Publications (18)65.32 Total impact
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Article: Congenital muscular dystrophies with cognitive impairment. A population study.
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ABSTRACT: Cognitive impairment has been reported in a significant proportion of patients with congenital muscular dystrophies (CMD), generally associated with brain changes. The aim of this study was to establish 1) the overall prevalence of CMD and cognitive impairment in the Italian population; 2) the frequency of individual genetically defined forms; and 3) the presence of distinct phenotypes not associated with mutations in the known genes. We included all patients with CMD and cognitive impairment followed in all the Italian tertiary neuromuscular centers. Clinical, brain MRI, and morphologic data were collected. Genetic screening of the known genes was performed according to clinical and muscle biopsy findings. Ninety-two of the 160 (58%) patients with CMD followed in our centers had cognitive impairment. alpha-Dystroglycan (alpha-DG) reduction on muscle biopsy was found in 73/92 (79%), with 42/73 carrying mutations in the known genes. Another 6/92 (7%) showed a laminin alpha2 deficiency on muscle biopsy and 5 of the 6 carried mutations in LAMA2. The remaining 13/92 (14%) patients had normal alpha-DG and laminin alpha2 expression on muscle. This is the first population study establishing the prevalence of CMD and cognitive impairment and providing a classification on the basis of clinical, MRI, and genetic findings. We also showed that cognitive impairment was not always associated with alpha-DG or laminin alpha2 reduction or with structural brain changes.Neurology 09/2010; 75(10):898-903. · 8.31 Impact Factor -
Article: Congenital muscular dystrophy with defective alpha-dystroglycan, cerebellar hypoplasia, and epilepsy.
Neurology 11/2009; 73(19):1599-601. · 8.31 Impact Factor -
Article: Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency.
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ABSTRACT: In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134-147 ms; normal <118 ms. We hypothesize that elevated GABA in ocular tissue of SSADH patients leads to a use-dependent downregulation of the major GABAergic receptor in eye, GABA(C), and that the VEP recordings' abnormalities, as evidenced by P100 latency and/or amplitude measurements, may be reflective of abnormalities within visual systems. This is a preliminary finding that may suggest the utility of performing VEP analysis in a larger sample of SSADH-deficient patients, and encourage a neurophysiological assessment of GABA(C) receptor function in Aldh5a1(-/-) mice to reveal new pathophysiological mechanisms of this rare disorder of GABA degradation.Journal of Inherited Metabolic Disease 05/2009; · 3.58 Impact Factor -
Article: Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.
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ABSTRACT: Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (alpha-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or putative glycosyltransferases. The aim of the study was to establish the prevalence of mutations in the six genes in the Italian population and the spectrum of clinical and brain MRI findings. As part of a multicentric study involving all the tertiary neuromuscular centers in Italy, FKRP, POMT1, POMT2, POMGnT1, fukutin, and LARGE were screened in 81 patients with CMD and alpha-DG reduction on muscle biopsy (n = 76) or with a phenotype suggestive of alpha-dystroglycanopathy but in whom a muscle biopsy was not available for alpha-DG immunostaining (n = 5). Homozygous and compound heterozygous mutations were detected in a total of 43/81 patients (53%), and included seven novel variants. Mutations in POMT1 were the most prevalent in our cohort (21%), followed by POMT2 (11%), POMGnT1 (10%), and FKRP (9%). One patient carried two heterozygous mutations in fukutin and one case harbored a new homozygous variant in LARGE. No clear-cut genotype-phenotype correlation could be observed with each gene, resulting in a wide spectrum of clinical phenotypes. The more severe phenotypes, however, appeared to be consistently associated with mutations predicted to result in a severe disruption of the respective genes. Our data broaden the clinical spectrum associated with mutations in glycosyltransferases and provide data on their prevalence in the Italian population.Neurology 04/2009; 72(21):1802-9. · 8.31 Impact Factor -
Article: POMT1 and POMT2 mutations in CMD patients: a multicentric Italian study.
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ABSTRACT: Mutations in POMT1 and POMT2 genes were originally identified in Walker-Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with alpha-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with alpha-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought.Neuromuscular Disorders 08/2008; 18(7):565-71. · 2.80 Impact Factor -
Article: [Neurobiology of autism: Study of a sample of autistic children].
