Biomedical subjects

L Lacomblez

Publications and source records attributed to L Lacomblez.

At least 19 recordsLinked to original sources

PubMed2006

Pentoxifylline in ALS: a double-blind, randomized, multicenter, placebo-controlled trial.

OBJECTIVE: To assess the efficacy and safety of pentoxifylline, a US Food and Drug Administration-approved drug, in patients with ALS treated with riluzole. METHODS: The authors conducted a double-blind, randomized, placebo-controlled, multicenter trial. Four hundred patients with probable or definite ALS and vital capacity less than 100% were randomly assigned to treatment with placebo or 1.2 g pentoxifylline daily. The primary outcome was death. Secondary outcomes were rates of deterioration of ALS Functional Rating Scale-Respiratory and muscle strength. The primary intention-to-treat analysis was the survival comparison of drug vs placebo, assessed before (log-rank test) and after adjustment (Cox model) for predefined prognostic factors. RESULTS: At the end of the study, after 547 days of follow-up, 103 patients (51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02). In contrast, analysis of secondary outcome functional variables did not show the same negative effect of the drug. The most common adverse reactions were nausea, dysphagia, and flushing, all reversible after stopping the drug. CONCLUSIONS: Pentoxifylline is not beneficial in ALS and should be avoided in patients treated with riluzole. The discrepancy between survival and measures of functional changes urges caution in equating these end points in phase III trials, and suggests that both survival and function should be used in phase III trials.

Adolescent↗

PubMed2006

[Measurement instruments and assessment scales for frontotemporal dementia].

In frontotemporal dementia (FTD), evaluation scales and measurement instruments are less codified than in Alzheimer's disease. Some nonspecific scales are available, two of which are very useful for early diagnose of the disease: Lebert and Pasquier's Frontotemporal Behavioral Scale (FBS) to assess behavioral disturbances and Dubois's Frontal Assessment Battery (FAB) to assess executive ability. However, these scales do not contain enough items to follow up FTD. The main scale used to follow up the disease is the Neuropsychiatric Inventory (NPI). The Frontal Behavioural Inventory (Kertesz) seems to be interesting, but has not yet been validated in France. The Mattis Dementia Rating Scale, not specific for FTD, is used to assess the cognitive rate. The activities of daily living scales and caregiver burden are not well known in FTD.

Alzheimer Disease↗

PubMed2006

[Amyotrophic lateral sclerosis: cognitive and behavioral evaluation].

Cognitive impairment in nondemented ALS patients has been demonstrated, although its incidence remains to be determined. FTD is the most frequently form of dementia in ALS. The clinical profile of patients with dementia or mild cognitive deficit evokes neuropsychological deficits and behavioural changes resulting from executive dysfunction. The psychometric evaluation, centred on executive disturbances, goes with behavioural scales in order to accurately appreciate the repercussion of cognitive and behavioural changes on daily life.

Amyotrophic Lateral Sclerosis↗

PubMed2005

Prognostic factors for survival in amyotrophic lateral sclerosis patients treated with riluzole.

The objective of this study was to identify prognostic factors for survival in amyotrophic lateral sclerosis from a large prospective observational study performed in France. The study included a cohort of 2069 patients fulfilling broad entry criteria treated with riluzole. Over 100 demographic, biological, clinical and quality-of-life variables were monitored and assessed for their effect on survival. Patients were randomized post hoc into two groups: one group (two-thirds of the patients) to generate the prognostic models and one group (one-third of the patients) to validate the resulting models. Thirteen variables were found to affect survival independently and were used to construct a survival prediction score, RL401. These included age, disease duration, slow vital capacity, intensity of tiredness (visual analogue scale), number of body levels with spasticity, atrophy and/or fasciculations, cough, distal muscle strength, household income, depression and two biological parameters, plasma creatinine levels and neutrophil counts. A simplified score, RL401S, was constructed, designed to be easy to use and interpret. The predictive powers of the two scores were similar.

Adult↗

PubMed2002

Parkinson's disease and sleepiness: an integral part of PD.

