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Biomedical subjects

A Berardinelli

Publications and source records attributed to A Berardinelli.

At least 19 recordsLinked to original sources
PubMed2006

Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy.

OBJECTIVE: To assess the efficacy of phenylbutyrate (PB) in patients with spinal muscular atrophy in a randomized, double-blind, placebo-controlled trial involving 10 Italian centers. METHODS: One hundred seven children were assigned to receive PB (500 mg/kg/day) or matching placebo on an intermittent regimen (7 days on/7 days off) for 13 weeks. The Hammersmith functional motor scale (primary outcome measure), myometry, and forced vital capacity were assessed at baseline and at weeks 5 and 13. RESULTS: Between January and September 2004, 107 patients aged 30 to 154 months were enrolled. PB was well tolerated, with only one child withdrawing because of adverse events. Mean improvement in functional score was 0.60 in the PB arm and 0.73 in placebo arm (p = 0.70). Changes in the secondary endpoints were also similar in the two study arms. CONCLUSIONS: Phenylbutyrate was not effective at the regimen, schedule, and duration used in this study.

Child↗
PubMed2006

POMT2 mutation in a patient with 'MEB-like' phenotype.

Mutations in POMT2 have so far only been reported in patients with Walker-Warburg phenotype. We report heterozygous POMT2 mutations in an a girl with a milder phenotype characterized by mental retardation, microcephaly, hypertrophy of the quadriceps and calf muscles, and structural brain changes mostly affecting the posterior fossa. Our findings suggest that, as previously reported for POMT1 and FKRP, mutations in the POMT2 can also be associated with clinical heterogeneity.

Amino Acid Sequence↗
PubMed2006

Reliability of the Hammersmith functional motor scale for spinal muscular atrophy in a multicentric study.

The aim of this study was to validate the Hammersmith functional motor scale for children with spinal muscular atrophy in a large cohort of 90 non-ambulant children with spinal muscular atrophy type 2 or 3. All had a baseline assessment (T0) and were reassessed either at 3 months (T1) (n = 66) or at 6 months (T2) (n = 24). Inter-observer reliability, tested on 13 children among 3 examiners, was > 95%. Of the 66 children examined after 3 months 4 had adverse effects in between assessments and were excluded from the analysis. Forty-two (68%) of the remaining 62 reassessed had no variation in scores between T0 and T1 and 13 (21%) were within +/- 1 point. 9 (37.5%) of the 24 children reassessed after 6 months had no variation in scores between T0 and T2 and another 9 (37.5%) had variations within +/- 1 point. Our study confirms previous observations of the reliability of the scale and helps to establish a baseline for assessing changes of functional ability over 3 and 6 month intervals. This information can be valuable in view of therapeutic trials.

Child↗
PubMed2004

LAMA2 loss-of-function mutation in a girl with a mild congenital muscular dystrophy.

The authors report a girl with autosomal recessive congenital muscular dystrophy linked to chromosome 6 (MDC1A) who carries a homozygous out-of-frame deletion in exon 56 of the LAMA2 gene but has a mild phenotype. She is still ambulant at age 13 years, shows white matter abnormalities on MRI, and traces of laminin alpha2 in her muscle biopsy with one of three antibodies used. This patient suggests that modulating factors can be associated with a less severe clinical phenotype in MDC1A.

Adolescent↗
PubMed2003

Measurement of skeletal muscle mass in Duchenne muscular dystrophy: use of 24-h creatinine excretion.

Creatinine concentration in 24-h urine has been proposed as an indirect measure of body skeletal muscle mass (SMM). We attempted to correlate urinary creatinine levels with SMM in eight patients with Duchenne muscular dystrophy, a progressive disease in which the degree of muscle wasting parallels the rate of progression. Magnetic resonance imaging and a newly developed protocol for image analysis were used for the measurement of SMM. The patients ate a creatine-free diet for the week before urine collection. Creatinine was measured with an enzymatic-colorimetric method. Mean (+/-SD) SMM value was 5.4+/-2.5 kg and urine creatinine levels 205.8+/-96.4 mg/day. Daily urinary creatinine excretion did not correlate with SMM. The simple creatinine determination in urine cannot predict SMM in Duchenne muscular dystrophy.

