Publications by authors named "Roberto Micheli"

16 Publications

  • Page 1 of 1

Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype-Phenotype Correlations in A Large Independent Cohort.

Cancers (Basel) 2019 11 21;11(12). Epub 2019 Nov 21.

Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, Italy.

The occurrence of optic pathway gliomas (OPGs) in children with neurofibromatosis type 1 (NF1) still raises many questions regarding screening and surveillance because of the lack of robust prognostic factors. Recent studies of an overall cohort of 381 patients have suggested that the genotype may be the main determinant of the development of OPG, with the risk being higher in patients harbouring mutations in the 5' tertile and the cysteine/serine-rich domain. In an attempt to confirm this hypothesis, we used strict criteria to select a large independent cohort of 309 NF1 patients with defined constitutional NF1 mutations and appropriate brain images (255 directly enrolled and 54 as a result of a literature search). One hundred and thirty-two patients had OPG and 177 did not. The association of the position (tertiles and functional domains) and type of mutation with the development of OPG was analysed using the χ2 test and Fisher's exact probability test; odds ratios (ORs) with 95% confidence intervals were calculated, and Bonferroni's correction for multiple comparisons was applied; multiple logistic regression was also used to study genotype-phenotype associations further. Our findings show no significant correlation between the site/type of NF1 mutation and the risk of OPG, and thus do not support the hypothesis that certain constitutional mutations provide prognostic information in this regard. In addition, we combined our cohort with a previously described cohort of 381 patients for a total of 690 patients and statistically re-analysed the results. The re-analysis confirmed that there were no correlations between the site (tertile and domain) and the risk of OPG, thus further strengthening our conclusions.
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http://dx.doi.org/10.3390/cancers11121838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966666PMC
November 2019

The formation of human populations in South and Central Asia.

Authors:
Vagheesh M Narasimhan Nick Patterson Priya Moorjani Nadin Rohland Rebecca Bernardos Swapan Mallick Iosif Lazaridis Nathan Nakatsuka Iñigo Olalde Mark Lipson Alexander M Kim Luca M Olivieri Alfredo Coppa Massimo Vidale James Mallory Vyacheslav Moiseyev Egor Kitov Janet Monge Nicole Adamski Neel Alex Nasreen Broomandkhoshbacht Francesca Candilio Kimberly Callan Olivia Cheronet Brendan J Culleton Matthew Ferry Daniel Fernandes Suzanne Freilich Beatriz Gamarra Daniel Gaudio Mateja Hajdinjak Éadaoin Harney Thomas K Harper Denise Keating Ann Marie Lawson Matthew Mah Kirsten Mandl Megan Michel Mario Novak Jonas Oppenheimer Niraj Rai Kendra Sirak Viviane Slon Kristin Stewardson Fatma Zalzala Zhao Zhang Gaziz Akhatov Anatoly N Bagashev Alessandra Bagnera Bauryzhan Baitanayev Julio Bendezu-Sarmiento Arman A Bissembaev Gian Luca Bonora Temirlan T Chargynov Tatiana Chikisheva Petr K Dashkovskiy Anatoly Derevianko Miroslav Dobeš Katerina Douka Nadezhda Dubova Meiram N Duisengali Dmitry Enshin Andrey Epimakhov Alexey V Fribus Dorian Fuller Alexander Goryachev Andrey Gromov Sergey P Grushin Bryan Hanks Margaret Judd Erlan Kazizov Aleksander Khokhlov Aleksander P Krygin Elena Kupriyanova Pavel Kuznetsov Donata Luiselli Farhod Maksudov Aslan M Mamedov Talgat B Mamirov Christopher Meiklejohn Deborah C Merrett Roberto Micheli Oleg Mochalov Samariddin Mustafokulov Ayushi Nayak Davide Pettener Richard Potts Dmitry Razhev Marina Rykun Stefania Sarno Tatyana M Savenkova Kulyan Sikhymbaeva Sergey M Slepchenko Oroz A Soltobaev Nadezhda Stepanova Svetlana Svyatko Kubatbek Tabaldiev Maria Teschler-Nicola Alexey A Tishkin Vitaly V Tkachev Sergey Vasilyev Petr Velemínský Dmitriy Voyakin Antonina Yermolayeva Muhammad Zahir Valery S Zubkov Alisa Zubova Vasant S Shinde Carles Lalueza-Fox Matthias Meyer David Anthony Nicole Boivin Kumarasamy Thangaraj Douglas J Kennett Michael Frachetti Ron Pinhasi David Reich

