Biomedical subjects

Elisa Fazzi

Publications and source records attributed to Elisa Fazzi.

18 recordsLinked to original sources

PubMed2006

Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.

Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.

Amino Acid Sequence↗

PubMed2006

Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome.

Joubert syndrome-related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal manifestations. CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies.

Animals↗

PubMed2006

Changes in the optic disc excavation of children affected by cerebral visual impairment: a tomographic analysis.

PURPOSE: To obtain quantitative data on the optic disc excavation in children affected by cerebral visual impairment (CVI) by using the Heidelberg Retinal Tomograph (HRT)-II (Heidelberg Engineering, Heidelberg, Germany). METHODS: A total of 24 subjects affected by CVI (mean age, 7.28 years) were examined: 16 in alert conditions and 8 under general anesthesia. The following parameters of the optic nerve head were examined: disc area, cup area, rim area, cup volume, rim volume, cup-to-disc area ratio, mean cup depth, maximum cup depth, cup shape measure, and mean retinal nerve fiber layer (RNFL) thickness. The tomographic results in children with CVI were compared with those of 88 normal, alert subjects of similar age. RESULTS: The optic disc of patients with CVI appeared smaller than normal. Its excavation, however, was more pronounced. Several tomographic parameters were altered in CVI-affected subjects. Statistical analysis showed a highly significant probability in cup-to-disc area ratio (P < 0.01, both eyes), rim area (P < 0.01, both eyes), cup shape measure (P < 0.01, right eye; P < 0.01, left eye), and mean RNFL thickness (P < 0.01, right eye; P < 0.01, left eye). A novel observation was temporal atrophy of the optic nerve head in CVI. CONCLUSIONS: The data provide a tridimensional, objective evaluation of the anatomic alterations of the optic nerve head in children with CVI. Furthermore, tomographic standards for optic disc shape in normal children are set for the first time.

Brain Ischemia↗

PubMed2005

Neurochemical evidence to implicate elevated glutamate in the mechanisms of high intraocular pressure (IOP)-induced retinal ganglion cell death in rat.

High intraocular pressure (IOP)-induced ischemia is a model for retinal neurodegeneration that recapitulates pathological features almost identical to those seen in patients after central retinal or ophthalmic artery occlusion and may also represent a model of acute angle closure glaucoma. Using this experimental model, we present data indicating that acute IOP elevation for 45 min is followed by a progressive decline in the number of retinal ganglion cells (RGC) which appear to die via an apoptotic mechanism. The observation that systemic treatment with MK801, a N-methyl-d-aspartate (NMDA) receptor antagonist, with GYKI52466, a non-NMDA receptor antagonist, or with l-NAME, an inhibitor of nitric oxide synthase (NOS), prevents the RGC loss observed 24 after IOP elevation strongly suggests an excitotoxic, glutamate-mediated, mechanism of RGC death. The latter deduction is strengthened by the evidence that a microdialysis probe placed into the retinal tissue of rats bearing IOP elevation revealed an increase (90% as compared to baseline value) in glutamate levels that peaked 130 min after the beginning of reperfusion and was reversed by a pre-treatment with MK801. Collectively, our data suggest that acute elevation of IOP increases intraretinal levels of glutamate with consequent abnormal activation of NMDA and non-NMDA subtypes of glutamate receptors and increased NOS activity leading to excitotoxic, glutamate-mediated, RGC death.

Animals↗

PubMed2005

Towards improved clinical characterization of Leber congenital amaurosis: neurological and systemic findings.

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy that presents in infancy. LCA is both clinically and genetically heterogeneous. The aim of our study was to clarify the clinical aspects of LCA and to contribute to improved characterization of the disorder. We studied 40 children affected by LCA (mean age at first observation: 19 months, range: 8-50 months), who underwent a comprehensive evaluation that included: neurophthalmological evaluation, electroretinogram (ERG), and visual evoked potentials (VEPs), general and neurological examinations, developmental assessment using scales for visually impaired children, neuroradiological examinations, hepatic and renal function and metabolic investigations, brainstem auditory evoked potentials (BAEPs), EEG, and hand radiographs. Analyses of known LCA genes are ongoing. The subjects are still being followed up at 6-/12-month intervals. All the subjects fulfilled De Laey's criteria for LCA. The neurological examination was abnormal in 31 cases (hypotonia, ataxia with/without associated cerebellar signs). Cognitive development was normal in 24 cases, borderline in five, and subnormal in 11. Mild and nonspecific alterations on MRI were present in seven cases, and "molar tooth" sign in four; all the others had a normal neuroradiological picture. Among the subjects presenting with neurological signs, a subgroup (13 patients) emerged that was characterized by systemic (skin, kidney, liver) involvement. Our data confirm that LCA is a heterogeneous entity that can present as an isolated ocular manifestation, or in association with neurological and systemic abnormalities and support the need for a multidisciplinary approach to this entity and for genotype-phenotype studies.