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ABSTRACT: Recent studies on the neuroanatomic, neurofunctional and/or neurochemical features of the autistic disorder (AD) gave many evidences suggesting the hypothesis that different organic factors may lead to a disruption of the cerebral development finally expressing with an autistic pattern. The aim of this study was to study a sample of subjects with AD with a wide protocol, including neurophysiological and radiological investigations as well as laboratory investigations in order to investigate the neurobiologic basis of the syndrome. The patients group included 80 subjects diagnosed as having AD. All were examined with a protocol of investigations including: brain MRI; wakefulness and sleep EEG; VEP, ABR; karyotype and search of the fragile X; serum and urinary levels of serotonin, catecolamines, omovanillic acid, aminoacids, ammonium, lactic acid, creatine kinase, piruvic acid, calcium, uric acid, total proteins, antibodies against neurotrophic agents. Eighty-eight percent of subjects had at least one pathologic neurobiological parameter. This study highlights the different noxae involved in the etiopathogenesis of AD and the percentage that every biological factor has in the development of the autistic phenotype. Furthermore, it confirms that AD corresponds to an atypical behavioural phenotype expression of a cerebral dysfunction with heterogeneous etiology.Minerva pediatrica 05/2006; 58(2):109-20. -
Article: Alternating hemiplegia of childhood successfully treated with topiramate: 18 months of follow-up.
Neurology 02/2006; 66(1):146. · 8.31 Impact Factor -
Article: Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries.
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ABSTRACT: Over a period of almost 10 yr, we carried out a prospective study of the neuropsychological development of the offspring of 16 women from a moderately iodine-deficient area (area A) and of 11 control women from a marginally iodine-sufficient area (area B) whose thyroid function had been monitored during early gestation. Attention deficit and hyperactivity disorder (ADHD) was diagnosed in 11 of 16 area A children (68.7%) but in none from area B. Total intelligence quotient score was lower in area A than in area B children (92.1 +/- 7.8 vs. 110 +/- 10) and in ADHD children when compared with both non-ADHD children from the same area and control children (88.0 +/- 6.9 vs. 99.0 +/- 2.0 and 110 +/- 10, respectively). Seven of 11 ADHD children (63.6%) were born to the seven of eight area A mothers who became hypothyroxinemic at early gestation, whereas only one of five non-ADHD children was born to a woman who was hypothyroxinemic at 20 wk of gestation. So far, a similar prevalence of ADHD has been reported only in children with generalized resistance to thyroid hormones. This might suggest a common ADHD pathogenetic mechanism consisting either of reduced sensitivity of the nuclear receptors to thyroid hormone (generalized resistance to thyroid hormones) or reduced availability of intracellular T3 for nuclear receptor binding. The latter would be the ultimate consequence of maternal hypothyroxinemia (due to iodine deficiency), resulting in a critical reduction of the source of the intracellular T3 available to the developing fetal brain.Journal of Clinical Endocrinology & Metabolism 01/2005; 89(12):6054-60. · 6.50 Impact Factor -
Article: Highly disabling cerebellar presentation in Huntington disease.
European Journal of Neurology 08/2003; 10(4):443-4. · 3.69 Impact Factor -
Article: Chiari I malformation mimicking myasthenia gravis.
Journal of Neurology Neurosurgery & Psychiatry 04/2003; 74(3):393. · 4.76 Impact Factor -
Article: Epileptic disorders with onset in the first year of life: neurological and cognitive outcome.
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ABSTRACT: We examined prospectively a series of 150 children with epilepsy beginning in the first year of life. We classified the types of epilepsy into five categories: West syndrome, other epileptic encephalopathies, generalized, partial and undetermined epilepsies. Of 150 patients, 15 died; 135 were followed for at least 4 years. In order to define possible factors influencing prognosis we evaluated neurological and cognitive outcome and made percentage comparisons between groups, for aetiology, age of onset, family history of epilepsy, and psychomotor development before onset. Epileptic encephalopathies as well as the symptomatic forms of West syndrome showed a very poor neurological and cognitive outcome. As previously recognized, only cryptogenic forms of West syndrome had a benign prognosis. For the generalized epilepsies, analysis of different factors, namely late age at onset, cryptogenicity and absence of primary cognitive impairment, indicated a good prognosis. In contrast, partial epilepsies usually had a poor outcome, irrespective of the aetiology, whether cryptogenic or symptomatic.European Journal of Paediatric Neurology 02/1999; 3(3):95-103. · 2.12 Impact Factor -
Article: Familial unilateral and bilateral occipital calcifications and epilepsy.
