Biomedical subjects

B Brochet

Publications and source records attributed to B Brochet.

At least 19 recordsLinked to original sources

PubMed2000

One year follow up study of primary and transitional progressive multiple sclerosis.

OBJECTIVE: To document clinical and magnetic resonance imaging (MRI) characteristics of a large cohort of primary and transitional progressive multiple sclerosis (PP and TP MS) patients over one year. INTRODUCTION: Patients with PP or TP MS have been shown to have low brain T2 and T1 lesion loads and slow rates of new lesion formation with minimal gadolinium enhancement, despite their accumulating disability. Serial evaluation of these patients is needed to elucidate the pathological processes responsible for disease progression and to identify clinical and MRI measures which can monitor these processes in treatment trials. METHOD: Patients, recruited from six European centres, underwent two assessments on the expanded disability status scale (EDSS) and MRI of the brain and spinal cord, 1 year apart. RESULTS: Of the 167 patients studied (137 with PP MS and 30 with TP MS), 41 (25%; 35 PP and six TP) showed a one step increase in the EDSS. The mean number of new brain lesions seen was 0.88 in the PP group and 0.47 in the TP MS group. Both groups demonstrated change in T2 lesion load over the year (p< or =0.002), with median percentage changes of 7.3% in the PP group and 10. 8% in the TP MS group. The PP group also showed a significant change in T1 load (p< 0.001, median change 12.6%). The number of new cord lesions seen was small (mean of 0.14 in the PP group and no new cord lesions in the TP group). Both groups demonstrated a decrease in cord cross sectional area (p< 0.001, median changes; PP 3.8%, TP 4. 9%), but only the PP group showed evidence of significant brain atrophy (p<0.001, 0.95%). CONCLUSION: Although the monitoring of disease progression in this patient group is difficult, this study demonstrates changes in both lesion load and atrophy, which, if shown to correlate with clinical change over a longer time will facilitate therapeutic trial design.

Atrophy↗

PubMed2000

Experimental allergic encephalomyelitis animal models for analyzing features of multiple sclerosis.

Various animal models with experimental allergic encephalomyelitis (EAE) have been developed applying immunologic, virologic, toxic and traumatic parameters in order to understand features of multiple sclerosis (MS). The main simulating aspects of the EAE models and the precautions for their interpretation in determining differences and common features between EAE and MS are presented. In view of an early diagnosis of CNS lesions in human, we present with particular interest the application of human-related technologies, such as MR imaging techniques, and the development of new markers to follow the dynamic of CNS lesions in vivo in EAE animal models.

Animals↗

PubMed2000

Diagnostic criteria for primary progressive multiple sclerosis: a position paper.

The unique clinical characteristics of primary progressive multiple sclerosis (PPMS) pose particular diagnostic difficulties, both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS, which is not adequately addressed by current diagnostic criteria. This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS. (We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made.) Three levels of diagnostic certainty have been defined-definite, probable, and possible--based on clinical findings, abnormal cerebrospinal fluid, abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord, and evoked potentials. In definite PPMS, evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required: (1) nine brain lesions, (2) two spinal cord lesions, or (3) four to eight brain lesions and one spinal cord lesion. Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS: 64% fulfilled the criteria for definite PPMS, 35% for probable PPMS, and only 1% for possible PPMS. These criteria now require prospective validation in a cohort of newly diagnosed patients and by postmortem examination.

Diagnosis, Differential↗

PubMed1999

[Diagnosis of multiple sclerosis].

Diagnosis of multiple sclerosis is based on detection of a disseminated demyelinating inflammatory disorder of the central nervous system with a progressive course and(or) exacerbations. Essential data is obtained by study of the cerebrospinal fluid and magnetic resonance imaging. Other causes of white matter disorders (vascular, compressive or tumoral) are less important in differential diagnosis than are other monophasic demyelinating inflammatory disorders, such as acute disseminated encephalomyelitis, idiopathic optic neuritis and idiopathic myelitis.

Central Nervous System↗

PubMed1999

Primary and transitional progressive MS: a clinical and MRI cross-sectional study.

