PubMed Health⌕ Search

Biomedical subjects

Giuseppe Moretto

Publications and source records attributed to Giuseppe Moretto.

18 recordsLinked to original sources
PubMed2007

Limb ataxia and proximal intracranial territory brain infarcts: clinical and topographical correlations.

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, aged 30-82 years (mean 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 damage to the ICP in the dorsolateral medulla, regardless of a hemispheric cerebellar lesion. In fact, among the nine patients with PICA stroke, limb ataxia was observed only in the two patients who also presented damage to the dorsolateral medulla involving the ICP. Of the seven patients with isolated dorsolateral medullary infarct, only five patients with ICP damage had limb ataxia. CONCLUSIONS: When correlating limb ataxia and acute P-PC infarcts, it is important to take into account the entire ICVA territory.

Adult↗
PubMed2006

Defective temporal processing of sensory stimuli in DYT1 mutation carriers: a new endophenotype of dystonia?

DYT1 primary torsion dystonia is an autosomal dominant movement disorder due to a 3-bp GAG deletion in the TOR1A gene, which becomes manifest in only 30-40% of mutation carriers. Investigating the factors regulating this reduced penetrance might add new insight into the mechanisms underlying the disease. The pathophysiology of dystonia has been related to basal ganglia dysfunctions that lead to the most prominent motor symptoms. However, subclinical sensory deficits have also been reported, particularly in adult-onset focal dystonia. Sensory abnormalities in different forms of sporadic dystonia have been revealed by using a psychophysical method, namely, the temporal discrimination threshold (TDT), quantified as the shortest time interval at which the two stimuli are perceived as separate. Little or no information about the presence of sensory abnormalities in DYT1 gene manifesting and non-manifesting carriers is available. With the aim of disclosing possible associations between sensory deficits and the DYT1 mutation, we assessed TDTs of DYT1 manifesting patients (n = 9); DYT1 non-manifesting relatives (n = 11); non-carrier relatives (n = 9); external control subjects (n = 11). Pairs of tactile, visual or visuo-tactile stimuli were delivered in blocked, counterbalanced order. Intervals between stimuli increased from 0 to 400 ms (in 10 ms steps). On each trial, subjects had to report whether stimuli occurred simultaneously or asynchronously. We measured the first out of three consecutive inter-stimulus intervals at which subjects recognized the two stimuli as temporally separated (TDT) and the first of three consecutive intervals at which they also reported correctly which stimulus in the pair preceded (or followed) the other temporal order judgment (TOJ). Results showed higher tactile and visuo-tactile TDTs and TOJs in DYT1 carriers, both manifesting and non-manifesting, compared with non-carrier relatives and with external control subjects (for all comparisons, P < 0.039). This finding indicates that the DYT1 mutation determines subclinical sensory alterations, which could be disclosed by a psychophysical task. Moreover, these results have the notable implication that sensory deficits in dystonia are not a mere consequence of abnormal movements, but they may even occur before overt clinical manifestations, representing a subclinical phenotype in DYT1 mutation carriers.

Adult↗
PubMed2006

Structural and phylogenetic approaches to assess the significance of human Apolipoprotein E variation.

Apolipoprotein E (APOE) is an important gene whose common polymorphism, and precisely the e *4 allele, has been reportedly associated with some disorders, including Alzheimer's disease (AD) and coronary artery disease. In the course of previous surveys on AD patients and healthy individuals some rare variants were detected by means of Isoelectric focusing and denaturing high-performance liquid chromatography techniques. After a mutation in a gene is identified, the problem arises to understand its effective significance. Structure modelling and phylogenetic analysis methods are widely used to establish the possible deleterious effect of mutations. In this study their usefulness in the analysis of APOE variants was evaluated. The two combined methods provided helpful indications for distinguishing between mutations possibly involved in AD susceptibility and not deleterious mutations.

Amino Acid Sequence↗
PubMed2006

Pisa syndrome without neuroleptic exposure in a patient with Parkinson's disease: case report.

We report on a patient affected by Parkinson's disease who developed over a period of a few weeks a tonic deviation of her head, neck, and trunk fitting the typical description of Pisa syndrome (PS). This patient was under stable levodopa and pramipexole treatment and had never been exposed to any psychotropic or antiemetic drugs before or at the time she developed the postural abnormality. Because dopamine transporter imaging revealed bilateral and symmetrical reduction of striatal uptake, we suggest that PS is not primarily related to side differences in dopaminergic denervation or drug exposure.

Aged↗
PubMed2006

Temporal discrimination of two passive movements in writer's cramp.

