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Biomedical subjects

P Tonali

Publications and source records attributed to P Tonali.

At least 91 records · Page 5Linked to original sources

Central scalp projection of the N30 SEP source activity after median nerve stimulation.

Conflicting results have been reported about abnormalities of the N30 somatosensory evoked potential (SEP) in movement disorders. In these studies, the N30 amplitude was measured in the frontal scalp region. Our aim was to identify the scalp electrodes recording the genuine activity of the N30 generator. In 18 subjects, we recorded the scalp SEPs from 19 electrodes and found a negative potential around 30 ms reaching its maximal amplitude in the frontal region. However, neither simple visual inspection of the frontal traces nor topographic analysis could distinguish the N24 from the N30 component of the frontal negativity. Brain electrical source analysis of SEPs showed that a four dipolar source model could well explain the scalp SEP distribution. We calculated the scalp field distributions of the source activities as modeled from the scalp recordings and observed that the maximal field distribution reflecting the activity of the N30 source was in the central region, whereas that reflecting the N24 source activity was frontal. We conclude that the negative response recorded around 30 ms in the central traces represents "genuine" N30 source activity, whereas the frontal negativity, which is higher in amplitude, is a mixture of the activities of both the N30 and N24 sources.

Adult↗

Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex.

The aim of the present study was to investigate whether muscarinic receptor blockade with scopolamine modifies the excitability of specific cortical networks of the human motor cortex as tested with transcranial magnetic stimulation. The effects of scopolamine on the excitability of human motor cortex were investigated in four healthy subjects using transcranial magnetic stimulation before and after an intravenous dose of scopolamine (0.006 mg/kg). We measured the threshold for motor responses, amplitude of motor responses, the duration of the cortical silent period, intracortical inhibition and facilitation, and short-latency inhibition produced by somatosensory input from the hand. In addition, we evaluated the amplitude of motor responses evoked by electrical anodal stimulation, since these responses originate from direct activation of corticospinal axons in the white matter and are not sensitive to changes in cortical excitability. Scopolamine decreased the threshold to magnetic stimuli and increased the amplitude of motor responses evoked by magnetic stimulation. In contrast, motor responses evoked by electrical stimulation were unaffected by administration of scopolamine. Scopolamine also led to a highly significant reduction in the amount of short-latency inhibition produced by somatosensory input from the hand. In contrast, short-latency intracortical inhibition and facilitation were not modified by scopolamine. The differential effect of scopolamine on motor responses evoked by magnetic and electrical stimulation of the motor cortex and the selective effect on somatosensory inhibition demonstrate that muscarinic blockade modifies the excitability of specific cortical networks in the human motor cortex.

Acetylcholine↗

Peroneal mononeuropathy: predisposing factors, and clinical and neurophysiological relationships.

The most common mononeuropathy in the lower extremity involves the nerve. We retrospectively evaluated the etiological predisposing factors and clinical-neurophysiological features of 36 patients affected by peroneal mononeuropathy (PM). In 30 patients, a clear predisposing factor was identified. PM was more frequently perioperative (11 cases), associated with axonal involvement. Unexpectedly, PM was not only due to surgery close to the peroneal region, but was mostly associated with hip surgery and, rarely, with thoracic-abdominal surgery. A postural predisposing factor of PM was also frequently observed, usually associated with a pure conduction block. Conversely, most patients with bedridden predisposing factor presented axonal involvement, which was rarely associated with conduction block. In 25 of 36 PM cases, a long-term follow-up lead to an improvement (12 cases) or to good recovery (13 cases) of PM. In conclusion, our study shows that: (1) in most PM cases it is possible to identify a predisposing factor; (2) there is a good correlation between predisposing factor and neurophysiological involvement, and (3) PM usually has usually a good prognosis.

Adolescent↗

An Italian family with autosomal recessive quadriceps-sparing inclusion-body myopathy (ARQS-IBM) linked to chromosome 9p1.

