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Biomedical subjects

N Rizzuto

Publications and source records attributed to N Rizzuto.

At least 19 recordsLinked to original sources
PubMed2007

The role of muscle biopsy in investigating isolated muscle pain.

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.

Adolescent↗
PubMed2006

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study.

BACKGROUND: 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. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: 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). CONCLUSIONS: 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.

Adolescent↗
PubMed2006

A novel missense mutation in the L1CAM gene in a boy with L1 disease.

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.

Abnormalities, Multiple↗
PubMed2006

Hyperpyrexia-triggered relapses in an unusual case of ataxic chronic inflammatory demyelinating polyradiculoneuropathy.

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.

Anti-Inflammatory Agents↗
PubMed2006

Variables influencing quality of life and disability in Charcot Marie Tooth (CMT) patients: Italian multicentre study.

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.

Adolescent↗
PubMed2005

Phosphorylated 14-3-3zeta protein in the CSF of neuroleptic-treated patients.

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.

14-3-3 Proteins↗
PubMed2005

Expression of late myogenic differentiation markers in sarcoplasmic masses of patients with myotonic dystrophy.

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.

Adult↗
PubMed2004

Segmental conduction abnormalities and myelin thickenings in Val102/fs null mutation of MPZ gene.

The authors report in patients with Val102/fs null mutation a possibly age dependent variability of clinical and electrophysiologic phenotype, segmental conduction abnormalities mainly in ulnar nerves at the elbow, and excessive myelin foldings and thickenings. The authors hypothesize that myelin thickenings at the paranodal region, in concurrence with compression at usual entrapment sites or minor repetitive trauma, may induce segmental conduction abnormalities.

Adult↗
PubMed2004

Expression of protein kinase C isoforms and interleukin-1beta in myofibrillar myopathy.

BACKGROUND: The term myofibrillar myopathy refers to a rare and clinically heterogeneous group of muscle disorders. The pathogenesis of this myopathy is not well understood. The morphologic hallmark is myofibrillar destruction with abnormal expression of numerous proteins, most consistently of desmin. METHODS: The authors investigated eight patients with myofibrillar myopathy belonging to four families. They studied the role of different protein kinase C isoforms and of interleukin-1beta, a cytokine that might activate protein kinase C and, in addition, mediate myofibrillar proteolysis. RESULTS: Immunohistochemical analysis showed the expression of alpha, eta, and zeta isoforms of protein kinase C and of interleukin-1beta in abnormal muscle fibers. Immunoblots confirmed the immunohistochemical data and revealed the absence of protein kinase C delta and epsilon in muscle fibers from patients and controls. CONCLUSIONS: These data suggest that protein kinase C and interleukin-1beta may play a role in the pathogenesis of myofibrillar myopathy.

Adenosine Triphosphatases↗
PubMed2004

Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E.

The axonal type 2 Charcot-Marie-Tooth disease (CMT2) is phenotypically poorly characterized. Here the authors report a family with a Pro22Ser mutation in the neurofilament-light gene (NF-L; CMT2E) manifesting electrophysiologically as the demyelinating type 1 CMT (CMT1) and pathologically as an axonopathy with giant axons and accumulation of disorganized NF. NF-L should be investigated in CMT2 as well as in CMT1 not associated with the usual genes PMP22, Cx32, and P0.

Adult↗
PubMed2004

Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease: facts and uncertainties underlying the causal link between animal and human diseases.

Following an outbreak of bovine spongiform encephalopathy (BSE) in dairy cows in the United Kingdom (UK), 153 definite and probable human cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been reported, almost exclusively in the UK. Although exposure to the BSE agent is the most plausible interpretation for the occurrence of nvCJD, the causal link between the BSE prion and nvCJD is still debated. This review discusses the pros and cons of nvCJD as a separate nosographic entity, the scientific basis for a correlation between BSE and nvCJD, the validity of the current diagnostic criteria for CJD and nvCJD, the contribution of epidemiology to the detection of a causal relation between BSE and nvCJD, and the present and future directions of the epidemiological research on BSE, CJD and nvCJD.

Animals↗
PubMed2003

Charcot-Marie-Tooth disease with giant axons: a clinicopathological and genetic entity.

The authors report an Italian family with autosomal-dominant Charcot-Marie-Tooth disease (CMT) in which there were giant axons in the sural nerve biopsy. Linkage to the known CMT2 loci (CMT2A, CMT2B, CMT2D, CMT2F) and mutations in the known CMT2 genes (Cx32, MPZ, NEFL), GAN, NEFM, and CMT1A duplication/HNPP deletion were excluded. This family with CMT and giant axons has a pathologic and genetic entity distinct from classic CMT.

Adult↗
PubMed2003

MELAS: clinical phenotype and morphological brain abnormalities.

We describe the clinical and neuropathological findings of three unrelated autopsy cases of MELAS harboring the A3243G transition in the mitochondrial DNA (mtDNA). Using immunohistochemical techniques, we studied the expression of several subunits of the respiratory chain in various brain regions from the same cases. In all three cases there was a reduced immunocytochemical staining for mtDNA-encoded subunits of the respiratory chain, confirming the presence of a defective mitochondrial protein synthesis in this disease. Mitochondrial abnormalities were mostly confined to multiple areas of different size and shape, in agreement with the focal character of the brain pathology in MELAS, and were most prominent in the cerebral cortex, providing a morphological contribution to the explanation of the cognitive regression of the patients. Immunoreactivity for mtDNA-encoded subunits was reduced in the walls of many pial and intracerebral arterioles of different brain regions but there was no clear correlation between territories of affected vessels and distribution of the histological and immunohistochemical lesions. Cerebral focal lesions in MELAS might have a metabolic nature and several pathogenetic mechanisms might be involved in the genesis of stroke-like episodes when there is a local increased ATP demand.

Adenosine Triphosphatases↗
PubMed2003

Hereditary neuropathy with liability to pressure palsies: electrophysiological and genetic study of a family with carpal tunnel syndrome as only clinical manifestation.

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.

Adolescent↗
PubMed2003

Hepatitis C virus infection and myositis: a virus localization study.

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.

Aged↗
PubMed2003

Paired transcranial magnetic stimulation for the early diagnosis of corticobasal degeneration.

OBJECTIVE: To investigate cortical excitability in patients with corticobasal degeneration (CBD) and to find a reliable diagnostic technique for differentiating CBD from Parkinson's disease (PD). METHODS: Using a paired transcranial magnetic stimulation technique, we studied motor cortex excitability at rest in 6 patients with clinically probable CBD, 10 patients with PD, and 10 normal subjects. The recovery cycle of the motor evoked potentials was tested by delivering paired magnetic stimulation over the hand area of the motor cortex at interstimulus intervals (ISIs) from 1 to 17ms. RESULTS: In patients with CBD, paired magnetic stimuli delivered at short ISIs invariably elicited enlarged test MEPs. At ISIs of 1-10ms, the conditioned test MEPs were significantly larger in patients with CBD than in control subjects; and at ISIs of 1, 2, 4, and 6ms,they were also larger in patients with CBD than in patients with PD. At the other ISIs tested, patients and control subjects had similar amplitude conditioned test responses. CONCLUSIONS: Our findings suggest that the unusual clinical manifestations of CBD might arise partly from motor cortex disinhibition. Paired magnetic stimulation could be a useful diagnostic test particularly in the early stages of the disease.

Aged↗