Biomarkers↗
PubMed2003

Body composition and energy expenditure in Duchenne muscular dystrophy.

OBJECTIVE: To investigate the relationship between resting energy expenditure (REE) and body composition in Duchenne Muscular Dystrophy (DMD). DESIGN: An observational study. SETTING: University Research Centre. SUBJECTS: Nine Duchenne children (age range 6-12 y), mean relative weight 128%, agreed to undergo the investigation and all of them completed the study; INTERVENTIONS: Assessment of body composition (total body fat and skeletal muscle mass) by magnetic resonance imaging and resting energy expenditure by indirect calorimetry. MAIN OUTCOME MEASURES: Fat mass (FM; kg and percentage weight), fat-free mass (FFM; kg and percentage weight), muscle mass (kg and percentage weight), resting energy expenditure (kJ/kg body weight and kJ/kg fat-free mass). RESULTS: : In Duchenne children fat mass averages 32% and total skeletal muscle mass 20% of body weight. Resting energy expenditure per kg of body weight falls within the normal range for children of the same age range, while when expressed per kg of FFM is significantly higher than reference values. No relationship was found between REE and total skeletal muscle mass. CONCLUSIONS: Our results do not demonstrate a low REE in DMD boys; on the contrary REE per kg of FFM is higher than normal, probably due to the altered FFM composition. We suggest that the development of obesity in DMD children is not primarily due to a low REE but to other causes such as a reduction in physical activity and or overfeeding.

Body Composition↗
PubMed2000

A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy.

We randomized 18 Duchenne muscular dystrophy (DMD) boys whose age ranged from 5.2 to 14.6 years (mean, 7.3 years) for treatment with either deflazacort (0.9 mg/kg/day) or prednisone (0.75 mg/kg/day) on the basis of age and functional score at the onset of treatment. We followed the patients every 3 months for 1 year, evaluating four limb muscles with the Medical Research Council scale and performance of four functions (walking, climbing stairs, Gowers' maneuver, and rising from a chair). Side effects were monitored by a questionnaire and by routine blood examination, and weight and height were recorded at each visit. At 12 months, the effect of both steroids was examined by comparing the status of the treated patients with another group of untreated DMD patients that served as natural history control. The two steroids were equally effective in improving motor function and functional performances. At 9 months, the average weight increase with respect to baseline value was 5% (2 kg) in the deflazacort group but 18% in the prednisone group (P < 0. 005), and the change remained significant after 12 months (P < 0.05). Other minor but nonsignificant side effects were observed. Steroid treatment with deflazacort appears to cause fewer side effects than with prednisone, particularly weight gain, which could be important to maximize motor performances.

Adolescent↗
PubMed1999

Heart involvement in muscular dystrophies due to sarcoglycan gene mutations.

Mutations in the sarcoglycan genes cause autosomal-recessive muscular dystrophies. Because sarcoglycan genes and their protein products are highly expressed both in skeletal and cardiac muscle, patients with these mutations might be expected to be at risk to develop dilated cardiomyopathy. We therefore studied 13 patients with alpha-, beta-, gamma-sarcoglycan gene mutations by thorough cardiological assessment. Electrocardiographic or echocardiographic abnormalities were observed in about 30% of cases showing a severe course of muscular dystrophy. No correlation was found between the presence of cardiac abnormalities and the type of mutation or sarcoglycan gene involved. The cardiac involvement was never severe, but it may be detected in early stages of the muscle disease. The absence of overt cardiac dysfunction may be due to lower sarcoglycan protein expression in cardiac than skeletal muscle or to less sarcolemmal instability at the myocardial level, possibly related to the different distribution of forces generated by contraction of the myocardium with respect to proximal limb-girdle muscles.

