S Orcesi

Publications (29)86.05 Total impact

• Source

  Available from: Cristina Cereda

  Article: Inhibition of the de-myelinating properties of Aicardi-Goutières Syndrome lymphocytes by cathepsin D silencing.

  A Pulliero, B Marengo, M Longobardi, E Fazzi, S Orcesi, I Olivieri, C Cereda, C Domenicotti, U Balottin, A Izzotti
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  ABSTRACT: Molecular mechanisms relating interferon-alpha (IFN-alpha) to brain damage have recently been identified in a microarray analysis of cerebrospinal fluid lymphocytes from patients with Aicardi-Goutières Syndrome (AGS). These findings demonstrate that the inhibition of angiogenesis and the activation of neurotoxic lymphocytes are the major pathogenic mechanisms involved in the brain damage consequent to elevated interferon-alpha levels. Our previous study demonstrated that cathepsin D, a lysosomal aspartyl endopeptidase, is the primary mediator of the neurotoxicity exerted by AGS lymphocytes. Cathepsin D is a potent pro-apoptotic, neurotoxic, and demyelinating protease if it is not properly inhibited by the activities of leukocystatins. In central nervous system white matter, demyelination results from cathepsin over-expression when not balanced by the expression of its inhibitors. In the present study, we used RNA interference to inhibit cathepsin D expression in AGS lymphocytes with the aim of decreasing the neurotoxicity of these cells. Peripheral blood lymphocytes collected from an AGS patient were immortalized and co-cultured with astrocytes in the presence of interferon alpha with or without cathepsin D RNA interference probes. Cathepsin D expression was measured by qPCR, and neurotoxicity was evaluated by microscopy. RNA interference inhibited cathepsin D over-production by 2.6 fold (P<0.01) in AGS lymphocytes cultured in the presence of interferon alpha. AGS lymphocytes treated using RNA interference exhibited a decreased ability to induce neurotoxicity in astrocytes. Such neurotoxicity results in the inhibition of astrocyte growth and the inhibition of the ability of astrocytes to construct web-like aggregates. These results suggest a new strategy for repairing AGS lymphocytes in vitro by inhibiting their ability to induce astrocyte damage and leukodystrophy.
  Biochemical and Biophysical Research Communications 12/2012; · 2.48 Impact Factor
• Article: Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes.

  A Pulliero, B Marengo, C Domenicotti, M G Longobardi, E Fazzi, S Orcesi, M Bianchi, U Balottin, A Izzotti
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  ABSTRACT: T lymphocytes play a major role in counteracting cancer occurrence and development. Immune therapies against cancer are focused on eliciting a cytotoxic T cell response. This anticancer activity is related to a variety of mechanisms including the activation of cytokines and proapoptotic mediators. Interferon α is an established inhibitor of cancer cell growth. A clinical situation involving the coexistence of high interferon α levels and lymphocyte activation is the Aicardi-Goutières syndrome, a progressive encephalopathy arising usually during the first year of life characterized by intracranial basal ganglia calcifications, leukodystrophy and microcephaly. Aicardi-Goutières syndrome 1 mutation silences the TREX1 gene, a major endogenous nuclease. The in vitro study presented herein evaluates the efficacy of the TREX1 mutation in potentiating the anticancer properties of T cells. A TREX1-mutated lymphocyte cell line was derived from an Aicardi-Goutières syndrome patient and co-cultured with neuroblastoma cells and vascular endothelial cells in the presence of interferon α. TREX1-mutated lymphocytes exerted marked inhibitory action on neuroblastoma cell growth. Cathepsin D was recognized by qPCR as the main mediator produced by TREX1-mutated lymphocytes involved in the inhibition of neuroblastoma cell growth. These effects were enhanced in the presence of interferon α. Similar inhibitory effects in cell growth were exerted by TREX1-mutated lymphocytes towards vascular endothelial cell angiogenesis as evaluated on Matrigel. The results obtained provide evidence that mutations of the TREX1 gene increase the capability of T-lymphocytes to inhibit growth of neoplastic neuronal cells and related angiogenesis.
  Oncology Reports 05/2012; 27(5):1689-94. · 1.84 Impact Factor
• Article: COL4A1 mutations associated with a characteristic pattern of intracranial calcification.