Science 2019 09;365(6457)

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.
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http://dx.doi.org/10.1126/science.aat7487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822619PMC
September 2019

Visuoperceptual Impairment in Children with NF1: From Early Visual Processing to Procedural Strategies.

Behav Neurol 2019 13;2019:7146168. Epub 2019 Jan 13.

Developmental Neurology Division, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy.

Visual-spatial impairment has long been considered a hallmark feature of neurofibromatosis type 1 (NF1). No study investigating the cognitive and neuropsychological profile of NF1 used the Rey Complex Figure Test (RCFT) task as the primary measure of visual-perceptual abilities taking into consideration all functions involved including the strategic processing style. We compared 18 children with NF1, 17 siblings (S), and 18 typically developing children (TD) at intelligence scale and RCFT copy, recall, and recognition trials; we also evaluated the copy strategy as a measure of a visual-processing style. Children with NF1 had normal total IQ, with cognitive weaknesses in the perceptual organization and working memory in line with the existing literature. At the RCFT copy, immediate and delay recall scores are significantly lower in NF1 than S and TD, while recognition is in the normal range in all groups. Copy style was poor and less efficient in children with NF1 and correlated to copy and recall ability, but the effect of the group in the RCFT copy and recall remained significantly controlling for strategic approach. The present study confirms visuospatial impairment in children with NF1, due to a deficit in perceptual analysis of shape and their spatial features, in visuomotor integration efficiency and strategies, in recall memory, while recognition memory is preserved. A more configural/holistic style may facilitate both the visual-perceptual and visuomotor ability and the recall process. Visuoperceptual impairment in NF1 seems to be a unified process from early visual processing to higher order functions (planning, strategy, and executive functioning).
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http://dx.doi.org/10.1155/2019/7146168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348799PMC
July 2019

Discovery of ancient Roman "highway" reveals geomorphic changes in karst environments during historic times.

PLoS One 2018 23;13(3):e0194939. Epub 2018 Mar 23.

Centro Fermi-Museo Storico della Fisica e Centro di Studi e Ricerche "Enrico Fermi", Roma, Italy.

Sinkholes are a well-known geologic hazard but their past occurrence, useful for subsidence risk prediction, is difficult to define, especially for ancient historic times. Consequently, our knowledge about Holocene carbonate landscapes is often limited. A multidisciplinary study of Trieste Karst (Italy), close to early Roman military fortifications, led to the identification of possible ancient road tracks, cut by at least one sinkhole. Electrical Resistivity Tomography through the sinkhole has suggested the presence of a cave below its bottom, possibly responsible of the sinkhole formation, while Ground Penetrating Radar has detected no tectonic disturbances underneath the tracks. Additionally, archaeological surveys led to the discovery of over 200 Roman shoe hobnails within or close to the investigated route. According to these data, the tracks are interpreted as the remains of a main Roman road, whose itinerary has been reconstructed for more than 4 km together with other elements of ancient landscape. Our results provide the first known evidence of a Roman main road swallowed by sinkholes and suggest that Holocene karst landscapes could be much different from what previously believed. In fact, sinkholes visible nowadays in the investigated region could have been flat areas filled by sediments up to the Roman time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194939PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866101PMC
July 2018

Neurovisual Assessment in Children with Ataxia Telangiectasia.

