182 results on '"Nicolo' Rizzuto"'
Search Results
2. Atypical Alzheimer’s disease: a case report
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Francesco Iemolo, Nicolo' Rizzuto, and Tiziana Cavallaro
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Adult ,Myoclonus ,medicine.medical_specialty ,Pathology ,Tomography Scanners, X-Ray Computed ,Neurology ,Plaque, Amyloid ,Dermatology ,Presenilin ,Angiopathy ,Atrophy ,Alzheimer Disease ,medicine ,Humans ,Senile plaques ,Family history ,Pathological ,Early onset dementia ,Brain ,Electroencephalography ,Neurofibrillary Tangles ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,Neuroscience - Abstract
This paper deals with an unusual case of Alzheimer's disease with early onset, no family history, myoclonus, tonic generalized seizures and pseudo-periodic spikes on EEG. The demise occurred after 8 years of progressive cognitive deterioration; the pathological examination showed "Pick-like" atrophy, neurofibrillary tangles, senile plaques, congophilic angiopathy and cerebellar amyloid plaques. The genetical research could not support the hypothesis of a mutation of Presenilin 1 and 2 genes. Anyway, the peculiarity of the phenotype is worthy to be described even in the absence of specific molecular findings.
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- 2010
3. Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H
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M. Casarotto, Sergio Ferrari, Vincent Timmerman, P. De Jonghe, Laura Bertolasi, T Deconinck, Gian Maria Fabrizi, Nicolo' Rizzuto, Tiziana Cavallaro, and Federica Taioli
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Proband ,Charcot-Marie-Tooth ,Pathology ,medicine.medical_specialty ,Molecular Sequence Data ,Neural Conduction ,medicine.disease_cause ,FGD4 gene ,Young Adult ,Degenerative disease ,CMT4H ,neuropathy ,mutation ,Charcot-Marie-Tooth Disease ,Charcot-Marie-Tooth disease type 4H ,Humans ,Medicine ,Amino Acid Sequence ,Child ,Mutation ,Nerve biopsy ,Base Sequence ,medicine.diagnostic_test ,Genetic heterogeneity ,business.industry ,Microfilament Proteins ,Peroneal muscular atrophy ,Myelin outfoldings ,medicine.disease ,Pedigree ,Female ,Human medicine ,Neurology (clinical) ,business ,Neuroscience - Abstract
Background: Autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy type 4H (CMT4H) manifests early onset, severe functional impairment, deforming scoliosis, and myelin outfoldings in the nerve biopsy. Mutations in the FGD4 gene encoding the Rho-GTPase guanine-nucleotide-exchange-factor frabin were reported in five families. Objective: To characterize a novel mutation in FGD4 and describe the related phenotype. Methods: A 20-year-old woman born of healthy consanguineous parents and affected with early-onset peroneal muscular atrophy underwent standard clinical, electrophysiologic, and pathologic (sural nerve biopsy) investigations. Mutational analysis of FGD4 was performed by direct sequencing of genomic DNA. Transcriptional analysis was done by reverse transcriptase PCR on leukocyte RNA. Results: The proband disclosed a moderately severe, scarcely progressive CMT, markedly slowed nerve conduction velocities, and a demyelinating neuropathy characterized by prominent myelin outfoldings. Mutational analysis disclosed a c.1762-2a>g transition in the splice-acceptor site of intron 14, which was predicted to cause a truncated frabin (p.Tyr587fsX14). Conclusions: The report confirms genetic heterogeneity of FGD4 , demonstrates that CMT4H has variable functional impairment, and suggests that frabin plays a crucial role during myelin formation.
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- 2009
4. Correlation between clinical/neurophysiological findings and quality of life in Charcot-Marie-Tooth type 1A
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Pietro Attilio Tonali, Aldo Quattrone, Michael E. Shy, Luca Padua, Irene Aprile, Nicolo' Rizzuto, Angelo Schenone, Tiziana Cavallaro, Davide Pareyson, and Giuseppe Vita
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Heel ,Adolescent ,Disease ,Cohort Studies ,Correlation ,Quality of life ,Charcot-Marie-Tooth Disease ,Humans ,Medicine ,In patient ,Aged ,Charcot-Marie-Tooth type 1A ,business.industry ,General Neuroscience ,Middle Aged ,Neurophysiology ,neurophysiology ,quality of life ,humanities ,nervous system diseases ,Electrophysiology ,Settore MED/26 - NEUROLOGIA ,stomatognathic diseases ,medicine.anatomical_structure ,Italy ,Cohort ,Charcot Marie Tooth ,Physical therapy ,Female ,Neurology (clinical) ,business ,Cohort study - Abstract
Quality of life (QoL), as defined by the Short Form 36, has previously been shown to be abnormal in patients with Charcot-Marie-Tooth disease (CMT), both for Physical Composite Scores (PCS) and Mental Composite Scores (MCS). We have now extended these observations in a multicenter evaluation of 89 patients with Charcot-Marie-Tooth disease type 1A, the most common form of CMT. Both the PCS and MCS were abnormal also in this cohort, compared with the Italian population at large. In particular, the ability to ambulate independently as well as toe and heel walk correlated well with QoL measures in our patients.
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- 2008
5. Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease
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Roberto Cerini, Gian Maria Fabrizi, Tiziana Cavallaro, Ilaria Cabrini, Nicolo' Rizzuto, Laura Bertolasi, and Moreno Ferrarini
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,dynamin-2 ,medicine.disease_cause ,CMT ,hereditary neuropathy ,Dynamin II ,Exon ,Degenerative disease ,Charcot-Marie-Tooth Disease ,medicine ,Humans ,Myopathy ,Autosomal dominant centronuclear myopathy ,Dynamin ,Genetics ,Mutation ,business.industry ,Middle Aged ,medicine.disease ,Axons ,Pedigree ,nervous system diseases ,Pleckstrin homology domain ,DNM2 ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Neuroscience - Abstract
Background: Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot–Marie–Tooth disease (CMT) type B. Objective: To assess the etiologic role of DNM2 in CMT. Methods: We performed a mutational screening of DNM2 exons 13 through 16 encoding the pleckstrin homology domain in a large series of CMT patients with a broad range of nerve conduction velocities and without mutations in more common genes. Results: We identified two novel DNM2 mutations that cosegregated with purely axonal CMT in two pedigrees without clinical evidence of primary myopathy. Conclusion: Patients with axonal Charcot–Marie–Tooth disease type 2 neuropathy without mutations in more common genes should undergo investigation for DNM2 pleckstrin homology.
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- 2007
6. Endothelial adhesion molecule expression is unaltered in the peripheral nerve from patients with AIDS and distal sensory polyneuropathy
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Nicolo' Rizzuto, Sergio Ferrari, Francesca Rossi, Marta Rava, Flavio Fenzi, and Tiziana Cavallaro
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Adult ,Male ,Nervous system ,Pathology ,medicine.medical_specialty ,Immunology ,Sural nerve ,Biology ,Blood vessels ,stomatognathic system ,medicine ,Humans ,Immunology and Allergy ,Platelet ,Endothelial dysfunction ,Acquired Immunodeficiency Syndrome ,Distal sensory polyneuropathy ,Cell adhesion molecule ,Endothelial Cells ,Peripheral Nervous System Diseases ,Adhesion ,Middle Aged ,HIV infection ,medicine.disease ,Immunohistochemistry ,Pathophysiology ,Endothelial adhesion molecules ,Endothelial stem cell ,medicine.anatomical_structure ,Neurology ,Female ,Neurology (clinical) ,Cell Adhesion Molecules - Abstract
Some evidence suggests that endothelial dysfunction, including altered expression of cell adhesion molecules contributes to pathophysiology of nervous system disorders in the course of HIV infection. In this immunohistochemical study we investigated and compared the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1) in peripheral nerve blood vessels from patients with distal sensory polyneuropathy (DSP) and control patients with other axonal neuropathies. Similar quantitative pattern of immunoreactivity was found in patients with DSP and controls. E-selectin and PECAM-1 immunostained vessels tended to increase in number only in patients with major CD4 cell depletion. The vascular endothelium of the peripheral nerve in HIV-infected subjects with DSP shows no changes facilitating the migration of infected or activated monocytes/macrophages into the nerve. These phenomena probably do not play a critical role in the development of axonal damage in DSP.
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- 2006
7. Hyperpyrexia-triggered relapses in an unusual case of ataxic chronic inflammatory demyelinating polyradiculoneuropathy
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Nicolo' Rizzuto, C Mezzina, Laura Bertolasi, Giuliano Tomelleri, Sergio Ferrari, and Sara Mazzucco
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Chronic inflammatory demyelinating polyradiculoneuropathy ,Male ,medicine.medical_specialty ,Neurology ,Fever ,Ataxic neuropathy ,Anti-Inflammatory Agents ,Tetraparesis ,Dermatology ,Sural Nerve ,Recurrence ,Humans ,Immunologic Factors ,Medicine ,Pathological ,Hyperpyrexia ,Unusual case ,Electromyography ,business.industry ,Immunoglobulins, Intravenous ,Polyradiculoneuropathy ,General Medicine ,Middle Aged ,medicine.disease ,Dysphagia ,Facial drooping ,Psychiatry and Mental health ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,Prednisone ,Ataxia ,Neurology (clinical) ,Neurosurgery ,medicine.symptom ,business - Abstract
The ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (ataxic-CIDP) has been recently described as a subtype of chronic ataxic neuropathy, distinguished by steroid responsiveness and relative preservation of myelinated fibres at sural nerve biopsy. We report on a case of progressive, predominantly sensory, steroid-responsive neuropathy with clinical, laboratory, electrophysiological and pathological features of this uncommon form of CIDP. Moreover, the present case displays peculiar hyperpyrexia-triggered relapses leading to transitory severe tetraparesis, bilateral facial drooping, dysphonia, dysphagia and dyspnoea, which leave clinicians with some unresolved questions.
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- 2006
8. SERCA1 and calsequestrin storage myopathy: a new surplus protein myopathy
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Tiziana Mongini, Giuliano Tomelleri, Paola Tonin, Laura Palmucci, Roberto L'erario, Matteo Marini, Nicolo' Rizzuto, and Gaetano Vattemi
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Adult ,Male ,Pathology ,medicine.medical_specialty ,inclusions ,surplus protein myopathy ,ATPase ,Sarcoplasm ,sarcoplasmic or endoplasmic reticulum calcium 1 (SERCA1) ATPase ,calsequestrin ,vacuolar myopathy ,chemistry.chemical_element ,Calcium-Transporting ATPases ,Calcium ,Calsequestrin ,Sarcoplasmic Reticulum Calcium-Transporting ATPases ,Muscular Diseases ,Internal medicine ,medicine ,Humans ,Muscle, Skeletal ,Terminal cisternae ,Myopathy ,Aged ,biology ,Endoplasmic reticulum ,Middle Aged ,musculoskeletal system ,Microscopy, Electron ,Sarcoplasmic Reticulum ,Endocrinology ,chemistry ,biology.protein ,Immunohistochemistry ,Female ,Neurology (clinical) ,medicine.symptom - Abstract
We describe four patients, from four different families, affected by a mild myopathy or asymptomatic elevated serum creatine kinase levels, in whom toluidine blue-stained semithin sections of muscle specimens revealed inclusions of different size and shape. The inclusions did not stain by routine histochemical studies. The sarcoplasmic or endoplasmic reticulum calcium 1 (SERCA1) ATPase and/or calsequestrin reactivity of inclusions, by immunohistochemistry, and the SERCA1- and calsequestrin-increased expression, by immunoblot, suggested that inclusions were constituted by an excess of proteins normally present in the terminal cisternae of sarcoplasmic reticulum. Our cases, both sporadic and familial, represent a new type of surplus protein myopathy.
