N Rizzuto

University of Verona, Verona, Veneto, Italy

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Publications (217)710.6 Total impact

  • Neurology 06/2010; 74(23):1919-21. DOI:10.1212/WNL.0b013e3181e240f9 · 8.29 Impact Factor
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    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.
    Neurological Sciences 12/2009; 31(2):175-8. DOI:10.1007/s10072-009-0202-z · 1.45 Impact Factor
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    ABSTRACT: 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. To characterize a novel mutation in FGD4 and describe the related phenotype. 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. 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). 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.
    Neurology 04/2009; 72(13):1160-4. DOI:10.1212/01.wnl.0000345373.58618.b6 · 8.29 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    European Neurology 11/2008; 61(1):46-9. DOI:10.1159/000165350 · 1.36 Impact Factor
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    ABSTRACT: 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). 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 10 microg/m(2) bs and 300 microg 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<0.00001). 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.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 09/2008; 19(3):205-10. DOI:10.1016/j.numecd.2008.06.010 · 3.32 Impact Factor
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    ABSTRACT: To assess which are the clinical examination tests that are more related to quality of life (QoL), depression, and disability in CMT patients. Large prospective multicenter study through the use of validated clinical, disability, and QoL measurements. Correlations between clinical pattern and disability/QoL and depression were studied. Departments of Neurology. 211 CMT patients (60% females, mean age 42.5 years). None. Sensory function was related to both mental and physical aspects of patient's QoL. Ability to walk on toes and heels was related to physical aspects of QoL/disability but also to bodily pain. Strength of forearm/hand intrinsic muscles was related to disability and physical aspects of QoL. Some clinical tests may be better outcome measures than others because they are related to aspects of life highly relevant to the patients. This information may be useful in clinical practice and in clinical trials to infer the patient's QoL.
    Neurological Sciences 07/2008; 29(3):157-62. DOI:10.1007/s10072-008-0928-z · 1.45 Impact Factor
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    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.
    Neuromuscular Disorders 04/2008; 18(3):199-203. DOI:10.1016/j.nmd.2007.11.008 · 2.64 Impact Factor

  • Clinical Therapeutics 12/2007; 29. DOI:10.1016/S0149-2918(07)80144-5 · 2.73 Impact Factor

  • Neuromuscular Disorders 10/2007; 17(9):830-831. DOI:10.1016/j.nmd.2007.06.235 · 2.64 Impact Factor
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    ABSTRACT: 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. To assess the etiologic role of DNM2 in CMT. 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. We identified two novel DNM2 mutations that cosegregated with purely axonal CMT in two pedigrees without clinical evidence of primary myopathy. Patients with axonal Charcot-Marie-Tooth disease type 2 neuropathy without mutations in more common genes should undergo investigation for DNM2 pleckstrin homology.
    Neurology 08/2007; 69(3):291-5. DOI:10.1212/01.wnl.0000265820.51075.61 · 8.29 Impact Factor
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    M Filosto · P Tonin · G Vattemi · L Bertolasi · A Simonati · N Rizzuto · G Tomelleri ·
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    ABSTRACT: To evaluate the muscle biopsy findings from 240 patients who had isolated muscle pain. 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). 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. 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.
    Neurology 02/2007; 68(3):181-6. DOI:10.1212/01.wnl.0000252252.29532.cc · 8.29 Impact Factor

  • European Journal of Neurology 02/2007; 14(1):e45-6. DOI:10.1111/j.1468-1331.2006.01545.x · 4.06 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the variables that influence quality of life (QoL) and disability in patients with Charcot-Marie-Tooth disease (CMT). We performed a prospective multicentre study using validated clinical disability and QoL measurements. Multivariate analysis was performed using QoL as a dependent variable and duration of symptoms, age, gender and CMT type, depression and disability measurements as independent variables. We enrolled 211 patients. QoL was highly significantly deteriorated with respect to the Italian normative sample. The physical aspect of QoL was mainly related to disability but it does not increase with the age, probably because of an adaptation between expectation and reality. The mental QoL is influenced by depression (hence we have to consider this aspect approaching CMT patients). Moreover, we observed that women complained of more severe symptoms than men. Finally, some CMT subtypes are related to more severe bodily pain symptoms than others. Multiperspective assessment of CMT showed new aspects of this disease, mainly regarding (1) differences between men and women and (2) the crucial role of pain and depression.
    Neurological Sciences 01/2007; 27(6):417-23. DOI:10.1007/s10072-006-0722-8 · 1.45 Impact Factor