  J Livingston, D Doherty, S Orcesi, D Tonduti, A Piechiecchio, R La Piana, E Tournier-Lasserve, A Majumdar, S Tomkins, G Rice, R Kneen, M van der Knaap, Y Crow
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  ABSTRACT: Intracranial calcification (ICC) is a relatively common radiological finding in children undergoing investigation for neurological disorders. Many causes are recognised, and ICC is often regarded as a non-specific sign.From an ongoing study of ICC, we identified 5 patients with characteristic radiological features, in whom a mutation in the COL4A1 gene was found.All patients had CT and MR imaging. MR images demonstrated features of periventricular leukomalacia with irregular dilatation of the lateral ventricles with or without porencephaly, loss of hemispheric white matter volume, and high signal on T2 and FLAIR sequences within periventricular and deep white matter. Calcification was apparent on MR in 4 patients. CT scans demonstrated spot and linear calcification in the subependymal region and around areas of porencephaly. Calcification was also visible in the deep cerebral white matter and basal ganglia. 1 patient showed calcification in the central pons.ICC occurs in COL4A1-related disease. The radiological features are distinct from other conditions demonstrating recognisable patterns of ICC, such as congenital cytomegalovirus infection and Aicardi-Goutiéres syndrome. In the absence of a known risk factor for periventricular leukomalacia, the presence of these radio-logical findings should suggest the possibility of COL4A1-related disease.
  Neuropediatrics 12/2011; 42(6):227-33. · 0.94 Impact Factor
• Article: The Aicardi-Goutières syndrome. Molecular and clinical features of RNAse deficiency and microRNA overload.

  A Pulliero, E Fazzi, C Cartiglia, S Orcesi, U Balottin, C Uggetti, R La Piana, I Olivieri, J Galli, A Izzotti
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  ABSTRACT: Intracellular RNAses are involved in various functions, including microRNA maturation and turnover. Mutations occurring in genes encoding RNAses cause Aicardi-Goutiéres syndrome (AGS). AGS mutations silence RNAse activity, thus inducing accumulation of endogenous RNAs, mainly consisting of short RNAs and microRNAs. Overload of intracellular RNA triggers Toll like receptor-dependent interferon-alpha production in the brain, which in turn activates neurotoxic lymphocytes and inhibits angiogenesis thus inducing the typical clinical phenotype of AGS. However, these pathogenic mechanisms are attenuated after three years of age by the endogenous production of DNAJP58IPK and Cystatin F, which arrest AGS progression. Because RNAses are involved in microRNA turnover, we evaluated the expression of 957 microRNAs in lymphocytes from AGS patients and control patients. Our results indicate that microRNA overload occurs in AGS patients. This upregulation inhibits microRNA turnover impeding the synthesis of the novel microRNAs required for the differentiation and myelination of the brain during the initial period of postnatal life. These pathogenic mechanisms result in AGS, a neurological syndrome characterized by irritability, mild hyperpyrexia, pyramidal and extrapyramidal signs, and spastic-dystonic tetraplegia. Typical cerebrospinal fluid alterations include lymphocytosis and elevated interferon-alpha levels. Brain imaging demonstrates cerebral calcifications, white matter abnormalities, and progressive cerebral atrophy.Thus, evidence exists that mutations silencing intracellular RNases affect microRNA turnover resulting in the severe clinical consequences in the brain characterizing the clinical feature of AGS.
  Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 04/2011; 717(1-2):99-108. · 2.85 Impact Factor
• Article: New molecular findings in congenital myopathies due to selenoprotein N gene mutations.