Neuropediatrics 2018 02 9;49(1):26-34. Epub 2017 Oct 9.

Unit of Child Neurology and Psychiatry, ASST Spedali Civili, Brescia, Italy.

Aim: Visual impairment is present in almost all patients with ataxia telangiectasia (AT) and, due to their early onset, constitute an important disabling aspect of the syndrome: the quality of vision is limited by dyspraxia and oculomotor abnormal movements. The purpose of this observational study was to describe visual disorders, notably oculomotor impairment, in a sample of children with AT.

Methods: Fifteen AT patients (mean age 12 years and 4 months) underwent a neurovisual evaluation, particularly focused on oculomotor functions (fixation, smooth pursuit, saccades, and abnormal ocular movements). We compared the visual profile obtained with that described using the International Cooperative Ataxia Rating Scale (ICARS) subscale of oculomotor dysfunction.

Results: Refractive errors were seen in eight patients and strabismus in three. Major oculomotor findings were fixation abnormalities (6/15), saccadic impairment (15/15), and abnormal smooth pursuit (14/15). Abnormal ocular movements were seen in 13/15 (saccadic intrusion in 8 and nystagmus in 5). Using ICARS scale, 13/15 children presented gaze-evoked nystagmus, 4/15 a clearly saccadic pursuit, and 11/15 dysmetria of saccades.

Discussion: We propose a clinical neurovisual evaluation, which could be integrated with ICARS scores in the study of oculomotor involvement in AT pediatric patients. We strongly recommend the empowerment of visual functions to slow down progressive global disability of these patients.
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http://dx.doi.org/10.1055/s-0037-1607216DOI Listing
February 2018

ATM splicing variants as biomarkers for low dose dexamethasone treatment of A-T.

Orphanet J Rare Dis 2017 07 5;12(1):126. Epub 2017 Jul 5.

Department of Biomolecular Sciences, University of Urbino "Carlo Bo", 61029, Urbino, PU, Italy.

Background: Ataxia Telangiectasia (AT) is a rare incurable genetic disease, caused by biallelic mutations in the Ataxia Telangiectasia-Mutated (ATM) gene. Treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this syndrome. Nevertheless, the molecular mechanism underlying the glucocorticoid action in AT patients is not yet understood. Recently, we have demonstrated that Dexamethasone treatment may partly restore ATM activity in AT lymphoblastoid cells by a new ATM transcript, namely ATMdexa1.

Results: In the present study, the new ATMdexa1 transcript was also identified in vivo, specifically in the PMBCs of AT patients treated with intra-erythrocyte Dexamethasone (EryDex). In these patients it was also possible to isolate new "ATMdexa1 variants" originating from canonical and non-canonical splicing, each containing the coding sequence for the ATM kinase domain. The expression of the ATMdexa1 transcript family was directly related to treatment and higher expression levels of the transcript in patients' blood correlated with a positive response to Dexamethasone therapy. Neither untreated AT patients nor untreated healthy volunteers possessed detectable levels of the transcripts. ATMdexa1 transcript expression was found to be elevated 8 days after the drug infusion, while it decreased 21 days after treatment.

Conclusions: For the first time, the expression of ATM splicing variants, similar to those previously observed in vitro, has been found in the PBMCs of patients treated with EryDex. These findings show a correlation between the expression of ATMdexa1 transcripts and the clinical response to low dose dexamethasone administration.
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http://dx.doi.org/10.1186/s13023-017-0669-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498894PMC
July 2017

The Key Search Subtest of the Behavioural Assessment of the Dysexecutive Syndrome in Children (BADS-C) Instrument Reveals Impaired Planning Without External Constraints in Children With Neurofibromatosis Type 1.

J Child Neurol 2017 03 20;32(4):387-396. Epub 2016 Dec 20.

