PubMed Health⌕ Search

Biomedical subjects

E Mercuri

Publications and source records attributed to E Mercuri.

At least 37 records · Page 2Linked to original sources
PubMed2004

Congenital form of spinal muscular atrophy predominantly affecting the lower limbs: a clinical and muscle MRI study.

We describe clinical and muscle magnetic resonance imaging (MRI) findings in 11 cases (three familial and eight sporadic) with the form of spinal muscular atrophy characterised by predominant involvement of the lower limbs with weakness of the proximal and distal muscles and marked atrophy of the distal leg and foot muscles. All patients presented at birth with talipes, which were in extension in seven of the 11. Arm muscle and function were preserved and lower limbs appeared to be disproportionately shorter compared to trunk and upper limbs. Functional abilities were markedly affected and only one of the 11 is able to walk independently for long distances, while six require support of crutches and two use callipers for walking. One child lost ambulation following a fall. The course of the disease is relatively stable and the progression of disability appeared to be related mostly to increased contractures rather than to loss of muscle strength. Respiratory and cardiac function were well preserved. A neurogenic disorder was suggested by electromyography and/or muscle biopsy in all patients, while motor nerve conduction was consistently normal. Muscle MRI of the thighs revealed diffuse atrophic appearance with relative hypertrophy of the adductor longus and of the semitendinosus. Genetic studies excluded the involvement of the survival motor neuron gene but none of these families was sufficiently informative to study linkage to the locus on chromosome 12q23-q24 previously found to be involved in patients with similar phenotype. In our experience this form of spinal muscular atrophy affecting predominantly the lower limbs is a relatively common form and should be considered in the differential diagnosis of infants with talipes and weakness in the lower limbs. The identical clinical and imaging features of the sporadic and familial cases suggest that these cases are likely to be affected by the same condition.

Adolescent↗
PubMed2004

Expanding the phenotype of potassium channelopathy: severe neuromyotonia and skeletal deformities without prominent Episodic Ataxia.

We report an unusual family in which the same point mutation in the voltage-gated potassium channel gene KCNA1 resulted in markedly different clinical phenotypes. The propositus presented in infancy with marked muscle stiffness, motor developmental delay, short stature, skeletal deformities, muscle hypertrophy and muscle rippling on percussion. He did not experience episodic ataxia. His mother presented some years later with typical features of Episodic Ataxia type 1 (EA1), with episodes of ataxia lasting a few minutes provoked by exercise. On examination she had myokymia, joint contractures and mild skeletal deformities. A heterozygous point mutation in the voltage-gated K(+) channel (KCNA1) gene (ACG-AGG, Thr226Arg) was found in both. We conclude that mutations in the potassium channel gene (KCNA1) can cause severe neuromyotonia resulting in marked skeletal deformities even if episodic ataxia is not prominent.

Adult↗
PubMed2004

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.

Abnormalities, Multiple↗
PubMed2004

Congenital muscular dystrophy with short stature, proximal contractures and distal laxity.

We report 5 cases (2 familial and 3 sporadic) who share a diagnosis of congenital muscular dystrophy (CMD) in association with short stature, proximal contractures, rigidity of the spine and distal joint laxity as well as early respiratory failure and mild to moderate mental retardation. The expression of collagen VI was confirmed to be normal on muscle biopsies of all 5 patients and in the informative family linkage to any of the three COL6 A loci was excluded. These findings extend the phenotypes within the CMD classification.

Adolescent↗
PubMed2004

Pilot trial of salbutamol in central core and multi-minicore diseases.

