PubMed Health⌕ Search

Biomedical subjects

L Lacomblez

Publications and source records attributed to L Lacomblez.

At least 37 records · Page 2Linked to original sources
PubMed2000

Bullous pemphigoid and amyotrophic lateral sclerosis: a new clue for understanding the bullous disease?

BACKGROUND: Bullous pemphigoid (BP) occurs in many patients with multiple sclerosis. Isolated cases of BP in patients with other neurological disorders further support a pathogenic association between cutaneous and neurological diseases. Any description of BP in patients with amyotrophic lateral sclerosis is lacking. OBSERVATIONS: We studied a French population of 168 patients with typical amyotrophic lateral sclerosis. Among these, 3 had clinical and histological features of BP. The mean age of the patients was 54 years. None was known to have autoimmune disorders. Results of immunoblot analysis disclosed both anti-BP antigen 1 and anti-BP antigen 2 antibodies. CONCLUSIONS: Bullous pemphigoid seems to be unexpectedly associated with amyotrophic lateral sclerosis. On the basis of the cases presented herein, we discuss the epidemiological significance of the association and the possible interrelation between BP antigen 1 and neurofilaments in the pathogenesis of both disorders.

Aged↗
PubMed2000

Apraxic disturbances in patients with mild to moderate Alzheimer's disease.

Twenty-two patients meeting the NINCDS-ADRDA diagnostic criteria for probable AD were included in the study, along with 10 matched controls. Praxic disturbances were investigated using eight tasks and the results were interpreted according to the neuropsychological model of Roy and Square modified by Rothi et al. (1988) [Aphasiology 21:381-388] which distinguishes a conceptual system concerned with knowledge of the action and function of gestures and a production system that effects gestures in the environment. Disturbance of the production system was found only in 17 patients. Disturbance of the production system was correlated to disturbance of verbal comprehension. The patients scored lower using the left hand than the right. Disturbance of the conceptual system was found in all patients and was not significantly correlated with other cognitive deficits. No significant difference in results was found according to the type of input to the conceptual system (visual or verbal). Deficits in tasks using real objects were correlated to disturbances of both the production and conceptual systems. Most patients performed poorly both in tasks exploring the conceptual system and in those exploring the production system. However, two patients performed badly in production tasks but had performances in the range of controls for conceptual tasks and one patient had the opposite pattern of dissociation. This provides evidence that the production and the conceptual system are independent. Impairment in the ability to perform everyday activities was correlated to disturbances of the conceptual system whereas poor performances in tasks exploring the production system or in using real objects were not.

Activities of Daily Living↗
PubMed2000

Diaphragmatic dysfunction and dyspnoea in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder of unknown origin. Respiratory involvement is the principal cause of death, and dyspnoea is a major source of discomfort. In this study, diaphragm function is described and its relationship with dyspnoea examined in 48 ALS patients (32 male, age 26-80 yrs). The detailed neurological and respiratory evaluation (clinical examination, pulmonary function tests, static pressures, mouth twitch pressures (Pm,t), electromyographic responses to phrenic nerve stimulation and cortical magnetic stimulation were analysed after stratification according to dyspnoea. Dyspnoeic (group I) and nondyspnoeic (group II) patients were similar, bulbar signs being more frequent in group I. Vital capacity was lower in group I (mean+/-SD 67.9+/-22.7 versus 87.9+/-15.6% of the predicted value, p=0.0028), as were maximal static inspiratory pressure (41+/-24 versus 60+/-27% pred, p=0.0242) maximal static inspiratory pressure (18+/-11 versus 32+/-14% pred, p=0.0042), and Pm,t (3.71+/-2.5 versus 7.26+/-3.45 cmH2O, p=0.0011). Abdominal (Abd) paradox and respiratory pulse were frequent in group I (15 of 25 and 14 of 25) but absent or rare in group II (0 of 23 and four of 23) (p<0.05). The electromyographic responses to phrenic and cortical stimulation were generally abnormal in group I but subnormal in group II. Multivariate analysis selected only signs of diaphragm dysfunction (namely, Abd paradox and abnormal electromyographic responses) as significant predictors of dyspnoea. It is concluded that dyspnoea in amyotrophic lateral sclerosis patients should prompt diaphragm function tests.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations?

