Biomedical subjects

L Mazzini

Publications and source records attributed to L Mazzini.

At least 19 recordsLinked to original sources

PubMed2000

Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis.

An immunologic pathogenesis for amyotrophic lateral sclerosis (ALS) has been recently proposed. We tested the whole tumour necrosis factor (TNF) system in the serum of 51 ALS patients at different stages of the disease and 36 healthy controls. Antigenic TNF-alpha and its soluble receptors (sTNF-Rs), measured by ELISA, were significantly higher in ALS patients than in healthy controls. However, biologically active TNF-alpha, corresponding to the sTNF-Rs-unbound trimeric TNFalpha molecule and assayed by its cytotoxic activity on a sensitive cell line, was similar between ALS patients and healthy controls. Neither antigenic TNF-alpha, bioactive TNF-alpha nor sTNF-Rs correlated with disease severity, disease duration, or weight loss. In conclusion, we reported an activation of the TNF system in ALS. The role of this activation in the pathogenesis of the disease remains elusive.

Amyotrophic Lateral Sclerosis↗

PubMed2000

A randomized controlled trial of recombinant interferon beta-1a in ALS. Italian Amyotrophic Lateral Sclerosis Study Group.

OBJECTIVE: To evaluate the efficacy of recombinant interferon beta (IFNbeta)-1a in the treatment of ALS. BACKGROUND: It has been proposed that IFNs affect the progression of ALS by interfering with putative immune mechanisms involved in the pathogenesis of the disease. METHODS: Patients (n = 61) 40 to 70 years of age with a 6- to 24-month history of confirmed ALS with mild to moderate disability received IFNbeta-1a, 12 mIU (n = 31), or placebo (n = 30) subcutaneously three times a week for 6 months and were followed up for an additional 6 months. Patients were assessed after 4, 12, 24, 36, and 48 weeks. Medical Research Council scale, Norris scale, and bulbar scores as well as forced vital capacity were used to assess disability. Selected electrophysiologic measures (latency, amplitude, and duration of the compound muscle action potential) were also used. RESULTS: Twenty patients randomized to IFNbeta-1a and 17 patients given placebo completed the study. A total of 16 patients receiving IFNbeta-1a became non-self-supporting compared with 16 on placebo (52% versus 53%). There were no significant differences between the two treatment groups for any of the measures of disease progression and disability. Deaths were reported in six patients treated with IFNbeta-1a and four patients on placebo. Adverse events were reported more frequently with IFNbeta-1a (77% of patients) compared with placebo (57%), with flu-like symptoms and local erythema being the commonest complaints. CONCLUSIONS: This pilot study suggests that IFNbeta-1a is not effective in the treatment of ALS.

Aged↗

PubMed2000

Measurement of isometric muscle strength: a reproducibility study of maximal voluntary contraction in normal subjects and amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of unknown cause, resulting in the progressive loss of voluntary motor activity. Traditional methods of evaluating patients with ALS (neurologic assessment, manual muscle testing and rating scales) involve subjective elements and lack the sensitivity needed to detect small but meaningful changes in deterioration and therapeutic efficacy. This paper presents a recently developed strength measurement instrument, useful for the long-term monitoring of muscle strength deterioration in ALS. In addition, a reproducibility study to assess the intra- and interobserver reliability of maximal voluntary isometric contraction is reported. The strength measurement instrument consists of a strain gauge force transducer, a bridge amplifier and a mechanical structure to counteract movements. A personal computer acquires the strength signal during each voluntary contraction and automatically computes the maximal value. Reproducibility of measurement was assessed in 18 normal subjects tested twice, on successive days, with the same examiner and under the same conditions. The interexaminer reproducibility of measurement was assessed in a group of 13 normal subjects and 10 ALS patients. Each subject of the two groups was independently examined by three examiners. The two reproducibility studies showed a high intraclass correlation coefficient (0.91-0.97) and low SEM and measurement error (3-10%) in all muscle regions tested. The Bland and Altman plots confirmed these results.

Adult↗

PubMed1999

Heterogeneous distribution of amyotrophic lateral sclerosis patients with SOD-1 gene mutations: preliminary data on an Italian survey.

We report the absence of superoxide dismutase (SOD-1) gene mutations in 30 patients with amyotrophic lateral sclerosis (ALS) including individuals with a confirmed family history of ALS (familial ALS/FALS), ALS with an unclear family history (UFALS) and sporadic ALS (SALS). Single strand conformation polymorphism (SSCP) and sequence analysis of the 5 SOD-1 gene exons were undertaken to improve the accuracy of the mutation detection. Our preliminary data appear to diverge from the results of studies by other groups using different populations. We discuss the possible reasons for this disparity and the apparent heterogeneous distribution of ALS with SOD-1 gene mutations among different ethnic groups.