OBJECTIVE: To investigate the potential causes of excessive daytime sleepiness in patients with PD-poor sleep quality, abnormal sleep-wakefulness control, and treatment with dopaminergic agents. METHODS: The authors performed night-time polysomnography and daytime multiple sleep latency tests in 54 consecutive levodopa-treated patients with PD referred for sleepiness, 27 of whom were also receiving dopaminergic agonists. RESULTS: Sleep latency was 6.3 +/- 0.6 minutes (normal >8 minutes), and the Epworth Sleepiness score was 14.3 +/- 4.1 (normal <10). A narcolepsy-like phenotype (> or = 2 sleep-onset REM periods) was found in 39% of the patients, who were sleepier (4.6 +/- 0.9 minutes) than the other 61% of patients (7.4 +/- 0.7 minutes). Periodic leg movement syndromes were rare (15%, range 16 to 43/h), but obstructive sleep apnea-hypopnea syndromes were frequent (20% of patients had an apnea-hypopnea index >15/h; range 15.1 to 50.0). Severity of sleepiness was weakly correlated with Epworth Sleepiness score (r = -0.34) and daily dose of levodopa (r = 0.30) but not with dopamine-agonist treatment, age, disease duration, parkinsonian motor disability, total sleep time, periodic leg movement, apnea-hypopnea, or arousal indices. CONCLUSIONS: In patients with PD preselected for sleepiness, severity of sleepiness was not dependent on nocturnal sleep abnormalities, motor and cognitive impairment, or antiparkinsonian treatment. The results suggest that sleepiness-sudden onset of sleep-does not result from pharmacotherapy but is related to the pathology of PD.

Aged↗

PubMed2002

APOE: a potential marker of disease progression in ALS.

Although documented in AD, the role of APOE remains unclear in ALS. APOE phenotype and plasma levels were measured in 403 patients with ALS and were correlated with clinical parameters and survival time. No correlations were observed between the APOE phenotype and these variables. In contrast, APOE plasma levels were correlated with both rate of deterioration and survival time and appeared to be an important risk factor for decreased survival time with a relative risk of 0.647 (95% CI: 0.465 to 0.901; p = 0.01).

Adult↗

PubMed2002

A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis.

Treatment with the neuroprotective drug riluzole has previously been shown to increase the probability of survival in patients with amyotrophic lateral sclerosis. This report describes a placebo-controlled, double-blind randomised clinical trial of riluzole carried out in ALS patients with advanced stage disease or aged over 75 years. The primary objective was to enable access to treatment to patients excluded from the pivotal trial which was run in parallel. Another goal was to assess the safety of riluzole in patients with advanced-stage disease. One hundred and sixty-eight patients were included, randomised to either riluzole 50 mg b. i. d. or to placebo, and treated for eighteen months. Riluzole was well-tolerated in this patient population, and the adverse events observed were similar in nature and frequency to those observed in previously published clinical trials in patients included in pivotal trials. The study could not include enough patients to reach adequate power to detect differences in survival between the two treatment groups, and no such difference was in fact observed. In conclusion, riluzole is well-tolerated in ALS patients with advanced stage disease.

Age Factors↗

PubMed2002

Long-term safety of riluzole in amyotrophic lateral sclerosis.

OBJECTIVES: This international, open-label, multicentre extension of riluzole pivotal studies was designed to assess the long-term safety of riluzole in the treatment of amyotrophic lateral sclerosis (ALS). METHOD: The studies were carried out at 31 different centres, 23 in Europe and eight in North America. 516 patients with diagnosed probable or definite ALS and who had participated previously in one of two international multicentre randomized double-blind placebo-controlled, parallel-group trials, were enrolled in the extensions. 58 of these patients had taken part in a randomized phase II trial (placebo or riluzole 100 mg/day) and 458 in a randomized, dose-ranging phase III trial (placebo or riluzole, 50, 100 or 200 mg/day). All participants in the open-label continuation received 100 mg/day of riluzole (50 mg b.i.d.) RESULTS: At the end of the open-label study, the average exposure time of the patients to riluzole was 28.7 +/- 14.4 months, with a maximum exposure time of 81 months. Most of the adverse events recorded reflected the progression of ALS, in particular the deterioration of the respiratory status of the patients. No particular adverse event, or frequency of adverse event, appeared to be related to the dose level of the previous double-blind riluzole treatment. Nor were any adverse events associated with the switch-over from double-blind placebo to open-label riluzole. CONCLUSIONS: This open-label extension study reinforces and extends the results of the preceding double-blind trials regarding the safety of riluzole and shows that the drug is well tolerated for long periods of up to almost 7 years.

Adult↗

PubMed2002

[Nocturnal oxymetry in patients with amyotrophic lateral sclerosis: role in predicting survival].