Adolescent↗
PubMed1999

Dolicho-vertebrobasilar abnormality and migraine-like attacks.

This is a study of two children with neuroradiologically diagnosed dolichobasilar anomaly: in both cases, the diagnosis was based on magnetic resonance imaging and magnetic resonance angiography findings. We examined the first child (R., aged 6 years and 8 months) following four episodes of intense pain in the left orbit, lasting between 10 and 30 min and accompanied by photophobia and vomiting. The second child (S., aged 9 years and 2 months), suffering from Marfan's syndrome, was examined following recurrent episodes of intense pain that started above the left orbit, moving to the homolateral orbit after a few minutes. These episodes, which lasted between 20 and 30 min, took place mainly at night and were accompanied by phono-photophobia and vomiting. In both cases, the pain attacks can be interpreted as a result of compression of the root of the trigeminal nerve caused by an arterial malformation.

Anticonvulsants↗
PubMed1998

The efficacy of noninvasive mechanical ventilation on nocturnal hypoxaemia in Duchenne's muscular dystrophy.

The aim of this 2 yr follow-up study was to evaluate the efficacy of nocturnal noninvasive mechanical ventilation in a group of 10 Duchenne's muscular dystrophy (DMD) patients who desaturated during the night but had normal daytime blood gases: mean (range) age 18.3 (15-22) yrs; mean (SD) vital capacity (VC) 752.5 (460-1,308) mL; mean time in bed (TIB) with arterial oxygen saturation (Sa,O2) < 90% 22.8% of total TIB (range: 16.6-32.0); mean arterial oxygen tension (Pa,O2) 10.3 (9.3-11.7) kPa (78 (70.0-87.8) mmHg); mean arterial carbon dioxide tension (Pa,CO2) 5.9 (4.8-6.5) kPa (44.3 (36.3-48.5) mmHg). All the patients were noninvasively ventilated during the night with a bilevel positive pressure ventilation (BiPAP) devise in spontaneous mode in order to correct the episodes of nocturnal desaturation. Nocturnal Sa,O2 values normalized during nocturnal noninvasive mechanical ventilation, and daytime sleep-disordered breathing disappeared, for the entire study period. No statistically significant differences were observed between baseline and follow-up daytime blood gas values, although a slight increase in Pa,O2 was found. During the follow-up, VC declined at a rate of 79.1 +/- 25 mL.yr-1, less than that generally reported in the past in untreated patients in the same age range. In conclusion, our data suggest that patients with advanced Duchenne's muscular dystrophy with pronounced nocturnal desaturation, not fulfilling criteria for imperative ventilation, could be successfully treated with "elective" nocturnal ventilation with immediate benefits consequent to the correction of the nocturnal blood gas anomalies and with long-term benefits related to the preservation of residual respiratory function, delay of development of chronic hypercapnia and thus the requirement for imperative mechanical ventilation.

Adolescent↗
PubMed1996

Monosomy of distal 4q does not cause facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary neuromuscular disorder transmitted in an autosomal dominant fashion. FSHD has been located by linkage analysis in the most distal part of chromosome 4q. The disease is associated with deletions within a 3.2 kb tandem repeat sequence, D4Z4. We have studied a family in which an abnormal chromosome 4 segregates through three generations in phenotypically normal subjects. This chromosome is the derivative of a (4;D or G) (q35;p12) translocation. Molecular analysis of the region 4q35 showed the absence of the segment ranging from the telomere to locus D4F104S1. Probe p13E-11 (D4F104S1), which detects polymorphic EcoRI fragments containing D4Z4, in Southern blot analysis showed only one allele in the carriers of the abnormal chromosome 4. Probe p13E-11 EcoRI fragments are contained in the subtelomeric region of 4q and their rearrangements associated with FSHD suggested that the gene responsible for the muscular dystrophy could be subject to a position effect variegation (PEV) because of its proximity to subtelomeric heterochromatin. The absence of the 4q telomeric region in our phenotypically normal cases indicates that haploinsufficiency of the region containing D4Z4 does not cause FSHD.