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- 2006
9. Overexpression of ErbB2 and ErbB3 receptors in Schwann cells of patients with Charcot–Marie–Tooth disease type 1A
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Roberto Bei, Giorgio Bernardi, M. B. Panico, Nicolo' Rizzuto, Andrea Modesti, Chiara Terracciano, Roberto Massa, Tiziana Cavallaro, and Camilla Palumbo
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Male ,Receptor, ErbB-3 ,Physiology ,Gene Expression ,Schwann cell ,Biology ,Connexins ,Cellular and Molecular Neuroscience ,ErbB Receptors ,Sural Nerve ,Charcot-Marie-Tooth Disease ,ErbB ,Physiology (medical) ,medicine ,Animals ,Humans ,ERBB3 ,Rats, Wistar ,skin and connective tissue diseases ,Receptor ,cell differentiation ,Charcot-Marie-Tooth disease type 1A ,ErbB receptors ,immunohistochemistry ,Schwann cells ,Axotomy ,Genes, erbB-2 ,Charcot-Marie-Tooth Disease Type 1A ,Immunohistochemistry ,Sciatic Nerve ,Rats ,medicine.anatomical_structure ,nervous system ,Cancer research ,Neuregulin ,Settore MED/26 - Neurologia ,Schwann Cells ,Neurology (clinical) ,Signal transduction ,Wallerian Degeneration ,Neuroscience - Abstract
Axon-derived neuregulins (NRGs) are a family of growth factors whose binding to ErbB tyrosine kinase receptors promotes the maturation, proliferation and survival of Schwann cells (SCs). Correct NRG/ErbB signaling is essential for the homeostasis of axonal-glial complexes and seems to play a role in peripheral nerve repair. The potential involvement of ErbB receptors in human peripheral neuropathies has not been clarified. Therefore, we assessed the immunoreactivity for EGFR (ErbB1), ErbB2, and ErbB3 in nerve biopsies from patients with different forms of Charcot-Marie-Tooth disease, type 1, (CMT1), as compared to others with inflammatory neuropathies and controls. The most notable changes consisted in the overexpression of ErbB2 and ErbB3 by SCs of nerves from CMT1A patients. These findings are consistent with an impairment of SC differentiation and expand the molecular phenotype of CMT1A. The upregulation of these receptors may play a role in the inhibition of myelination or in the promotion of recurrent demyelination and axonal damage.
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- 2006
10. Identification of Distinct N-terminal Truncated Forms of Prion Protein in Different Creutzfeldt-Jakob Disease Subtypes
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Pier Giorgio Righetti, Salvatore Monaco, Frances Prelli, Alessia Farinazzo, Matteo Gelati, Nicolo' Rizzuto, Gianluigi Zanusso, Michele Fiorini, Sergio Ferrari, and Blas Frangione
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Adult ,Male ,Gene isoform ,Glycosylation ,PrPSc Proteins ,Prions ,Protein Conformation ,animal diseases ,Proteolysis ,prion disease ,Blotting, Western ,Detergents ,Immunoblotting ,Biology ,medicine.disease_cause ,Biochemistry ,Creutzfeldt-Jakob Syndrome ,chemistry.chemical_compound ,Protein structure ,Sporadic Creutzfeldt-Jakob disease ,medicine ,Humans ,Protein Isoforms ,Electrophoresis, Gel, Two-Dimensional ,Molecular Biology ,Aged ,chemistry.chemical_classification ,Mutation ,Binding Sites ,Methionine ,medicine.diagnostic_test ,Brain ,Cell Biology ,Middle Aged ,Immunohistochemistry ,Protein Structure, Tertiary ,nervous system diseases ,Amino acid ,Blot ,Phenotype ,chemistry ,biology.protein ,Female ,Isoelectric Focusing ,Antibody ,Peptides - Abstract
In prion diseases, the cellular prion protein (PrP(C)) is converted to an insoluble and protease-resistant abnormal isoform termed PrP(Sc). In different prion strains, PrP(Sc) shows distinct sites of endogenous or exogenous proteolysis generating a core fragment named PrP27-30. Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disease, clinically presents with a variety of neurological signs. As yet, the clinical variability observed in sCJD has not been fully explained by molecular studies relating two major types of PrP27-30 with unglycosylated peptides of 21 (type 1) and 19 kDa (type 2) and the amino acid methionine or valine at position 129. Recently, smaller C-terminal fragments migrating at 12 and 13 kDa have been detected in different sCJD phenotypes, but their significance remains unclear. By using two-dimensional immunoblot with anti-PrP antibodies, we identified two novel groups of protease-resistant PrP fragments in sCJD brain tissues. All sCJD cases with type 1 PrP27-30, in addition to MM subjects with type 2 PrP27-30, were characterized by the presence of unglycosylated PrP fragments of 16-17 kDa. Conversely, brain homogenates from patients VV and MV with type 2 PrP27-30 contained fully glycosylated PrP fragments, which after deglycosylation migrated at 17.5-18 kDa. Interestingly, PrP species of 17.5-18 kDa matched deglycosylated forms of the C1 PrP(C) fragment and were associated with tissue PrP deposition as plaque-like aggregates or amyloid plaques. These data show the presence of multiple PrP(Sc) conformations in sCJD and, in addition, shed new light on the correlation between sCJD phenotypes and disease-associated PrP molecules.
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- 2004
11. An unusual transthyretin gene missense mutation (TTR Phe33Val) linked to familial amyloidotic polyneuropathy
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Elio Agostoni, Roberta Frigerio, Nicolo' Rizzuto, Gian Maria Fabrizi, Carlo Ferrarese, Laura Brighina, Guido Cavaletti, Patrizia Santoro, Moreno Ferrarini, Tiziana Cavallaro, Frigerio, R, Fabrizi, G, Ferrarini, M, Cavallaro, T, Brighina, L, Santoro, P, Agostoni, E, Cavaletti, G, Rizzuto, N, and Ferrarese, C
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Adult ,medicine.medical_specialty ,phenylalanine ,Genetic Linkage ,hereditary amyloidosis ,familial amyloidotic polyneuropathy ,transthyretin ,mutation ,valine ,Mutation, Missense ,medicine.disease_cause ,Exon ,Sural Nerve ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Prealbumin ,Missense mutation ,Transversion ,Amyloid Neuropathies, Familial ,Mutation ,biology ,business.industry ,Restrictive cardiomyopathy ,nutritional and metabolic diseases ,Autosomal dominant trait ,hereditary amyloidosi ,medicine.disease ,Pedigree ,Transthyretin ,Endocrinology ,biology.protein ,Female ,business ,Polyneuropathy - Abstract
Familial amyloidotic polyneuropathy is a rare autosomal dominant disease, with clinical symptoms beginning in most kindreds within the third to seventh decades of life. The primary defect results from one of a number of mutations in the transthyretin (TTR) gene. Over 80 mutations in the TTR gene have been described. Most mutations give rise to adult onset progressive peripheral and autonomic neuropathy, due to amyloid deposition within the nerves, and often subclinical cardiac amyloid and vitreous deposits. We report here the clinical and molecular characterization of a rare TTR missense mutation discovered in a young woman from Macedonia, showing severe axonal sensory-motor polyneuropathy, restrictive cardiomyopathy and bilateral vitreous deposits. The transthyretin gene, analyzed by direct nucleotide sequencing, demonstrated a T to G transversion at nucleotide 183 in the exon 2 which is predicted to cause a heterozygous valine for phenylalanine substitution at codon 33 (TTR Phe33Val). This mutation has been previously reported only twice, without complete clinical descriptions.
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- 2004
12. Mutations in a Gene Encoding a Novel SH3/TPR Domain Protein Cause Autosomal Recessive Charcot-Marie-Tooth Type 4C Neuropathy
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Reinhard Büttner, Roman Chrast, Kathrin Huehne, Volker Straub, Claudia Stendel, Nathalie Verpoorten, Carsten Bergmann, Vincent Timmerman, Haluk Topaloglu, Sevim Erdem, Gian Maria Fabrizi, Eva Nelis, Yesim Parman, Ersin Tan, J. Michael Schröder, Nicolo' Rizzuto, Jörg Klepper, Greg Lemke, Manfred Stuhrmann, Wolfgang Müller-Felber, Jutta Kirfel, Stephan Züchner, Sabine Rudnik-Schöneborn, Andreas Hahn, Mark H.G. Verheijen, Jan Senderek, Esra Battaloglu, Peter De Jonghe, Bernd Rautenstrauss, Klaus Zerres, Eckhard Buchheim, and Çocuk Sağlığı ve Hastalıkları
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Adult ,Male ,Adolescent ,Protein family ,Molecular Sequence Data ,Medizin ,Genes, Recessive ,Locus (genetics) ,Biology ,Compound heterozygosity ,src Homology Domains ,Consanguinity ,Autosomal recessive trait ,Charcot-Marie-Tooth Disease ,SH3TC2 ,Genetics ,medicine ,Animals ,Humans ,Genetics(clinical) ,Amino Acid Sequence ,RNA, Messenger ,Allele ,Child ,Genetics (clinical) ,Genetics & Heredity ,Base Sequence ,Genome, Human ,Gene Expression Profiling ,Intracellular Signaling Peptides and Proteins ,Infant ,Proteins ,Articles ,Middle Aged ,Disease gene identification ,medicine.disease ,Pedigree ,Alternative Splicing ,Phenotype ,Haplotypes ,Child, Preschool ,Mutation ,Chromosomes, Human, Pair 5 ,Female ,Hereditary motor and sensory neuropathy - Abstract
Charcot-Marie-Tooth disease type 4C (CMT4C) is a childhood-onset demyelinating form of hereditary motor and sensory neuropathy associated with an early-onset scoliosis and a distinct Schwann cell pathology. CMT4C is inherited as an autosomal recessive trait and has been mapped to a 13-cM linkage interval on chromosome 5q23-q33. By homozygosity mapping and allele-sharing analysis, we refined the CMT4C locus to a suggestive critical region of 1.7 Mb. We subsequently identified mutations in an uncharacterized transcript, KIAA1985, in 12 families with autosomal recessive neuropathy. We observed eight distinct protein-truncating mutations and three nonconservative missense mutations affecting amino acids conserved through evolution. In all families, we identified a mutation on each disease allele, either in the homozygous or in the compound heterozygous state. The CMT4C gene is strongly expressed in neural tissues, including peripheral nerve tissue. The translated protein defines a new protein family of unknown function with putative orthologues in vertebrates. Comparative sequence alignments indicate that members of this protein family contain multiple SH3 and TPR domains that are likely involved in the formation of protein complexes.
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- 2003
13. Hereditary neuropathy with liability to pressure palsies: electrophysiological and genetic study of a family with carpal tunnel syndrome as only clinical manifestation
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M. Silvestri, Tiziana Cavallaro, M. Turazzini, R. Del Colle, Gian Maria Fabrizi, and Nicolo' Rizzuto
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Neurology ,Adolescent ,Genetics, Medical ,Neural Conduction ,Dermatology ,Disease ,17p11.2 deletion ,Humans ,Medicine ,Carpal tunnel syndrome ,Neuroradiology ,Family Health ,Nerve biopsy ,medicine.diagnostic_test ,business.industry ,Electrodiagnosis ,Molecular analysis ,Hereditary neuropathy with liability to pressure palsies ,Autosomal dominant trait ,General Medicine ,Middle Aged ,medicine.disease ,Carpal Tunnel Syndrome ,Pedigree ,Surgery ,Electrophysiology ,Psychiatry and Mental health ,Entrapment Neuropathy ,Female ,Neurology (clinical) ,Neurosurgery ,Hereditary Sensory and Motor Neuropathy ,business - Abstract
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease characterized by recurrent sensory or motor manifestations. The molecular basis of HNPP is a deletion on chromosome 17p11.2. We studied a family (father, 61 years; mother, 55 years; 6 children of mean age 25.3 years) showing symptoms of carpal tunnel syndrome in 4 members (the parents and 2 sons). No one of them reported episodes of nerve palsy. In all the patients, except the mother and the younger son, electrophysiologic evaluation showed a sensorimotor polyneuropathy with delayed sensorimotor latencies. Genetic analysis was carried out in the parents and the eldest son. The 17p11.2 deletion was detected in the father and son, indicating paternal transmission of the disease. Clinical manifestations of HNPP may be atypical. Sometimes there is no history of acute nerve palsy, as in this family. For this reason, the frequence of HNPP might be underestimated. Electrophysiological examination is of great importance for the diagnosis of HNPP. Genetic analysis is a rapid and reliable diagnostic tool that can be combined with simplified electrophysiological examination, avoiding the need for nerve biopsy. In conclusion, the diagnosis of HNPP should be invoked in early onset entrapment neuropathies.