Blindness↗

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

Prognostic value of umbilical artery Doppler studies in unselected preterm deliveries.

OBJECTIVE: To evaluate the prognostic value of umbilical artery Doppler studies in premature deliveries. METHODS: In this cohort study of 582 singleton pregnancies delivered between 24 and 35 weeks of gestation, we evaluated the ratio of peak-systolic to end-diastolic (S/D) blood flow velocities in the umbilical artery of all the patients. The correlations among the results of the Doppler studies, short-term neonatal complications, and the infants' neurodevelopmental outcome at 2 years were studied by univariable and multivariable methods. RESULTS: The prevalences of either neonatal death or cerebral palsy among the 266 (45.7%) growth restricted fetuses were 3.4% (3/88) in pregnancies with a S/D ratio below the 95th percentile, 4.9% (5/103) in pregnancies with a S/D at or above the 95th percentile, and 17.3% (13/75) in those with absent or reversed end-diastolic blood flow in the umbilical artery (P for trend = .001). The corresponding figures in the 316 pregnancies with adequate fetal growth were 6.4% (15/234) and 4.3% (3/69) among pregnancies with a S/D ratio below and at or above 95th percentile, respectively, whereas no cases of either neonatal death or cerebral palsy were recorded in the 13 pregnancies with adequate fetal growth and absent or reversed end-diastolic blood flow velocity (P for trend = .28; chi(2) for heterogeneity of linear trends compared with growth-restricted infants = 7.02, P = .008). In logistic regression, in pregnancies complicated by fetal growth restriction, absent or reversed end-diastolic blood flow in the umbilical artery was still associated with an increased risk of either neonatal death or cerebral palsy even after adjustment for gestational age and proportion of expected birth weight, (odds ratio 3.2, 95% confidence interval 1.18-8.66, P = .02). CONCLUSION: Absent or reversed end-diastolic flow in the umbilical artery is an independent predictor of either neonatal death or cerebral palsy in preterm growth-restricted fetuses. In the absence of fetal growth restriction, umbilical artery Doppler study was associated with none of the infant outcome parameters studied.

Adult↗

PubMed2005

Factors predicting the efficacy of botulinum toxin-A treatment of the lower limb in children with cerebral palsy.

Botulinum toxin A is widely used for spasticity management in children with cerebral palsy, although outcomes are unpredictable. The aim of this study was to identify criteria for selecting patients most likely to benefit from botulinum toxin A treatment. Fifty-five subjects, aged 2.5 to 18 years, were recruited. The assessment covered measures of spasticity (Modified Ashworth Scale), function (using the Gross Motor Function Measure and the Physician's Rating Scale), selective motor control, static range of motion at the ankle with knee extended and flexed, range of motion of the knee flexors, central and peripheral vision, and cognitive ability. Outcomes at 3 months were compared with baseline values. All of the scales showed significant differences between pre- and postinjection values. Significantly increased Gross Motor Function Measure scores were found in children aged 48 months or under and in those able to walk with support. Greater improvements in selective motor control and Physician's Rating Scale were seen in those with a less severe pattern of paralysis, lower levels of impairment, the ability to walk (with or without support), normal visual acuity, and normal or borderline cognition. We identified factors that mark out patients as most likely to achieve functional gains: young age, hemiplegia or diplegia, slight to moderate disability, walking with support, normal or borderline cognition, and normal or borderline visual acuity.

Adolescent↗

PubMed2004

Two-year infant neurodevelopmental outcome after single or multiple antenatal courses of corticosteroids to prevent complications of prematurity.

