Biomedical subjects

L Mazzini

Publications and source records attributed to L Mazzini.

At least 19 recordsLinked to original sources

PubMed2006

SOD1 gene mutations in Italian patients with Sporadic Amyotrophic Lateral Sclerosis (ALS).

Mutations in the SOD1 gene exons and exon/intron boundaries were searched in 66 sporadic and 4 familial Italian ALS cases consecutively referred to our centre from different Italian regions. A mutation was found in three sporadic cases (4.5%): a new nonsense mutation in exon 5 (K136X) in a patient with a rapid and severe disease course and two previously described missense nucleotide substitutions (N65S and A95T) in two patients with a mild disease course. Comparison of the clinical characteristics with previously reported patients carrying the same or similar mutations showed a remarkable genotype-phenotype correlation. No association was found with intronic sequence variations by comparing their frequency in the patients and in 181 matched controls.

Amyotrophic Lateral Sclerosis↗

PubMed2005

The structured assessment of depression in brain-damaged individuals: translation and validation study of the Italian version.

The aim of this study was to translate the structured assessment of depression in brain-damaged individuals (SADBD) questionnaire into the Italian language, validate, and test reliability and validity of the Italian version. Consecutive patients with stroke were screened in the Department of Neurology, Avogadro University in Novara and the Department of Neurorehabilitation, Maugeri Foundation, Veruno, Italy. Thirty patients were included in the study. The internal consistency ranged between 0.78 and 0.87. The intra-rater test-retest reliability was 0.93 for BDIderived items and 0.82 for HRSD-derived items; while the inter-rater test-retest reliability was 0.94 for BDI-derived items and 0.93 for HRSD-derived items. Correlation between the SADBD diagnosis made by the physician and the nurse was 0.51; correlation between caregiver and physician diagnosis was 0.60. The Italian version of the SADBD was demonstrated to be acceptable, reliable and a valid measure of depression in patients with stroke.

Aged↗

PubMed2002

Early symptom progression rate is related to ALS outcome: a prospective population-based study.

OBJECTIVE: To define the factors related to ALS outcome in a population-based, prospective survey. METHODS: The 221 patients (120 men and 101 women) listed in the Piemonte and Valle d'Aosta ALS Register between 1995 and 1996 were enrolled in the study. The patients were prospectively monitored with a standard evaluation form after diagnosis. RESULTS: Mean age at onset was 62.8 (SD = 11.2) years. According to El Escorial diagnostic criteria (EEDC), 112 patients had definite ALS, 85 probable ALS, 18 possible ALS, and six suspected ALS. The median survival time from symptom onset was 915 days (95% CI = 790 to 1065). The median survival time from diagnosis was 580 days (95% CI = 490 to 670). In univariate analysis, outcome was significantly related to age, onset site, EEDC classification, and symptom progression rate (i.e., the rate of decline of muscle strength and bulbar and respiratory function in the 6 months after diagnosis). In the Cox multivariate model, age, progression rate of respiratory, bulbar, and lower limb symptoms, EEDC classification, percutaneous endoscopic gastrostomy, and treatment with riluzole were significantly related to outcome. CONCLUSIONS: The rate of progression of symptoms in early ALS is predictive of disease outcome.

Aged↗

PubMed2002

SOD1 activity and protective factors in familial ALS patients with L84F SOD1 mutation.

METHOD: The activity and amount of SOD1 in erythrocyte lysates and the plasma amino acid content were evaluated in four familial ALS patients bearing the L84F SOD1 mutation (fALS), in an asymptomatic family member with the mutation (L84F(5)), in sporadic ALS patients (sALS) and controls. Three of the fALS patients and the L84F(5) subject were tested once a year for three consecutive years. RESULTS: At the first evaluation SOD1 activity was similar in controls, sALS and fALS; the amount of SOD1 protein was lower (P < 0.01) in fALS. In the subsequent 2 years, 34% and 52% decrease of SOD1 activity was recorded in fALS patients. The plasma amino acid pattern did not differ between controls and sALS, whereas fALS patients displayed high levels of plasma aspartate and glutamate. Aspartate was in the normal range but glutamate was still elevated in the subsequent evaluations. The L84F(5) subject had remarkably low levels of aspartate, glutamate and branched-chain amino acids. CONCLUSIONS: The method of measuring mutant SOD1 amount is indirect but the results are indicative of a reduction of mutant SOD1 taking place during fast-worsening phases of the disease. Since the disease onset of fALS patients is 42.8 +/- 11.3 years and the L84F(5) family member is asymptomatic at the age of 66, low levels of excitotoxic and branched-chain amino acids in plasma may constitute a protective factor against disease development.

Amino Acids↗

PubMed2001

Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results.