Autosomal dominant DOPA-responsive dystonia (DRD) is usually caused by mutation in the gene encoding guanosine triphosphate-cyclohydrolase I (GTPCH I). We studied 22 families with a phenotype of levodopa-responsive dystonia by sequencing the six coding exons, the 5'-untranslated region and the exon-intron boundaries of the GTPCH I gene. Eleven heterozygous mutations were identified, including five missense mutations, one splice site mutation, two small deletions and two nonsense mutations, in 12 families that included 27 patients and 13 asymptomatic carriers. Six mutations were new and five had already been reported. Four of the mutations caused truncation of the GTPCH I protein. One family carried a base-pair change in the 5'-untranslated region, not detected in controls, that could be responsible for the phenotype. Three of the remaining 10 families had deletions in the parkin gene on chromosome 6, underlining how difficult it is to distinguish, in some cases, between DRD and parkin mutations. No mutations were identified in seven families. The clinical spectrum extended from the classical DRD phenotype to parkinsonism with levodopa-induced dyskinesias, and included spastic paraplegia as well as the absence of dystonia.

Adolescent↗
PubMed2000

What has changed with riluzole?

Riluzole, after two significant trials, was introduced as the first standard treatment of amyotrophic lateral clerosis (ALS) in the early 95'. After 5 years what has changed in the field of ALS? In the field of basic science, riluzole as an active drug has largely contributed to stimulate the research of the possible role of glutamate in the genesis of ALS. However, the apparent simplicity of the relation between the drug and its mechanisms has to modulated in the light of the negativity of other trials (gabapentin) and the display of other mechanisms of the disease and of the compound. Possible relation with other putative mechanisms of ALS, as oxydative stress or growth factors, could be (and probably are) also involved. In the field of its activity, riluzole has an impact on the survival rate which has been largely debated. Comparison with historical databases are supporting the results of the two initial trials. Other information have been published supporting the probable activity of the drug on the muscle strength decline, a controversial matter. They strengthen the initial data and give additional reasons to use riluzole as a standard treatment of patients. In the field of the daily care, riluzole provided a real and unique hope for ALS sufferers. Even if its activity is not as complete as patients would have expected, it provides a hope for slowing down the rate of evolution and abolishes the myth of "no hope, no cure" which was the leitmotiv of patients care until recently. We have to better define the mode of administration with regard to the clinical status of the patients (respiratory disorders, fatigue, stiffness). In the field of care givers, riluzole was one major factor which provided the basis for national and international collaborations either for therapeutic trials or for standard of care. It made possible large collaborative programs in and among many countries. We do hope that this impulse will continue and be stimulated by additional results both in the field of basic science and clinical research.

Aged↗
PubMed1999

Plasma and cerebrospinal fluid human immunodeficiency virus type-1 (HIV-1) RNA levels in HIV-related cognitive impairment.

Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.

AIDS Dementia Complex↗
PubMed1999

Memory complaints in young and elderly subjects.

OBJECTIVE: To compare the quantitative and qualitative aspects of memory complaints in cognitively normal subjects aged under and above 50 years. SETTING: A memory clinic located in a general hospital in a suburb of Paris offering direct access to subjects. DESIGN: Retrospective review of the files of consecutive patients who attended the clinic during one year. PARTICIPANTS: Subjects were included if (a) they presented with memory complaints, (b) they had normal general cognitive functioning according to age and educational level, (c) they were devoid of present or past history of neurologic or psychiatric disorders. METHODS: Subjects rated the severity of memory complaints as major or minor and filled in a 8-item questionnaire assessing various memory difficulties in everyday life. Relationship between severity of memory complaints and demographic data, memory performance and affective status was compared in 183 non-depressed, non-cognitively impaired healthy adults aged 50 years and over, and in 77 younger adults. RESULTS: Semiologic aspects and correlates of memory complaints were similar in younger and older adults. No close relationship was found between severity of memory complaints and memory performance. In both age groups, memory complaints were strongly related to affective status, mainly to the severity of anxious symptomatology. Memory complaints were related to gender in younger subjects, and to subjective assessment of well-being in older. CONCLUSION: Memory complaints of elderly do not appear basically different from memory complaints of younger subjects. They constitute a complex psychological symptom unlikely to be explained by a few variables and cannot be reduced to the subjective counterpart of memory performance decline associated with age.