  R Cagliani, M E Fruguglietti, A Berardinelli, M G D'Angelo, A Prelle, S Riva, L Napoli, K Gorni, S Orcesi, C Lamperti, A Pichiecchio, E Signaroldi, R Tupler, F Magri, A Govoni, S Corti, N Bresolin, M Moggio, G P Comi
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  ABSTRACT: Selenoprotein N-related myopathy (SEPN1-RM) is an early-onset muscle disorder that can manifest clinically as congenital muscular dystrophy with spinal rigidity and can result in specific pathological entities such as multiminicore disease, desmin-related myopathy with Mallory body-like inclusions, and congenital fiber-type disproportion. Here we describe the clinical, histopathological, muscle magnetic resonance imaging (MRI) and genetic findings of three Italian SEPN1-RM families. Proband 1 is a 31-year-old female who was floppy at birth and developed axial and mild lower limb-girdle weakness. The second proband is a 13-year-old boy with RSMD1. Probands 3 and 4 were brothers showing clinical phenotype of congenital myopathy. Muscle MRI demonstrated selective involvement of sartorius, gluteal muscles and distal gastrocnemius and sparing of rectus femoris and gracilis. Muscle histopathology showed in proband 1 myopathic changes with mild connective tissue increase and some fibres lacking the Z-line, while probands 2 and 3 had multiminicores. SEPN1 gene analysis revealed five mutations, three of which are novel. Proband 1 was a compound heterozygote for a 92-bp (exon 1) and a 1-bp deletion (exon 9); proband 2 had a 99-bp deletion and a 10-bp duplication in exon 1, and proband 3 presented a novel homozygous mutation in intron 10 acceptor splice site.
  Journal of the neurological sciences 10/2010; 300(1-2):107-13. · 2.32 Impact Factor
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  Available from: bh4.org

  Article: Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency.

  L Brun, L H Ngu, W T Keng, G S Ch'ng, Y S Choy, W L Hwu, W T Lee, M A A P Willemsen, M M Verbeek, T Wassenberg, [......], J E Abdenur, S Tay, G F Allen, S Heales, I Kern, M Kato, A Burlina, C Manegold, G F Hoffmann, N Blau
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  ABSTRACT: To describe the current treatment; clinical, biochemical, and molecular findings; and clinical follow-up of patients with aromatic l-amino acid decarboxylase (AADC) deficiency. Clinical and biochemical data of 78 patients with AADC deficiency were tabulated in a database of pediatric neurotransmitter disorders (JAKE). A total of 46 patients have been previously reported; 32 patients are described for the first time. In 96% of AADC-deficient patients, symptoms (hypotonia 95%, oculogyric crises 86%, and developmental retardation 63%) became clinically evident during infancy or childhood. Laboratory diagnosis is based on typical CSF markers (low homovanillic acid, 5-hydroxyindoleacidic acid, and 3-methoxy-4-hydroxyphenolglycole, and elevated 3-O-methyl-l-dopa, l-dopa, and 5-hydroxytryptophan), absent plasma AADC activity, or elevated urinary vanillactic acid. A total of 24 mutations in the DDC gene were detected in 49 patients (8 reported for the first time: p.L38P, p.Y79C, p.A110Q, p.G123R, p.I42fs, c.876G>A, p.R412W, p.I433fs) with IVS6+ 4A>T being the most common one (allele frequency 45%). Based on clinical symptoms, CSF neurotransmitters profile is highly indicative for the diagnosis of aromatic l-amino acid decarboxylase deficiency. Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. Only 15 patients with a relatively mild form clearly improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors.
  Neurology 07/2010; 75(1):64-71. · 8.31 Impact Factor
• Article: Aicardi-Goutieres syndrome: neuroradiologic findings and follow-up.