Adult↗

PubMed1999

Somatosensory and motor evoked potentials at different stages of recovery from severe traumatic brain injury.

OBJECTIVE: To detect changes of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) at different stages of recovery from severe brain injury and to determine whether they can be used to predict late functional outcome. DESIGN: Correlational study on a prospective cohort. SETTING: Brain injury rehabilitation center. PATIENTS: Twenty-seven consecutively sampled patients with severe traumatic brain injury referred to the inpatient intensive rehabilitation unit of primary care in a university-based system. MAIN OUTCOME MEASURES: (1) Glasgow Outcome Scale, Disability Rating Scale, and Functional Independence Measure; (2) SEPs and MEPs from upper limbs (ULs) and lower limbs (LLs). Outcome was assessed at 6 and 12 months after trauma. Correlations were computed with the nonparametric test of Spearman-Rank. RESULTS: Both SEPs and MEPs showed dynamic changes (p < .02 for N20, p < .05 for N30, P40, and N45), with a trend toward a progressive normalization. N30 was more frequently abnormal than N20. SEPs from LLs were more frequently and more persistently abnormal than those from ULs. Clinical and functional outcome was strongly correlated with the degree of abnormality of SEPs from LLs (p < .002), whereas only mild relationships were found with SEPs from ULs. Both SEPs and MEPs showed a high negative predictive value (83% for N30 and 83% for P40), but only SEPs from LLs also had a high positive predictive value (72% for P40). Sensitivity was 88% both for N30 and P40. Specificity was 50% for N30 and 70% for P40). CONCLUSION: SEPs from LLs can be very useful in monitoring the postacute phase of traumatic brain injury and in identifying patients who require further intensive rehabilitation. MEPs may be of questionable value.

Adolescent↗

PubMed1999

Motor neuron disease: usefulness of transcranial magnetic stimulation in improving the diagnosis.

Clinical upper motor neuron (UMN) involvement is sometimes difficult to detect in motor neuron disease (MND). For this reason we performed transcranial magnetic stimulation (TMS) to find out whether this technique may be useful in revealing signs of pyramidal tract impairment. Fifty-five MND patients, clinically divided into 22 amyotrophic lateral sclerosis (ALS), 18 ALS with probable UMN signs (ALS-PUMNS), 10 pure lower motor neuron syndrome (LMNS), and 5 progressive bulbar palsy (PBP), underwent standard TMS, recording from abductor digiti minimi and flexor allucis muscles. Prolongation of cortical motor evoked potential (MEP) latency and central conduction time (CCT) and absent MEP were considered as pathologic. ALS-PUMNS and LMNS patients were clinically reclassified after 1 year. TMS was abnormal in 95.4% of ALS, 72.2% of ALS-PUMNS, 50% of LMNS and 20% of PBP. Correlations between TMS parameters and both clinical signs of UMN involvement and disease severity were highly significant. TMS showed a high sensitivity, but lacked specificity. After 1 year, 11 patients among the ALS-PUMNS group were clinically reclassified as definite ALS: all of them had shown TMS abnormalities at the first examination. In conclusion, TMS provides important diagnostic information for an early prediction of ALS in those MND patients presenting with clinically equivocal UMN impairment.

Adult↗

PubMed1998

The natural history and the effects of gabapentin in amyotrophic lateral sclerosis.

Glutamate excitotoxicity seems to play an important role in the aetiopathogenesis and progression of Amyotrophic Lateral Sclerosis (ALS). Gabapentin is a modulator of the glutamatergic system and has been shown to prolong survival in the transgenic model of familial ALS. It has also been demonstrated to slow the decline of arm strength in human sporadic cases. The aim of our study was to assess the effects of different dosages and duration of treatment of gabapentin on the natural history and survival of ALS patients. A total of 110 patients affected by definite ALS entered the study. After a 6-12 month period of observation, patients were randomly assigned to receive oral gabapentin 500 mg/day (Group A) or 1000 mg/day (Group B) for 6 months. In addition a group of patients received gabapentin 500 mg/day for 6 months and 1000 mg/day for a further 6 months (Group C). A group of 121 patients referred to our Institute, who received only symptomatic treatment, was considered as the control group (Group D). Each patient was seen at entry and every 3 months. All average slopes were negative but the comparison of all slopes showed a trend toward a slower rate of decline of muscle strength loss in all treated groups of patients compared with the control group. The differences were statistically significant. Analysis between the pretreatment and treatment period showed a statistically significant decrease of the decline of muscle strength and Norris score during the treatment period. Survival analysis showed a significantly longer survival in treated patients of Groups B and C. Our study suggests that gabapentin may be an effective drug for ALS; hence a controlled trial involving a sufficient large number of patients is warranted.

Acetates↗

PubMed1997

H-reflex changes in the course of amyotrophic lateral sclerosis.