Death is the most important end point along the course of amyotrophic lateral sclerosis (ALS). It is commonly attributed to a respiratory failure in relation with a restrictive respiratory disorder. However, in clinical practice, it is frequent to observe that death has not direct relation with the values of the respiratory function, at least measured with vital capacity. It is also frequent that relatives report sudden death during nocturnal sleep. All these features raised the question of the possible relation between death and nocturnal oxymetry in ALS patients. In a prospective study, we studied 69 ALS patients. We recorded demographic data, clinical parameters as manual muscle testing and functional scales, various parameters of oxymetry measured by pulse oxymetry recorded during night, slow vital capacity and survival time. There is a strong correlation between survival time measured by Kaplan Meier curves and log rank and the mean nocturnal saturation. We determined 93 mmHg as a threshold value. Below this threshold, mean survival time was 7.5+/-1.6 months and above it was equal to 18.5+/-1.5; relative risk was 3.31. These data confirm the importance of nocturnal oxymetry on survival in ALS patients both in clinical practice and in view of therapeutic trials.

Aged↗

PubMed2002

[Perturbations of activities of daily living in Alzheimer's disease. A study of 172 patients with the using a questionnaire completed by caregivers].

Functional decline was studied retrospectively in 172 patients with Alzheimer's disease, AD, using a questionnaire completed by the caregiver. Ninety-nine of these patients had a second assessment after a follow-up of 22.1 +/- 13.8 months. The questionnaire included French versions of the Physical Self-Maintenance Activities, ADL, and of the Instrumental Activities of Daily Living, IADL (Lawton and Brody, 1969). A third part assessing social activities, SADL, was derived from Katz and Lyerly (1963). The earliest and most frequent perturbations in early AD involved SADL, mainly a reduction in social and leisure activities, appearing in subjects with a MMSE score > 26. The earliest decline in IADL involved the ability for handling finances, odd jobs-sewing, and shopping, which were more frequently perturbed than ability to use telephone, traveling or handling medication. The most interesting results of our study were as follows. Functional decline did not allow to distinguish patients with early AD (MMSE score > or = 24) from those with mild dementia (MMSE score 20-23). Mild perturbations of ADL, mainly dressing and walking, were observed in early AD. There was a good correlation, but no parallelism, between functional decline and cognitive decline. Disturbances in ADL and SADL significantly differed only between patients with severe dementia (MMSE < 10) and those of the three other groups. Apathy appeared to be a stronger predictor of functional decline than the score on the MMSE in the early stages of AD. There was a great variability among the patients regarding the type of functional decline as well as the rate of decline. Functional decline is very useful for detecting early AD. However, its specificity seems to be low and the diagnosis should be supported by cognitive assessment.

Activities of Daily Living↗

PubMed2001

Primary lateral sclerosis: further clarification.

Primary lateral sclerosis (PLS) has been defined as a rare. Non-hereditary disease characterized by progressive spinobulbar spasticity, related to the exclusive involvement of precentral pyramidal neurons, with secondary pyramidal tract degeneration and a preservation of anterior horn motor neurons, the latter allowing PLS to be distinguish from amyotrophic lateral sclerosis (ALS). However, a clear distinction between the two diseases remains a subject of debate. With this in mind, we assessed patients with meeting the previously published criteria for PLS in a prospective, longitudinal study. At regular intervals, we analyzed various clinical and electrophysiological parameters in nine patients with a diagnosis of PLS. We made a deltoid muscle biopsy and PET study.Our results provide evidence that degeneration in PLS is not restricted to the upper motor neurons but also affects the lower motor neurons. The distinction between ALS and PLS is related to the degree and stability of lower motor neuron involvement. In view of the similarities with ALS, we consider that PLS may represent a slowly progressive syndrome closely related to this disease.

Adult↗

PubMed2001

Clinical and spectroscopic improvement in HIV-associated cognitive impairment.

To assess the impact of highly active antiretroviral therapy (HAART) on AIDS-associated cognitive impairment, 22 patients with AIDS with (n = 11) and without (n = 11) cognitive deficit were evaluated clinically and by MRS every 3 months for 9 months. Nineteen patients were on HAART at study entry, 21 after 2 months. Cognitively impaired patients presented with a subcorticofrontal deficit and decreased N-acetyl-aspartate in frontal white matter. These clinical and metabolic abnormalities reversed partially on HAART, whereas they remained within normal limits in cognitively unimpaired patients.