We report an Italian family with autosomal recessive quadriceps-sparing inclusion-body myopathy (ARQS-IBM). The patients (two second cousins) developed a slowly progressive distal and proximal myopathy with complete sparing of the quadriceps. Muscle biopsy showed rimmed vacuoles in numerous muscle fibers, and electron microscopy documented accumulation of 15-21 nm filaments. DNA analysis established linkage to 9p1 and haplotype analysis revealed that the patients shared a recombined common haplotype. The gene locus of ARQS-IBM was initially mapped to chromosome 9p1-q1 in families of Iranian-Jewish origin and later confirmed in a few other ethnic groups. This is the first report of Italian patients with ARQS-IBM showing positive linkage to chromosome 9p1. Our data suggest that patients having distal and proximal myopathy with rimmed vacuoles and possible recessive inheritance, often classified as distal myopathies, should be thoroughly investigated according to the diagnostic criteria of h-IBM and, when positive, studied for linkage to chromosome 9p1.

Arm↗

Sources of cortical responses to painful CO(2) laser skin stimulation of the hand and foot in the human brain.

OBJECTIVES: To investigate whether the same dipolar model could explain the scalp CO(2) laser evoked potential (LEP) distribution after either hand or foot skin stimulation. METHODS: LEPs were recorded in 14 healthy subjects after hand and foot skin stimulation and brain electrical source analysis of responses obtained in each individual was performed. RESULTS: A 5 dipolar sources model explained the scalp LEP topography after both hand and foot stimulation. In particular, we showed that the co-ordinates of the two earliest activated dipoles were compatible with source locations in the upper bank of the Sylvian fissure on both sides. These sources did not change their location when the stimulation site was moved from the upper to the lower limb. The other 3 dipoles of our model were activated in the late LEP latency range with a biphasic profile and a location compatible with activation of the cingulate gyrus and deep temporo-insular structures. CONCLUSIONS: The dipolar model previously proposed for the hand stimulation LEPs can also satisfactorily explain the LEP distribution obtained after foot stimulation. The earliest activated Sylvian dipolar sources did not change their location when the upper or lower limb was stimulated, as expected from the close projections of hand and foot in the second somatosensory area. No source in the primary somatosensory area was necessary to model the scalp topography of LEPs to hand and foot stimulation.

Adult↗

SFEMG in ocular myasthenia gravis diagnosis.

BACKGROUND AND OBJECTIVE: In typical cases, the patient's history and clinical examination make it possible to diagnose ocular myasthenia gravis (OMG). But, in many cases a clear clinical picture is not present and OMG diagnosis is very difficult because gold diagnostic standard tests are not available. The diagnostic tests for OMG are usually unable to display a good sensitivity and specificity simultaneously. In this paper, we studied 86 cases submitted for suspected OMG. METHODS: The patients were studied clinically and with various other tests used in OMG diagnosis (SFEMG, repetitive nerve stimulation, Ab anti AChR titration, tensilon test). RESULTS AND CONCLUSION: SFEMG showed the highest sensitivity (100%) while Ab anti AChR showed the highest specificity (100%). To our knowledge this is the largest population of suspected OMG studied using most of the diagnostic parameters, reported in the literature.

Adult↗

Scalp distribution of the earliest cortical somatosensory evoked potential to tibial nerve stimulation: proposal of a new recording montage.

OBJECTIVE: To investigate the most reliable method to record the earliest cortical somatosensory evoked potential (SEP) after tibial nerve stimulation. The 'gating' phenomenon was used to dissociate the overlapping cortical SEP components. METHODS: In 11 subjects we recorded the scalp SEPs at rest, during the voluntary (active gating) and passive (passive gating) foot movement and during the isometric calf muscle contraction (isometric gating). RESULTS: At the vertex the P40 amplitude was reduced in all the gating conditions. Instead, both the P40 response recorded in the parietal region ipsilateral to the stimulation (indicated as P40par) and the fronto-temporal N37 potential were reduced in amplitude only during the passive foot movement. CONCLUSIONS: The same behaviour of the N37 and P40par potentials suggests that they can represent the opposite counterparts of the same dipolar generator. Instead, the real P40 amplitude, which is affected in all the gating conditions, is recorded at the vertex and might be generated by a different source. We conclude that the montage obtained by referring a temporal electrode contralateral to the stimulation to an ipsilateral parietal lead can reliably record the earliest cortical component (N37/P40par) after tibial nerve stimulation.

Adult↗

Unmasking of an early laser evoked potential by a point localization task.