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- 2003
14. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 46
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Davide Pareyson, Gianluca Vita, A. Schenone, Luca Padua, Aldo Quattrone, and Nicolo' Rizzuto
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congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Weakness ,business.industry ,General Neuroscience ,Public health ,Disease ,Outcome assessment ,nervous system diseases ,Natural history ,Physical medicine and rehabilitation ,Peripheral nerve ,medicine ,Physical therapy ,Neurology (clinical) ,medicine.symptom ,business ,Pathological ,Inherited neuropathy - Abstract
Traditional outcome assessment in neurological diseases has always been based on physician-derived and instrumental findings. Over the last two decades, clinical and public health researchers emphasized the need for a thorough evaluation of concepts such as Health Related Quality of Life (HRQoL) to study the impact of chronic illnesses and their treatments on the patient's life. The most frequent inherited neuropathy is Charcot-Marie-Tooth disease (CMT). CMT Patients develop progressive weakness and sensory disturbances, becoming sometimes severely disabled even at very young age. In CMT clinic, neurophysiologic, pathologic and genetic evaluation, are considered fundamental to assess nerve involvement and diagnose, but how these findings are related to HRQoL and disability is not assessed. We propose a prospective follow-up (24–30 months) of CMT patients with multiple measurements of CMT. Besides conventional clinic, pathologic, neurophysiologic and genetic measurements we adopt validated patient-oriented measurements to assess HRQoL and disability. Aims of the study are: 1) to assess HRQoL and disability of CMT patients in a wide and well-represented sample and to evaluate the relationships between conventional parameters and the patient's perception of his own HRQoL and disability; 2) to evaluate natural history of HRQoL and disability in CMT, and to evaluate the predictive value of phenotype, genetic picture, neurophysiological and pathological pattern 3) to develop a national network and a database on CMT disease (this aim includes the standardization, based on a consensus validation process, of the most used terms and measurements in CMT and the development of a database software). In a preliminary reunion, the authors developed a dedicated database for patients affected by CMT. Details about this database will be presented.
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- 2003
15. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 69
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Camilla Palumbo, Tiziana Cavallaro, Nicolo' Rizzuto, Roberto Massa, Giorgio Bernardi, Roberto Bei, Andrea Modesti, Chiara Terracciano, A. Di Muzio, and M. B. Panico
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Pathology ,medicine.medical_specialty ,Wallerian degeneration ,biology ,General Neuroscience ,Schwann cell ,medicine.disease ,ErbB Receptors ,medicine.anatomical_structure ,ErbB ,Epidermal growth factor ,biology.protein ,medicine ,Neuregulin ,ERBB3 ,Neurology (clinical) ,Neuregulin 1 - Abstract
Demyelination and Schwann cell (SC) proliferation are hallmarks of hypertrophic demyelinating neuropathies, of which Charcot-Marie-Tooth type 1 A (CMT1A) neuropathy is the typical example. In CMT1A, an altered dosage of the PMP22 gene determines a defect of myelination and an abnormal SC phenotype, characterized by hyperplasia and abnormal differentiation. The Epidermal Growth Factor (EGF) family of proteins, including EGF and neuregulins, and their receptors, namely EGFr and the erbB family, control growth and development of SC. Their expression in mature SC is down-regulated but, during Wallerian degeneration or chemical myelinolysis, these receptors are transiently over-expressed, suggesting a potential autocrine mechanism. On the other hand, neuregulin 1 inhibits SC myelination and induces demyelination and SC dedifferentiation and proliferation. These effects might play a role in the pathogenesis of hypertrophic demyelinating neuropathies. We have therefore immunolocalized EGF, EGFr and the erbB receptors (erbB 2, 3 and 4) in sural nerve biopsies from patients with CMT1A as compared to chronic inflammatory demyelinating neuropathy (CIDP) nerve biopsies and to normal nerves, in order to evaluate if the expression of these molecules is up- or down-regulated in these disorders. Among CMT1A nerves, immunoreactivity for EGF, EGFr, erbB2 and erbB3 was moderately to markedly increased in SC, particularly in onion bulbs, in most cases, while a mild to moderate expression of erbB 4 in SC cytoplasm was observed in a few cases. On the other hand in CIDP, which shares with CMT1A histopathological features such as de-remyelination and SC hyperplasia, only the expression of erbB 3 was up-regulated in a minority of cases. Since in SC the functional neuregulin receptor is a heterodimer, composed by erbB2 and erbB3, the parallel up-regulation of these two molecules in CMT1A may bear a functional significance. This would be confirmed if an overexpression of neuregulins could be demonstrated, along with our finding of an increased expression of EGF and its receptor. In conclusion, it can be hypothesized that, in CMT1A, a persistent activation of neuregulin signaling pathways not only is indicative of SC dedifferentiation but also may contribute to demyelination and onion bulb formation or maintenance.
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- 2003
16. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 49
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M. De Angelis, Chiara Angiari, Nicolo' Rizzuto, CM Caporale, M Capasso, Gian Maria Fabrizi, A. Di Muzio, and A Uncini
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Proband ,Pes cavus ,medicine.diagnostic_test ,business.industry ,General Neuroscience ,Elbow ,Neurological examination ,Anatomy ,Deep Tendon Reflex ,medicine.disease ,Median nerve ,Frameshift mutation ,Myelin ,medicine.anatomical_structure ,medicine ,Neurology (clinical) ,business - Abstract
A 65-year-old woman was referred because of bilateral foot drop, pes cavus and distal muscular atrophy. Electrophysiological studies showed prolonged distal motor latencies and conduction velocities ranging from 33 to 42 m/s in upper limb nerves. A conduction block (P/D area = 0.4) was present in the wrist elbow segment of median nerve. Her 42-year-old daughter was asymptomatic and neurological examination revealed only absent deep tendon reflex. The 35-year-old son complained of positional paresthesias and had normal examination. The 13-year-old nephew was completely normal. There was no history of pressure palsies. All three proband's relatives showed: 1) normal or slightly slowed motor conduction velocities; 2) slowing of conductions in the above-below elbow segment of both ulnar nerves (difference of velocity with the below elbow-wrist segment ranging from 16 to 25 m/s). Sural nerve biopsy in the proband showed at light microscopy a chronic demyelinating and remyelinating process. On teased-fiber examination virtually all fibers showed myelin thickenings or classical tomacula. Molecular analysis showed neither deletion of the 17p11.2 segment nor mutation of the PMP 22 gene. The sequence of MPZ/PO revealed a 306delA at codon 102 in the proband and three relatives. The mutation was of non-sense type and causes a frameshift with a premature stop codon (Val102fs). Motor conduction velocities in CMT1B are usually
- Published
- 2003
17. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 50
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Ilaria Cabrini, Tiziana Cavallaro, Chiara Angiari, Gian Maria Fabrizi, Moreno Ferrarini, Alessandro Simonati, and Nicolo' Rizzuto
- Subjects
Genetics ,Mutation ,Transition (genetics) ,Genetic heterogeneity ,General Neuroscience ,Chromosome ,Pedigree chart ,Biology ,medicine.disease_cause ,Molecular biology ,medicine ,Coding region ,Neurology (clinical) ,Restriction fragment length polymorphism ,Gene - Abstract
The axonal form of Charcot-Marie-Tooth neuropathy (CMT type 2) has autosomal dominant inheritance and is genetically heterogeneous. Only 2 genes are known so far. Two unrelated Caucasian pedigrees (from Russia and Belgium) had 2 distinct mutations in the neurofilament-light gene (NF-L)(CMT2E, chromosome 8p21); a single Japanese pedigree had a mutation in the kinesin 1B gene (KIF1B)(CMT2A, chromosome 1p35-p36). We aimed at investigating the epidemiological relevance of NF-L in an Italian series with CMT2. The series included 30 index cases with CMT2 diagnosed according to clinical, electrophysiological and pathological criteria, in whom we have ruled out mutations of MPZ/P0 and CX32. In the selected series, the entire coding region of NF-L was investigated by automated direct nucleotide sequencing. Direct molecular test of the novel identified mutation was performed by analyzing a restriction fragment length polymorphism (RFLP) for AatII. In a single five-generation pedigree, with 3 affected member examined, we identified a novel heterozygous c.64C > T transition which substitutes a proline with a serine at amino acid residue 22 (Pro22Ser). The mutation appeared to be pathogenic because it co-segregated with the disease in the pedigree and it was absent in more than 100 healthy controls. The amino acid change occurs in the N-terminal head domain which regulates the assembly of neurofilaments. The report emphasizes the etiological role of NF-L in CMT2.
- Published
- 2003
18. Transcription factors c-Jun/activator protein-1 and nuclear factor-kappa B in oxidative stress response in mitochondrial diseases
- Author
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Giuliano Tomelleri, Chiara Savio, Gaetano Vattemi, Nicolo' Rizzuto, Paola Tonin, and Massimiliano Filosto
- Subjects
Histology ,Activator (genetics) ,Kinase ,Mitochondrial disease ,c-jun ,Skeletal muscle ,Biology ,medicine.disease ,medicine.disease_cause ,Pathology and Forensic Medicine ,Cell biology ,medicine.anatomical_structure ,Neurology ,Biochemistry ,Physiology (medical) ,Gene expression ,medicine ,Neurology (clinical) ,Transcription factor ,Oxidative stress - Abstract
M. Filosto, P. Tonin, G. Vattemi, C. Savio, N. Rizzuto and G. Tomelleri (2003) Neuropathology and Applied Neurobiology 29, 52–59 Transcription factors c-Jun/activator protein-1 and nuclear factor-kappa B in oxidative stress response in mitochondrial diseases Mitochondrial dysfunction leads to oxygen free radical (ROS) generation with consequent oxidative stress and cellular damage. Recently, activation of the cellular antioxidant system and apoptosis were demonstrated in skeletal muscle fibres from patients with mitochondrial diseases, but the underlying mechanisms remain unknown. Hydrogen peroxide, a by-product of ROS generation, is a chemical inducer of gene expression able to activate apoptosis and to promote the antioxidant response through the activation of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) transcription factor. Using immunohistochemistry and confocal microscopy, we evaluated the expression of NF-κB and AP-1 in muscle biopsies from patients with mitochondrial disease. In addition, we examined the expression of factors involved in their activation, such as NF-κB inducing kinase (NIK) and phosphorylated Jun-N-terminal kinase (p-JNK). Most fibres with respiratory chain dysfunction displayed nuclear staining for activated c-Jun/AP-1, but not for NF-κB. The same fibres reacted for p-JNK. Only some ragged red fibres immunoreacted for NIK. These data suggest that AP-1 is involved in the oxidative stress response in muscle fibres from patients with mitochondrial disease.
- Published
- 2003
19. Hepatitis C virus infection and myositis: a virus localization study
- Author
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Bruno Bonetti, Antonino Uncini, A. Di Muzio, Margherita Capasso, E. Pizzigallo, Nicolo' Rizzuto, and L. Panzeri
- Subjects
Pathology ,medicine.medical_specialty ,Hepatitis C virus ,Hepacivirus ,Viral Nonstructural Proteins ,medicine.disease_cause ,Polymerase Chain Reaction ,Immunoglobulin G ,Virus ,Major Histocompatibility Complex ,Antigen ,medicine ,Humans ,RNA, Messenger ,In Situ Hybridization ,Genetics (clinical) ,Myositis ,Aged ,NS3 ,Muscle biopsy ,biology ,medicine.diagnostic_test ,Fibrinogen ,Hepatitis C ,Hepatitis C, Chronic ,medicine.disease ,Immunohistochemistry ,Virology ,Microscopy, Electron ,Neurology ,Pediatrics, Perinatology and Child Health ,biology.protein ,RNA, Viral ,Female ,Neurology (clinical) - Abstract
We report a case of myositis associated with chronic hepatitis C virus infection. Muscle biopsy and immunohistochemistry showed perifascicular atrophy, few necrotic and regenerating fibres, scarce perivascular infiltrates, deposits of immunoglobulin G, C3, fibrinogen and MAC in muscle vessel walls, and non-uniform expression of major histocompatibility complex-I antigens among muscle fibres. Hepatitis C virus NS3 antigen and hepatitis C virus RNA were detected in infiltrating cells but not within muscle fibres or endothelial cells. Our findings suggest that humoral-mediated immune mechanisms, not directly related to hepatitis C virus infection of muscle structures, may sustain the local inflammatory reaction in this patient.
