muscle involvement but also were relatively frequent in infants with genetic or metabolic syndromes (sensitivity 69.2%, specificity 61.3%). Reduced fetal movements and abnormal liquor were frequent but not present consistently in infants with neuromuscular disorders (sensitivity 46.1% and 38.4%) and were found rarely in infants with other disorders (specificity 88.6% and 75.0%). CONCLUSIONS: Severe muscle weakness and contractures are the most reliable indicators of a neuromuscular disorder and should be carefully assessed in an infant with neonatal hypotonia.

Algorithms↗

PubMed2005

Muscle MRI in Ullrich congenital muscular dystrophy and Bethlem myopathy.

The aim of this study was to evaluate the spectrum of muscle involvement on Magnetic Resonance Imaging (MRI) in patients with collagen VI related disorders. Nineteen patients with genetically confirmed collagen VI related disorders, 10 with Bethlem myopathy and 9 with Ullrich congenital muscular dystrophy (CMD), had muscle MRI of their legs using T1 sequences through calves and thighs. In patients with Bethlem myopathy the vasti muscles appeared to be the most frequently and most strikingly affected thigh muscles, with a rim of abnormal signal at the periphery of each muscle and relative sparing of the central part. Another frequent finding was the presence of a peculiar involvement of the rectus femoris with a central area of abnormal signal within the muscle. Patients with Ullrich CMD had a more diffuse involvement of the thigh muscles with relative sparing of sartorius, gracilis and adductor longus. In 8 of the 9 patients with Ullrich CMD, we also observed the peripheral rim of the vastus lateralis and the central area in the rectus femoris observed in patients with Bethlem myopathy. At calf level the results were more variable but a significant proportion of patients with both Bethlem myopathy (8/10) and Ullrich CMD (6/9) showed a rim of abnormal signal at the periphery of soleus and gastrocnemii. Bethlem myopathy and Ullrich CMD patients have distinct patterns of muscle involvement on MRI with some overlap between the two forms. Our results suggest that muscle MR may be used, as an additional tool, to identify patients with collagen VI related disorders. This information is even more important in the patients with a typical Ullrich CMD clinical phenotype but with normal collagen expression of VI in muscle and/or skin.

Adolescent↗

PubMed2005

Cognitive competence at the onset of West syndrome: correlation with EEG patterns and visual function.

The aim of this study was to evaluate cognitive development at the onset of West syndrome (WS) with regard to electroencephalogram (EEG) patterns and visual function. Twenty-five patients (14 males, 11 females) at the onset of spasms (T0) in WS and 2 months later (T1) underwent a full clinical evaluation, including neuroimaging, cognitive assessment, video-EEG, and visual function. Mean age of the patients at spasm onset was 5.9 months (SD 2.5; range 2 to 13mo). Cognitive development, assessed with Griffiths Mental Development Scales (GMDS), was generally impaired at T0 and was significantly related to visual function (p<0.001) at both T0 and T1. In general, there was a specific major impairment in the eye-hand coordination scale of the GMDS which tended to disappear after 2 months in less severe cases. At the onset of spasms, sleep EEG organization seemed to be better related to cognitive abilities than awake hypsarrhythmia. These results support a close link between visual function and cognitive competence in WS and provide additional information to improve the understanding of possible mechanisms underlying cognitive impairment.

Child Development↗

PubMed2005

Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients.

Spinal muscular atrophy (SMA) is caused by insufficient levels of survival motor neuron (SMN) protein. Recently, we found that sodium 4-phenylbutyrate (PB), a well-tolerated FDA approved drug, enhances SMN gene expression in vitro. We provide here the first evidence that oral administration of PB (triButyrate significantly increases SMN expression in leukocytes of SMA patients. This finding provides a strong rationale to further investigate the effects of PB as also supported by preliminary clinical data.

Administration, Oral↗

PubMed2005

Muscle imaging in clinical practice: diagnostic value of muscle magnetic resonance imaging in inherited neuromuscular disorders.

PURPOSE OF REVIEW: This review reports on the use of muscle magnetic resonance imaging as a clinical and research tool in inherited neuromuscular disorders. RECENT FINDINGS: Several papers published during the past few years have reported on the value of muscle magnetic resonance imaging in detecting patterns of muscle involvement in various muscular dystrophies and other inherited myopathies. The patterns of muscle involvement observed on muscle magnetic resonance imaging are often specific for distinct genetic entities. SUMMARY: Our review of the literature suggests that muscle magnetic resonance imaging can provide information that is useful in clinical practice and may be used as an additional tool in a diagnostic flow chart to select appropriate genetic and biochemical investigations.

Diagnosis, Differential↗

PubMed2005

Magnetic resonance image correlates of hemiparesis after neonatal and childhood middle cerebral artery stroke.