OBJECTIVES: The investigation of the CO(2) laser evoked potential (LEP) modifications following a point localization task. METHODS: LEPs were recorded from 10 healthy subjects in two different conditions. (1) Task condition: laser stimuli were shifted among 3 different locations on the right hand dorsum, and the subjects were asked to identify the stimulated area. The mean error rate in point localization was 4.5%. (2) Non-task condition: laser pulses were delivered on the first intermetacarpal space, and the subject was asked to count the number of stimuli. The mean error rate in counting was 5.8%. RESULTS: In the task condition, the temporal traces contralateral to the stimulation showed an early positive component (eP, mean peak latency 83 ms) preceding the N1 negativity (mean peak latency 144 ms). At the eP peak latency, topographic maps showed a positivity highly focused on the contralateral temporal region. In the non-task recordings no reliable response was identifiable before the N1 potential. CONCLUSIONS: While no LEP component earlier than the middle-latency N1 potential can be recorded in the non-task condition, a positive response (eP) preceding the N1 component is identifiable in the contralateral temporal region during the spatial localization of painful stimuli. The eP scalp distribution is compatible with its origin from a radial source in the second somatosensory (or insular) area, thus suggesting that the opercular cortex is involved not only in the middle-latency (N1 potential), but also in early pain processing.

Adult↗

Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex.

OBJECTIVES: The present study explored the effects of lorazepam, a benzodiazepine with agonist action at the GABA(A) receptor, on human motor cortex excitability as tested using transcranial magnetic stimulation. METHODS: We recorded directly the descending volley evoked by single and paired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral dose of lorazepam. We evaluated the effects of lorazepam on the descending volleys evoked by a single magnetic stimulation and paired cortical stimulation using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprathreshold conditioning stimulus). RESULTS: Using a single magnetic stimulus lorazepam decreased the amplitude of the later I waves in the descending volley; this was accompanied by a decrease in the amplitude of the evoked EMG response. Using the intracortical inhibition paradigm lorazepam increased the amount of corticocortical inhibition, particularly at 4 and 5 ms interstimulus intervals. There was no effect on the amount of facilitation observed in the short latency intracortical facilitation paradigm. CONCLUSIONS: The present findings provide direct evidence that lorazepam increases the excitability of inhibitory circuits in the human motor cortex.

Aged↗

Therapeutic apheresis in myasthenia gravis.

Plasma exchange (PE) is an easily applicable technique for rapid and massive removal of antibodies, and its beneficial role is well established in the management of myasthenia gravis (MG), an antibody-mediated disorder of the neuromuscular junction. PE is useful in myasthenic crisis, in most severe forms of MG before thymectomy, in the early postoperative period, and in cases of symptom worsening during tapering or initiation of immunosuppressive therapy. Clinical efficacy varies from 55% to 100%, and improvement rarely persists for more than 4-10 weeks; thus immunosuppressive therapy has to be associated. New apheretic techniques (double filtration plasmapheresis, immunoadsorption systems with staphylococcal protein A columns or thryptophan-polyvinyl alcohol gel columns) that allow the selective removal of IgG and anti-AChR antibody were recently used in the management of MG with positive effects. Whether their therapeutic effect and cost effect prove more favorable than those obtained by PE still must be demonstrated.

Autoantibodies↗

Apoptosis in mitochondrial encephalomyopathies with mitochondrial DNA mutations: a potential pathogenic mechanism.

Mitochondrial encephalomyopathies caused by mitochondrial DNA (mtDNA) defects are a genetically and phenotypically heterogeneous group of disorders. The site, percentage and distribution of mutations do not explain the overall clinical heterogeneity that is found. Apoptosis (programmed cell death) is an evolutionarily conserved mechanism that is essential for tissue development and homeostasis. Dysregulation of apoptosis has been implicated in the pathogenesis of various human diseases, such as cancer and autoimmune and neurodegenerative disorders. Recent in vitro evidence has indicated the central role of mitochondria in the apoptotic process. We investigated the occurrence of apoptosis in muscle biopsies of 36 patients carrying different mtDNA mutations and four patients with inclusion body myositis and mitochondrial abnormalities. Apoptotic features, mainly localized in cytochrome c oxidase-negative fibres, were observed in muscle fibres of patients carrying a high percentage of single mtDNA deletions (>40%) and of tRNA point mutations (>70%). By contrast, no apoptotic changes were observed in inclusion body myositis and in patients carrying mutations of mtDNA structural genes. Our study suggests that apoptosis is not simply a means whereby cells with dysfunctional mitochondria are eliminated, but that it seems to play a role in the pathogenesis of mitochondrial disorders associated with mtDNA defects affecting mitochondrial protein synthesis. The imbalance and relative abundances of nuclear-encoded and mtDNA-encoded subunits may favour cytochrome c inactivation and release. Cytochrome c, together with respiratory chain dysfunction, could activate apoptotic pathways that, in turn, inhibit the rate of mitochondrial translation and the importation of nuclear-encoded mitochondrial protein precursors. This vicious circle may amplify the biochemical defects and tissue damage and contribute to the modulation of clinical features.