- Published
- 2003
20. Prevalence of Dementia and Apolipoprotein E Genotype Distribution in the Elderly of Buttapietra, Verona Province, Italy
- Author
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S. Filipponi, Alessandro Salviati, E. Fincati, L. De Togni, M. D. Benedetti, M. Gomez Lira, G. Stenta, M. Manfredi, M. Pampanin, Nicolo' Rizzuto, and G. Danti
- Subjects
Male ,Apolipoprotein E ,Gerontology ,Genotype ,Epidemiology ,Polymerase Chain Reaction ,Apolipoproteins E ,Alzheimer Disease ,Risk Factors ,Alzheimer's disease ,Dementia ,Prevalence study ,Prevalence ,medicine ,Humans ,Distribution (pharmacology) ,Genetic Predisposition to Disease ,Aged ,DNA Primers ,Aged, 80 and over ,business.industry ,medicine.disease ,Genetics, Population ,Italy ,Female ,lipids (amino acids, peptides, and proteins) ,Neurology (clinical) ,business - Abstract
We investigated the prevalence of dementia and the apolipoprotein E (APOE) genotype distribution in the elderly of Buttapietra, a village near Verona, Italy. All residents over the age of 74 (n = 238), including those who were institutionalized, were studied using a direct-contact, single-phase design. The overall prevalence of dementia, clinically defined by DSM-III-R criteria, was 15.8 cases per 100 population, with age-specific figures increasing steeply with advancing age in both sexes. Alzheimer’s disease (AD) was the most frequent dementing disorder (43%). APOE genotyping was determined after DNA amplification by restriction isotyping. We found that the Ε4 allele and the Ε3/Ε4 genotype were associated with all types of dementia, although only the association of Ε3/Ε4 with AD reached statistical significance (odds ratio 4.5, 95% confidence interval 1.3–16.1). However, as reported in other Mediterranean countries, the frequency of the Ε4 allele in our population was low (8.9%), suggesting that the population-attributable risk for AD, at least for elderly individuals (≧75 years), could be small.
- Published
- 2002
21. A new mutation in the mitochondrial tRNAAla gene in a patient with ophthalmoplegia and dysphagia
- Author
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Nicolo' Rizzuto, Gaetano Vattemi, Paola Tonin, Michele Spagnolo, Giuliano Tomelleri, and Massimiliano Filosto
- Subjects
Ophthalmoplegia, Chronic Progressive External ,Mitochondrial DNA ,chronic progressive external ophthalmoplegia ,Molecular Sequence Data ,RNA, Transfer, Ala ,mitochondrial DNA ,tRNA(Ala) gene ,DNA, Mitochondrial ,medicine ,Humans ,Point Mutation ,gene ,tRNA ,Genetics (clinical) ,Genetics ,Base Sequence ,Transition (genetics) ,biology ,Point mutation ,Cytochrome c ,Ala ,Middle Aged ,medicine.disease ,Molecular biology ,Heteroplasmy ,Neurology ,Pediatrics, Perinatology and Child Health ,Transfer RNA ,Mutation (genetic algorithm) ,biology.protein ,Nucleic Acid Conformation ,Female ,Neurology (clinical) ,Deglutition Disorders ,Chronic progressive external ophthalmoplegia - Abstract
We describe a new mutation in the tRNA(Ala) gene, a T-->C transition at nucleotide position 5628, in a 62-year-old woman with late onset chronic progressive external ophthalmoplegia, dysphagia and mild proximal myopathy. The mutation is heteroplasmic and disrupts a highly conserved A-U base pair within the anticodon stem of the tRNA(Ala). Cytochrome c oxidase-negative fibers harbor a significantly higher level of mutated mtDNA than cytochrome c oxidase-positive fibers. This is the first mutation in the tRNA(Ala) gene which satisfies accepted criteria for pathogenicity.
- Published
- 2001
22. A novel 4-bp deletion creates a premature stop codon and dramatically decreases HEXB mRNA levels in a severe case of Sandhoff disease
- Author
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Alessandro Salviati, Monica Mottes, Chiara Perusi, Rosanna Gatti, P.F. Pignatti, Nicolo' Rizzuto, and Macarena Gomez-Lira
- Subjects
Male ,Nonsense mutation ,Sandhoff disease ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Frameshift mutation ,Exon ,Hexosaminidase B ,Gangliosidoses, GM2 ,Infantile Sandhoff disease ,medicine ,Humans ,stop codon ,mutation ,RNA, Messenger ,Frameshift Mutation ,Molecular Biology ,Sequence Deletion ,Genetics ,Mutation ,Base Sequence ,Infant ,Sandhoff Disease ,Cell Biology ,medicine.disease ,Molecular biology ,beta-N-Acetylhexosaminidases ,Stop codon ,HEXB ,Codon, Terminator ,Heteroduplex - Abstract
We present the molecular genetic analysis of an infantile-onset Sandhoff disease patient. Genomic DNA amplification, heteroduplex analysis, cloning and sequencing revealed a 4-bp deletion in exon 4 (497 ΔAGTT). The result is a frameshift mutation that leads to a stop codon in exon 5. This mutation is associated with a dramatic decrease of HEXB mRNA levels.
- Published
- 2001
23. Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families
- Author
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V. Bosello, Gian Maria Fabrizi, L. Vallo, S. Baratta, Franco Taroni, E. Righetti, M. L. Mostacciuolo, Nicolo' Rizzuto, M. Milani, F. Schiavon, Gabriele Siciliano, Michela Zortea, and Luciano Merlini
- Subjects
Duplication ,DNA Mutational Analysis ,Déjérine-Sottas syndrome ,MPZ ,medicine.disease_cause ,Connexins ,Hereditary motor and sensory neuropathy type I ,Cx32 ,Cohort Studies ,Gene Frequency ,Charcot-Marie-Tooth Disease ,Gene Duplication ,Peripheral myelin protein 22 ,Gene duplication ,CMTX1 ,Mutation frequency ,Genetics (clinical) ,DSS ,Genetics ,CMT1 ,HMSN1 ,Mutation ,education.field_of_study ,GJB1 ,Myelin protein zero ,Phenotype ,Italy ,Connexin 32 ,EGR2 ,Gap junction protein 1 ,Myelin P0 Protein ,Myelin Proteins ,Genotype ,Italian ,Early growth response 2 ,Biology ,CMT4E ,Genes, Duplicate ,medicine ,Humans ,Point Mutation ,Genetic Testing ,Charcot-Marie-Tooth disease type 1 ,education ,Genetic heterogeneity ,Point mutation ,Neuropathy ,PMP22 ,Hereditary Sensory and Motor Neuropathy ,HNPP ,Chromosomes, Human, Pair 17 - Abstract
Charcot-Marie-Tooth neuropathy type 1 (CMT1), the most common hereditary neurological disorder in humans, is characterized by clinical and genetic heterogeneity. It is caused mainly by a 1.5 Mb duplication in 17p11.2, but also by mutations in the myelin genes PMP22 (peripheral myelin protein 22), MPZ (myelin protein zero), Cx32 (connexin 32; also called GJB1), and EGR2 (early growth response 2). In this study, we have screened 172 index cases of Italian families in which there was at least one subject with a CMT1 diagnosis for the duplication on 17p11.2 and mutations in these genes. Among 170 informative unrelated patients, the overall duplication frequency was 57.6%. A difference could be observed between the duplication frequency in familial cases (71.6%) and that observed in non-familial cases (36.8%). Among the non-duplicated patients, 12 were mutated in Cx32, four in MPZ, two in PMP22, and none in the EGR2. In the non-duplicated cases, the overall point mutation frequency for these genes was 25.0%. We describe the mutations identified, and consider possible genotype-phenotype correlation.
- Published
- 2001
24. SEVERE CMT TYPE 2 WITH FATAL ENCEPHALOPATHY ASSOCIATED WITH A NOVEL MFN2 SPLICING MUTATION
- Author
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Tiziana Cavallaro, Maria Giovanna Rossetto, Andrea Vettori, Maria Muglia, Valerio Carelli, Nicolo' Rizzuto, Leonardo Salviati, Maria Luisa Mostacciuolo, Francesca Boaretto, Andrea Martinuzzi, Giovanni Vazza, Alberto Casarin, Boaretto F., Vettori A., Casarin A., Vazza G., Muglia M., Rossetto M.G., Cavallaro T., Rizzuto N., Carelli V., Salviati L., Mostacciuolo M.L., and Martinuzzi A.
- Subjects
Foot drop ,medicine.medical_specialty ,Pathology ,Neurology ,Mammillary body ,RNA Splicing ,Encephalopathy ,GTP Phosphohydrolases ,Mitochondrial Proteins ,Central nervous system disease ,Charcot-Marie-Tooth Disease ,medicine ,Humans ,Family Health ,Brain Diseases ,business.industry ,NEUROPATHY ,Membrane Proteins ,Dysautonomia ,Chorea ,Middle Aged ,medicine.disease ,Introns ,Hyperintensity ,Mutation ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Mutations in the MFN2 gene, encoding mitofusin2, cause autosomal dominant axonal Charcot-Marie-Tooth type 2 (CMT2A, MIM: 608507).1 MFN2 mutations are also found in CMT2 subjects with optic atrophy2 or cognitive impairment.3 The sibship we studied comprised 3 affected and 3 apparently healthy individuals (figure e-1 on the Neurology ® Web site at www.neurology.org). ### Standard protocol approvals, registrations, and patient consents. The study was approved by the institutional ethics committee. Written informed consent was obtained from all participants in the study. ### Clinical cases and results. For more information, see e-Methods. A 48-year-old woman presented with a 10-year history of progressive leg weakness, foot drop, hypotrophy, areflexia, intact sensation, and cognition. Neurophysiology (table e-1) revealed a severe axonal polyneuropathy. The sural nerve biopsy (figure e-2, A and B) showed reduced fiber densities, loss of large myelinated fibers, and marginal Wallerian degeneration. Teased fibers were thin, with shortened internodes, some ongoing remyelination, and no demyelination. She was wheelchair-bound within 1 year. At age 50, after colectomy, she developed a progressive brainstem syndrome with vomiting, nystagmus, chorea, clouded consciousness, and dysautonomia (hyperthermia, breathing irregularities). MRI showed diffuse T2 hyperintensities in the upper brainstem and periaqueductal gray (figure 1A). Blood and CSF examinations were unremarkable. The patient progressively worsened in spite of aggressive management, including thiamine supplementation, and died 7 days later. Brain pathology revealed symmetric vasculonecrotic lesions in the brainstem and the periaqueductal gray with small hemorrhagic component (figure e-2, C and D). Figure 1 Neuroimaging and molecular data of index case (A) Fluid-attenuated inversion recovery axial (a) and coronal (b) images of case II-7 2 days after onset of the encephalopathic symptoms. Symmetric high signal intensity alterations surround the aqueduct, involve the medial thalami, the mammillary bodies, and the tegmental area. (B) Sequence of the wild-type (WT) and mutated (Mut) MFN2 …
- Published
- 2010
25. Neuronal ceroid lipofuscinoses: pathological features of bioptic specimens from 28 patients
- Author
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Alessandro Simonati and Nicolo' Rizzuto
- Subjects
Brain atrophy ,medicine.medical_specialty ,Pathology ,Neurology ,Biopsy ,Dermatology ,White matter ,Cytosol ,Magnetic resonance imaging ,Neuronal Ceroid-Lipofuscinoses ,medicine ,Humans ,Lymphocytes ,Child ,Muscle, Skeletal ,Pathological ,Progressive encephalopathy ,Neuroradiology ,Tripeptidyl-Peptidase 1 ,medicine.diagnostic_test ,business.industry ,Brain biopsy ,Rectum ,Brain ,Infant ,General Medicine ,Cerebral cortex ,Microscopy, Electron ,Psychiatry and Mental health ,medicine.anatomical_structure ,CLN3 ,Child, Preschool ,Basal ganglia ,Neurology (clinical) ,Neurosurgery ,Lysosomes ,business - Abstract
Clinical findings and pathological features of 28 patients affected with neuronal ceroid lipofuscinoses (NCL) are reviewed. The patient group included 15 children affected with the late-infantile form of NCL (LINCL), 10 patients affected with the juvenile form (JNCL), and 3 adult cases. Ultrastructural examinations of 50 biopsies from 6 tissues were consistent with clinical features in all LINCL and JNCL cases but one. The importance of electron microscopic (EM) examination of blood lymphocytes in these forms is outlined, particularly when combined with molecular analysis of the CLN2 or CLN3 genes, respectively. This approach leads to a definite diagnosis of LINCL and JNCL in a relatively short time. In adult NCL, diagnosis still relies on pathological grounds, and difficulties in interpreting the osmiophilic storage bodies in different tissues are outlined. EM investigation of blood lymphocytes was not helpful in any case of adult NCL. Results of one stereotactic brain biopsy are also reported.