  C Uggetti, R La Piana, S Orcesi, M G Egitto, Y J Crow, E Fazzi
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  ABSTRACT: To date, few studies have focused specifically on imaging findings in Aicardi-Goutières syndrome (AGS). We set out to evaluate retrospectively neuroradiologic data from a large sample of patients with AGS, focusing on the pattern of white matter abnormalities and the temporal evolution of the cerebral involvement to establish the radiologic natural history of the disease. Thirty-six patients, 18 girls and 18 boys, were included. All had a clinical diagnosis of AGS, genetically confirmed in 31 of them. For every subject, we reviewed at least 1 CT and 1 MR imaging study; 19 (52.7%) had multiple examinations. In all, we reviewed 109 examinations. Clinical-neuroradiologic comparisons were analyzed by using the chi(2) test. Calcifications were found in all subjects, mainly in the basal ganglia, lobar white matter, and dentate nuclei. Abnormal white matter was present in all the subjects, showing 2 patterns of distribution: diffuse in 18 (50%) and an anteroposterior gradient in 18 (50%). Cystic areas were observed in the temporal and/or frontal lobes in 12/36 patients (33.3%). A correlation was found between early age at onset and severity of the leukoencephalopathy in the frontal (P = .024) and temporal (P = .034) regions. A significant degree of cerebral atrophy was found in 31/36 subjects (86.1%). The neuroradiologic presentation remained substantially stable with time. The different neuroradiologic presentations of AGS are here outlined for the first time in a large sample of patients. These findings may facilitate more precise and earlier diagnosis of this rare but probably underdiagnosed syndrome.
  American Journal of Neuroradiology 08/2009; 30(10):1971-6. · 2.93 Impact Factor
• Article: Aicardi-Goutieres syndrome.

  S Orcesi, R La Piana, E Fazzi
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  ABSTRACT: Aicardi-Goutières syndrome (AGS) is an autosomal recessive encephalopathy characterized by acquired microcephaly, cerebral calcifications, leukodystrophy, cerebral atrophy and cerebrospinal fluid findings of chronic lymphocytosis and raised interferon-alpha (INF-alpha). The main extraneurological symptoms are chilblain-like skin lesions, usually on the fingers, toes and ears. This review is based on a search of the published literature on AGS from 1984 onwards (particularly the most recent papers) and on knowledge and experience gained through the authors' work with the International Aicardi-Goutières Syndrome Association (IAGSA). It is accepted that AGS can be mistaken for a congenital infection and that the diagnostic significance of its cardinal signs (raised INF-alpha levels, basal ganglia calcifications) is different in different stages of the disease. Currently, we know of four genes that, if mutated, can give rise to AGS, but at least one other gene is believed to exist. These genes are involved in the DNA damage response, a defect of which could provoke an inappropriate innate immune response, triggering increased secretion of INF-alpha, ultimately responsible for the main features of the disease. The natural history of AGS has not yet been definitively described given the lack of extensive, long-term neuroradiological follow-up studies. Furthermore, it is not yet clearly understood how the innate immune system is activated, what triggers the onset of the disease or why it tends to 'burn out' after several months. Immunosuppressive therapy in the active stage of the disease does not seem to produce any real change in the clinical course, but more data are needed. Current studies aim to clarify the molecular mechanisms underlying the pathogenesis of AGS and to establish the exact pathway by which retained nucleic acids activate the immune system. This knowledge could allow the development of therapeutic strategies.
  British Medical Bulletin 02/2009; 89:183-201. · 4.54 Impact Factor
• Article: Brain damage as detected by cDNA-microarray in the spinal fluid of patients with Aicardi-Goutieres syndrome.

  A Izzotti, E Fazzi, S Orcesi, C Cartiglia, M Longobardi, V Capra, P Lebon, A Cama, A Pulliero, R La Piana, G Lanzi
  Neurology 08/2008; 71(8):610-2. · 8.31 Impact Factor
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  Available from: aicardi-goutieres.org

  Article: Aicardi-Goutières syndrome presenting atypically as a sub-acute leukoencephalopathy.