Although movement abnormalities are predominant symptoms of dystonia, patients also have alterations in temporal as well as spatial discrimination of cutaneous inputs. Here, we use a recently described method to test whether deficits also exist in temporal discrimination of proprioceptive inputs. Percutaneous electrical stimulation of the motor point of the first dorsal interosseous (FDI) muscle, and of the flexor carpii radialis (FCR) muscle separately, was used to produce a nonpainful contraction of the muscles that caused index finger abduction and wrist flexion, respectively. In 10 patients with writer's cramp and in 10 healthy subjects, pairs of stimuli separated by different time intervals were given and subjects were asked to report whether they perceived a single or a double index finger abduction movement or wrist flexion. The threshold value was the shortest interval at which the subjects reported two separated movements (temporal discrimination motor threshold [TDMT]). In both writer's cramp patients and controls, TDMTs were higher for FCR than for FDI. But in contrast to the reduced temporal discrimination reported for cutaneous sensation, there was no significant difference in either muscle between TDMT in patients and normal subjects. We conclude that temporal processing of muscle and cutaneous afferents is differentially affected in focal hand dystonia.

Adult↗
PubMed2006

Atypical phenotypes and clinical variability in a large Italian family with DYT1-primary torsion dystonia.

The GAG deletion in the DYT1 gene usually causes a typical form of primary torsion dystonia (PTD) with early onset in a limb, rapid generalization, and sparing of cranial-cervical muscles, but atypical phenotypes have often been reported. Here, we describe a large DYT1 Italian family with phenotypically heterogeneous PTD that recapitulates all the atypical features associated with the DYT1 mutation, including late age at onset, focal or segmental phenotypes, onset or spreading of dystonia to the cranial-cervical muscles. Of 38 healthy family members, 15 also carried the DYT1 mutation, with an estimated penetrance of 21%. A literature review of atypical familial cases of DYT1-PTD showed that late onset, cervical involvement, and limited progression of dystonia are features frequently seen in DYT1 families. However, nearly all of these atypical patients fall within at least one of the clinical categories that best predict the DYT1 carrier status, namely, early onset, onset in a limb, and family history positive for early-onset dystonia.

Adult↗
PubMed2006

Effects of transcutaneous electrical nerve stimulation on motor cortex excitability in writer's cramp: neurophysiological and clinical correlations.

We recently reported that transcutaneous electrical nerve stimulation (TENS) applied over forearm flexor muscles, a paradigm producing in physiological conditions transient changes in corticomotoneuronal excitability of forearm muscles, may improve motor symptoms in writer's cramp (WC). In the present study, we explored the possibility that one or repeated sessions of TENS might have beneficial effects on handwriting in WC by remodulating cortical excitability of forearm agonist and antagonist muscles. Motor evoked potentials (MEPs) after transcranial magnetic stimulation of the left motor cortex were recorded from the right flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, before and after 1 and 15 sessions of TENS applied over flexor muscles in patients and in a control group. One session of TENS induced a significant smaller reduction of MEPs from the FCR and a smaller increase of the MEPs from the ECR in patients than in normal subjects. In WC, repeated sessions of TENS had the effect to decrease MEP amplitude in the FCR and to increase it in the ECR. This modulation was paralleled by a handwriting improvement. In conclusion, repeated TENS sessions may have the effect to re-modulate excitability of the motor cortex in WC and this modulation might partially play a role in temporarily improving the handwriting.

Adult↗
PubMed2005

Palatal tremor suppressed by mouth opening: clinical and neurophysiological correlations in two patients.

We report clinical and neurophysiological findings in two patients with palatal tremor (PT). In both patients a prompt and persistent suppression of palatal movements and clicking sounds is caused by slight passive or active mouth opening. One patient has a typical essential palatal tremor (EPT) according to current classification criteria. The other one has a PT characterized by involuntary activation of levator veli palatini and genioglossus muscles. Objective clicking sounds were observed late during the course of the disease. A symptomatic aetiology was excluded, suggesting a diagnosis of atypical EPT. Our observations further confirm that unusual features of some cases may not fit current PT classification criteria. These two cases have several features that distinguish them from voluntary PT and from psychogenic PT. We emphasize that clear cut modulating phenomena may be relevant features in both typical and atypical involuntary EPT. We finally focus on the significance of jaw posture in determining PT suppression in our patients.

Adult↗
PubMed2005

Temporal discrimination of two passive movements in humans: a new psychophysical approach to assessing kinaesthesia.