- Published
- 2000
26. Cell proliferation and death: Morphological evidence during corticogenesis in the developing human brain
- Author
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Cinzia Tosati, Elena Piazzola, Nicolo' Rizzuto, Alessandro Simonati, and Tiziana Rosso
- Subjects
Telencephalon ,Programmed cell death ,Cerebellum ,Histology ,CNS development ,Cell division ,Gestational Age ,Cerebellar Cortex ,Embryonic and Fetal Development ,In Situ Nick-End Labeling ,medicine ,PCNA ,Humans ,Instrumentation ,Mitosis ,TUNEL ,mitosis ,Cell Death ,biology ,Cell growth ,apoptosis ,Cell biology ,Proliferating cell nuclear antigen ,Medical Laboratory Technology ,Corticogenesis ,medicine.anatomical_structure ,Cerebellar cortex ,biology.protein ,Anatomy ,Neuroscience ,Cell Division - Abstract
Cell proliferation and death account for the refinement of the cell number during corticogenesis. These processes have been investigated in the human developing telencephalon (12th-24th week of gestation) and cerebellum (16th-24th week). Only foetal brains, which had normal neuropathological examination, were utilised. Cell proliferation was analysed by classical histology and PCNA immunohistochemistry; cell death was investigated by the TUNEL method, which makes evident the different stages of apoptosis. High figures of mitotic nuclei were seen in the ventricular zone at the 12th-15th week of gestation, before sharply declining. The decrease of the proliferating cells occurs synchronously in both frontal and occipital germinal zones. Conversely, a slow increase of the number of the mitotic cells was observed in the more dorsal regions, probably due to the presence of proliferating glial elements. The amount of apoptotic nuclei was always remarkably low in the transient compartments of the wall of the telencephalon. The moderate number of apoptotic cells suggests that cellular mechanisms other than apoptosis are involved in the dissolution of the ventricular zone. Neither proliferating nor apoptotic cells were seen in the cortical plate. The topography of cell proliferation and death in the developing cerebellum did not account for a mutual relationship between the two events. The prolonged duration of the cell-cycle in the human developing CNS may explain its increased vulnerability to various DNA-damaging conditions, which can lead to either destructive lesions or malformations.
- Published
- 1999
27. Neuromuscular complications of kidney diseases
- Author
-
M Cobelli, Nicolo' Rizzuto, Giuliana Galassi, and Sergio Ferrari
- Subjects
medicine.medical_specialty ,Internal medicine ,medicine ,Humans ,Renal Insufficiency ,Myopathy ,Uremia ,Transplantation ,Kidney ,business.industry ,Peripheral Nervous System Diseases ,Muscle weakness ,Neuromuscular Diseases ,medicine.disease ,Electrophysiology ,Protein catabolism ,Endocrinology ,medicine.anatomical_structure ,Nephrology ,Peripheral nervous system ,Kidney Diseases ,medicine.symptom ,business ,Polyneuropathy ,Kidney disease - Abstract
affected than females [2,6 ]. Bolton pointed out that The uraemic syndrome is characterized by overall 60% of patients receiving haemodialysis for uraemia deterioration of biochemical and physiological funchave neuropathy by electrodiagnostic criteria [2]. The tions in parallel with the progression of renal failure. main symptoms are restless legs, spontaneous cramps, Uraemia results in variable symptoms pointing to distal paresthesias, numbness and burning feet, which, damage of multiple organs, due to retention of comhowever, are not necessarily related to the neuropathy, pounds normally cleared by the healthy kidneys [1]. but due possibly to transient disturbances of peripheral The identified mechanisms currently are attributed to sensory receptors, induced by fluctuation in water and increased protein catabolism, reduced excretory electrolytes [2]. Symptoms may occur either prior to capacity and altered water–electrolyte homeostasis [2]. or during a regular haemodialysis programme; the Major neurotoxins accumulating in uraemia are latter could indicate that the achieved control is not urea, creatinine, guanidine compounds, a number of optimal [2,3]. Clinical signs of uraemic polyneuropathy aromatic acids, uric and ossalic acids, myo-inositol, include symmetric muscle weakness, areflexia and ‘middle molecules’, b2-microglobulin, amines and parasensory loss for all modalities, especially pin-prick and thyroid hormone (PTH) [2]. The nervous system, both vibration. An early finding is elevation of the vibratory central and peripheral, may show changes, mimicking threshold [2,3,6 ] (Table 2). exogenous poisoning or drug overdose [1]. Here we review the clinical, electrophysiological and morpholoPathology of uraemic polyneuropathy gical aspects of peripheral nervous system syndromes
- Published
- 1998
28. Neuropsychological and neuroimaging correlates in corticobasal degeneration
- Author
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Emma Frasson, M. Pampanin, R. Tanel, Alberto Beltramello, Nicolo' Rizzuto, G. Moretto, C. Stegagno, and Nicola Smania
- Subjects
Male ,Dermatology ,Neuropsychological Tests ,Apraxia ,Neuroimaging ,Neuropsychology ,Functional neuroimaging ,medicine ,Humans ,Corticobasal degeneration ,Neuropsychological assessment ,Aged ,Neuroradiology ,medicine.diagnostic_test ,General Neuroscience ,Putamen ,Brain ,Neurodegenerative Diseases ,General Medicine ,Middle Aged ,medicine.disease ,Executive functions ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,PET ,MRI ,SPECT ,Female ,Neurology (clinical) ,Psychology ,Neuroscience ,Psychomotor Performance - Abstract
The aim of this study was to correlate neuropsychological and neuroimaging findings in corticobasal degeneration (CBD). Three patients with clinical criteria for CBD were examined by means of neuropsychological tests, brain magnetic resonance imaging (MRI), and flow and metabolism neuroimaging techniques. Neuropsychological assessment revealed impairment in executive functions, manual dexterity and motor programming with significant asymmetry between upper limbs. Ideomotor and oral apraxia were also detected, and memory deficits were observed in one patient. MRI revealed cortical dilation of the frontal and peri-rolandic regions, symmetrical in one case and asymmetrical in the other two cases. An increased T2 signal intensity in the posterolateral putamen and substantia nigra ipsilateral to the cortical atrophy was observed in one patient. Asymmetries of both frontal and parietal cortices and basal ganglia were detected in all three patients by 18-fluorodeoxyglucose positron emission tomography; temporal region hypometabolism was associated in one patient. These cortical and subcortical asymmetries were observed in two patients by single photon emission tomography with the tracer technetium Tc 99m hexamethyl propylenamine oxime; cortical asymmetry was observed in only one patient. The results showed that functional neuroimaging findings correlated well with neuropsychological aspects in CBD. Neuroimaging and neuropsychological correlations may contribute toward understanding anatomical and functional abnormalities associated with this neurodegenerative disorder.
- Published
- 1998
29. Molecular genetic characterization of two metachromatic leukodystrophy patients who carry the T799G mutation and show different phenotypes; description of a novel null-type mutation
- Author
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Pier Franco Pignatti, Macarena Gomez-Lira, Chiara Perusi, Michela Manfredi, Nicolo' Rizzuto, Alessandro Salviati, and Monica Mottes
- Subjects
Adult ,Male ,Heterozygote ,Biology ,Compound heterozygosity ,complex mixtures ,Cricetinae ,Genotype ,Genetics ,medicine ,Animals ,Humans ,Child ,Gene ,Cells, Cultured ,Cerebroside-Sulfatase ,Genetics (clinical) ,Cerebroside-sulfatase ,Heterozygote advantage ,Leukodystrophy, Metachromatic ,Fibroblasts ,medicine.disease ,Phenotype ,Human genetics ,Metachromatic leukodystrophy ,Amino Acid Substitution ,Mutation ,Female - Abstract
Metachromatic leukodystrophy (MLD) is an autosomal recessive storage disease caused by deficiency of the lysosomal enzyme, arylsulfatase A. Two common mutations causing MLD have been characterized and correlations between phenotype and genotype have been established. A third common mutation, T799G, has also been identified in European MLD patients, and is associated with the late-onset forms of the disease. We report the molecular analysis of two Italian MLD patients, with juvenile and adult onset of the disease, respectively, who carried the T799G mutation in compound heterozygosity with different null mutations. A novel rapid mutation detection method is demonstrated for patient screening. One patient has a novel mutation, a T553C [corrected] transition that results in the substitution of Pro for Leu at codon 135, and produces no enzymatic activity in transfection experiments.
- Published
- 1998
30. Ponto-cerebellar hypoplasia with dystonia: clinico-pathological findings in a sporadic case
- Author
-
R. Colombari, Alessandro Simonati, Nicolo' Rizzuto, and Bernardo Dalla Bernardina
- Subjects
Microcephaly ,Cerebellum ,CNS development ,Atrophy ,Pons ,medicine ,Humans ,Psychomotor retardation ,business.industry ,Ponto-cerebellar hypoplasia ,General Medicine ,Anatomy ,medicine.disease ,Congenital dystonia ,Hypoplasia ,Dystonia ,Dentate nucleus ,medicine.anatomical_structure ,Child, Preschool ,Cerebellar cortex ,Pediatrics, Perinatology and Child Health ,Pattern formation ,Female ,Neurology (clinical) ,Cerebellar hypoplasia (non-human) ,medicine.symptom ,business - Abstract
Microcephaly, absent psychomotor development and dystonic limb movements were the main clinical features of a 3-year-old girl affected by hypoplasia of the pontocerebellar structures. As in the few previously reported cases there are discrepancies between the severity of lesions in the supratentorial and infratentorial compartments. Pathological features such as size reduction of the ventral pons, inferior olive atrophy, dentate nucleus fragmentation, and thinning of the cerebellar cortex suggest an impaired maturation of the involved structures due to a prenatal condition (dated at about 20-28 weeks of gestation). Somatotopic analysis failed to provide conclusive evidence on the primary target of the disease. The affected structures originate from the dorsal rhombencephalic region at about the same gestational age, and their maturation is probably under the control of sets of genes which regulate pattern formation. Early abnormal functioning of such genes might lead to the selected morphogenetical alterations observed in ponto-cerebellar hypoplasia. The normal morphogenetic pattern of the supratentorial structures and the mild lesions observed suggest that their late involvement can be related to a different pathogenetic process.
- Published
- 1997
31. Human neoplastic Schwann cells: changes in the expression of neurotrophins and their low‐affinity receptor p75
- Author
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Bruno Bonetti, Nicolo' Rizzuto, G. Moretto, Marco Carner, L. Panzeri, and Giuseppe Zamboni
- Subjects
Adult ,Male ,Histology ,Cell ,Schwann cell ,Receptors, Nerve Growth Factor ,Neurotrophin-3 ,Polymerase Chain Reaction ,Receptor, Nerve Growth Factor ,Neurotrophins ,Pathology and Forensic Medicine ,Tumours ,Neurotrophin 3 ,Physiology (medical) ,Biomarkers, Tumor ,otorhinolaryngologic diseases ,medicine ,Humans ,Schwann cells ,Neoplastic transformation ,Nerve Growth Factors ,Receptor ,Acoustic Schwannoma ,biology ,S100 Proteins ,p75 receptor ,RT in situ PCR ,Immunohistochemistry ,Nerve growth factor ,medicine.anatomical_structure ,nervous system ,Neurology ,Immunology ,Cancer research ,biology.protein ,Female ,sense organs ,Neurology (clinical) ,Neurilemmoma ,Neurotrophin - Abstract
Neurotrophins are known to influence Schwann cells during development and to promote peripheral nerve regeneration after axonal damage. In neoplastic conditions. Schwann cells from experimentally-induced schwannomas appear to retain their responsiveness to nerve growth factor (NGF), although the role of neurotrophins in the neoplastic process in poorly understood. In this study, human neoplastic Schwann cells (five cases of acoustic schwannoma and two cases of malignant peripheral nerve sheath tumours [MPNST]) were investigated for the expression in situ of molecules of the neurotrophin system. In particular, we studied the 75 kDa low-affinity receptor (p75) and the mRNA for its ligands, NGF and neurotrophin-3 (NT-3). By immunohistochemistry, the p75 receptor was found to be the present at high levels in Schwann cells from acoustic schwannomas, whereas it was very weak or absent in MPNST. Messenger RNA for NGF and NT-3 was detected by reverse transcriptase in situ polymerase chain reaction technique and showed the same fluctuation of p75, being up-regulated in acoustic schwannomas and very weak or absent in MPNST. In normal non-neoplastic tissue, no detectable amounts of either ligand or receptor were observed. Our results indicate that changes in the expression of neurotrophins and their p75 receptor occurred during the neoplastic transformation of Schwann cells. In benign schwannomas, such changes are likely to reflect the loss of axonal contact, while in MPNST they may be related to a complete derangement of cell machinery in the tumour cells.