Creatine supplementation in humans has been reported to enhance power and strength both in normal subjects and in patients with various neuromuscular diseases. The purpose of this study was to examine the effects of supplementation on exercise performance and maximal voluntary isometric muscular contraction (MVIC) in Amyotrophic Lateral Sclerosis (ALS) patients. We report the results obtained in 28 patients with probable/definite ALS. In each patient we acquired the dynamometric measurement of MVIC in 10 muscle groups of upper and lower limbs and a measure of fatigue by means of an high-intensity intermittent protocol in elbow flexors and knee extensors muscles. All patients completed the protocols at the baseline and after supplementation of 20 g per day for 7 days and after supplementation of 3 g per day for 3 and 6 months. MVIC increased after 7 days of supplementation in 20 patients (70%) in knee extensors and in 15 (53%) of them also in elbow flexors. A statistically significant difference between pre and post-treatment mean values of MVIC was found both in elbow flexors (P<0.05) and knee extensors (p<0.04). The analysis of the slopes of fatigue test showed a statistically significant improvement after 7 days of supplementation in 11 patients (39%) in elbow flexors and in 9 patients (32%) also in knee extensors muscles. During the 6-month follow-up period all the examined parameters showed a linear progressive decline. In conclusion, our preliminary results have demonstrated that supplementation temporary increases maximal isometric power in ALS patients so it may be of potential benefit in situations such as high intensity activity and it can be proposed as a symptomatic treatment.

Administration, Oral↗

PubMed2001

Long-latency auditory-evoked potentials in severe traumatic brain injury.

OBJECTIVE: To detect the effects of different deviant stimuli on long-latency auditory-evoked potentials (LLAEPs) in patients with severe impairment of consciousness from traumatic brain injury (TBI) and to define their prognostic value for late functional outcome. DESIGN: Correlational study on a prospective cohort. SETTING: Brain injury rehabilitation center. PATIENTS: Eleven volunteers and 21 consecutively sampled patients with severe TBI referred to the inpatient intensive rehabilitation unit of primary care in a university-based system. MAIN OUTCOME MEASURES: The LLAEPs recorded with different paradigms; and the Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS), FIMtrade mark instrument, and Neurobehavioural Rating Scale (NBHRS). RESULTS: N100-P150 complex showed high reliability. Patients with good outcomes showed N100 and P150 mean latencies similar to those of unimpaired patients and shorter than patients with unfavorable outcomes. When the deviant stimulus was the patient's name, N100 latency showed high correlations with DRS (p <.007), FIM (p <.01), and NBHRS (p <.009). P250 and P300 showed a low percentage of occurrence with passive paradigms in both patients and controls. Their scores were inversely correlated to the Glasgow Coma Scale (p <.03) and the Innsbruck Coma Scale (p <.003), but no significant correlations were found with functional and behavioral outcomes. Patients with GOS score 1-2 1 year posttrauma had significantly longer latency and lower amplitude of N100 and P150 than those with GOS score 4-5. CONCLUSIONS: LLAEPs can be recorded in patients with severe impairment of consciousness by means of passive paradigms. The use of a stimulus that is relevant for the patient can enhance the accuracy of the test and its relationship with functional outcome.

Adolescent↗

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

Patients with amyotrophic lateral sclerosis and cancer do not differ clinically from patients with sporadic amyotrophic lateral sclerosis.

We examined whether patients with both amyotrophic lateral sclerosis (ALS) and cancer differ from classical ALS patients, and whether motor neuron disease responds to oncological therapy. We analyzed clinical and immunological features of 14 patients (9 men, 5 women; mean age 65.3 years) with pure/definite ALS and cancer. Patients with solid tumor cancer and definite ALS were selected according to the E1 Escorial criteria; cases with ALS plus were excluded. Four patients had breast cancer, three lung adenocarcinoma, and three bowel tumor; hepatocarcinoma, kidney cancer, and mesothelioma were observed in one case each, and in one patient the primary tumor was unidentified. Patients' sera were examined for antinervous system antibodies by means of immunohistochemistry and western blot analysis. Of five patients who underwent surgical therapy, two worsened during the procedure, while the other three had no benefit. The remaining two patients did not improve after chemotherapy and radiotherapy. In none of our cases did the oncological disease progress. Death was a consequence of ALS in all eight patients who died. Median survival was 18 months and did not differ from that of 28 ALS patients matched for age, sex, and onset features (bulbar or spinal). Anti-nervous system antibodies were never detected. We conclude that our group of pure ALS patients with cancer do not significantly differ from patients with classical ALS. They usually die as a consequence of the motor neuron syndrome in the absence of cancer progression. To date we have not observed any response of ALS to antitumor therapy.

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↗

PubMed2000

An overview of H-reflex studies in amyotrophic lateral sclerosis.

H-reflex methods were used to investigate motor neuron excitability and the basic physiology of segmental spinal reflexes. While many studies have been performed using these electrophysiological techniques, in both normal subjects and patients with different neurological diseases, few studies have focused on patients affected by amyotrophic lateral sclerosis (ALS). This article reviews the various electrophysiological techniques which use H-reflex to study the physiology of segmental spinal reflexes in motor neuron diseases. Their possible applications for elucidating pathophysiological mechanisms in ALS and for monitoring the disease during clinical trials are discussed.

Electrophysiology↗

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↗