Several studies have documented positive effects of beta-adrenergic agonists on human skeletal muscle with regard to muscle mass and strength. The aim of this pilot study was to evaluate the effect of the beta2-agonist salbutamol (albuterol) in a group of children with central core disease and multi-minicore disease. Thirteen patients, 8 with central core disease (mean age 17.5 years) and 5 with minicore disease (mean age 13.6 years) received oral salbutamol at a dose of 2 mg four times a day. Measures of efficacy were the change from baseline at 3 and 6 months in muscle strength, assessed by MRC score, myometry, functional measures and forced vital capacity. Statistical analysis was performed using repeated measures ANOVA (significance level < 0.05). Two patients with central core disease stopped the medication after one month because they did not notice any improvement and another one with minicore disease after 4 months because of increased tremors and palpitations. The remaining ten (6 with central core and 4 with minicore disease) completed the course of salbutamol without any significant adverse effects. There were significant increases in myometry, MRC scores and forced vital capacity between baseline and the six-month assessments. For both myometry and MRC the difference was already significant at 3 months and this was associated with a significant increase in functional abilities assessed with a structured functional scale. Our results suggest that salbutamol was overall well tolerated and might be beneficial in both central core and minicore patients. Larger prospective randomised, double-blind, placebo-controlled trials with salbutamol will be needed to confirm these preliminary findings.

Adolescent↗
PubMed2004

Bone mineral density in a paediatric spinal muscular atrophy population.

BACKGROUND/OBJECTIVE: Reduced bone mineral density is a feature of patients with reduced mobility. The aim of this study was to assess bone mineral density in children with spinal muscular atrophy (SMA) and to evaluate bone mineral density in relation to age and motor disability. PATIENTS AND METHODS: We analysed bone mineral density measurements on twelve patients (4 with SMA type II, mean age 8.2 years [range 6.2 - 11.8]; 8 with SMA type III, mean age 11.8 years [range 5.5 - 20]). Dual-energy X-ray absorptiometry (DXA) was used to determine total body bone mineral density. The results were matched with published normative data for age and sex for a white Caucasian population. RESULTS: The total body bone mineral density values were in the normal range in 10 out of the 12 SMA patients studied, all below the age of 17 (mean age 8.8 years [range 5.5 - 16.33]). Four of them had SMA II and six had had SMA III and were still ambulant. Total body bone mineral density was, however, below 2 SD in the remaining 2 patients aged 19.7 and 20 years, respectively. Both had SMA III but had lost independent ambulation for a period of 3.5 years. CONCLUSION: Our results suggest that bone mineral density was surprisingly normal in most of the young SMA children studied. This is in contrast to what is reported in other conditions characterised by reduced mobility such as Duchenne muscular dystrophy. However, there was a tendency to decreasing bone mineral density with increasing age, not always related to the ability to walk, with the two eldest patients having the lowest values in spite of a relatively good mobility. These findings suggest that factors other than mobility are likely to have an effect on SMA bone mineral density.

Absorptiometry, Photon↗
PubMed2004

Can the Griffiths scales predict neuromotor and perceptual-motor impairment in term infants with neonatal encephalopathy?

AIMS: To examine the predictive value of early developmental testing for identifying neuromotor and perceptual-motor impairment at school age in children with neonatal encephalopathy (NE). METHODS: Eighty full term infants with NE were followed longitudinally. Where possible, children were tested on the Griffiths scales at 1 and 2 years and at 5-6 years, on the Touwen Examination, Movement ABC, and WPPSI. The relation between the Griffiths scores and later outcome measures was examined using correlation coefficients and sensitivity and specificity values. RESULTS: By 2 years, 25 children with cerebral palsy were too severely impaired to be formally assessed and remained so at 5-6 years. Abnormal Griffiths scores were obtained by 12% and 7% of the children at 1 and 2 years respectively. At 5-6 years, 33% had poor Movement ABC scores and 15% poor WPPSI scores. The highest correlation between Griffiths scores and the outcome measures was for the Movement ABC (0.72), although this accounted for only 50% of the variance. Sensitivity scores for the Movement ABC were below 70% but specificity was 100%. CONCLUSIONS: A poor score on the Griffiths scales at 1 and/or 2 years is a good predictor of impairment at school age. However, a normal score in the early years cannot preclude later neurological, perceptual-motor, or cognitive abnormalities.

Brain Diseases↗
PubMed2004

Visual function at school age in children with neonatal encephalopathy and low Apgar scores.