OBJECTIVE: This study was undertaken to evaluate the effect of exposure to multiple antenatal steroid courses on short-term neonatal morbidity and 2-year infant neurodevelopmental outcome. STUDY DESIGN: This was a prospective observational study of 201 preterm singleton infants who received 1 or more courses of corticosteroids to prevent complications of prematurity and were delivered between 24 and 34 weeks' gestation at a single institution. Neurodevelopmental outcome of the infants was evaluated at 2 years corrected age. Logistic regression analysis was used to perform multivariate analyses of associations and trends. RESULTS: One hundred thirty-eight subjects (68.7%) received at least 1 complete course of betamethasone, whereas 63 (31.3%) patients were treated with dexamethasone. The prevalence of multiple steroid doses exposure was 26.8% (37/138) in betamethasone and 52.4% (33/63) in dexamethasone group. The prevalence of infant leukomalacia, including both prolonged echogenicity and cystic leukomalacia, was 25.9% (34/131) after a complete corticosteroid course, 40% (6/15) after 1, 42.3% (12/28) after 2, and 44.4% (12/27) after more than 2 additional courses, respectively (adjusted P for trend=.011). In the same categories of steroid exposure, the corresponding prevalences of 2-year infant neurodevelopmental abnormalities were 18% (20/111), 21.4% (3/14), 29.2% (7/24), and 34.8% (8/23), respectively (adjusted P for trend=.038). Multivariate study of first grade interaction suggested that the risk of leukomalacia and 2-year infant neurodevelopmental abnormalities associated with multiple doses exposure was confined to dexamethasone. In fact, compared with betamethasone, exposure to multiple doses of dexamethasone was associated with an increased risk of leukomalacia (19/33 compared with 11/37; odds ratio [OR]=3.21, 95% CI=1.07-9.77) and overall 2-year infant neurodevelopmental abnormalities (12/28 compared with 6/35; OR=3.63, 95% CI=1.03-13.58). CONCLUSION: In this study, multiple antenatal courses of dexamethasone but not betamethasone were associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities.

Betamethasone↗

PubMed2004

Visual-perceptual impairment in children with periventricular leukomalacia.

We set out to define visuo-perceptual impairment related to periventricular leukomalacia (PVL) using the Developmental Test of Visual Perception (DTVP). Correlations were sought between visual-perceptual deficits and DTVP profile and neuroradiological and neurophthalmological findings. The DTVP was administered to 20 children (m/f: 10/10), aged between 5 and 8 years (mean: 6.95 years), presenting with: spastic diplegia; PVL documented by brain MRI; normal or mildly impaired visual acuity; mild-moderate upper limb functional impairment. The mean General Visual-Perceptual Quotient was impaired, showing a great variability among the patients. Despite this, an uneven DTPV profile, characterised by a significant difference between the VMIQ and the Non-Motor Visual-Perceptual Quotient (P < 0.001) and a poor result on the Closure subtest (identification of whole figures from incomplete visual information) was observed in all the subjects. This profile reflects a deficit in eye-hand coordination and in praxic-constructional abilities and could be the expression of malfunctioning of the occipital-parietal pathway of visual integration, the so-called 'dorsal stream,' a hypothesis reinforced by the emergence of a statistically significant correlation between the neuroradiological data and the presence of visual-perceptual impairment.

Brain↗

PubMed2004

Fetal growth and infant neurodevelopmental outcome after preterm premature rupture of membranes.

OBJECTIVE: To evaluate the prognostic values of fetal size before birth and fetal growth during the latency period in patients with preterm premature rupture of the membranes (PROM). METHODS: A prospective cohort study of 69 singleton pregnancies complicated by prolonged (14 days or more) PROM (24 to 31 weeks of gestation). Measures of fetal size and growth were compared with corresponding expected values from our reference curves. The correlations between deviations from expected measures of fetal size and growth, short-term neonatal complications, and infant neurodevelopmental outcome at 2 years were studied by univariate methods and logistic regression. RESULTS: The mean gestational ages and standard deviations at membrane rupture and at birth were 27.9 +/- 2.4 and 31.5 +/- 2.1 weeks. At a corrected age of 2 years, of the 65 (94.2%) survivors, 3 infants (4.6%) had cerebral palsy, 13 (20%) had minor neurodevelopmental impairment, and 49 (75.4%) were judged to have had normal development. Compared with surviving infants without a major handicap, the group of infants who died and those with cerebral palsy had lower proportions of expected birth weight (0.766 +/- 0.1 as compared with 0.859 +/- 0.13, P =.029), head (0.869 +/- 0.07 as compared with 0.950 +/- 0.07, P =.05), and abdominal (0.793 +/- 0.04 as compared with 0.888 +/- 0.1, P =.001) circumference growth during latency period. In logistic regression analysis, lower-than-expected ultrasound measures of fetal abdominal circumference before birth (odds ratio 1.09; 95% confidence interval 1.01, 1.18) or of abdominal circumference growth during the latency period (odds ratio 1.1; 95% confidence interval 1.01, 1.2) were significantly associated with an increased likelihood of an infant neurodevelopmental abnormality at 2-year follow-up. CONCLUSION: In pregnancies complicated by preterm PROM, lower-than-expected measures of fetal size and fetal growth were associated with an increased rate of infant neurodevelopmental outcome at 2-year follow-up. LEVEL OF EVIDENCE: II-2

Birth Weight↗

PubMed2004

Visual function in infants with West syndrome: correlation with EEG patterns.