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ABSTRACT: No familial cases of epilepsy associated with bilateral occipital calcifications (EBOC) have been reported so far. This paper describes the clinical, electrophysiological and radiological study of two sisters affected by partial epilepsy, one with unilateral and the other with bilateral occipital calcifications. Celiac disease was excluded in both patients, even though they presented the same HLA pattern usually found in coeliac subjects.Neuropediatrics 01/1994; 24(6):341-2. · 0.94 Impact Factor -
Article: Bilateral occipital calcification, epilepsy and coeliac disease: clinical and neuroimaging features of a new syndrome.
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ABSTRACT: Twenty patients affected by bilateral occipital cortical-subcortical calcification (BOC) are described, 19 (95%) had epilepsy. In 8 of 16 cases studied, intestinal biopsy revealed coeliac disease. Fourteen patients had occipital partial epilepsy with a relatively benign outcome, while 4 patients were affected by a severe form of epilepsy, with very frequent, drug-resistant, generalised and partial seizures with mental deterioration. One patient had a single episode of convulsive status epilepticus at four months of age. The neurological examination was normal in all patients. CT showed flocculo-nodular, cortico-subcortical BOC, without enhancement and without lobar or hemispheric atrophy. MRI was normal. The clinical and neuroimaging features of these patients are different therefore from those with the Sturge-Weber Syndrome. The study confirms a high prevalence of coliac disease in patients with BOC, but the relationship between these two pathologies still needs to be clarified.Journal of Neurology Neurosurgery & Psychiatry 09/1993; 56(8):885-9. · 4.76 Impact Factor -
Article: [Neonatal familial benign convulsions].
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ABSTRACT: Some neonatal benign convulsions are genetic in origin, with a dominant mode of inheritance. A girl was placed on continuous EEG recording from her 2d day of life because of her family history. The first clonic seizures occurred on the 4th day; they appeared again on the 6th day and became prolonged with an abnormal EEG pattern. The seizures were well controlled with phenobarbital, that was gradually discontinued when the child was 3 months old. Seizures occurred again when she was 4 months old and were again controlled with phenobarbital. Her father had had neonatal convulsions which were not well analysed. Her brother also had clonic seizures at the 4th day of life; they disappeared after 1 month. Her sister suffered from clonic seizures when she was 3 days old, and these became prolonged. She was given phenobarbital until she was 1 year old. She developed benign rolandic epilepsy at the age of 10 years. This family suffers from neonatal familial benign convulsions and rolandic epilepsy. The frequency of neonatal familial benign epilepsy is probably under-estimated.Archives françaises de pédiatrie 02/1993; 50(1):31-3. -
Article: Familial dysautonomia in a non-Jewish girl, with histological evidence of progression in the sural nerve.
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ABSTRACT: A case of typical familial dysautonomia (HSN, type III) in a non-Jewish girl is reported. The number of unmyelinated fibres was found to be reduced and sural nerve biopsy showed evidence of past axonal degeneration. There was also marked endoneurial fibrosis and a lack of the largest myelinated fibres. Signs of histological progression not yet described in the sural nerve and other clinical and morphological features could be explained by different penetrance degrees of the disease.Developmental Medicine & Child Neurology 03/1986; 28(1):62-8. · 2.92 Impact Factor -
Article: [Gelastic epilepsy. Report of a case].
Minerva pediatrica 10/1983; 35(18):899-902. -
Article: [The Sotos syndrome in 2 brothers. Confirmation of a recessive autosomal heredity?].
Minerva pediatrica 12/1982; 34(22):983-6. -
Article: Epileptic disorders with onset in the first year of life: neurological and cognitive outcome
[show abstract] [hide abstract]
ABSTRACT: We examined prospectively a series of 150 children with epilepsy beginning in the first year of life. We classified the types of epilepsy into five categories: West syndrome, other epileptic encephalopathies, generalized, partial and undetermined epilepsies. Of 150 patients, 15 died; 135 were followed for at least 4 years. In order to define possible factors influencing prognosis we evaluated neurological and cognitive outcome and made percentage comparisons between groups, for aetiology, age of onset, family history of epilepsy, and psychomotor development before onset. Epileptic encephalopathies as well as the symptomatic forms of West syndrome showed a very poor neurological and cognitive outcome. As previously recognized, only cryptogenic forms of West syndrome had a benign prognosis. For the generalized epilepsies, analysis of different factors, namely late age at onset, cryptogenicity and absence of primary cognitive impairment, indicated a good prognosis. In contrast, partial epilepsies usually had a poor outcome, irrespective of the aetiology, whether cryptogenic or symptomatic.European Journal of Paediatric Neurology.
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Institutions
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1994–2003
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Università degli Studi di Messina
Messina, Sicily, Italy
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1999
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ucsc
Concepción, Region del Biobio, Chile
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