Percutaneous electrical stimulation of the motor point of the first dorsal interosseous muscle (FDI) was used to produce a non-painful contraction of the FDI muscle that caused index finger abduction movement but no radiating cutaneous paraesthesias or sharp sensations localized to joints. Pairs of stimuli separated by different time intervals were given and subjects were asked to report whether they perceived a single or a double index finger abduction movement. The threshold value was the shortest interval for which the subjects reported two separate index finger abduction movements. Temporal discrimination movement thresholds (TDMT) were measured for both right and left hand. To assess the possible role of muscle and cutaneous afferents in temporal discrimination, we investigated the effects of high-frequency (20 Hz) electrical stimulation of the right ulnar and radial nerves on TDMT. In humans, muscle afferents from FDI are supplied by the ulnar nerve whereas the cutaneous territory overlying the muscle and joint is supplied by the radial and median nerves. Threshold values were not significantly different for right (75.1 ms) and left (75.6 ms) hands. During ulnar and to a lesser extent during radial nerve stimulation, TDMT values were significantly increased (119.2 and 93.5 ms, respectively) compared with baseline conditions (78.0 ms) whereas no changes were observed during median nerve stimulation (80.5 ms). These results suggest that muscle, and in part cutaneous, afferents contribute to temporal discrimination of a dual movement. The technique may provide a useful way of measuring temporal discrimination of kinaesthetic inputs in humans.

Adult↗
PubMed2005

Task-specific impairment of motor cortical excitation and inhibition in patients with writer's cramp.

Abnormalities in motor cortical excitation and inhibition have been reported in patients with writer's cramp, at rest and during muscle activation. We were interested in whether such abnormalities might be task-specific and depended on the type of movement task used to activate the dystonic hand. We therefore assessed motor-evoked potentials (facilitation/rest MEP amplitude ratio) and duration of the cortical silent period (CSP) from the right first dorsal interosseus (FDI) muscle to transcranial magnetic stimulation (TMS) in 10 patients with writer's cramp and in 10 healthy volunteers performing pincer and power gripping tasks. The mean facilitation/rest MEP amplitude ratio measured during the pincer grip task was significantly larger in dystonic subjects than in controls, but in the power grip condition was similar in the two groups. The CSP measured in the power grip condition was of similar length in normal controls and dystonic subjects, but in the pincer grip condition was significantly shorter in patients than in controls. These results indicate a task-specific impairment of motor cortical excitation and inhibition in writer's cramp.

Adult↗
PubMed2004

Long-lasting modulation of human motor cortex following prolonged transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of reciprocal inhibition and facilitation.

Several lines of evidence indicate that motor cortex excitability can be modulated by manipulation of afferent inputs, like peripheral electrical stimulation. Most studies in humans mainly dealt with the effects of prolonged low-frequency peripheral nerve stimulation on motor cortical excitability, despite its being known from animal studies that high-frequency stimulation can also result in changes of the cortical excitability. To investigate the possible effects of high-frequency peripheral stimulation on motor cortical excitability we recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex from the right flexor carpi radialis (FCR), extensor carpi radialis (ECR), and first dorsal interosseous (FDI) in normal subjects, before and after transcutaneous electrical nerve stimulation (TENS) of 30 min duration applied over the FCR. The amplitude of MEPs from the FRC was significantly reduced from 10 to 35 min after TENS while the amplitude of MEPs from ECR was increased. No effects were observed in the FDI muscle. Indices of peripheral nerve (M-wave) and spinal cord excitability (H waves) did not change throughout the experiment. Electrical stimulation of the lateral antebrachial cutaneous nerve has no significant effect on motor cortex excitability. These findings suggest that TENS of forearm muscles can induce transient reciprocal inhibitory and facilitatory changes in corticomotoneuronal excitability of forearm flexor and extensor muscles lasting several minutes. These changes probably may occur at cortical site and seem to be mainly dependent on stimulation of muscle afferents. These findings might eventually lead to practical applications in rehabilitation, especially in those syndromes in which the excitatory and inhibitory balance between agonist and antagonist is severely impaired, such as spasticity and dystonia.

Adult↗
PubMed2004

The H+ allele of the lipoprotein lipase (LPL) HindIII intronic polymorphism and the risk for sporadic late-onset Alzheimer's disease.

A sample of 243 Italian patients affected by the sporadic late-onset form of Alzheimer's disease (AD) was studied for the HindIII intronic polymorphism of the lipoprotein lipase (LPL) gene and compared with a sample of 148 healthy subjects. Since this polymorphism has been reported to be associated with CAD and because the two pathologies share common aspects, we decided to study it in AD too. We found a difference in the allele distribution, in that the H+ allele was more frequent in patients (0.782) than in controls (0.720); this difference was not quite significant (P = 0.059). The odds ratio from the logistic regression analysis for the H+ carrying genotypes was 2.7 (95% CI = 1.01-7.21; P = 0.048). When the separate genotypes H+H+ and H+H- were entered into the analysis, only H+H+ was found to significantly increase the risk with respect to H-H- (P = 0.029). This means that carrying this allele significantly increases the risk of developing AD, and the risk is mostly associated with the H+H+ genotype.