Adolescent↗

Clinical characteristics and prognosis of myasthenia gravis in older people.

OBJECTIVES: To investigate the characteristics of myasthenia gravis (MG) in older people and to evaluate the benefits of immunosuppressive treatments at this age. BACKGROUND: Myasthenia gravis in older adults has not been extensively studied. In patients with disease onset after the age of 60, treatment mainly relies on medical therapy because thymectomy is generally not performed unless a thymoma is present. METHODS: Of 837 myasthenic patients followed since 1978, we identified 172 cases with onset after age 60. All patients were treated with anticholinesterases. In the decade from 1978 to 1988, immunosuppressive therapy was performed mainly with corticosteroids (prednisone); since 1989, azathioprine alone or, more often, associated with prednisone, has been increasingly used in MG patients. Long-term outcome was evaluated in 149 cases with follow-up longer than 1 year. Remission, pharmacological remission, and marked improvement with reduction in drug dosage were considered good results. RESULTS: Patients older than age 60 at onset of the disease were 20.5% of our series, male/female ratio was 1.9, age at onset ranged from 61 to 86 years, 87.2% patients had generalized disease, thymoma was detected in 37 patients (21.5%). Of 149 cases with sufficient follow-up data, 9 were in remission, 111 achieved good results, 3 died of MG, and 120 required immunosuppressive therapy at some time. Sixty-seven patients had been treated with prednisone for 0.5-16 years (mean, 5 years); good results were recorded in 51 patients (76.1%) and severe side effects in 12 (17.9%). Forty-six patients had received combined therapy with prednisone and azathioprine for 1 to 12 years (mean, 3.9 years); good results were recorded in 41 patients (89.1%) and severe side effects in six (19.5%). Seven patients had been treated with azathioprine alone for 1 to 4 years (mean, 2.3 years) with good results in five and with no side effects. CONCLUSIONS: The prognosis of MG in older people seems to be favorable, although full remission is rare and MG weakness, treatment side effects, and associated thymoma can contribute to mortality rate. In our experience, the combined therapy with prednisone and azathioprine was more effective than prednisone alone, and steroid-related side effects were more frequent than those related to azathioprine.

Aged↗

Somatosensory evoked potentials after multisegmental lower limb stimulation in focal lesions of the lumbosacral spinal cord.

OBJECTIVES: Recording techniques permit the separate analysis of the response from cauda equina roots and the spinal potential that is probably generated by the activation of dorsal horn cells. To improve the functional assessment of focal lesions of the lumbosacral cord, lower limb somatosensory evoked potentials (SEPs) were measured by multisegmental stimulation. METHODS: Common peroneal and tibial nerves SEPs were recorded in 14 patients in whom MRI demonstrated compressive cord damage ranging from T9 to L1 levels. SEPs were recorded in each patient at the lumbar level (cauda equina response), lower thoracic level (spinal response), and from the scalp (cortical response). RESULTS: Abnormalities in spinal response occurred in 50% and 70% of tibial and common peroneal nerve SEPs respectively; these findings were well explained by the radiological compression level, involving in most of the patients lumbar rather than sacral myelomeres. The SEPs were often more effective than the clinical examination in showing the actual extension of damage. CONCLUSIONS: The recording of spinal SEPs after multisegmental lower limb stimulation proved useful in assessing cord dysfunction and determining the cord levels mainly involved by the compression.

Adult↗

Acute challenge with apomorphine and levodopa in Parkinsonism.