AIDS Dementia Complex↗

PubMed2001

Case report of pallido-pyramidal disease with supplementary motor area involvement.

An C-flumazenil positron emission tomography (PET) study in a patient with pallido-pyramidal disease revealed a marked decrease in benzodiazepine-receptor density in the precentral gyrus cortex and the mesial frontal cortex. We suggest that, in addition to dysfunction of basal ganglia-dependent systems, degeneration of the supplementary motor area could also be involved in the patient's bradykinesia.

Adult↗

PubMed2001

Does primary lateral sclerosis exist? A study of 20 patients and a review of the literature.

The question of whether primary lateral sclerosis (PLS) is a nosological entity distinct from amyotrophic lateral sclerosis (ALS) has been the subject of controversy since it was first described in the nineteenth century. PLS has been defined as a rare, non-hereditary disease characterized by progressive spinobulbar spasticity, related to the selective loss of precentral pyramidal neurones, with secondary pyramidal tract degeneration and preservation of anterior horn motor neurones. In the recent clinical literature, the frontier between ALS and neurodegenerative disease remains poorly defined. We studied 20 patients with a diagnosis of PLS. We carried out a variety of tests in order to determine the presence of a more diffuse neurodegenerative process. We also performed a longitudinal electrophysiological evaluation. Our clinical, electrophysiological and pathological investigations provide evidence that the disease has a heterogeneous clinical presentation and that degeneration is not restricted to the central motor system.

Adult↗

PubMed2001

Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontané; FFAACS).

BACKGROUND: A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation. OBJECTIVE: Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin (100 mg) in patients with high-risk atrial fibrillation. METHODS: A multicenter, placebo-controlled, double-blind, randomized trial was conducted at 49 investigating centers in France. Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension, a recent episode of heart failure or decreased left ventricular function were included in the study. Patients were treated with fluindione plus placebo (i.e. anticoagulant alone) or fluindione plus aspirin (i.e. combination therapy), with an international normalized ratio target of between 2 and 2.6. The combined primary endpoint was stroke (ischemic or hemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. The secondary endpoint was the incidence of hemorrhagic complications. RESULTS: The 157 participants (average age 74 years; 52% women; 42% with paroxysmal atrial fibrillation) were followed for an average of 0.84 years. Three nonfatal thromboembolic events were observed (1 in the anticoagulation group, 2 in the combination group) and 6 patients died (3 in the anticoagulation group, 3 in the combination group), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe hemorrhagic complications (1 in the anticoagulation group, 2 in the combination group). Nonfatal hemorrhagic complications occurred more often in the combination group (n = 10, 13.1%) compared to the anticoagulation group (n = 1, 1.2%) (p = 0.003). CONCLUSION: The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients. The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events.

Administration, Oral↗

PubMed2001

[Noncognitive symptoms in Alzheimer's disease. A study of 150 community-dwelling patients using a questionnaire completed by the caregiver].

UNLABELLED: We studied the noncognitive symptoms in 150 community-dwelling Alzheimer's patients using a questionnaire completed by the caregiver, the Echelle Psychopathologique de la Démence de Type Alzheimer, EPDTA (Psychopathologic Scale of Dementia of Alzheimer Type). EPDTA is a 44-item questionnaire derived from the BEHAVE-AD and the Depressive Mood Scale, covering many aspects of the behavior, affective and psychiatric disturbances. Each item is rated from 0 (never observed) to 6 (most of the time). Frequency (percentage of symptom present) and severity (mean score when the symptom was present) were assessed for each item. The cognitive status and severity of the disease were assessed by the MMSE and two scales completed by the caregiver assessing the Activities of Daily Living scale (ADL) and the Cognitive Difficulties Scale (CDS). Noncognitive symptoms were present in all patients but remained moderate in severity. A principal component analysis of the 33 items exploring the affective disturbances showed seven clinically relevant factors: apathy, anxiety, anosognosia-irritability, euphoria, dysphoria, emotional incontinence and agitation. The most frequent noncognitive symptoms were the affective disturbances, especially apathy, and the sexual behavioural disturbances. No correlation were found between the overall severity of behavioural disturbances and cognitive status, duration of the disease nor demographic variables. However, a slight negative correlation was found between scores on apathy and on the MMSE. A second evaluation was performed in 59 patients after a mean follow-up of 18,2 months. The patients showed a progression of the disease evidenced by the scores on the MMSE, ADL and CDS scales. However, the frequency and severity of the noncognitive symptoms remained identical except for eating disorders, psychotic symptoms and agitation which were more frequent at the second examination and negatively correlated with the MMSE score. Most patients showed affective disturbances and scored high for apathy and anxiety-emotional incontinence dimensions. Like in a previous study, we found a double dissociation between these two dimensions in some patients, suggesting that they depend from different mechanisms. Agressivity, mostly verbal, was found in three quarters of the patients and was correlated to apathy, anosognosia and psychotic symptoms. CONCLUSION: The relationship between noncognitive manifestations and cognitive deficits in AD is not clear, suggesting that they depend from different biological and psychological mechanisms. Various dimensions may be described in the behavioural disturbances but their relationship with hypothetical biological mechanisms remains difficult. Our study stresses the importance of apathy, which was corelated with various noncognitive psychobehavioral manifestations in AD patients.