BACKGROUND: Ten percent of patients with MS have a progressive course from onset with no history of relapses or remissions. A smaller subgroup follow a similar progressive course but have a single relapse at some point (transitional progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials. OBJECTIVE: To document the clinical and MRI characteristics of a large cohort of progressive patients, including 158 with primary progressive (PP) MS and 33 with TPMS. Data from a small reference group of 20 patients with secondary progressive (SP) MS are also presented for reference. METHODS: Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the brain and spinal cord. RESULTS: The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group. The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years). On MRI the PP group had lower mean brain T2 and T1 hypointensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015). The SP and TP cohorts had significantly more T2-weighted lesions in the spinal cord than the PP patients, and the SP cohort had the greatest degree of atrophy. There was a correlation in the PP and TP patients between EDSS score and brain and spinal cord atrophy (r = 0.3, 0.2, p < or = 0.006) but not with brain lesion load. The PP and TP patients who presented with spinal cord pathology had significantly lower brain T2 and T1 lesion loads than those with non-spinal cord presentations (p = 0.002). CONCLUSIONS: The monitoring of disease progression in PPMS is difficult, although measures of atrophy correlate with the EDSS and appear most promising. This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.

Adult↗

PubMed1999

In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance.

Cell-specific imaging has been proposed to increase the potential of magnetic resonance imaging (MRI) for tissue analysis. The hypothezis of the present work was that following intravenous injection of ultra-small particle iron oxide, a contrast agent that accumulates in mononuclear phagocyte cells, macrophages with iron burden would be detectable by MRI within the central nervous system at sites of inflammatory cellular activity. In experimental autoimmune encephalomyelitis in Lewis rats (in which intense macrophage activity results from both hematogenous macrophages and activated microglia), lesions have been seen by MRI as low signal intensities related to magnetic susceptibility effects induced by iron particles. Electron microscopy has revealed the presence of such particles within the cytoplasm of cells that had the morphological aspect of macrophages. Macrophage activity imaging might increase MRI capability with regard to the in vivo pathophysiological aspects of central nervous system (CNS) diseases and might help in therapeutic trials in the numerous CNS diseases in which macrophages are involved.

Animals↗

PubMed1999

Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates.

The relative rarity of primary progressive (PP) and transitional progressive (TP) multiple sclerosis has meant that little documentation of cognitive function in such patients is currently available. The aim of this study was to investigate the cognitive skills of patients with PP and TP multiple sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters. Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same cognitive tasks as the patient group. The neuropsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of depression. Patients also underwent T1- and T2-weighted brain MRI. These patients were taken from a larger cohort (158 PP, 33 TP) in whom it had been demonstrated that the re were no significant differences between the mean scores of the PP and TP groups on any of the cognitive variables. The 63 patients were therefore taken as one group for comparison with the healthy controls. These patients performed significantly worse than the controls in tests of verbal memory, attention, verbal fluency and spatial reasoning. An impairment index was constructed and applied to the patient data. This correlated modestly with T2-lesion load (r = 0.45, P = 0.01), T1-hypointensity load (r = 0.45, P = 0.01) and cerebral volume (r = -0.35, P = 0.01). Thus, PP and TP multiple sclerosis patients demonstrate significant cognitive dysfunction when compared with matched healthy controls. The relationship between this impairment and MRI parameters is moderate, suggesting that cognitive dysfunction in PP and TP multiple sclerosis has a complex and multifactorial aetiology, which is not adequately explained by pathology as demonstrated on conventional MRI.

Adult↗

PubMed1999

Pathological correlates of magnetization transfer imaging abnormalities in animal models and humans with multiple sclerosis.

Magnetization transfer imaging is used in multiple sclerosis because of its sensitivity to tissue destruction; in particular, to demyelination. This sensitivity was established in animal models and human diseases. Studies in experimental auto-immune encephalomyelitis have shown that the magnetization transfer ratio is slightly decreased in inflammatory lesions of the central nervous system white matter without demyelination but is more decreased in demyelinated lesions according to the level of myelin loss. Toxic demyelination studies and human studies in progressive multifocal leukoencephalopathy have confirmed that pure moderate to severe demyelination can be monitored by this technique. Axon loss can also contribute to the decrease of this ratio. Magnetization transfer is a validated technique to assess tissue destruction in central nervous system white matter diseases.

Animals↗

PubMed1998

The effects of capsaicin on the neurogenic hyperreflexic detrusor. A double blind placebo controlled study in patients with spinal cord disease. Preliminary results.