PURPOSE: Several studies have reported behavioral and electrophysiological evidence of visual impairment during the active stage of West syndrome. The underlying mechanisms are, however, poorly understood, and little has been reported about the correlation between visual impairment, EEG patterns, and brain lesions. The aim of the study was to assess visual function at the onset of spasm and 2 months thereafter and relate visual findings to brain lesions and EEG features. METHODS: Twenty-five infants with West syndrome were enrolled and studied with (a) a full clinical assessment including a battery of tests specifically designed to assess visual function, (b) a video-polygraphic study, and (c) brain magnetic resonance imaging (MRI). Besides brain neuroimaging and EEG comparison with visual function, an intra-EEG analysis was performed to investigate the possible relation of EEG patterns to fluctuating visual behavior (fixation and following). RESULTS: Twenty-two children had at least one abnormal result on one or more of the tests assessing visual function at T0. Visual impairment at the spasm onset was related to the sleep disorganization rather than to the hypsarrhythmic pattern in awake EEG. After 2 months, both EEG features become significantly linked to visual function. Visual function improved in several cases after 2 months, in parallel with the seizure regression. No relation was found between EEG patterns and fluctuating visual behavior. CONCLUSIONS: The study supplies new evidence of the involvement of visual function in West syndrome. The presence of abnormal visual findings in infants without lesions on brain MRI suggests that visual abnormalities are due not only to brain injury but also to epileptic disorder per se. New insight is also provided into the possible mechanisms underlying clinical and EEG abnormalities.

Brain↗

PubMed2004

Obstetric risk factors and persistent increases in brain parenchymal echogenicity in preterm infants.

OBJECTIVE: To assess the risk of persistent (>7 days) increases in brain parenchymal echogenicity in preterm infants and their association with known obstetric risk factors. DESIGN: Case-control study of prospectively collected data. SETTING: A University hospital in Northern Italy. POPULATION: Eighty-five singleton infants between 24 and 34 weeks of gestation with a cranial ultrasonographic diagnosis of persistently increased parenchymal echogenicity without development of cystic degeneration, and 170 control infants with negative cranial ultrasonographic findings. METHODS: A comparison of the prevalence of selected obstetric risk factors between infants with persistent echo-dense lesions and negative controls. MAIN OUTCOME MEASURES: Odds ratios of persistent echo-dense lesions including first-degree interactions between variables. RESULTS: After adjusting for birthweight, logistic regression analysis showed that the only factor associated with an increased risk of persistent brain echo-dense lesions in infants was multiple courses of antenatal steroids (OR = 2.14, 95% CI = 1.11-4.15, P= 0.024). In this group, the risk of persistent echo-dense lesions was particularly high in: (i) mothers receiving dexamethasone rather than betamethasone (P value for interaction = 0.015) and (ii) after expectant management of pre-eclampsia or intrauterine growth retardation (P value for interaction = 0.03). CONCLUSIONS: Multiple doses of antenatal steroids, especially dexamethasone, could influence the prevalence of persistent increases in brain parenchymal echogenicity in preterm infants.

Brain Diseases↗

PubMed2003

Leber's congenital amaurosis: an update.

Leber's congenital amaurosis (LCA) is a clinically and genetically heterogeneous disorder characterized by severe loss of vision at birth. It accounts for 10-18% of cases of congenital blindness. Some patients exhibit only blindness of retinal origin whereas others show evidence of a multi-systemic involvement. We review the literature relating to this severe disorder, highlighting unresolved questions, in particular the nature of the association of LCA with mental retardation and with systemic findings and syndromic pictures. In recent years, genetic advances in the diagnosis of LCA have opened up new horizons, also from a therapeutic point of view. A better understanding of this pathology would be valuable for paediatric neurologists.

Blindness↗

PubMed2002

Aicardi-Goutières syndrome: a description of 21 new cases and a comparison with the literature.