In this study the H-reflex and M-wave were evoked in a group of ALS patients, to correlate the findings with the clinical state, and to investigate whether a statistical approach for assessing H-reflex changes in the presence of a constant M-wave could be reproducible and helpful in monitoring the course of amyotrophic lateral sclerosis (ALS). The H-reflex and M-wave from the soleus muscle were evoked at different stimulus strengths in 35 patients with definite ALS during the course of their illness. The mean amplitude of the H-reflexes (H-mean) obtained in different sessions within an established range of mean M-response amplitude (M-mean) was calculated. For each patient, M-mean was made constant across sessions. H-mean showed high reproducibility and two different trends of changes which emerged in a 1 year follow-up within the population: a significant progressive increase and a steady decrease. When grouped on the basis of their H-mean trend, the patients did not differ in terms of any clinical variables considered. However, the group with progressive increase of H-mean showed a better prognosis. This study has shown that H-mean is effective in assessing the clinical course of ALS and could be useful in monitoring drug effects during clinical trials.

Adult↗

PubMed1996

Muscle relaxation in Parkinson's disease: a reaction time study.

We tested the hypothesis that the relaxation reaction time in Parkinson's disease (PD) is delayed, as a sign of disorder in the control of voluntary motoneuron derecruitment. We compared, in the triceps brachii muscle, the reaction times (RTs) of the onset (O-RT) of electromyographic (EMG) activity during initiation of a contraction with the RTs of the termination of EMG tonic activity during full relaxation (R-RTs). Fourteen patients with idiopathic PD and 10 normal controls were examined. Mean R-RTs for all controls were 30 ms shorter than mean O-RTs. Mean R-RTs for all patients were approximately 70 ms longer than mean O-RTs. In two untreated patients levodopa therapy improved both O-RT and R-RT, but the difference between the two was unchanged. There was no correlation between EMG level and R-RT or between peak force and O-RT in either controls or patients. O-RT and R-RT were correlated with the bradykinesia score. In some patients, bursts of late activity were recorded after the R-RT; the duration of this activity was correlated with the duration and staging of the disease and with bradykinesia and rigidity scores. The reversed latency of onset and termination of muscle contraction in PD suggests an abnormality in the inhibitory spinal mechanisms, possibly stemming from a defect in the pathways descending to the spinal cord.

Aged↗

PubMed1996

Amyotrophic lateral sclerosis: oxidative energy metabolism and calcium homeostasis in peripheral blood lymphocytes.

There is evidence of oxidative injury in postmortem brain, spinal cord, and CSF of patients with sporadic amyotrophic lateral sclerosis (SALS patients). We investigated the oxidative metabolism and calcium homeostasis in peripheral blood lymphocytes from such patients and did not find statistical differences in the basal oxygen consumption rate (QO2), cytochrome c oxidase activity, catalase activity, and lactate production. However the increase in QO2, induced by an uncoupler of oxidative phosphorylation, was depressed and the basal (resting) level of free cytosolic calcium ([Ca2+]in) was higher in lymphocytes from SALS patients (p < 0.01). Further increase in free [Ca2+]in challenged by a K+ channel blocker or by an uncoupler of oxidative phosphorylation was similar in SALS and control lymphocytes. The results show that systemic changes consistent with the presence of mitochondrial and of calcium metabolism dysfunction are present in SALS.

Adult↗

PubMed1995

Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis.

Bulbar involvement in amyotrophic lateral sclerosis (ALS) is often related to a worse prognosis on account of the higher risk of pulmonary aspiration and undernutrition due to dysphagia. The aim of our study was to assess the effects of enteral feeding by percutaneous endoscopic gastrostomy (PEG) in a long-term follow-up of ALS patients. We report the results of PEG in 31 ALS patients with bulbar involvement. The patients were observed at 3-monthly intervals over a period of 2 years after PEG. All the data were compared with those obtained from a control group of 35 ALS patients who refused PEG. Mortality did not differ significantly between the two groups of patients during the first 6 months of observation, whereas after this period it was lower in the PEG group. In the patients who had had PEG, the body mass index showed a mild but statistically significant improvement after tube insertion while in the control group it decreased significantly. The findings of this study demonstrate that PEG can improve survival in elderly and young ALS patients with bulbar involvement; it enhances their quality of life and helps their integration in their social and family surroundings. We think that PEG should be included symptomatic treatment of all ALS patients with bulbar involvement from the onset of symptoms.

Adult↗

PubMed1994

Abnormalities of somatosensory evoked potentials in spasmodic torticollis.