  • Clinical Neurophysiology 09/2006; 117:1-2. DOI:10.1016/j.clinph.2006.06.162 · 3.10 Impact Factor

  • Clinical Neurophysiology 09/2006; 117:186-187. DOI:10.1016/j.clinph.2006.06.338 · 3.10 Impact Factor
  • S Mazzucco · S Ferrari · C Mezzina · G Tomelleri · L Bertolasi · N Rizzuto ·
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    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.
    Neurological Sciences 08/2006; 27(3):176-9. DOI:10.1007/s10072-006-0664-1 · 1.45 Impact Factor
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    ABSTRACT: A novel missense mutation of the L1CAM gene (Xq28) is described in an adult patient affected with severe mental retardation, spastic paraparesis, adducted thumbs, agenesis of corpus callosum and microcephaly (L1 disease). We detected a transition c2308G-->A in exon 18 that caused an amino acid change in codon 770. The patient's mother and two sisters were heterozygous for the same mutation. This newly described mutation predicts the substitution of an aspartate by asparagine (D770N) in the second fibronectin (Fn2) domain of the extracellular portion of the mature L1 protein. Even if amino acid substitution does not significantly change the physico-chemical properties of the Fn2 domain, it seems clear that the integrity of this domain is required to maintain the biological functions of the protein. The feature peculiar to this patient is the decelerated head growth post-natally, leading to microcephaly. Mutations of L1CAM associated with prolonged survival may hamper post-natal brain and head growth.
    Neurological Sciences 07/2006; 27(2):114-7. DOI:10.1007/s10072-006-0610-2 · 1.45 Impact Factor
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    ABSTRACT: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin.
    Neurology 05/2006; 66(8):1207-10. DOI:10.1212/01.wnl.0000208402.10512.4a · 8.29 Impact Factor
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    ABSTRACT: The authors describe 12 neuroleptic-treated patients with dementia of various etiologies who showed CSF elevation of phosphorylated 14-3-3zeta and normal tau protein levels. This contrasted with elevated amounts of 14-3-3 gamma, epsilon, and unphosphorylated zeta coupled to high tau protein levels in Creutzfeldt-Jakob disease and negative 14-3-3 assay in drug-free patients with dementia. Characterization of CSF 14-3-3 isoforms and determination of tau protein level can help to distinguish different etiologies of dementia.
    Neurology 06/2005; 64(9):1618-20. DOI:10.1212/01.WNL.0000160397.81314.84 · 8.29 Impact Factor
  • G Vattemi · G Tomelleri · M Filosto · C Savio · N Rizzuto · P Tonin ·
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    ABSTRACT: Sarcoplasmic masses contain disorganized myofibrillar material and are a striking feature of myotonic dystrophy. However their significance is still unclear. Using immunocytochemistry we studied the expression of cytoskeletal proteins (desmin and vimentin), dystrophin, markers of myogenic differentiation (foetal myosin, neural cell adhesion molecule, bcl-2, insulin-like growth factor-I, fibroblast growth factor, retinoblastoma protein and myoD1), cell cycle regulators (Cdk2, p16, p27 and p57) and muscle proteases (ubiquitin, micro and m calpain and cathepsin D) in muscle biopsies from four patients with myotonic dystrophy. Sarcoplasmic masses were strongly positive for desmin, neural cell adhesion molecule, bcl-2, insulin-like growth factor I, retinoblastoma protein and p57, weakly positive for dystrophin and p16 and negative for vimentin, fibroblast growth factor, myoD1, Cdk2 and p27. Immunoreactivity for foetal myosin was detected only in a few fibres (< 1%). Our data suggest that the late myogenic differentiation programme is activated in sarcoplasmic masses although these areas do not reach complete maturation.
    Neuropathology and Applied Neurobiology 02/2005; 31(1):45-52. DOI:10.1111/j.1365-2990.2004.00602.x · 3.93 Impact Factor

Publication Stats

3k Citations
710.60 Total Impact Points


  • 1977-2010
    • University of Verona
      • • Department of Neurological and Visual Sciences
      • • Section of Neurology
      Verona, Veneto, Italy
  • 1995
    • University of Pavia
      Ticinum, Lombardy, Italy
  • 1978-1989
    • University of Bologna
      • Institute of Cancerology
      Bolonia, Emilia-Romagna, Italy
  • 1985
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 1979-1983
    • University of Padova
      Padua, Veneto, Italy
  • 1982
    • Università degli Studi Europea di Roma
      Roma, Latium, Italy
  • 1981
    • Università di Pisa
      Pisa, Tuscany, Italy