1 Developmental Neurology Division, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.

Studies of executive function and its relationship with brain T2-weighted hyperintensities in children with neurofibromatosis type 1 (NF1) have yielded inconsistent results. We examined 16 children with NF1 aged 8 to 15 years, of normal intelligence, and compared their findings to those of 16 siblings and 16 typically developing children using the Behavioural Assessment of the Dysexecutive Syndrome in Children (BADS-C). NF1 patients had an adequate overall score at BADS-C, but showed significantly lower performance than typical peers in the Key Search subtest. This is a task that must be solved without any given rules, in which subjects must devise a strategy and an efficient search pattern transferable to other similar real situations. The Key Search scores were not correlated with number and signal characteristics of T2-weighted hyperintensities. Planning without external indications is impaired in children with NF1 because they have to rely entirely on self-organization and monitoring; this study provides information for remediation programs designed to improve functioning in daily life.
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http://dx.doi.org/10.1177/0883073816683322DOI Listing
March 2017

Novel compound heterozygous mutations in a child with Ataxia-Telangiectasia showing unrelated cerebellar disorders.

J Neurol Sci 2016 Dec 13;371:48-53. Epub 2016 Oct 13.

Unit of Child Neurology and Psychiatry, Spedali Civili and University of Brescia, Brescia, Italy.

We report the case of a 6-year-old female patient with Ataxia Telangiectasia, an extremely rare condition, who developed in addition a left cerebellar astrocytoma and a right cerebellar infarction, considered as two independent events. Children with AT have an increased risk of developing cancer, but only few cases of glioma are reported and, at our knowledge, no other case of unrelated cerebellar glioma and cerebellar infarction in with the same AT patient have been described. The molecular analysis of ATM (Ataxia Telangiectasia Mutated) gene showed that the patient is compound heterozygote for two previously unreported mutations: c.3291delC (p.Phe1097fs) at exon 25 and c.8198A>C (p.Gln2733Pro) at exon 58. The role of the identified ATM gene mutations in the pathogenesis of Ataxia Telangiectasia and the coexisting cerebellar disorders is discussed.
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http://dx.doi.org/10.1016/j.jns.2016.10.014DOI Listing
December 2016

Development of global rating instruments for pediatric patients with ataxia telangiectasia.

Eur J Paediatr Neurol 2016 Jan 25;20(1):140-6. Epub 2015 Sep 25.

Pediatric Neurology Unit, Edmond and Lilly Safra Pediatric Hospital, Sheba Medical Center, Ramat Gan, Israel; The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Introduction: Ataxia telangiectasia (AT) is a neurodegenerative disorder with cerebellar and extrapyramidal features. Interventional and epidemiological studies in AT should rely on specific scales which encompass the specific neurological features, as well the early progressive course and the subsequent plateau. The aim of this study was to build a scale of the CGI type (Clinical Global Impression) which is disease specific, as well as to check the feasibility of the ICARS scale for ataxia in this population.

Methods: We recruited 63 patients with ataxia, aged 10.76 ± 3.2 years, followed at 6 international AT centers, 49 of them (77.8%) with classical AT. All patients were evaluated for ataxia with ICARS scale. In patients with AT, two CGI scales were scored, unstructured as structured for which separate anchors were provided.

Results: Mean ICARS score was 44.7 ± 20.52, and it's severity positively correlated with age (Spearman correlation, r = 0.46, p < 0.01). Mean CGI score was 2 (moderately involved). There was a high correlation between the structured and unstructured CGIs (Spearman correlation, r = 0.87, p < 0.01). Both CGI scales showed positive correlation between severity and increasing age (Spearman correlation r = 0.59, p < 0.01 for structured CGI and r = 0.61, p < 0.01 for unstructured).