Affect↗

PubMed2000

[Diagnosis of Alzheimer's disease in the predementia phase: possibilities and benefits].

THE PREDEMENTIA PHASE: Alzheimer's disease is a progressive condition. The state of dementia defined by international criteria only appears after brain lesions have become important. Dementia is defined by the presence of multiple cognitive deficits and restricted independence. Prior to this, the patient experiences isolated memory impairment, either alone or associated with behavior changes which have little effect on his/her independence (predementia phase). The goal of diagnosis at this time is to reduce psychic suffering for the patient and family as well as the social cost of the disease by retarding the onset of dementia. DIAGNOSIS IN THE PREDEMENTIA PHASE: Diagnosis is based on i) evidence of an alteration of the internal temporal regions leading to memory deficit due to impaired memorization processes. There is an elective impairment of recent memory rapidly leading to difficulties perceived by the family and which diminish performance in complex activities of daily living. Recall processes lose their efficacy. ii) Tomoscintigraphic evidence of a perfusion defect or structural imaging evidence of atrophy of the hippocampal regions. iii) Presence of associated psychoaffective changes (apathy). When these three elements are found, the diagnosis of Alzheimer's disease is highly probable and should be made. If all three are not present, it would be advisable to diagnose what is termed "mild cognitive impairment", defined as a group of subjects with a high risk of progressing to dementia in a few years. PATIENT CARE AT THIS PHASE: Neuroprotective drugs may be prescribed in association with psychological and cognitive support within the framework of regular follow-up.

Aged↗

PubMed2000

Blood oxidative stress in amyotrophic lateral sclerosis.

It has been suggested that amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder resulting in motor neuron death, is associated with oxidative damage induced by free radicals. Our study aimed to get an assessment of the blood oxidative stress status in a population of 167 ALS patients (aged 59+/-13 years), treated or not with riluzole, compared with 62 age-matched healthy control subjects (aged 60+/-11 years) simultaneously included in the study. We determined the level of plasma lipid peroxidation (thiobarbituric acid-reactive substances, TBARS); the status of the major lipophilic plasma antioxidant defenses (vitamin E, vitamin A and beta-carotene); the activities of erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and of plasma and erythrocyte glutathione peroxidase (GSH-Px). Plasma selenium was also determined as a trace element essential to the activity of the GSH-Px. In comparison with controls, we observed in ALS patients (mean+/-S.D.) significantly higher TBARS values (ALS=1.34+/-0.28 micromol/l; controls=1.11+/-0. 20 micromol/l) and a significant enhancement of the erythrocyte SOD activity (ALS=710+/-114 U/g Hb; controls=667+/-93 U/g Hb). No differences were observed for selenium level, GSH-Px activity, plasma vitamin E, beta-carotene and vitamin A concentrations. These data confirm the presence of an oxidative stress in blood of ALS patients. The elevated plasma TBARS, without any deficiency in plasma lipophilic antioxidants such as vitamin E, vitamin A and beta-carotene, suggest an enhancement in the production of free radicals. No correlation was found in our study between the level of any of the blood oxidative stress markers and the disease duration. Comparison between patients treated or not with riluzole did not display any modification of the plasma TBARS concentration, but we observed a slight decrease of erythrocyte SOD activity in treated patients (treated=705+/-113 U/g Hb; not treated=725+/-118 U/g Hb), suggesting a possible activity of riluzole on the oxygenated free radical production.

Aged↗