OBJECTIVE: To assess different aspects of visual function at school age in children who suffered from neonatal encephalopathy. METHOD: Thirty nine full term infants with neonatal encephalopathy, low Apgar scores, and early neonatal imaging were studied using a battery of tests assessing different aspects of visual function (crowding acuity, stereopsis, visual fields) at school age. The results were compared with brain magnetic resonance imaging (MRI) findings and, when possible, with the results of the assessment of visual function performed at 5 and 12 months, available in 24 of the 39 children examined at school age. RESULTS: Sixteen of the 39 children (41%) had abnormal results at school age in at least one of the visual tests used. Seven of these 16 were untestable on all tests. The remaining 23 children (59%) had normal results. CONCLUSIONS: The presence and severity of visual impairment was related to the severity of brain lesions. Moderate or severe basal ganglia lesions and severe white matter changes were always associated with abnormal visual function. Infants with normal MRI, minimal basal ganglia lesions, and minimal or moderate white matter involvement tended to have normal vision. It was also found that the assessment of visual function performed in the first year was a reliable indicator of visual function at school age. With two exceptions, the results on the 5 month visual assessment were predictive of visual outcome at school age. In the remaining two cases, a normal visual outcome at 5 years was associated with visual abnormalities at 5 months but these had already normalised by the age of 1 year.

Apgar Score↗
PubMed2003

Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation.

X-linked myotubular myopathy is a severe congenital myopathy in males, caused by mutations in the myotubularin (MTM1) gene on chromosome Xq28. In heterozygous carriers of MTM1 mutations, clinical symptoms are usually absent or only mild. We report a 6-year-old girl presenting at birth with marked hypotonia and associated feeding and respiratory difficulties. A muscle biopsy performed at 5 months suggested a diagnosis of myotubular myopathy. On examination at 6 years she had marked facial weakness with bilateral ptosis and external ophthalmoplegia, severe axial and proximal weakness and a mild scoliosis. Muscle magnetic resonance imaging showed a distinctive pattern of muscle involvement. Molecular genetic investigation of the MTM1 gene identified a heterozygous mutation in exon 12. X-inactivation studies in lymphocytes showed an extremely skewed pattern (97:3). This case emphasizes that investigation of the MTM1 gene and X-inactivation studies are indicated in isolated females with histopathological and clinical findings suggestive of myotubular myopathy.

Child↗
PubMed2003

Muscle magnetic resonance imaging in patients with congenital muscular dystrophy and Ullrich phenotype.

The aim of this study was to evaluate muscle magnetic resonance imaging findings in patients with congenital muscular dystrophy and Ullrich phenotype. Fifteen children with congenital muscular dystrophy and Ullrich phenotype were included in the study. All patients had collagen VI studies in muscle and, when family structure was informative, linkage studies to the collagen 6 loci. Three of the 15 patients had reduced collagen in muscle. One of the three was from an informative family and linked to one of the collagen 6 loci. Another patient was linked to one of the collagen 6 loci but had normal expression of collagen in muscle. The remaining 11 all had normal collagen expression in muscle. Only two of these 11 were from informative families and linkage to collagen 6 loci was excluded in them. All patients had muscle magnetic resonance imaging of their leg muscles using transverse T1 sequences. With the exception of the two patients in whom linkage to the collagen 6 loci was excluded, the other 13 patients showed the same pattern of selective involvement on magnetic resonance imaging of thigh muscles. This consisted of relative sparing of sartorius, gracilis, adductor longus and rectus. This pattern was also found in the case linked COL6A1/A2 locus but with normal collagen. This finding, and the striking clinical and magnetic resonance imaging concordance between patients with normal and reduced collagen VI in muscle suggest that collagen VI could still be the culprit in several cases with normal collagen expression, or alternatively a primary defect in a protein that closely interacts with collagen VI. Mutation analysis of the collagen 6 genes in cases with normal collagen VI expression is needed to resolve this issue.

Adolescent↗
PubMed2003

General movements detect early signs of hemiplegia in term infants with neonatal cerebral infarction.