- Published
- 1997
32. Delayed spongiform leukoencephalopathy after heroin abuse
- Author
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Tiziana Cavallaro, Marco Sparaco, Michela Morbin, Luigi Gaetti, Giulio Boso, Sergio Ferrari, and Nicolo' Rizzuto
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Respiratory chain ,Rhabdomyolysis ,Pathology and Forensic Medicine ,Leukoencephalopathy ,Cellular and Molecular Neuroscience ,medicine ,Humans ,Substance Abuse, Intravenous ,Coma ,Brain Diseases ,business.industry ,medicine.disease ,Immunohistochemistry ,Astrogliosis ,Heroin ,Peripheral neuropathy ,Injections, Intravenous ,Neurology (clinical) ,Astrocytosis ,medicine.symptom ,business ,Demyelinating Diseases ,Spongiosis - Abstract
Here we report the clinical and pathological findings in a 30-year-old drug addict in whom an intravenous injection of heroin led to reversible coma with respiratory depression and heart failure. On regaining consciousness, the patient was found to have rhabdomyolysis with renal failure requiring dialysis and peripheral neuropathy. Three weeks later his neurological condition suddenly deteriorated and delayed encephalopathy developed, leading to death 20 days later. The neuropathological study of the brain disclosed pale, spongy myelin with diffuse reactive astrogliosis and microglial proliferation, without hypoxic necrotic lesions. The cerebral and cerebellar cortices were unchanged. The absence of typical hypoxic lesions and the presence of spongiosis with massive astrocytosis distinguished this case from the previously reported cases of delayed leukoencephalopathy following severe hypoxia. An immunocytochemical study designed to exclude an underlying alteration of the metabolic oxidative pathway detected normal expression of the respiratory chain complexes IV, III and V. Despite the absence of an oxidative chain alteration in our patient, we cannot exclude the possibility that an individual predisposition played a pathogenetic role in this delayed leukoencephalopathy.
- Published
- 1997
33. Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy
- Author
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Sandra Galiazzo-Rizzuto, Salvatore Monaco, Bruno Bonetti, Michela Morbin, Sergio Ferrari, Giampietro Zanette, Nicolo' Rizzuto, Laura Bertolasi, and Tiziana Cavallaro
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Biopsy ,Population ,Complement receptor ,Pathology and Forensic Medicine ,Pathogenesis ,Cellular and Molecular Neuroscience ,Ganglia, Spinal ,Peripheral Nervous System ,medicine ,Humans ,education ,In Situ Hybridization ,Acquired Immunodeficiency Syndrome ,education.field_of_study ,Nerve biopsy ,medicine.diagnostic_test ,business.industry ,pathogenesis ,HIV ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Electrophysiology ,medicine.anatomical_structure ,Peripheral neuropathy ,Peripheral nervous system ,Immunology ,Female ,Autopsy ,Neurology (clinical) ,Endoneurium ,business ,distal symmetrical peripheral neuropathy ,Polyneuropathy - Abstract
We report the results of a clinical, electrophysiological and pathological study conducted in 18 AIDS patients presenting a distal symmetrical predominantly sensory polyneuropathy (DSPN) characterized by painful dysesthesias as main complaint. Onset of the neuropathy was at CDC (Center for Disease Control) stage II in 2 patients, at CDC stage III in 5 patients and at CDC stage IV in the remainder. Electrophysiological investigation confirmed the presence of an axonal alteration in the sensory nerves, but also revealed motor involvement in all cases. The neuropathological features of sensory nerves were fiber loss and axonal degeneration with macrophagic activation. The expression of monocyte-macrophage markers and of major histocompatibility complex class II antigens appeared up-regulated in endoneurial ramified cells, while expression of CR3, a complement receptor involved in the process of phagocytosis, was down-regulated. In six nerve biopsy samples and in two out of five DSPN dorsal root ganglia we found HIV-related mRNA and protein located in scattered cells of the endoneurium which we presume to be macrophages. These data suggest that: (a) DSPN may occur early in the course of the disease and is not limited to later stages; (b) DSPN is not a ganglionitis but is actually a sensory-motor neuropathy; (c) the virus enters the peripheral nervous system and induces changes in the immunocompetent cell population with activation of macrophages. Storage of the virus inside macrophages may act both as a reservoir for the virus and as a putative cause of nerve damage, probably through release of cytotoxins and/or interaction with trophic factors.
- Published
- 1995
34. Spinal Somatosensory Evoked Potentials in Patients with Tethered Cord Syndrome
- Author
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Nicolo' Rizzuto, Paolo Manganotti, Giampietro Zanette, Alberto Polo, Laura Bertolasi, and Domenico De Grandis
- Subjects
Adult ,Male ,Cord ,Neural Conduction ,Spina Bifida Occulta ,Lesion ,White matter ,Interneurons ,Evoked Potentials, Somatosensory ,medicine ,Humans ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,General Medicine ,Anatomy ,Middle Aged ,Spinal cord ,Magnetic Resonance Imaging ,Electrophysiology ,Radiography ,medicine.anatomical_structure ,Spinal Cord ,Neurology ,Somatosensory evoked potential ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Lumbosacral joint - Abstract
We studied the electrophysiological changes occurring in six patients with tethered cord syndrome. Evidence of spinal malformations was provided by magnetic resonance imaging. The functional assessment of the spinal cord was performed by analysing both spinal and cortical somatosensory evoked potentials. The evoked electrospinogram was recorded from the thoracic and lumbosacral spinous processes. The N22 lumbosacral potential was selectively affected, being rostrocaudally displaced and reduced in amplitude or even absent in patients with neurological signs indicating a segmental lower cord lesion. Inter-peak somatosensory evoked potentials latency was normal in all cases, suggesting that ascending axonal potentials in the dorsal column fibres may be synchronized. Segmental potentials of the lumbosacral response, originating from the post-synaptic activity of dorsal horn interneurons, are selectively affected in this syndrome resulting from the rostrocaudal displacement of the spinal cord due to tethering. Our findings in the clinical field are consistent with previous experimental evidence indicating a different sensitivity of the gray vs. white matter to progressive stretching.
- Published
- 1994
35. Myelin oligodendrocyte glycoprotein polymorphisms and multiple sclerosis
- Author
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Alessandro Salviati, Giuseppe Moretto, M. D. Benedetti, Deborah Bonamini, Macarena Gomez-Lira, P.F. Pignatti, and Nicolo' Rizzuto
- Subjects
Central Nervous System ,Male ,Multiple Sclerosis ,DNA Mutational Analysis ,Immunology ,Biology ,Polymophisms ,Myelin oligodendrocyte glycoprotein ,Myelin ,Gene Frequency ,Leukocytes ,medicine ,Humans ,Immunology and Allergy ,Genetic Testing ,Sclerosis multipla ,Gene ,Allele frequency ,Myelin Sheath ,Regulation of gene expression ,Genetics ,Polymorphism, Genetic ,Base Sequence ,Myelin-associated glycoprotein ,Multiple sclerosis ,MOG gene ,medicine.disease ,Molecular biology ,Axons ,Oligodendrocyte ,Myelin-Associated Glycoprotein ,medicine.anatomical_structure ,Gene Expression Regulation ,Neurology ,Mutation ,biology.protein ,Female ,Myelin-Oligodendrocyte Glycoprotein ,Neurology (clinical) ,Myelin Proteins - Abstract
A detailed analysis of the coding sequences of myelin oligodendrocyte glycoprotei (MOG) gene was performed in multiple sclerosis (MS) patients and in control individuals and three new polymorphisms are described: T636C, nt 571+77C→T (IVS 4), and nt 710−44A→G (IVS 6). Screening studies demonstrated that T636C was present in three MS patients and in no control individual and that polymorphisms nt 571+77C→T (IVS 4), and nt 710−44A→G (IVS 6), were present with no significant frequency differences in MS patients and control individuals. No mutations were found after sequencing the coding sequences of the extracellular domain of MOG gene in 20 MS patients and 20 control individuals. Screening studies were also performed for known polymorphisms: G15A, Val142Leu, nt 571+68A→G (IVS 4), and 571+92C→G (IVS 4). Polymorphism Val 142 Leu, which is linked to nt 571+68A→G (IVS 4), resulted under-represented in MS patients.
- Published
- 2002
36. IDPN impairs post-traumatic regeneration of rat sciatic nerve
- Author
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Michela Morbin, Giampietro Zanette, Nicolo' Rizzuto, and Salvatore Monaco
- Subjects
Male ,medicine.medical_specialty ,Histology ,Neurofilament ,medicine.medical_treatment ,Neurotoxins ,Biology ,Nerve Fibers, Myelinated ,neurofilaments ,Pathology and Forensic Medicine ,Rats, Sprague-Dawley ,Lesion ,axon reaction ,axonal swelling ,axonal transport ,egeneration ,IDPN ,Physiology (medical) ,Internal medicine ,Nitriles ,medicine ,Animals ,Axon ,Anatomy ,Sciatic Nerve ,Nerve Regeneration ,Rats ,Electrophysiology ,Microscopy, Electron ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Neurology ,Axoplasmic transport ,Neurology (clinical) ,Sciatic nerve ,Axotomy ,medicine.symptom ,Reinnervation - Abstract
The role played by cytoskeletal proteins in nerve regeneration was investigated in a model in which the axonal transport of neurofilaments (NF) is almost selectively impaired. The administration of beta, beta'-iminodipropionitrile (IDPN), a synthetic lathyrogenic compound, induces an axonopathy characterized by proximal axonal enlargements, due to NF accumulation, and by diffuse atrophic changes associated with spatial segregation of NF from microtubules (MT). We investigated post-axotomy regeneration of rat sciatic nerve following IDPN administration. Changes induced by IDPN, as examined in the proximal and distal nerve stump at 15 and 30 days after lesion, consisted of a statistically significant reduction of the mean axonal diameter (P < 0.0001) as compared to control rats. In addition, the number of regenerating myelinated fibres was smaller in dosed rats (P < 0.001) 15 days after crush, whereas at the later stage the number of axons approached that of control animals. Electrophysiological investigation revealed a delay in target reinnervation in dosed rats. Regenerating IDPN axons, both 15 and 30 days after crush contained fewer NF (P < 0.001), while the number of MT was slightly increased as compared to controls. Taken together, our results suggest that severe alteration of NF transport, coupled with mild alteration of other components of cytoskeletal proteins, impairs the longitudinal and radial growth of regenerating myelinated axons and confirm that the number of NF is the major determinant of the cross-sectional area of each segment of the axon.