The International Aicardi-Goutières Syndrome Association (IAGSA) was founded in 2000, its aim being to collect and analyse all available information on this rare syndrome (whose true incidence is not known) in order to increase knowledge of the pathology and the number of reported cases. We analysed the clinical, neuroradiological and biological characteristics of 21 new Aicardi-Goutières syndrome subjects (seven observed directly and 14 on whom we gathered detailed clinical information) and compared our findings with data in the literature. The main clinical symptoms (pyramidal and extrapyramidal symptoms, psychomotor delay, microcephaly) and neuroradiological features (basal ganglia calcification, atrophy, white matter alterations) observed show a greater homogeneity in our subjects than in the literature cases, which indicates an improvement in the diagnostic accuracy of Aicardi-Goutières syndrome. Other symptoms, such as feeding difficulties and irritability are less frequent, but characteristic and present early (even at onset of the disease). In the literature, doubts are expressed as to whether lymphocytosis and/or raised interferon-alpha in cerebrospinal fluid are crucial for a diagnosis of Aicardi-Goutières syndrome. Our data suggest that they are, and in particular that an important role is played by raised interferon-alpha. The clinical course seems to show different stages: early onset, rapid progression, severe deterioration, stabilization. Our follow-up seems to indicate a trend not necessarily towards a worsening, but instead towards a stabilization or even a slight improvement of the clinical picture.

Adolescent↗

PubMedDate not supplied

Visual acuity in the first two years of life in healthy term newborns: an experience with the teller acuity cards.

Teller Acuity Cards are a new "preferential looking" procedure for the evaluation of visual acuity in newborns and infants. We used this test to assess, longitudinally, visual acuity in 60 healthy term newborns followed up from birth to two years of age. In order to have a set of comparison parameters for use in studies of newborns at risk of developing visual system impairment, the relative maturational curve was plotted. The acuity values of our sample are in line with those reported by other authors in the literature and they represent the first set of such data referring to a group of healthy term newborns in Italy. This paper provides a visual acuity curve for the first two years of life obtained from healthy term newborns, a curve which could prove useful for reference when this technique is used on newborns at risk of developing neurological and especially visual problems.

Child, Preschool↗

PubMedDate not supplied

Aicardi-Goutières syndrome: differential diagnosis and aetiopathogenesis.

Aicardi-Goutières syndrome (AGS) is a progressive encephalopathy with onset in the first year of life and a recessive autosomal pattern of inheritance. The syndrome is characterised by acquired microcephaly, basal ganglia calcifications, white matter abnormalities, chronic cerebrospinal fluid (CSF) lymphocytosis and raised interferon-alpha (INF-alpha) in the CSF. AGS is diagnosed on the basis of a clinical picture characterised by microcephaly and by the onset of encephalopathy associated with severe psychomotor delay, spasticity and extrapyramidal signs. CT is very important in the diagnosis of AGS, demonstrating clearly the presence of calcifications at basal ganglia level: these are often bilateral and symmetrical. CT scan and MRI reveal leukodystrophy and progressive cerebral atrophy. A raised level of INF-alpha in the CSF constitutes a marker of the syndrome: this level, which falls with age, is higher in the CSF than in the serum, suggesting intrathecal synthesis. Differential diagnosis in AGS is carried out to exclude the presence of other neurological and endocrinological pathologies characterised by the presence of intracranial calcification; considering the white matter abnormalities, it is necessary to exclude forms of leukodystrophy associated with metabolic defects, known or otherwise. One fundamental aspect that remains to be clarified is the aetiopathogenetic mechanism underlying AGS: the most well-founded hypotheses are reported. There does not exist, to date, any causal therapy for AGS, although genetic studies, particularly those focusing on interferon-regulating genes, may well provide some therapeutic indications.

Basal Ganglia Diseases↗

PubMedDate not supplied

A questionnaire on sleep behaviour in the first years of life: preliminary results from a normative sample.

The authors developed a questionnaire in Italian for investigating sleep problems in infants and toddlers. Applying the questionnaire, they conducted an exploratory investigation into the sleep behaviour of a sample of normal children during their first three years of life in order to gather preliminary data regarding the ease of use of the instrument. The questionnaire and the results of its first application (in an Italian sample of 50 healthy children aged 10-39 months) are presented. The results provide interesting information on the sleep behaviour of the young children in our sample and prompt reflections in relation to the instrument employed. The sleep behaviour questionnaire emerged, above all, as easy to use and readily comprehensible to those participating in this research study. Furthermore, it provided parents with an opportunity to reflect upon their child and his/her rhythms (in particular sleep-wake rhythms) and upon their own ability to manage these rhythms. This instrument seems, on the basis of these preliminary data, to allow the tracing of a well-defined and complete picture of the sleep behaviour of the healthy child in the first years of life.

Adult↗