Background. Studies have reported that infants with hemiplegia of congenital origin may have a period between birth and up to 12 months when clinical signs of hemiplegia are not evident. The aim of this study was to establish whether the assessment of general movements (GMs) may help in the earlier detection of signs of hemiplegia. Subjects and Methods. Eleven infants with cerebral infarction on brain MRI, and eleven normal controls were enrolled in the study. Quality of GMs was assessed from videotapes between 3 and 6 weeks and between 9 and 16 weeks. Neurological outcome was evaluated at least at two years. Results. Seven of the 11 infants had an assessment performed between 3 and 6 weeks: abnormal GMs were observed in all the infants who developed hemiplegia, but one child had abnormal GMs and a normal outcome. All 11 infants had a scorable assessment between 9 and 16 weeks. In all a specific type of GMs, fidgety movements (FMs), were predictive of neurological outcome. The presence of early asymmetries at both 3 - 6 and 9 - 16 weeks was also significantly associated with later signs of hemiplegia. Conclusions. The assessment of GMs after the neonatal period appears to be very useful in the early identification of hemiplegia in infants with cerebral infarction. Whilst the prediction of hemiplegia should be possible from early neonatal MRI brain scans, this facility is not always available. Observation of GMs is a bedside clinical approach that allows confirmation of early prediction from MRI, early rehabilitation if needed and reassurance that neurological outcome will be good where that is appropriate.

Cerebral Infarction↗
PubMed2003

Occipito-temporal polymicrogyria and subclinical muscular dystrophy.

We report a two-year-old Caucasian boy who had neonatal seizures and was found to have bilateral occipito-temporal polymicrogyria on neonatal brain MRI. The child had no additional neurological abnormality other than the neonatal seizures, but serum CK was found to be elevated (5 - 7 times normal values) and the muscle biopsy showed evidence of early muscular dystrophy. Detailed protein and genetic studies did not allow the identification of a known form of muscular dystrophy. The boy has been followed regularly and he currently has mild global developmental delay but no clinical signs of muscle involvement. The association of polymicrogyria and muscular dystrophy is known to occur in Fukuyama and Walker Warburg muscular dystrophies, in muscle-eye-brain disease and in some patients with merosin deficient CMD. However the absence of weakness and of eye involvement, the normal expression of merosin and alpha dystroglycan and the pattern of brain involvement make it very unlikely that the child is affected by one of these forms. As the pattern of brain involvement and the muscle pathology is not typical of one of the forms of neuronal migration disorders secondary to a known gene defect, we suspect that the combination of muscle and brain involvement found in this child is not coincidental. Our findings suggest that serum CK should be determined in children with undiagnosed polymicrogyria, even in the absence of weakness. This may lead to an expansion of our understanding of muscle dystrophies and cortical dysplasias.

Child, Preschool↗
PubMed2003

Neonatal cerebral infarction and visual function at school age.

OBJECTIVE: To assess various aspects of visual function at school age in children with neonatal cerebral infarction. PATIENTS AND METHODS: Sixteen children born at term, who had cerebral infarction of perinatal onset on neonatal magnetic resonance imaging (MRI) were assessed using a battery of visual tests. This included measures of crowding acuity (Cambridge Crowding Cards), stereopsis (TNO test), and visual fields. The results of the visual assessment were compared with the type and the extent of the lesion observed on neonatal MRI. RESULTS: Only six of the 16 children (28%) had some abnormalities of visual function on these tests. Visual abnormalities were more common in children with more extensive lesions involving the main branch of the middle cerebral artery and were less often associated with lesions in the territory of one of the cortical branches of the middle cerebral artery. The presence of visual abnormalities was not always associated with the involvement of optic radiations or occipital primary visual cortex. Abnormal visual fields were only found in children who also developed hemiplegia. CONCLUSIONS: Abnormality of visual function is not common in children who had neonatal infarction and, when present, tends to be associated with hemiplegia and more extensive lesions.

Cerebral Infarction↗
PubMed2002

Pilot trial of albuterol in spinal muscular atrophy.

The aim of this pilot study was to evaluate the effect of albuterol in children with spinal muscular atrophy (SMA). Thirteen patients (five with SMA II and eight with SMA III) were given oral albuterol for 6 months. There was a significant increase in myometry, forced vital capacity, and lean body mass between the baseline and the 6-month assessments (p < 0.05). Albuterol may have a beneficial effect in patients with SMA without causing any significant adverse effects. Larger randomized, placebo-controlled trials are needed to confirm this observation.