This study examined the N20 and N30 waves of somatosensory evoked potentials (SEPs) from median nerve stimulation at three different stimulation rates (1, 3, and 6 Hz) in patients with idiopathic spasmodic torticollis (ST). The data were compared with those collected from a group of patients affected by Parkinson's disease (PD) and normal age-matched subjects. N30 amplitude was significantly decreased in both groups of patients with respect to the controls. The decrease was larger in patients with ST. The N20 wave remained stable. The latencies of both waves were unchanged. When the stimulus rate was increased, the N30 amplitude decreased significantly, with a similar trend observed in both patients and controls. The isolated abnormalities of the N30 wave in both ST and PD support the hypothesis of a common physiopathogenetic mechanism that involves the basal ganglia or their connections with the supplementary motor area.

Adult↗

PubMed1994

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis.

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25-80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.

Adult↗

PubMed1994

Short-latency neck muscle responses to vertical body tilt in normal subjects and in patients with spasmodic torticollis.

EMG responses in the sternocleidomastoid (SCM) and dorsal neck muscles (DNM) to vertical head acceleration were studied in normal subjects and in patients with spasmodic torticollis, standing on a platform that could be tilted upwards. The vertical body displacement and the induced changes in the head-neck angle (a flexion-extension sequence) were recorded. Excitatory responses, symmetrical on the two sides, were elicited in normal subjects in both muscle groups, at a latency of about 60 msec (DNM) and 90 msec (SCM). With the head initially extended, the latency of DNM response increased, leaving that of SCM unchanged. During an isometric rotatory effort, an early inhibitory period was recorded in the active muscles at a latency of about 40 msec. Downward tilt did not evoke the responses. The DNM excitatory responses appeared to be related to muscle stretch, while those in SCM, as well as the inhibitory responses in both muscles, were thought to originate in the vestibular receptors. During active head rotation the response increased in amplitude in the active SCM and decreased in the lengthened antagonist; decreased responses in the lengthened muscle persisted during passive head rotation. This was attributed to an influence from the tonic neck receptors. In the patients, SCM responses had normal latency, but were reduced in amplitude or absent in the dystonic muscle, in spite of tilt-induced head movements comparable to those recorded in normals. The diminution was even bigger if compared to normal subjects with the head actively rotated to a similar extent. It persisted when the head was returned to normal position by the "geste antagoniste." The inhibitory responses were unaffected in the active normal and dystonic muscles. The possible role of a deficit of the central vestibular connections in the decreased excitatory SCM response in dystonic patients is considered.

Adult↗

PubMed1992

Activation of the neck muscles from the ipsi- or contralateral hemisphere during voluntary head movements in humans. A reaction-time study.

Reaction times (RTs) of EMG onset of agonist right and left sternocleidomastoid (SCM) and splenius (SPL) muscles in response to acoustic (AC) or unilateral somatosensory (SS) stimulation were measured in normal subjects, during head rotation (to the right or to the left) and flexion. No significant difference was present in the AC-RT of SCM muscles of the two sides between rotations or flexion. The same was true for the SPL. Under the tactile condition, in which the stimulus was delivered to one index finger, the RTs of both agonist muscles were shorter during head rotation toward the stimulus than away from it: the SCM contralateral to the stimulated finger was faster than the ipsilateral SCM, while the reverse was true for the SPL. During flexion, the SS-RTs of the SCM of both sides were similar, and similar in turn to the SCM-RT during rotation away from the stimulus. When the stimulus was delivered to the shoulder, the RT difference between the agonist SCMs disappeared. The delay in the activation of the SCM ipsilateral to the stimulated finger is compatible with the interhemispheric transmission time in the absence of callosal connection between the hand areas of the primary somatosensory cortex. The data favour the hypothesis that SCM activation during voluntary head rotation is controlled by the ipsilateral hemisphere.

Adult↗

PubMed1992

Methylbromide intoxication: a case report.

This work focuses on the neurophysiological features in a patient with action myoclonus and mental deterioration following methylbromide intoxication. The patient is a 28-year-old man, without respiratory distress or exposure to other toxics. Myoclonus improved with polytherapy (clonazepam, 5-HT, carbidopa, GABA). The neurophysiological and neuropsychological evidence in this patient suggests a possible double site of action of methylbromide at cortical and subcortical levels.

Adult↗

PubMed1991

Amyotrophic lateral sclerosis: a possible example of autosomal recessive inheritance.

A family is reported in which three out of four siblings of a consanguineous healthy couple developed adult onset Amyotrophic Lateral Sclerosis (ALS). All patients showed a similar clinical course with regard to disease progression and absence of cognitive deterioration. Laboratory findings included modification of Spinal Evoked Potential (SEP) and normal value of thiamine and thiamine monophosphate in cerebrospinal fluid (CSF). These data suggest an autosomal recessive mode of inheritance of ASL in this family.

Adult↗

PubMed1990

Post-traumatic extrapyramidal syndrome: case report.

We report the case of a young man with possible post-traumatic extrapyramidal syndrome. Some features of this case have a bearing on the controversy surrounding the existence of post-traumatic Parkinson disease.

Adolescent↗