Discussion: We succeeded to build two CGI scales: structured and unstructured, which are disease specific for AT. The unstructured scale showed better connection to disease course; the sensitivity of the unstructured scale could be improved by adding anchors related to extrapyramidal features. In addition we showed that ataxia can be reliably measured in children with AT by using ICARS.
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http://dx.doi.org/10.1016/j.ejpn.2015.09.002DOI Listing
January 2016

Positive effect of erythrocyte-delivered dexamethasone in ataxia-telangiectasia.

Neurol Neuroimmunol Neuroinflamm 2015 Jun 9;2(3):e98. Epub 2015 Apr 9.

Department of Pediatrics, Child Neurology and Psychiatry (V.L., D.D., T.V.), Department of Molecular Medicine (I.Q.), and Department of Clinical and Molecular Medicine (L.C.), Sapienza University of Rome, Italy; Unit of Child Neurology and Psychiatry (R.M., E.F.), Department of Clinical and Experimental Sciences, Pediatrics Clinic (A.P., A.S., M. Marini, P.F.L.), and Institute of Molecular Medicine A. Nocivelli (A.P., A.S., M. Marini, P.F.L.), Spedali Civili and University of Brescia, Brescia, Italy; School in Reproductive and Developmental Science (A.M.), University of Trieste and University of Brescia, Brescia, Italy; Department of Pediatrics (M.C.P.), University of Milan, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Pediatrics (A.F.), Bambino Gesù Children's Hospital and University of Tor Vergata, Rome, Italy; Department of Biomolecular Sciences (M. Magnani), University of Urbino "Carlo Bo," Urbino, Italy; and EryDel SpA (M. Magnani), Urbino, Italy.

Objective: Ataxia-telangiectasia (AT) is a rare, devastating neurodegenerative disease presenting with early-onset ataxia, oculocutaneous telangiectasia, immunodeficiency, radiosensitivity, and proneness to cancer. In a previous phase 2 study, we showed that 6 monthly infusions of autologous erythrocytes loaded with dexamethasone (EryDex; EryDel, Urbino, Italy) were effective in improving neurologic impairment in young patients with AT. The present article reports the results of the extension of this study for an additional 24-month period.

Methods: After the end of the first trial, 4 patients continued to be treated with monthly EryDex infusions for an additional 24 months, and their clinical outcome was compared with that of 7 age-matched patients who stopped the treatment after the first 6 infusions. The protocol included serial assessment of ataxia (by International Cooperative Ataxia Rating Scale) and adaptive behavior (by Vineland Adaptive Behavior Scales) and clinical and laboratory tests revealing treatment- and steroid-dependent adverse effects, if present.

Results: Patients in the extended study experienced a continuous neurologic improvement with respect to their pretreatment status, whereas controls showed a progressive neurologic deterioration (according to the natural history of the disease) after the discontinuation of the treatment. The delivery system we adopted proved to be safe and well-tolerated, and none of the side effects usually associated with the chronic administration of corticosteroids were observed during the entire trial.

Conclusions: These promising preliminary results call for a large-scale controlled study on protracted treatment of patients with AT with dexamethasone-loaded erythrocytes.
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http://dx.doi.org/10.1212/NXI.0000000000000098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396528PMC
June 2015

Early Roman military fortifications and the origin of Trieste, Italy.

Proc Natl Acad Sci U S A 2015 Mar 16;112(13):E1520-9. Epub 2015 Mar 16.

Multidisciplinary Laboratory, The "Abdus Salam" International Centre for Theoretical Physics, 34014 Trieste, Italy; Centro Fermi, Museo Storico della Fisica e Centro di Studi e Ricerche "Enrico Fermi," 00184 Rome, Italy; Centre for Archaeological Science, University of Wollongong, Wollongong, NSW 2522, Australia.