OBJECTIVE: Motor impairment after neonatal and childhood-onset ischemic stroke (IS) is common, although the prevalence and type of hemiparesis differs between the 2 age groups. Lesion topography is an important predictor of hemiparesis after neonatal IS, but it is not known if the same topographic predictors of adverse motor outcome apply to childhood-onset IS. We used a consistent approach to define lesion topography and evaluate motor outcome in both age groups to (1) investigate whether early topographic predictors of hemiparesis after unilateral middle cerebral artery-territory stroke are the same in neonates and older children and (2) compare the prevalence of dystonia and loss of independent finger movements between the 2 age groups. DESIGN: Twenty-eight patients with neonatal-onset IS (Hammersmith Hospital, London, United Kingdom) were studied together with 43 patients with childhood-onset IS (Great Ormond Street Hospital, London, United Kingdom). All patients had exclusive unilateral middle cerebral artery-territory IS. Lesion topography was studied by using the first magnetic resonance image acquired after the onset of symptoms and was coded for involvement of cerebral cortex (CC), posterior limb of the internal capsule (PLIC), basal ganglia (BG), and white matter. The primary outcome was hemiparesis, and secondary outcomes were dystonia and loss of age-appropriate independent finger movements. RESULTS: Hemiparesis was more common after childhood-onset IS (56%) than neonatal-onset IS (24%). In neonatal-onset IS, concomitant involvement of BG, CC, and PLIC predicts the development of hemiparesis (odds ratio: 99; 95% confidence interval: 5.2-1883.8), and no child with 1 or 2 of these structures involved developed hemiparesis. In contrast, in childhood-onset IS, concomitant BG, CC, and PLIC lesions tended to be associated with hemiparesis (9 of 11), but this adverse outcome was seen also among patients with 1- or 2-site involvement. However, hemiparesis was less likely if the infarction involved BG only (odds ratio: 0.162; 95% confidence interval: 0.036-0.729). Dystonia was present in 15 of 24 in the childhood-onset group with hemiparesis but was not seen after neonatal-onset IS. In both age groups upper-limb impairment was more severe than lower-limb impairment, with frequent loss of independent hand function among hemiparetic patients. CONCLUSIONS: In neonatal and childhood-onset IS, early magnetic resonance imaging provides useful prognostic information about subsequent motor outcome. There are differences in the functional response of the neuromotor system to injury between the 2 age groups that cannot be attributed to methodological differences alone.

Adolescent↗

PubMed2005

Congenital muscular dystrophy.

Explore the source record for details and available documents.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Neurological examination in healthy term infants aged 3-10 weeks.

OBJECTIVES: The neurodevelopmental progress of newborn term infants is checked routinely at around 6 weeks of postnatal age. The maturation of neurological signs in this age range however has not been systematically studied and normative data are not available. The aim of this study was to document any changes in posture, tone, reflexes, behaviour and movements in low-risk full-term infants between 3 and 10 weeks of postnatal age. STUDY DESIGN: We performed a structured neurological examination previously standardised in full-term newborns in the first 48 h after birth. In the current study, a total of 76 examinations were performed between 3 and 10 weeks of age in low-risk full-term infants. RESULTS: The results of the examinations were divided according to postnatal age. In most items, the scores changed with time, with a definite shift in their distribution occurring around 6 weeks. At this age, a reduction in flexor tone of the limbs was observed, together with an increase in active neck tone. Visual orientation in contrast had already improved by 3 weeks when all infants were able to follow a target in a full circle compared to newborns that are often only able to follow a target in an arc. CONCLUSIONS: Our results suggest that 6 weeks post-term birth is an important milestone for changes in neurological signs, particularly those related to muscle tone and posture, probably reflecting maturation of the nervous system. These findings provide important guidelines for the interpretation of the neurological examination performed at this age.

Child Development↗

PubMed2004

Muscle MRI findings in patients with limb girdle muscular dystrophy with calpain 3 deficiency (LGMD2A) and early contractures.

Limb girdle muscular dystrophy 2A is a common variant secondary to mutations in the calpain 3 gene. A proportion of patients has early and severe contractures, which can cause diagnostic difficulties with other conditions. We report clinical and muscle magnetic resonance imaging findings in seven limb girdle muscular dystrophy 2A patients (four sporadic and three familial) who had prominent and early contractures. All patients showed a striking involvement of the posterior thigh muscles. The involvement of the other thigh muscles was variable and was related to clinical severity. Young patients with minimal functional motor impairment showed a predominant involvement of the adductors and semimembranosus muscles while patients with restricted ambulation had a more diffuse involvement of the posterolateral muscles of the thigh and of the vastus intermedius with relative sparing of the vastus lateralis, sartorius and gracilis. At calf level all patients showed involvement of the soleus muscle and of the medial head of the gastrocnemius with relative sparing of the lateral head. MRI findings were correlated to those found in two patients with the phenotype of limb girdle muscular dystrophy 2A without early contractures and the pattern observed was quite similar. However, the pattern observed in limb girdle muscular dystrophy 2A is different from that reported in other muscle diseases such as Emery-Dreifuss muscular dystrophy and Bethlem myopathy which have a significant clinical overlap with limb girdle muscular dystrophy 2A once early contractures are present. Our results suggest that muscle MRI may help in recognising patients with limb girdle muscular dystrophy 2A even when the clinical presentation overlaps with other conditions, and may therefore, be used as an additional investigation to target the appropriate biochemical and genetic tests.

Adolescent↗

PubMed2004

Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant.

BACKGROUND: Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, have been associated with 7 distinct pathologic conditions. OBJECTIVE: To report 5 cases with the same missense mutation in exon 6 of the LMNA gene, resulting in an E358K substitution in the central rod domain. DESIGN: Case report. SETTING: Three muscle centers in England. PATIENTS: Five patients with missense mutations of the LMNA gene. RESULTS: All 5 individuals had muscle involvement, but the onset, severity, distribution of muscle weakness, and presence of associated features were highly variable. Three patients had humeroperoneal distribution of weakness and typical features of Emery-Dreifuss muscular dystrophy. Two other patients showed additional novel features. One had congenital onset and predominant axial weakness, with poor neck control and inability to sit independently at the age of 21 months. Another patient presented in childhood with an unusual pattern of muscle weakness, short stature, and midface hypoplasia with striking fat accumulation around the face and neck, in contrast to wasting of adipose tissue and muscle in the limbs. She developed both respiratory failure and cardiac arrhythmias in her late 20s. CONCLUSION: Our cases expand the clinical spectrum associated with mutations in the LMNA gene and further illustrate the overlapping phenotypes of the laminopathies.

Adult↗