- Published
- 1993
37. Methodological Issues in Right-to-Left Shunt Detection in CADASIL Patients
- Author
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Gian Paolo Anzola, Sara Mazzucco, and Nicolo' Rizzuto
- Subjects
Advanced and Specialized Nursing ,medicine.medical_specialty ,business.industry ,Right-to-left shunt ,Foramen ovale (skull) ,medicine.disease ,medicine.anatomical_structure ,medicine.artery ,medicine ,Neurology (clinical) ,Radiology ,Ultrasonography ,Cardiology and Cardiovascular Medicine ,CADASIL ,business - Abstract
To the Editor: With regard to the article from Zigari et al,1 we would like to add some comments to the authors’ reply2 to our letter.3 The authors are very welcome to …
- Published
- 2009
38. Natural history of Charcot-Marie-Tooth 2: 2-year follow-up of muscle strength, walking ability and quality of life
- Author
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Davide Pareyson, Nicolo' Rizzuto, Giuseppe Vita, Irene Aprile, Tiziana Cavallaro, Pietro Attilio Tonali, A. Schenone, DA Quattrone, and Luca Padua
- Subjects
Adult ,Male ,medicine.medical_specialty ,Neurology ,Adolescent ,Dermatology ,Disease ,Walking ,Disability Evaluation ,Young Adult ,Quality of life ,Charcot-Marie-Tooth Disease ,Medicine ,Humans ,Charcot–Marie-Tooth ,Muscle Strength ,Neurological evaluation ,Muscle, Skeletal ,Neuroradiology ,Neurologic Examination ,business.industry ,General Medicine ,Middle Aged ,Mental health ,Natural history ,Clinical trial ,Settore MED/26 - NEUROLOGIA ,Psychiatry and Mental health ,Charcot Marie-Tooth ,Physical therapy ,Disease Progression ,Quality of Life ,Female ,Neurology (clinical) ,Neurosurgery ,business ,Follow-Up Studies - Abstract
Charcot-Marie-Tooth (CMT) disease is the most frequent inherited neuropathy, no therapies are available at the moment but clinical trials are ongoing. For that reason it is very important to know the natural history of the disease. We report the results of the natural history of clinical features and quality of life (QoL) in patients with CMT2. Twenty patients were enrolled. At recruitment and at follow-up (2 years), all patients underwent neurological evaluation, QoL and disability assessments. The study-end evaluation took place 20-28 months after the baseline evaluation. During the 2-year follow-up period, CMT2 patients showed a mild reduction of strength of distal muscles of upper limbs and proximal muscles of lower limbs, a worsening sensory function and a mild increase in walking disability. However, there was no relevant worsening of QoL, except for a mild deterioration of one mental health domain.
- Published
- 2009
39. Evaluating endothelial function of the common carotid artery: An in vivo human model
- Author
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Sara Mazzucco, Francesco Bifari, Gian Cesare Guidi, Riccardo C. Bonadonna, Maddalena Trombetta, G. P. Anzola, Nicolo' Rizzuto, and Maria Angela Mazzi
- Subjects
Adult ,Male ,Middle Cerebral Artery ,Carotid Artery, Common ,Vasodilator Agents ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Blood Pressure ,Sublingual administration ,Nitroglycerin ,Young Adult ,Cerebral circulation ,Bolus (medicine) ,Reference Values ,medicine.artery ,Humans ,Medicine ,cardiovascular diseases ,Common carotid artery ,Nutrition and Dietetics ,business.industry ,Acetazolamide ,Carotid ultrasound ,Endothelial function ,Flow-mediated dilation ,Transcranial Doppler ,Blood flow ,Vasodilation ,Blood pressure ,Regional Blood Flow ,Cerebrovascular Circulation ,Anesthesia ,Middle cerebral artery ,cardiovascular system ,Female ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,Blood Flow Velocity - Abstract
Background and aims Flow mediated dilation (FMD) of peripheral conduit arteries is a well-established tool to evaluate endothelial function. The aims of this study are to apply the FMD model to cerebral circulation by using acetazolamide (ACZ)-induced intracranial vasodilation as a stimulus to increase common carotid artery (CCA) diameter in response to a local increase of blood flow velocity (BFV). Methods and results In 15 healthy subjects, CCA end-diastolic diameter and BFV, middle cerebral artery (MCA) BFV and mean arterial blood pressure (MBP) were measured at basal conditions, after an intravenous bolus of 1g ACZ, and after placebo (saline) sublingual administration at the 15th and 20th minute. In a separate session, the same parameters were evaluated after placebo (saline) infusion instead of ACZ and after 10μg/m 2 bs and 300μg of glyceryl trinitrate (GTN), administered sublingually, at the 15th and 20th minute, respectively. After ACZ bolus, there was a 35% maximal MCA mean BFV increment (14th minute), together with a 22% increase of mean CCA end-diastolic BFV and a CCA diameter increment of 3.9% at the 3rd minute ( p =0.024). There were no MBP significant variations up to the 15th minute ( p =0.35). After GTN administration, there was a significant increment in CCA diameter ( p Conclusions ACZ causes a detectable CCA dilation in healthy individuals concomitantly with an increase in BFV. Upon demonstration that this phenomenon is endothelium dependent, this experimental model might become a valuable tool to assess endothelial function in the carotid artery.
- Published
- 2009
40. Epilepsy in glioblastoma multiforme: Correlation with glutamine synthetase levels
- Author
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Alessia Tomassini, Klaus Maier, Alessandro Padovani, Anna Rosati, Bruno Bonetti, Emanuela Maderna, Silvia Marconi, Nicolo' Rizzuto, Bianca Pollo, Laura Lovato, and Andreas Schwartz
- Subjects
Adult ,Male ,Cancer Research ,Blotting, Western ,Biology ,Epileptogenesis ,Cerebral glioma ,Glutamine synthetase ,Epilepsy ,Stroma ,Glutamate-Ammonia Ligase ,Glioma ,medicine ,Humans ,Aged ,Brain Neoplasms ,Astrocytes ,Middle Aged ,medicine.disease ,Blot ,Neurology ,Oncology ,Biochemistry ,Gliosis ,Giant cell ,Cancer research ,Female ,Neurology (clinical) ,medicine.symptom ,Glioblastoma - Abstract
Purpose The hypothesis addressed by this study is that a glutamine synthetase (GS) deficiency in neoplastic astrocytes is a possible molecular basis associated with seizure generation in glioblastoma multiforme (GBM). Methods Quantitative Western blot analysis of GS was performed in 20 individuals operated for malignant glioma. Results The levels of GS in patients with GBM and epilepsy were significantly lower (range 0.04–1.15; mean 0.35 ± 0.36; median 0.25) than in non-epileptic GBM individuals (range 0.78–3.97; mean 1.64 ± 0.99; median 1.25; P = 0.002). No relationship has been found between histological features (i.e. necrosis, gliosis, stroma, inflammatory cells, giant cells, and haemosiderine) and GS expression or epilepsy. Discussion Even though the epileptogenesis in glioma is multifactorial, it is conceivable that a down-regulation of GS may have an important pro-epileptogenic role in GBM, through the slowing of glutamate-glutamine cycle. This study suggests that seizures in GBM are coupled with a highly localized enzyme deficiency. The manipulation of GS activity might constitute a novel principle for inhibiting seizures in patients with glioma epilepsy.
- Published
- 2009
41. The epidemiology of inflammatory polyradiculoneuropathy. A critical review of the distribution, characteristics and outcome of the disease
- Author
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P.A. Tonali, Nicolo' Rizzuto, M. Marconi, Ettore Beghi, and Ferdinando Cornelio
- Subjects
medicine.medical_specialty ,Pathology ,Pediatrics ,Neurology ,business.industry ,General Neuroscience ,medicine.medical_treatment ,Neuritis ,Chronic inflammatory demyelinating polyneuropathy ,Polyradiculoneuropathy ,Dermatology ,General Medicine ,Disease ,medicine.disease ,Psychiatry and Mental health ,Epidemiology ,medicine ,Etiology ,Plasmapheresis ,Neurology (clinical) ,business - Abstract
An outline of the principal reports dealing with the definition, distribution, course and treatment of the inflammatory polyradiculoneuropathies, including the Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), is given. Current diagnostic criteria for GBS are reaffirmed while the diagnosis of CIDP lacks proper standardization. Then, the bounderies between the two disorders are ill-defined. While GBS is rare and homogeneously distributed across developed and developing countries, the prevalence rate of CIDP is unknown. Several antecedent events have been implicated in the pathogenesis of GBS; yet, except for the swine-flu vaccine, the relation between infectious or toxic agents and the occurrence of the disease is purely anecdotal. The only factors known to influence the outcome of GBS are age, severity of opening symptoms, abnormal electrophysiologic characteristics of peripheral nerve function, and plasmapheresis. However, responders and non-responders to current treatment are far from defined. Although similarities have been found between experimental allergic neuritis and experimental allergic encephalomyelitis, the degree of CNS impairment in patients with inflammatory polyradiculoneuropathies needs further refinement. To provide a tentative answer to some of the unsolved questions on inflammatory polyradiculoneuropathies, a multicenter cohort study on newly diagnosed patients submitted to standard clinical and laboratory evaluation, and given common therapeutic regimes, is awaited.
- Published
- 1991
42. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and right-to-left shunt: lack of evidence for an association in a prevalence study
- Author
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Sara Mazzucco, G. P. Anzola, Nicolo' Rizzuto, Gian Maria Fabrizi, Federica Taioli, Silvia Olivato, A. P. Burlina, and Moreno Ferrarini
- Subjects
Adult ,Male ,medicine.medical_specialty ,Stroke patient ,Ultrasonography, Doppler, Transcranial ,Right-to-left shunt ,Migraine with Aura ,CADASIL ,Heart Septal Defects, Atrial ,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy ,Migraine ,Transcranial Doppler ,medicine.artery ,Internal medicine ,mental disorders ,Prevalence ,Medicine ,Humans ,Receptor, Notch3 ,Aged ,Receptors, Notch ,business.industry ,Middle Aged ,medicine.disease ,humanities ,Migraine with aura ,Shunt (medical) ,Neurology ,Mutation ,Cardiology ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Background /Aims: Up to more than 50% of cryptogenetic stroke patients and patients with migraine with aura (MA) are found to have a right-to-left shunt (RLS), which is usually due to a patent foramen ovale. Moreover, both MA and stroke are cardinal features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Notch3 mutations have been suggested to induce an abnormally high incidence of atrial septal defects in a family harbouring an Arg141Cys pathogenetic mutation. We sought to determine the prevalence of RLS in CADASIL patients with different Notch3 mutations, both with and without migraine as a clinical feature. Methods: Subjects with a molecular diagnosis of CADASIL were tested for the presence of an RLS by means of contrast-enhanced transcranial Doppler (TCD). The diagnosis of migraine was made according to the 2004 International Headache Classification. Results: Sixteen CADASIL patients were tested; 6 had MA. Four patients displayed an RLS on contrast-enhanced TCD examination. Three of these patients had MA. Both patients with Arg141Cys displayed a large RLS. Conclusion: We conclude that RLS is not necessarily linked to CADASIL as a comorbidity factor. Nevertheless, there could be a relation between RLS and specific Notch3 mutations, such as Arg141Cys.
- Published
- 2008
43. Ataxia and migraine-like headache in a girl with a cerebellar developmental venous anomaly
- Author
-
Nicolo' Rizzuto and Flavio Fenzi
- Subjects
medicine.medical_specialty ,Ataxia ,Adolescent ,Migraine Disorders ,Neurological disorder ,Cerebral venous congestion ,Cerebellar developmental venous anomaly ,Central nervous system disease ,Cerebellar hemisphere ,Vertigo ,Migraine-like headache ,medicine ,Humans ,medicine.diagnostic_test ,biology ,business.industry ,Magnetic resonance imaging ,medicine.disease ,biology.organism_classification ,Cerebral Veins ,Magnetic Resonance Imaging ,Cerebral Angiography ,Neurology ,Migraine ,Anesthesia ,Female ,Neurology (clinical) ,Radiology ,medicine.symptom ,business ,Venous malformation - Abstract
Cerebral developmental venous anomalies (DVAs) are generally considered as anatomical variants of the venous system without clinical importance. We report the case of a 15-year-old girl with recurrent episodes of migraine-like headache who presented with subacute vertigo and ataxia associated with intense occipital pain. Magnetic resonance imaging (MRI) showed a DVA with signal modifications of the surrounding brain parenchyma in the left cerebellar hemisphere. The patient's ataxia regressed completely within about 2 months. On a follow-up MRI 4 years later the venous malformation and the parenchymal abnormalities were unchanged. We attribute the patient's focal neurological dysfunction to regional changes in the brain parenchyma, possibly secondary to venous hypertension. Our report provides evidence that also uncomplicated DVAs can become symptomatic and supports the role of the venous congestion within the DVA territory in pathogenesis of some brain parenchymal abnormalities associated with DVAs.