An interdisciplinary study of the archaeological landscape of the Trieste area (northeastern Italy), mainly based on airborne light detection and ranging (LiDAR), ground penetrating radar (GPR), and archaeological surveys, has led to the discovery of an early Roman fortification system, composed of a big central camp (San Rocco) flanked by two minor forts. The most ancient archaeological findings, including a Greco-Italic amphora rim produced in Latium or Campania, provide a relative chronology for the first installation of the structures between the end of the third century B.C. and the first decades of the second century B.C. whereas other materials, such as Lamboglia 2 amphorae and a military footwear hobnail (type D of Alesia), indicate that they maintained a strategic role at least up to the mid first century B.C. According to archaeological data and literary sources, the sites were probably established in connection with the Roman conquest of the Istria peninsula in 178-177 B.C. They were in use, perhaps not continuously, at least until the foundation of Tergeste, the ancestor of Trieste, in the mid first century B.C. The San Rocco site, with its exceptional size and imposing fortifications, is the main known Roman evidence of the Trieste area during this phase and could correspond to the location of the first settlement of Tergeste preceding the colony foundation. This hypothesis would also be supported by literary sources that describe it as a phrourion (Strabo, V, 1, 9, C 215), a term used by ancient writers to designate the fortifications of the Roman army.
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http://dx.doi.org/10.1073/pnas.1419175112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386398PMC
March 2015

Legius Syndrome: two novel mutations in the SPRED1 gene.

Hum Genome Var 2015 3;2:15051. Epub 2015 Dec 3.

Laboratory of Experimental Neurobiology, 'C. Mondino' National Neurological Institute , Pavia, Italy.

The SPRED1 gene encodes a protein involved in the Ras/MAPK (mitogen-activated protein kinase) signaling pathway. Mutations in SPRED1 have been reported to cause Legius Syndrome, a rare developmental disorder that shares some clinical features with Neurofibromatosis-1. Direct sequencing was used to define SPRED1 mutations. We present two previously undescribed mutations: a frameshift mutation causing a stop codon, which was identified in an Italian family (p.Ile60Tyrfs*18) and a missense variation, which was identified in one sporadic Italian case (p.Pro422Arg). Our results led us to hypothesize that these modifications may contribute to the Legius Syndrome phenotype. Further studies will be needed to determine the roles of these mutations in the mechanisms of Legius Syndrome.
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http://dx.doi.org/10.1038/hgv.2015.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785569PMC
April 2016

Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia teleangiectasia patients: results of a phase 2 trial.

Orphanet J Rare Dis 2014 Jan 9;9. Epub 2014 Jan 9.

Department of Pediatrics and Child Neurology and Psychiatry, Sapienza Università di Roma, via dei Sabelli 108, 00185 Roma, Italy.

Background: Ataxia Teleangiectasia [AT] is a rare neurodegenerative disease characterized by early onset ataxia, oculocutaneous teleangiectasias, immunodeficiency, recurrent infections, radiosensitivity and proneness to cancer. No therapies are available for this devastating disease. Recent observational studies in few patients showed beneficial effects of short term treatment with betamethasone. To avoid the characteristic side effects of long-term administration of steroids we developed a method for encapsulation of dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EryDex) allowing slow release of dexamethasone for up to one month after dosing. Aims of the study were: the assessment of the effect of EryDex in improving neurological symptoms and adaptive behaviour of AT patients; the safety and tolerability of the therapy.

Methods: Twenty two patients (F:M=1; mean age 11.2 ± 3.5) with a confirmed diagnosis of AT and a preserved or partially supported gait were enrolled for the study. The subjects underwent for six months a monthly infusion of EryDex. Ataxia was assessed by the International Cooperative Ataxia Rating Scale (ICARS) and the adaptive behavior by Vineland Adaptive Behavior Scales (VABS). Clinical evaluations were performed at baseline and 1, 3, and 6 months.