  S Orcesi, A Pessagno, R Biancheri, R La Piana, M Mascaretti, A Rossi, G I Rice, Y J Crow, E Fazzi, E Veneselli
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  ABSTRACT: Aicardi-Goutières syndrome is an autosomal recessive encephalopathy characterised by acquired microcephaly, basal ganglia calcifications, leukodystrophy, cerebral atrophy, chronic cerebrospinal lymphocytosis, and raised titres of interferon alpha in the cerebrospinal fluid. The disease onset is generally within the first months of life. We here report a case of Aicardi-Goutières syndrome presenting atypically as a sub-acute leukoencephalopathy following satisfactory psychomotor development up to the age of 16 months. This case highlights the importance of considering Aicardi-Goutières syndrome in the differential diagnosis of an unexplained leukoencephalopathy and the possibility of later onset of the disease.
  European Journal of Paediatric Neurology 01/2008; 12(5):408-11. · 2.12 Impact Factor
• Article: The Hammersmith functional score correlates with the SMN2 copy number: a multicentric study.

  F D Tiziano, E Bertini, S Messina, C Angelozzi, M Pane, A D'Amico, P Alfieri, S Fiori, R Battini, A Berardinelli, [......], T Mongini, L Morandi, S Orcesi, M Pelliccioni, A Pini, M Villanova, G Vita, M Locatelli, E Mercuri, C Brahe
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  ABSTRACT: Previous studies showed that SMN2 copy number correlates inversely with the disease severity. Our aim was to evaluate SMN2 copy numbers and the Hammersmith functional motor scale in 87 patients with SMA II in order to establish whether, within SMAII, the number of copies correlates with the severity of functional impairment. Our results showed a relative variability of functional scores, but a significant correlation between the number of SMN2 genes and the level of function.
  Neuromuscular Disorders 06/2007; 17(5):400-3. · 2.80 Impact Factor
• Article: Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy.

  E Mercuri, E Bertini, S Messina, A Solari, A D'Amico, C Angelozzi, R Battini, A Berardinelli, P Boffi, C Bruno, [......], L Morandi, G Neri, S Orcesi, M Pane, M Pelliccioni, A Pini, F D Tiziano, M Villanova, G Vita, C Brahe
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  ABSTRACT: 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. 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. 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. Phenylbutyrate was not effective at the regimen, schedule, and duration used in this study.
  Neurology 02/2007; 68(1):51-5. · 8.31 Impact Factor
• Article: Reliability of the Hammersmith functional motor scale for spinal muscular atrophy in a multicentric study.

  E Mercuri, S Messina, R Battini, A Berardinelli, P Boffi, R Bono, C Bruno, N Carboni, C Cini, F Colitto, [......], S Orcesi, M Pelliccioni, M Pane, A Pini, A V Swan, M Villanova, G Vita, M Main, F Muntoni, E Bertini
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  ABSTRACT: 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.
  Neuromuscular Disorders 02/2006; 16(2):93-8. · 2.80 Impact Factor
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  Available from: Pierre Lebon

  Article: The natural history of Aicardi-Goutières syndrome: follow-up of 11 Italian patients.

  G Lanzi, E Fazzi, S D'Arrigo, S Orcesi, I Maraucci, C Uggetti, E Bertini, P Lebon
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  ABSTRACT: Described are the outcomes of 11 Italian patients with Aicardi-Goutières syndrome. Neurologic symptoms progressed in the first year of life and stabilized by the end of the second year in 10 patients. White matter abnormalities remained stable; cerebral atrophy was stable in four patients and progressive in two. Calcifications increased (in number and size) in two of six patients. Serial CSF and serum interferon-alpha measurements (three patients) showed reduced CSF interferon-alpha levels.
  Neurology 06/2005; 64(9):1621-4. · 8.31 Impact Factor
• Article: Prevalence of tic disorders among primary school students in the city of Pavia, Italy.