PURPOSE: Several recent open studies have provided encouraging results as to the efficacy of intravesical installations of capsaicin for neurogenic hyperreflectivity. The present trial was performed to verify these results under controlled conditions. Intravesical installation of capsaicin represents a new therapeutic hope for the treatment of the neurogenic hyperrelfexic bladder. METHOD: This randomized, double-blind study compared the results of the intravesical installation of 30 mg capsaicin in 100 ml of 30% alcohol (experimental group) with those of installing 100 ml 30% alcohol alone (control group). On day 0 and day 30, urodynamic and biopsic examinations were performed in all subjects of each group. PATIENTS: All the subjects included in the study had a functionally disabling form of neurogenic hyperreflexic bladder resistant to the usual therapies. Cystoscopy and retrograde cystography were performed to exclude any patient who presented with a tumor-like lesion or had vesicoureteral reflux. RESULTS: Twelve paraplegic of tetraplegic subjects, seven women and five men whose average age was 46, were included. Eight had multiple sclerosis, and four had sustained a traumatic spinal cord injury. The patients were randomly separated into two groups of six. Initially, there was no clinical or urodynamic differences in these groups. Installation immediately triggered side effects and during the first 7 days (suprapubic burning sensation, sensory urgency, hot flushes, autonomic hyperreflexia, hematuria) in five of the six subjects in both groups. Bladder biopsy revealed no significant deterioration. On day 30, there was improvement in all of the experimental-group of patients with significant regression of leakage (P = 0.002) and of sensory urgency (P = 0.01). Only one control subject had amelioration. Urodynamic examination showed a rise in bladder capacity from 172.5 to 312.3 ml in the experimental group, significantly greater (P = 0.03) than the rise from 129 to 175.3 ml observed in the control group. CONCLUSION: This trial fully confirms the efficacy of intravesical installations of capsaicin, an efficacy obtained at the cost of nonnegligible side effects. An intermediate-term follow-up of this treatment will be necessary before considering more widespread use of this agent.

Adult↗

PubMed1998

Controlled therapeutic trials of pentoxifylline in relapsing-experimental auto-immune encephalomyelitis.

This study was designed to assess the capacity of several doses of pentoxifylline to prevent or treat chronic-relapsing-EAE (CR-EAE) exacerbations induced in the Lewis rat. Pentoxifylline (PTX) is a methylxanthine derivative that inhibits the production of TNF-alpha, a cytokine involved in EAE and multiple sclerosis physiopathology. Three blind placebo-controlled randomized studies were performed in respectively 40, 30 and 18 rats: a trial of different (PTX) dosages (8, 30, 50, 100 and 200 mg/kg) versus placebo to prevent EAE onset; a trial of PTX (8, 30 or 50 mg/kg) versus placebo to prevent 2 attacks of EAE and a trial of PTX (100 mg/kg) versus placebo to abrogate ongoing clinical EAE. No statistically significant difference was observed between groups in any trial. PTX was ineffective to prevent or treat CR-EAE in these studies.

Animals↗

PubMed1998

Early structural changes in acute MS lesions assessed by serial magnetization transfer studies.

BACKGROUND: Whether acute MS lesions are primarily inflammatory or demyelinative is unresolved. Our study examined acute MS lesions longitudinally by quantitative magnetization transfer (MT), an MRI technique that identifies tissue integrity and destruction. METHODS: Four MS patients were studied by serial MRI including MT, conventional T2-weighted images, and postgadolinium T1-weighted images for 9 to 12 months. In 15 new lesions, the MT ratio (MTR) was calculated retrospectively. RESULTS: In 13 lesions, a marked decrease in the MTR was present early during the first 2 months after the onset of the lesion and was followed by a variable increase. In two other lesions, the MTR progressively declined. CONCLUSIONS: These results suggest that major early structural changes compatible with demyelination and followed by remyelination and gliosis, or by continuous demyelination, occur in new MS lesions. The various MTR profiles provide in vivo confirmation of the current knowledge of the progression in MS lesions. Furthermore, MTR may be used to monitor in vivo drug efficacy in new MS lesions.

Adult↗

PubMed1998

[Non-specific immunosuppression and multiple sclerosis].

Several series of arguments favor at least partial efficacy of immunosuppression in multiple sclerosis. Immunosuppression can often treat experimental autoimmune encephalitis, and imperfect model of multiple sclerosis. Certain agents have been shown to affect the pathophysiological processes seen indirectly on magnetic resonance imaging (mitoxantrone and Campath, for example). Therapeutic trials have their methodological weaknesses but do allow certain conclusions. The progressive forms of multiple sclerosis are the most widely studied. Massive but short-term immunosuppression does not appear to affect the course of progression but prolonged immunosuppression would appear to slow down the process, at least in responders. The effect on disease progression is modest and preference should go to well-tolerated treatments. Immunosuppression appears to effectively decrease the number of acute episodes and reduce the number of new lesions detectable by magnetic resonance imaging. The effect of immunosuppression is limited however by the fact that the clinical course of progressive forms depends less on the development of new lesions than on an aggravation of the demyelinization process and possible axon loss within constituted lesions. This is a further argument favoring early immunosuppressive treatment at a stage when it can be most effective.