- Published
- 2008
44. Right-to-left shunt in CADASIL patients: a comorbidity factor?
- Author
-
Nicolo' Rizzuto, Sara Mazzucco, and Gian Paolo Anzola
- Subjects
Advanced and Specialized Nursing ,Pediatrics ,medicine.medical_specialty ,High prevalence ,business.industry ,Right-to-left shunt ,medicine.disease ,Comorbidity ,medicine.artery ,mental disorders ,Medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,CADASIL - Abstract
To the Editor: In 2001 Angeli et al1 reported a remarkably high prevalence of right to left shunt (RLS) in a single CADASIL pedigree, suggesting “a possible association between CADASIL and RLS”. Surprisingly, and notwithstanding the large volume of data building up on CADASIL pathogenesis and diagnosis, no further data has followed this first and only publication on this topic up to now. This is why we read with much interest the article from Zicari et al,2 reporting on a very high prevalence of RLS (71%) in a sample of 21 patients with CADASIL. However, some concerns have to be issued. …
- Published
- 2008
45. Familial spastic paraplegia with peroneal amyotrophy. A family with hypersensitivity to pyrexia
- Author
-
G Arrigoni, M Serena, Nicolo' Rizzuto, and Giuseppe Moretto
- Subjects
Adult ,Foot Deformities ,Male ,medicine.medical_specialty ,Neurology ,Adolescent ,Fever ,Pain ,Tetraparesis ,Dermatology ,Nerve conduction velocity ,medicine ,Spastic ,Humans ,Paresthesia ,Muscle biopsy ,Reflex, Abnormal ,medicine.diagnostic_test ,Spastic Paraplegia, Hereditary ,business.industry ,General Neuroscience ,Peroneal Nerve ,General Medicine ,Amyotrophy ,medicine.disease ,Pedigree ,Surgery ,Muscular Atrophy ,Psychiatry and Mental health ,Scoliosis ,Asthenia ,Child, Preschool ,Anesthesia ,Etiology ,Female ,Neurology (clinical) ,business ,Paraplegia - Abstract
We describe 4 siblings with spastic paraparesis and peroneal amyotrophy who were prone to severe pain and painful dysesthesias, tetraparesis and pyramidal signs during pyrexial episodes of variable etiology. These symptoms cleared almost completely in 10-20 days. Nerve conduction velocity was reduced more markedly during the spells of fever. Muscle biopsy specimen was normal. Some transient functional disturbance of membrane equilibrium of the nervous pathways of both central and peripheral nervous systems was probably responsible for the attacks during pyrexial episodes.
- Published
- 1990
46. Natural history of CMT1A including QoL: a 2-year prospective study
- Author
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Davide Pareyson, Luca Padua, Giuseppe Vita, Irene Aprile, Aldo Quattrone, Tiziana Cavallaro, A. Schenone, Pietro Attilio Tonali, and Nicolo' Rizzuto
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,Physical examination ,Disease ,Disability Evaluation ,Physical medicine and rehabilitation ,Quality of life ,Charcot-Marie-Tooth Disease ,Surveys and Questionnaires ,Medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Child ,Genetics (clinical) ,Depression (differential diagnoses) ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,CMT ,Reproducibility of Results ,Middle Aged ,Natural history ,Clinical trial ,Settore MED/26 - NEUROLOGIA ,Neurology ,Pediatrics, Perinatology and Child Health ,Physical therapy ,Disease Progression ,Quality of Life ,Female ,Neurology (clinical) ,business ,Neurological impairment ,Follow-Up Studies - Abstract
The Italian CMT study group performed a multicentre, multidimensional, longitudinal 2-year follow-up study using validated measurements of neurological impairment, disability and quality of life. The aim of the study was to evaluate the natural history of clinical features, disability and QoL in patients with CMT1A. On clinical examination, CMT1A patients showed a significant reduction in muscle strength and sensory function during the 2-year follow-up period. However, there was no worsening of QoL or disability, nor was depression observed. The discrepancy between the evolution of clinical features and the evolution of QoL and disability may be due to the development of compensatory strategies that help patients cope with the slow progression of the disease. Our observations provide information which may be useful when designing clinical trials in CMT.
- Published
- 2007
47. Novel mitochondrial tRNA Leu(CUN) transition and D4Z4 partial deletion in a patient with a facioscapulohumeral phenotype
- Author
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Giuliano Tomelleri, Chiara Savio, Massimiliano Filosto, Michelangelo Mancuso, Mauro Scarpelli, Gaetano Vattemi, Nicolo' Rizzuto, Paola Tonin, Rossella Tupler, Francesca Greco, and Vittorio Govoni
- Subjects
Mitochondrial DNA ,RNA, Transfer, Leu ,Biopsy ,Molecular Sequence Data ,Biology ,DNA, Mitochondrial ,Mitochondrial myopathy ,medicine ,Facioscapulohumeral muscular dystrophy ,Humans ,FSHD ,mtDNA ,Muscle, Skeletal ,Genetics (clinical) ,Genetics ,Muscle biopsy ,medicine.diagnostic_test ,Transition (genetics) ,Base Sequence ,Point mutation ,Middle Aged ,medicine.disease ,Molecular biology ,Heteroplasmy ,Muscular Dystrophy, Facioscapulohumeral ,Phenotype ,Neurology ,Pediatrics, Perinatology and Child Health ,Transfer RNA ,Nucleic Acid Conformation ,Female ,Neurology (clinical) ,Gene Deletion ,Polymorphism, Restriction Fragment Length - Abstract
Point mutations in mtDNA-encoded tRNA genes frequently cause isolated myopathies but rarely cause the facioscapulohumeral phenotype. We report on a patient affected with chronic progressive weakness of facioscapulohumeral/peroneal muscles whose muscle biopsy showed a mitochondrial myopathy. mtDNA direct sequencing and RFLP analysis revealed a heteroplasmic transition T12313C which disrupts a conserved site in the TΨC stem of the tRNALeu(CUN) gene and fulfills the accepted criteria of pathogenicity. A partial deletion of the nuclear DNA D4Z4 region with residual repeat sizes of 25 kb was also found in the patient and in her mother. This is the first reported case of mitochondrial myopathy/facioscapulohumeral muscular dystrophy (FSHD) “double trouble”.
- Published
- 2007
48. The role of muscle biopsy in investigating isolated muscle pain
- Author
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Massimiliano Filosto, Laura Bertolasi, Gaetano Vattemi, Alessandro Simonati, Nicolo' Rizzuto, Giuliano Tomelleri, and Paola Tonin
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,Pain ,Metabolic myopathy ,patients ,Risk Assessment ,Sensitivity and Specificity ,Muscular Diseases ,Risk Factors ,Biopsy ,Prevalence ,Medicine ,Humans ,isolated muscle pain ,Myopathy ,Child ,Muscle, Skeletal ,muscle biopsy ,Aged ,Aged, 80 and over ,Muscle biopsy ,biology ,medicine.diagnostic_test ,business.industry ,Biopsy, Needle ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Phosphofructokinase deficiency ,Italy ,biology.protein ,Histopathology ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Dystrophin ,Central core disease - Abstract
Objective: To evaluate the muscle biopsy findings from 240 patients who had isolated muscle pain. Methods: Histopathology, immunohistochemistry for dystrophin, dystrophin-related proteins, major histocompatibility complex type I, and biochemical analysis of glycolytic and mitochondrial respiratory chain enzymes were performed on muscle biopsies. An attempt was made to correlate pathologic data and clinical findings (sex, age, quality and distribution of symptoms, serum CK levels, and EMG recording). Results: We have described five groups of patients based on muscle biopsy findings: 51.6% had heterogeneous myopathic abnormalities; only 19% of them had a specific myopathic picture, i.e., central nuclei myopathy, central core disease, myopathy with tubular aggregates or with trabecular fibers or abnormalities of fiber typing; 20% had signs of respiratory chain dysfunction but only one patient had a probable mitochondrial disease; 7% had a neurogenic pattern; 2.4% had a metabolic myopathy (phosphorylase or phosphofructokinase deficiency); and 19% had normal muscle biopsy. No clear-cut correlation between muscle biopsy and clinical data was observed except for those patients with a metabolic myopathy. Conclusions: The probability that a patient complaining only of muscle pain and with a normal neurologic examination has a definite muscle pathology is 2%. Only patients with sole exercise-related muscle pain and sCK seven times higher than the normal value are strongly suspected of having a metabolic myopathy. A rigorous selection of patients is needed before performing a muscle biopsy.
- Published
- 2007
49. Limb ataxia and proximal intracranial territory brain infarcts: clinical and topographical correlations
- Author
-
Giuseppe Moretto, Paolo Bovi, Michele Tinazzi, Cristina Deluca, and Nicolo' Rizzuto
- Subjects
Paper ,Adult ,Male ,Cerebellum ,Inferior cerebellar peduncle ,Ataxia ,Vertebral artery ,registry ,Central nervous system disease ,medicine.artery ,medicine ,inferior cerebellar artery ,Humans ,Medulla ,Vertebral Artery ,Aged ,Aged, 80 and over ,stroke ,business.industry ,Limb ataxia ,Anatomy ,Cerebral Infarction ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Posterior inferior cerebellar artery ,medicine.anatomical_structure ,Surgery ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Background: Limb ataxia is classically attributed to cerebellar hemispheric lesions, although isolated lesions of the inferior cerebellar peduncle (ICP) in the medulla may also cause this sign. It is still unclear why only some patients with acute cerebellar infarcts in the posterior inferior cerebellar artery (PICA) territory present with limb ataxia. The proximal intracranial posterior circulation (P-PC) territory includes structures fed by the intracranial vertebral arteries (ICVAs): the medulla, supplied by small ICVAs branches, and posterior inferior portion of the cerebellum, fed by PICA. ICP and PICA territory cerebellar infarcts most often occur independently but occasionally occur together. Objective: To identify structures responsible for limb ataxia in acute P-PC brain infarcts correlating clinical and topographical findings. Methods: Sixteen patients (8 women) were included with ages ranging from 30 to 82 years (mean age, 62 years) with isolated acute strokes in the P-PC territory. Results: The cases reported here indicate that limb ataxia in acute P-PC territory infarcts may be associated with a damage to the ICP in the dorsolateral medulla, regardless of a hemispheric cerebellar lesion. In fact among the 9 patients with PICA stroke, limb ataxia was observed only in the 2 patients who also presented a damage to the dorsolateral medulla involving the ICP. Of the 7 patients with isolated dorsolateral medullary infarct, only 5 patients with an ICP damage had limb ataxia. Conclusions: When correlating limb ataxia and acute P-PC infarcts it is important to take in account the entire ICVA territory.
- Published
- 2007
50. A novel mutation of aprataxin associated with ataxia ocular apraxia type 1: phenotypical and genotypical characterization
- Author
-
Sergio Ferrari, Nicolo' Rizzuto, Gian Maria Fabrizi, Giovanna Squintani, Moreno Ferrarini, and Tiziana Cavallaro
- Subjects
genetica molecolare ,Adult ,Pathology ,medicine.medical_specialty ,Ataxia ,genetic structures ,Cerebellar Ataxia ,Genotype ,Apraxias ,apratassina ,DNA Mutational Analysis ,aptX ,Mutation, Missense ,Consanguinity ,Biology ,Apraxia ,Alcoholic Neuropathy ,atassia ,Ocular Motility Disorders ,Cerebellum ,medicine ,Missense mutation ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Oculomotor apraxia ,Genetics ,Aprataxin ,Cerebellar ataxia ,Nuclear Proteins ,Electroencephalography ,medicine.disease ,Magnetic Resonance Imaging ,Pedigree ,DNA-Binding Proteins ,Phenotype ,Neurology ,Amino Acid Substitution ,Positron-Emission Tomography ,Mutation ,Female ,Neurology (clinical) ,medicine.symptom ,Atrophy - Abstract
Ataxia oculomotor apraxia type 1 (AOA1) is the most common form of autosomal recessive ataxia in Japan, and the second in Portugal after Friedreich ataxia. AOA1 is typically characterized by early-onset cerebellar ataxia, oculomotor apraxia, hypoalbuminemia, hypercholesterolemia and late axonal sensori-motor neuropathy. AOA1 is associated with the aprataxin gene (APTX) encoding a protein involved in DNA repair. We characterized a novel homozygous missense mutation of APTX in a 34 year-old female patient born from consanguineous parents. The mutation, a Val230Gly caused by a c.689 T>G substitution, involved the histidine-triad (HIT) domain of the protein, affected a phylogenetically conserved amino acid and was absent in the control population. We described the clinical and neurophysiological features, the findings at structural and functional brain imaging, and the pathological picture of the sural nerve biopsy. The report emphasized the genetical and phenotypical heterogeneity of AOA1 by demonstrating atypical features such as absence of oculomotor apraxia and signs of pyramidal involvement. Expression studies by Western blotting on fibroblasts demonstrated that the homozygous Val230Gly mutation was associated with decreased levels of APTX indicating a loss-of-function mechanism.
- Published
- 2007
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