Aged↗
PubMed2004

Hashimoto's encephalopathy: epidemiologic data and pathogenetic considerations.

BACKGROUND: Hashimoto's encephalopathy (HE) is a condition believed to complicate Hashimoto's thyroiditis (HT). The diagnosis is suspected in the presence of high levels of serum anti-thyroid antibodies. We have recently demonstrated that in patients with HE there is an intrathecal synthesis of anti-thyroid antibodies, and concluded that the diagnosis of HE should be based on this cerebrospinal fluid (CSF) finding. OBJECTIVE: getting an estimate of the prevalence of the disease, verifying the association with HT and investigating the pathogenetic role of anti-thyroid antibodies. METHODS: 34-months prospective study in a hospital setting serving a community of 150,000 people. Patients with unexplained symptoms of acute or subacute encephalopathy or myelopathy or with a history of thyroid disorders were selected for the measurement of anti-thyroid antibodies. In the presence of high serum levels of autoantibodies, the same tests were performed in the CSF. RESULTS: Twelve patients had increased concentrations of serum autoantibodies but HE was diagnosed only in nine patients. The estimated prevalence of HE is 2.1/100,000. Only six HE patients had also HT. Four patients received corticosteroids, five patients were not treated. Five patients improved, four patients spontaneously, one patient after corticosteroids. Repeated CSF examinations showed that the titer of CSF autoantibodies did not correlate with the clinical stage of the disease nor was influenced by corticosteroids. In addition, the course of symptoms was independent of therapy. CONCLUSIONS: The association of encephalopathy and high titers of anti-thyroid antibodies is not sufficient to make a diagnosis of HE. Independent of the clinical status of the thyroid gland, the intrathecal synthesis of autoantibodies is a distinctive marker of this elusive condition.

Adolescent↗
PubMed2003

T-cell cytotoxicity of human Schwann cells: TNFalpha promotes fasL-mediated apoptosis and IFN gamma perforin-mediated lysis.

The ability of resident cells to induce apoptosis of invading immune cells is a major regulatory factor operating in immune-privileged tissues, including the nervous system. We investigated the cellular and molecular factors participating in modulation of immune response in peripheral nerves, focusing on two cytotoxic pathways: fas ligand (fasL) and perforin. fasL and perforin expression was found by immunochemistry on Schwann cells (Sc) in nerve biopsies from patients with chronic inflammatory demyelinating polyneuritis and on human Sc cultures. Treatment of Sc with tumor necrosis factor (TNF) alpha and interferon (IFN) gamma upregulated the expression of both molecules. In a coculture model, Sc exposed to TNFalpha or IFN gamma were able to induce both apoptotic and lytic injury of T-lymphocytes. Inactivation of fasL with the neutralizing antibody NOK-2 abolished T-cell apoptosis induced by Sc treated with TNFalpha, but not by Sc treated with IFN gamma. Conversely, T-cell lysis was significantly decreased when IFN gamma-activated Sc were treated with concanamycin A, which inhibited perforin release. At variance with T-lymphocytes, B-cells were less sensitive to cytokine-treated Sc toxicity. Thus, Sc exposed to inflammatory cytokines have the capacity of inducing selective damage of T-lymphocytes and have the potential of regulating the immune response in the peripheral nervous system.

Apoptosis↗
PubMed2002

Spinal cord mGlu1a receptors: possible target for amyotrophic lateral sclerosis therapy.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons, whose pathogenesis, probably multifactorial, is thought to involve AMPA/kainate receptor-mediated Ca2+ influx and excitotoxicity. We evaluated the possible involvement of Group I metabotropic glutamate (mGlu) receptors in the control of motor neuron viability. mGlu1a receptor distribution was analyzed in rat and human spinal cord by immunohistochemistry. In both species, the expression of mGlu1a receptor was developmentally regulated and showed a general trend to increase during foetal and postnatal maturation, reaching the maximum level of expression in the dorsal laminae I-II and in motor neurons in adult life. Exposure of spinal cord slices from adult rats to 300 microM kainate for 30 min induced motor neuron death, which was prevented by the Group I mGlu receptor agonist 3-hydroxyphenylglycine (3-HPG; 100 microM). Since motor neurons do not express mGlu5 receptors, mGlu1a receptor activation might be responsible for the observed neuroprotection. mGlu1a immunohistochemistry was conducted on spinal cord autoptic specimens from ALS and control subjects. Surviving motor neurons from ALS spinal cord still revealed the presence of mGlu1a at levels comparable to that from controls. We suggest that mGlu1a receptors may act as suitable targets for ALS experimental therapies.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Enhanced expression of NGF receptors in multiple sclerosis lesions.