  G Lanzi, C A Zambrino, C Termine, M Palestra, O Ferrari Ginevra, S Orcesi, P Manfredi, E Beghi
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  ABSTRACT: The prevalence of tic disorders in children varies from 1% to 29% depending on the characteristics of the study population, the diagnostic criteria, and the study design and methods. To calculate the prevalence of tic disorders among primary school children in Italy. The study population comprised 2347 primary school children from the city of Pavia (pop. 80 073), Northern Italy. Using trained school teachers as the source of cases, all children with motor or vocal tics occurring intermittently and unpredictably out of a background of normal motor activity were accepted. The type, frequency, and circumstances of tic disorders were noted. School performance was correlated to the presence of tics. A total of 68 children (56 boys, 12 girls) aged 6-11 years were identified with tic disorders. The period prevalence was 2.9% (95% CI 2.3 to 3.7). The prevalence was 4.4% in boys and 1.1% in girls, with no detectable trends at age 6-11. Motor tics were present in 46 cases, vocal tics in 6, and motor and vocal tics in 16. Situation related tics were noted in 37 cases. A significant correlation was found between the presence of tic disorders and impaired school performance. Tic disorders are a fairly uncommon but disabling clinical disorder among primary school children from an urban community. The fairly low prevalence of this clinical condition, as compared to other reports, can be explained by the choice of stringent diagnostic criteria and the exclusion of patients with other movement disorders.
  Archives of Disease in Childhood 02/2004; 89(1):45-7. · 2.88 Impact Factor
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  Available from: Anna Pichiecchio

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

  D Franciotta, M C Zanardi, L Albertotti, S Orcesi, A Berardinelli, A Pichiecchio, C Uggetti, A Tagliabue
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  ABSTRACT: 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.
  Acta Diabetologica 11/2003; 40 Suppl 1:S290-2. · 2.78 Impact Factor
• Article: Body composition and energy expenditure in Duchenne muscular dystrophy.

  M C Zanardi, A Tagliabue, S Orcesi, A Berardinelli, C Uggetti, A Pichiecchio
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  ABSTRACT: To investigate the relationship between resting energy expenditure (REE) and body composition in Duchenne Muscular Dystrophy (DMD). An observational study. University Research Centre. Nine Duchenne children (age range 6-12 y), mean relative weight 128%, agreed to undergo the investigation and all of them completed the study; Assessment of body composition (total body fat and skeletal muscle mass) by magnetic resonance imaging and resting energy expenditure by indirect calorimetry. 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). : 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. 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.
  European Journal of Clinical Nutrition 03/2003; 57(2):273-8. · 2.46 Impact Factor
• Article: Measurement of skeletal muscle mass in Duchenne muscular dystrophy: use of 24-h creatinine excretion

  D. Franciotta, M.C. Zanardi, L. Albertotti, S. Orcesi, A. Berardinelli, A. Pichiecchio, C. Uggetti, A. Tagliabue
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  ABSTRACT: 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 5.42.5 kg and urine creatinine levels 205.896.4 mg/day. Daily urinary creatinine excretion did not correlate with SMM. The simple creatinine determination in urine cannot predict SMM in Duchenne muscular dystrophy.
  Acta Diabetologica 01/2003; 40:s290-s292. · 2.78 Impact Factor
• Article: Dystrophinopathies: peculiar clinical and laboratory aspects.

  A Berardinelli, K Gorni, S Orcesi, A Tagliabue, C Uggetti, G Lanzi
  Functional neurology 02/2001; 16(4 Suppl):255-62. · 1.52 Impact Factor
• Article: A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy.

  M D Bonifati, G Ruzza, P Bonometto, A Berardinelli, K Gorni, S Orcesi, G Lanzi, C Angelini
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  ABSTRACT: 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.
  Muscle & Nerve 09/2000; 23(9):1344-7. · 2.37 Impact Factor