BACKGROUND: The diagnosis of different parkinsonian syndromes and the ability to predict long-term drug efficacy constitute important clinical issues. DESIGN: Motor responses to the acute administration of levodopa and apomorphine were analyzed in a series of 134 parkinsonian patients, including 83 patients with a clinical diagnosis of idiopathic Parkinson's disease (PD), 28 patients with multiple-system atrophy (MSA), 6 with progressive supranuclear palsy, and 17 with an unclassified parkinsonian syndrome. METHODS: The patients received oral levodopa/carbidopa (250/25 mg) and subcutaneous apomorphine (1.5, 3 and 4.5 mg). Clinical variations of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score were evaluated 1 h following levodopa administration or 20 min following apomorphine. The motor improvement produced by each acute challenge was matched with the clinical diagnosis and with the response to chronic levodopa treatment. The diagnosis was verified by repeated clinical assessments or by autopsy in 2 cases. A receiver operating characteristics curve was plotted comparing PD vs. non-PD, PD vs. MSA and chronic responders vs. nonresponders. Cutoff threshold improvement was defined as the value closest to the crossing point for 80% sensitivity and 80% specificity, corresponding to the best trade-off for a predictive evaluation. RESULTS: UPDRS motor score improvement was on average higher in PD than in non-PD patients (levodopa: 29.8 vs. 12.2%; apomorphine 1.5 mg: 27.1 vs. 10.5%; apomorphine 3 mg: 27.7 vs. 9.7%; apomorphine 4.5 mg: 28.8 vs. 11.8%; p < 0.01 with Student's t test). When PD patients were compared to non-PD patients, levodopa challenge had the best diagnostic accuracy with a threshold improvement of 16%. Apomorphine had the best diagnostic accuracy with a threshold improvement of 13.5% for 1.5 mg, 13% for 3 mg, and 16% for 4.5 mg. This meant that patients improving at least 16% in all tests had the highest probability of having PD. When PD patients were compared to MSA patients, levodopa acute challenge had the best diagnostic accuracy with a threshold improvement of 17%. Apomorphine had the best diagnostic accuracy with an improvement of 13% for 1.5 mg, 15% for 3 mg, and 18% for 4.5 mg. This meant that patients improving at least 18% in all tests had the highest probability of having PD rather than MSA. When patients who responded to chronic levodopa treatment were compared to those who did not, acute challenge with levodopa had the best predictive accuracy with a threshold improvement of 14.5%. Apomorphine had the best predictive accuracy with an improvement of 13% for 1.5 mg, and 14% for 3 and 4.5 mg. This meant that patients improving at least 14.5% in all tests had the highest probability of responding to chronic treatment. CONCLUSION: A good agreement was found between acute challenges with levodopa/carbidopa and apomorphine, and the use of both improved the reliability of the test. Different threshold improvements after acute challenges would support a diagnosis of PD or the exclusion of MSA, and would have a predictive value for subsequent response to chronic levodopa therapy.

Age of Onset↗

Multiperspective assessment of carpal tunnel syndrome: a multicenter study. Italian CTS Study Group.

OBJECTIVE: To assess the clinical and neurophysiologic dissociation often observed in clinical practice, and to improve patient evaluation for diagnosis of carpal tunnel syndrome (CTS). METHODS: The Italian CTS Study Group studied 1,123 idiopathic CTS hands with multiple measurements-clinical, neurophysiologic, and patient-oriented-of CTS. RESULTS: Clinical and neurophysiologic relationships were very strong when the clinical picture was evaluated by the hand functional measurements, with an exponential increase in functional impairment as the classification of neurophysiologic severity progressed. Conversely, symptoms and pain did not increase as the classification of neurophysiologic severity progressed: 1) A large part of the CTS population complained of severe symptoms, although minimal functional impairment and minimal or no electrophysiologic abnormalities were observed; and 2) symptoms improved in the patients with more severe neurophysiologic and clinical examination scenarios. CONCLUSIONS: Multiperspective and multimeasurement assessment, even when using a validated patient-oriented tool, provided interesting information that confirmed and clarified the clinical neurophysiologic dissociation often observed in carpal tunnel syndrome (CTS) patients. Furthermore, CTS appeared to be an ideal model for evaluating the importance of patient-oriented measurement.

Adult↗