Adult↗
PubMed1999

Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type.

OBJECTIVE: To study the unawareness of cognitive deficits in patients with mild dementia of Alzheimer type (DAT). DESIGN: Retrospective study. We surveyed the medical records of outpatients meeting the NINCDS-ADRDA criteria for probable DAT who were able to complete the Cognitive Difficulties Scale (CDS) and had a close informant relative (IR) who could complete the family form of the same questionnaire. SETTING: A department of neurology in a general teaching hospital. SUBJECTS: Eighty-eight patients, aged 73.2+/-8.6 years with a mean MMSE score of 22.5+/-3.2. Fifty-two of the 88 patients had a follow-up examination after a mean interval of 21 months. METHODS: Awareness of cognitive deficits was mainly assessed as the difference between the scores on the CDS completed by the IR and the patient (Index of Unawareness, IU). Two secondary assessments of unawareness were performed: (1) an assessment by the clinician on the basis of the patient's answers to questions probing the awareness of memory deficits; (2) an evaluation by the IR of the frequency of behavioural manifestations of unawareness in everyday life. SPECT was performed in 78 patients to study the relationship between unawareness and the topography of perfusion deficits. RESULTS: Awareness of the cognitive deficits varied greatly between patients, according to the assessment method used and the stage of progression of the disease. Most patients with mild DAT were cognitively aware of their cognitive deficits but failed to appraise their severity and their consequences in everyday life. Decreased awareness was positively correlated with age and perfusion deficits in the frontal regions and negatively with the anxious symptomatology. However, the main correlate of unawareness was apathy. CONCLUSION: The nature of unawareness of cognitive deficits appeared to be more dimensional than categorical. In patients with mild dementia, decreased awareness appeared to be more related to affective disturbances, especially to emotional deficit or apathy, than to cognitive deficits.

Affect↗
PubMed1998

[Drug therapy strategies in Alzheimer's disease].

Treatments in Alzheimer's disease include treatment of cognitive impairment and behavioral manifestations (agitation, depression, anxiety, delusions). It should be noted that many non cognitive behaviors may have some relations to underlying cognitive impairment. In the not too distant future, physicians can expect to see a variety of medications and controversies over the benefits of slowing symptoms with cholinergic therapeutics approved for clinical use and (or) preventing progression of Alzheimer's disease assessed in clinical trials will emerge.

Aggression↗
PubMed1998

High-performance liquid chromatography with ultraviolet and fluorimetric detection for the simultaneous determination of tacrine, nimodipine, and their respective metabolites in the plasma of patients with Alzheimer disease.

A new high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of tacrine (THA), nimodipine, and their three metabolites (MI, MII, and MIII) using a 1-ml plasma sample volume. A liquid-liquid extraction procedure was coupled with a reverse-phase HPLC separation. Quantification was performed by fluorometric detection for THA and metabolites and by ultraviolet detection for nimodipine and metabolites. Peak-height ratios were linear across the ranges 0.5 to 100 micro/l for THA and its three metabolites; 2 to 500 microg/l for nimodipine, MII, and MIII; and 4 to 500 microg/l for MI. Correlation coefficients were better than 0.998 for all compounds. Accuracy and precision were less than 12% for the entire concentration range for each substance. This method is sensitive and selective. Analysis of plasma samples collected from patients with Alzheimer disease demonstrated that the assay is suitable for clinical and pharmacokinetic trials including drug-drug interactions studies.

Alzheimer Disease↗
PubMed1998

[Cognitive disorders in AIDS: clinical, virological and neuroradiological features].