Base Sequence↗
PubMed1995

Prospective study of gross motor development in children with SMA type II.

The natural history of SMA and the identification of predictive criteria of functional development are still a matter of discussion. This prospective study involved 20 children with SMA, aged between 3.10 and 15.7 years. The patients were followed from 1979 to 1992 in order to try to develop a greater understanding of the natural history of SMA at a very early age. A standardized protocol was used at regular intervals to assess parameters such as joint contractures, scoliosis and the milestones of gross motor functions. Our findings agree with the data in the literature concerning the early and generalized onset of joint contractures and scoliosis. A significant correlation was found between the level of acquired gross motor functions and walking with support. The acquisition of rolling by 5 years of age was the milestone that best correlated with the acquisition of walking with crutches and braces; furthermore the inability to roll seemed to correlate with the severity of the disease. These findings should be useful in planning a more rational rehabilitation program.

Adolescent↗
PubMed1995

Somatosensory and visual evoked potentials in congenital muscular dystrophy: correlation with MRI changes and muscle merosin status.

Congenital muscular dystrophy comprises a heterogeneous group of disorders, that have in common an early onset and a dystrophic picture on the muscle biopsy. The "pure" form of congenital muscular dystrophy is not associated with severe mental retardation or structural changes in the brain, though white matter changes on brain imaging have been detected in a significant proportion of cases. In this study we evaluated the incidence of sensory abnormalities (somatosensory and visual evoked responses) in a group of 17 patients with "pure" congenital muscular dystrophy and correlated the results of the evoked responses with the presence or absence of white matter changes on brain magnetic resonance imaging. Our results show close correlation between the presence of MRI white matter changes and abnormalities in the sensory evoked potentials. Conversely, all patients with normal brain MRI had normal somatosensory evoked potentials (SEP). Visual evoked potentials were less sensitive than somatosensory evoked potentials in detecting abnormalities in children with white matter changes on MRI. With the recent discovery of deficiency in merosin expression in the skeletal muscle of a subgroup of patients with CMD, we also correlated the presence or absence of white matter changes and the SEP responses with the merosin status. The results indicate that all merosin-negative patients had abnormal SEP as well as abnormal MRI, whilst no patient with normal merosin expression had an abnormal scan or abnormal SEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Minor neurological and perceptuo-motor deficits in children with congenital muscular dystrophy: correlation with brain MRI changes.

Diffuse white matter changes on magnetic resonance imaging (MRI) have been a consistent feature in some children with the "pure" form of congenital muscular dystrophy (CMD) in which there are no structural changes in the brain or severe mental retardation. The aim of this study was to assess fine motor and perceptuo-motor abilities in children with CMD with and without MRI changes. Twenty-two children with "pure" CMD were investigated with a standard neurological examination and a battery of tests (Manual dexterity from the Movement ABC, test of visual-motor integration, Zurich Neuromotor test) which have already been used to detect minor neurological signs related to white matter changes. The cohort was then divided in two groups for analysis depending on the presence or the absence of diffuse white matter changes. A significant difference was found for all the tests between the group of the CMD children with normal MRI and the group with diffuse white matter changes. The manual dexterity and the Zurich Neuromotor tests showed a greater sensitivity than the test of visual-motor integration, which had some false negatives. It is of interest that in the group with diffuse white matter changes the presence of contractures or weakness did not seem to affect the quality of the performance; all these children scored abnormally on the test, irrespective of the severity or the extent of contractures and weakness. In contrast, in children with normal MRI severe contractures and weakness did affect the performances. Our results demonstrate that perceptuo-motor difficulties and minor neurological soft signs are a consistent feature in CMD children with diffuse MRI changes but not with normal MRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