The receptor for nerve growth factor (NGF) comprises a 75-kDa (NGFRp75) and a tyrosine kinase A (TrkA) subunit. In view of conflicting opinions on the identity of glial targets of NGF in human central nervous system (CNS), we examined the cellular distribution of both NGF receptor subunits in normal CNS and in chronic multiple sclerosis (MS) lesions. For this, we compared the pattern of recognition of 2 monoclonal antibodies (mAbs) and a polyclonal antiserum to NGFRp75. Only the 2 mAbs specifically recognized NGFRp75, while the polyclonal antiserum showed widespread reactivity. In normal CNS and silent MS lesions, immunohistochemistry with anti-NGFRp75 mAbs and for TrkA revealed perivascular cell reactivity. At the edge of chronic active MS lesions, selective NGFRp75 staining was prominent on reactive astrocytes, while throughout the lesion, NGFRp75 was expressed on microglia/macrophages. The vast majority of mature or precursor oligodendrocytes did not express NGFRp75. Both NGF receptors were co-expressed on a subset of inflammatory cells. Immunoreactivity for NGFRp75 on glial and immune cells did not correlate with the distribution of apoptotic figures, as detected by TUNEL. Thus, expression of NGF receptors in active MS lesions suggests a role for NGF in regulating the autoimmune response at both immune and glial cell levels.

Antibodies↗
PubMedDate not supplied

[Dissection of epiaortic vessels: clinical appearance and potentiality of imaging techniques].

PURPOSE: To analyse the major radiological and clinical features of dissections of the epiaortic vessels and evaluate the potential of imaging techniques on the basis of the findings reported in the literature over the last few years. MATERIALS AND METHODS: We evaluated 9 dissections (7 carotid lesions and 2 vertebral lesions) in 9 patients (5 women and 4 men; age range: 30-56 years) who came to our attention between September 1999 and June 2002. These were all stenoses and obstructions located in the cervical region and, in two patients, extended intracranially. The morphologic features were assessed in each case by colour-Doppler US, CT, MR or conventional angiography and correlated with clinical, therapeutic and distant progression patterns. Colour-Doppler US of the neck vessels was performed in 4 patients; CT angiography of neck and intracranial vessels was performed in 4 patients using a single-slice spiral scanner and a single contrast medium bolus injection, following unenhanced examination of the brain; MR angiography was performed in 6 patients after baseline examination using flow-dependent and/or angiographic sequences; conventional angiography was performed in 7 patients. Clinical manifestations at onset were peripheral neurological lesions in 5 cases and central ischaemic lesions in the remaining 4 cases. All patients underwent medical therapy (anticoagulants or antiaggregants). The follow-up was done by colour-Doppler US, MR and/or MR angiography; follow-up conventional angiography at 6-9 months was also performed in 6 patients. Distant progression was assessed on the basis of the degree of vascular re-canalization and the residual signs and symptoms. RESULTS: MR- and CT-angiography were diagnostic in all cases. In particular, diagnosis was obtained by MR-angiography in 4 patients and by CT-angiography in 3 patients. Conventional angiography yielded a diagnosis in 2 cases which had previously undergone non-contrast brain CT or MR without examination of neck vessels alone. Colour-Doppler US revealed non-specific wall and flow alterations in 2 cases, thus requiring further diagnostic studies. In patients with central neurological symptoms at onset the diagnosis was obtained within 48-72 hours, whereas in patients with initial peripheral neurological symptoms the time to diagnosis was significantly longer (up to 10 days) due to the poor specificity of the clinical picture and/or failed detection of the warning symptoms. Medical treatment gave rise to no major complications. Overall, distant progression was good: 6 patients recovered completely and 3 had mild to moderate residual neurological deficits. DISCUSSION AND CONCLUSIONS: Dissection of epiaortic vessels should always be considered as a probable cause of cerebral ischaemia in adults aged 20-50 years, particularly in the absence of vascular risk factors. Clinical assessment is fundamental for the diagnosis and treatment. Currently, CT and MR imaging techniques providing similar information are reliable diagnostic tools that can rapidly and non-invasively clarify suspicious clinical cases. Nevertheless, angiography continues to have an important role in the overall evaluation of disease severity in view of the possible endovascular or surgical treatment of complications.

Adult↗