HIV-associated neurocognitive disorders are mainly reported during the late stages of the disease, in deeply immunosuppressed patients Clinically, they present as a subcortical cognitive impairment, dominated by reduced psychomotor speed and memory deficit. Encephalic magnetic resonance imaging shows in most cases a diffuse leucoencephalopathy, and there is often a poor correlation between clinical status and neuroradiological findings. The diagnostic and prognostic value of HIV load in blood and cerebrospinal fluid is currently under investigation. Finally, the efficacy of new antiretroviral drugs on HIV dementia remains uncertain.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive disease with no effective treatment. In an initial study, riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients. We have carried out a double-blind, placebo-controlled, multicentre study to confirm those findings and to assess drug efficacy at different doses. METHODS: 959 patients with clinically probable or definite ALS of less than 5 years' duration were randomly assigned treatment with placebo or 50 mg, 100 mg, or 200 mg riluzole daily; randomisation was stratified by centre and site of disease onset (bulbar or limb). The primary outcome was survival without a tracheostomy. Secondary outcomes were rates of change in functional measures (muscle strength, functional status, respiratory function, patient's assessments of fasciculation, cramps, stiffness, and tiredness). The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat. Drug-effect on survival was assessed before (log-rank test) and after adjustment for known prognostic factors (Cox's model). FINDINGS: At the end of the study, after median follow-up of 18 months, 122 (50.4%) placebo-treated patients and 134 (56.8%) of those who received 100 mg/day riluzole were alive without tracheostomy (unadjusted risk 0.79, p = 0.076; adjusted risk 0.65, p = 0.002). In the groups receiving 50 mg and 200 mg riluzole daily, 131 (55.3%) and 141 (57.8%) patients were alive without tracheostomy (relative to placebo 50 mg adjusted risk 0.76, p = 0.04; 200 mg 0.61, p = 0.0004). There was a significant inverse dose response in risk of death. No functional scale discriminated between the treatment groups. The most common adverse reactions were asthenia, dizziness, gastrointestinal disorders, and rises in liver enzyme activities; they were commonest with the 200 mg dose. INTERPRETATION: Overall, efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio. This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Sexual behavioral changes in Alzheimer disease.

The frequency and correlates of sexual behavioral changes in Alzheimer disease (AD) were assessed in two studies. In the first study, we reviewed the medical records of 135 consecutive community-living patients who fit the criteria of the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association for probable or possible AD, and we asked spouses to complete a questionnaire that included two questions about sexual activity. Indifference to sexual activity was reported by 70% of the spouses, and sexual behavioral modifications were reported by 50%. No correlation was found between sexual changes and the general characteristics of the patients, the severity of the disease, or depressive symptomatology. Sexual changes were correlated to the severity of behavioral and mood disorders, mainly to a reduction of activity and emotional deficit. Seventy-seven of the patients had a second examination after an interval of 18.9 +/- 9.9 months. The links between sexual changes and the other variables were similar to those found by the first examination. In the second study, a questionnaire was sent by mail to the spouses of 100 patients. No relationship was found between sexual changes and the severity of cognitive deficits, previous sexual agreement, age, or gender. Sexual changes were considered a factor of maladjustment for the couple by 46% of the spouses.

Aged↗
PubMed1996

A special form of cerebral lacunae: expanding lacunae.

The case of a 42 year old man with headache, blurred vision, and diplopia allowed the description of a particular form of cerebral lacunae-that is, expanding lacunae. Brain MRI showed hydrocephalus and multiple lesions in the thalamomesencephalic region. The radiological features of these lesions were similar to the histological brain coronal section of a case reported in 1983 in which expanding lacunae were related to a dilatation of the perivascular spaces and a focal segmental necrotising angiitis. The role of the lymphatic drainage of the brain is discussed to explain the dilatation of the perivascular spaces. The hypothesis of a hydrodynamic factor being responsible for the expanding character of the lacunae was suggested by the location of the lesions and the influence of various clinical events on the symptomatology.

Adult↗
PubMed1996

A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II.

ALS is a progressive motor neuron disease with no effective treatment. The anti-excitotoxic drug riluzole (100 mg/day) has been shown to decrease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 ALS outpatients treated for up to 18 months. Primary efficacy criterion was survival and the effect of treatment was analyzed before (Wilcoxon and log rank tests) and after adjustment on prognostic factors (Cox model). Secondary efficacy criterion was disease progression assessed through change in functional measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank test), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100-mg dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirms the therapeutic effect of riluzole in a large representative ALS sample, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.

Amyotrophic Lateral Sclerosis↗