Results: An improvement in ICARS (reduction of the score) was detected in the intention-to-treat (ITT) population (n=22; p=0.02) as well as in patients completing the study (per protocol PP) (n=18; p=0.01), with a mean reduction of 4 points (ITT) or 5.2 points (PP). When compared to baseline, a significant improvement were also found in VABS (increase of the score) (p<0.0001, ITT, RMANOVA), with statistically significant increases at 3 and 6 months (p<0.0001). A large inter-patient variability in the incorporation of DSP into erythrocytes was observed, with an evident positive effect of higher infusion dose on ICARS score decline. Moreover a more marked improvement was found in less neurologically impaired patients. Finally, a 19 month-extension study involving a subgroup of patients suggested that Erydex treatment can possibly delay the natural progression of the disease.EryDex was well tolerated; the most frequent side effects were common AT pathologies.

Conclusions: EryDex treatment led to a significant improvement in neurological symptoms, without association with the typical steroid side effects.

Trial Registration: Current Controlled Trial 2010-022315-19SpA.
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http://dx.doi.org/10.1186/1750-1172-9-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904207PMC
January 2014

A randomized trial of oral betamethasone to reduce ataxia symptoms in ataxia telangiectasia.

Mov Disord 2012 Sep 23;27(10):1312-6. Epub 2012 Aug 23.

Child Neurology and Psychiatry Unit, Azienda Ospedaliera Universitaria Senese/University of Siena, Policlinico Le Scotte, Siena, Italy.

No controlled studies exist regarding the pharmaceutical reduction of ataxia symptoms in ataxia telangiectasia (A-T). In a multicenter, double-blind, randomized, placebo-controlled crossover trial, oral betamethasone (BETA) and placebo were compared in terms of their reduction of ataxia symptoms as assessed with the International Cooperative Ataxia Rating Scale (ICARS). In this study of 13 A-T children, betamethasone reduced the ICARS total score by a median of 13 points in the intent-to-treat population and 16 points in the per-protocol population (ie, median percent decreases of ataxia symptoms of 28% and 31%, respectively). In conclusion, Oral betamethasone could be a promising therapy to relieve ataxia symptoms in A-T patients; however, long-term effectiveness and safety must be established. (Current Controlled Trials, number ISRCTN08774933.)
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http://dx.doi.org/10.1002/mds.25126DOI Listing
September 2012

T-lymphocyte production, function, and death in children who recovered from opsoclonus-myoclonus syndrome.

Pediatr Hematol Oncol 2007 Jan-Feb;24(1):23-7

Laboratorio di Biotecnologie, Spedali Civili of Brescia, Brescia, Italy.

Reduced CD4+ lymphocytes have been recently found in peripheral blood of children with active opsoclonus-myoclonus syndrome. The authors identified 2 children who recovered from this syndrome, one of whom showed reduced CD4+ lymphocytes 2 years after the disease onset. Except for a decrease of "naive" CD45RA+ CD4+ population and a mild restriction of T-cell heterogeneity in this patient, probably related to the immune response to viral infections, no alterations of T-cell homeostasis and function were found in either child. Therefore, the decrease of CD4+ cells may persist after clinical recovery, but the causes of this abnormality cannot be ascribed to intrinsic T-cell defects.
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http://dx.doi.org/10.1080/08880010601001446DOI Listing
December 2006

Detection of herpesvirus-6A in a case of subacute cerebellitis and myoclonic dystonia.

J Med Virol 2005 Mar;75(3):427-9

Department of Biomedical Science and Technology, University of Milan, Milan, Italy.

This is a case study of a child who developed roseola infantum first, then varicella, and was later affected by acute cerebellar syndrome, severe truncal ataxia, and myoclonic dystonia. Human herpesvirus 6 (HHV-6) A and B were detected in the cerebrospinal fluid (CSF) and peripheral blood, respectively, upon ataxia onset. The intricacy of this case suggests multifaceted conclusions ranging from the need for a multidirectional approach to neurological diseases, to confirmation of a more pronounced neurotropism of HHV-6A and a possible role of viruses in myoclonic dystonia syndrome, although this last hypothesis should be confirmed by larger studies.
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http://dx.doi.org/10.1002/jmv.20285DOI Listing
March 2005