Absorptiometry, Photon↗
PubMed2002

Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.

Central core disease (CCD) is a congenital myopathy due to dominant mutations in the skeletal muscle ryanodine receptor gene (RYR1). The authors report three patients from two consanguineous families with symptoms of a congenital myopathy, cores on muscle biopsy, and confirmed linkage to the RYR1 locus. Molecular genetic studies in one family identified a V4849I homozygous missense mutation in the RYR1 gene. This report suggests a congenital myopathy associated with recessive RYR1 mutations.

Biopsy↗
PubMed2002

Collagen VI involvement in Ullrich syndrome: a clinical, genetic, and immunohistochemical study.

BACKGROUND: Ullrich congenital muscular dystrophy (UCMD) is a form of merosin-positive congenital muscular dystrophy characterized by proximal contractures, distal laxity, rigidity of the spine, and respiratory complications. Recently, a deficiency of collagen VI on muscle and skin biopsy together with recessive mutations in the collagen 6A2 gene were reported in three families with UCMD. However, the clinical spectrum, frequency, and level of heterogeneity of this disorder are not known. SUBJECTS AND METHODS: The authors studied 15 patients (aged 3 to 23.6 years) with a clinical diagnosis of UCMD. Linkage analysis to the three collagen VI genes was performed in all informative families (n = 7), whereas immunohistochemical analysis of collagen VI expression in muscle was performed in the remaining cases. RESULTS: An immunocytochemical reduction of collagen VI was observed in six patients. Three of the six patients belonged to informative families, and haplotype analysis clearly suggested linkage to the COL6A1/2 locus in two cases and to the COL6A3 loci in the third case. In the remaining nine patients, primary collagen VI involvement was excluded based on either the linkage analysis (four families) or considered unlikely based on normal immunolabeling of collagen VI. Age and presentation at onset, the distribution and severity of weakness and contractures, and the frequency of nonambulant patients were similar in the patients with and without collagen VI involvement. Distal laxity, rigidity of the spine, scoliosis, failure to thrive, and early and severe respiratory impairment were found in all patients by the end of the first decade of life, irrespective of their maximum motor functional ability or their collagen status. CONCLUSIONS: These results suggest that collagen VI involvement is relatively common in UCMD (40%); however, the role of this molecule was excluded in a number of cases, suggesting genetic heterogeneity of this condition.

Adolescent↗
PubMed2002

Hypermyelinating neuropathy, mental retardation and epilepsy in a case of merosin deficiency.

Children with a deficiency of laminin alpha 2 chain generally show an involvement of skeletal muscles, cerebral white matter and peripheral nerves. Among these patients, however, there is increasing evidence of molecular and phenotype heterogeneity. We report a 19-year-old girl with distal weakness, mental retardation and refractory epilepsy in whom elevated serum CK suggested a myopathy. Electrophysiological and neuroimaging examinations as well as studies of nerve and muscle biopsies were performed. Nerve conduction velocities were definitely reduced and brain MRI demonstrated a diffuse white matter involvement. The muscle biopsy showed both myopathic and neurogenic features. By immunohistochemistry laminin alpha 2 chain was mildly reduced in muscle and virtually absent in peripheral nerve. Teasing of sural nerve fibers showed a 'globular' hypermyelination characteristically located at the paranodal regions. A mild loss of myelinated fibers without any demyelination-remyelination changes was found. Haplotype analysis suggested linkage to the LAMA2 locus. Our case is peculiar as the putative mutation probably affects the expression of laminin alpha 2 chain is affected in a tissue specific manner: the protein is virtually absent in peripheral nerves but only mildly reduced in skeletal muscle. As to the disorder of nerve myelination, an absence or abnormal functioning of laminin alpha 2 chain can alter the feed-back control during myelinogenesis, leading to an over-ensheathment of axon. Alternatively, a compensatory up-regulation of other laminins can induce the hyperproduction of myelin sheaths. This case provides new evidence of the phenotypical heterogeneity of the LAMA2 gene and sheds light in understanding the role of laminin alpha 2 chain in myelination of peripheral nerve.

Adult↗