Antibodies, Monoclonal↗

PubMed1997

Enzyme immunoassay for myelin basic protein in cerebrospinal fluid.

Myelin basic proteins (MBPs) are a set of proteins making up about 30% of the protein content of the central nervous system myelin. Four human isoforms have been identified. The most abundant is a highly conserved 18.5 kDa polypeptide. For this species, the amino acid sequence homologies between human and monkey or human and chick are 98.2% and 71.1%, respectively. As a consequence, there is a very good immunological cross-reactivity between the mammalian MBP. This protein has been extensively used to induce experimental allergic encephalomyelits (EAE) in numerous animals. The evolution of chronic EAE in animal is similar to that of multiple sclerosis (MS), a demyelinating human pathology, and chronic EAE is considered to be an animal model of MS. In demyelinating pathologies, MBP concentration in the cerebrospinal fluid (CSF) is considered to be a good marker of demyelination. MBP concentration, in biological fluids, is generally determined by radioimmunoassay (RIA). The RIA technique currently used is highly sensitive (0.1-2.5 ng/ml) but has the drawback of requiring the handling of radioactivity and frequent labelling of MBP. So we developed a new enzyme immunoassay (EIA) technique. Our technique has the same sensitivity as RIA, needs only small volumes of CSF (50 microliters) and the enzyme-labelled MBP tracer is stable for at least 12 months.

Alkaline Phosphatase↗

PubMed1997

Primary progressive multiple sclerosis.

Patients with multiple sclerosis who develop progressive disability from onset without relapses or remissions pose difficulties in diagnosis, monitoring of disease activity and treatment. There is a need to define the diagnostic criteria for this group more precisely and, in particular, to describe a comprehensive battery of investigations to exclude other conditions. The mechanisms underlying the development of disability and the role of MRI in monitoring disease activity in this clinical subgroup require elucidation, particularly in view of the lack of change on conventional imaging in the presence of continuing clinical deterioration. The prognosis is poor and there are currently no treatment trials for this form of the disease.

Disease Progression↗

PubMed1997

Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria.

OBJECTIVE: To evaluate the efficiency of mitoxantrone in multiple sclerosis. METHODS: Forty two patients with confirmed multiple sclerosis, selected as having a very active disease on clinical and MRI criteria were randomised to receive either mitoxantrone (20 mg intravenously (IV) monthly) and methylprednisolone (1 g iv monthly) or methylprednisolone alone over six months. In the steroid alone group five patients dropped out due to severe exacerbation. RESULTS: Blinded analysis of MRI data showed significantly more patients with no new enhancing lesions in the mitoxantrone group compared with the steroid alone group, (90% v 31%, P < 0.001). In the mitoxantrone group there was a month by month decrease almost to zero in the number of new enhancing lesions, and in the total number of enhancing lesions, whereas both remained high in the steroid alone group. The differences were significant for both indices at all months from 1-6. Unblinded clinical assessments showed a significant improvement in change in EDSS at months 2-6 in the mitoxantrone group, with a final mean improvement of more than one point (-1.1 v + 0.3; P < 0.001). There was a significant reduction in the number of relapses (7 v 31; P < 0.01), and an increase in the number of patients free of exacerbation (14 v 7; P < 0.05). CONCLUSION: In this selected group of patients with multiple sclerosis with very active disease, mitoxantrone combined with methylprednisolone was effective in improving both clinical and MRI indices of disease activity over a period of six months whereas methylprednisolone alone was not. Further double blinded long term studies are needed to properly evaluate the effect of mitoxantrone on progression in disability.

Adjuvants, Immunologic↗

PubMed1997

Transitional progressive multiple sclerosis: a clinical and imaging study.

OBJECTIVE: To study the prevalence and the natural course of transitional progressive multiple sclerosis (TPMS). This clinical form is defined by a progressive course beginning many years after an isolated bout. METHODS: 214 consecutive outpatients with definite or probable multiple sclerosis were studied. The prevalence of TPMS was established. Patients with TPMS were compared with patients with other progressive forms of multiple sclerosis according to the clinical course. A prospective one year follow up study was performed in a subgroup of patients to compare progression of the disease using clinical indices and MRI. RESULTS: In this clinical population of 214 outpatients with multiple sclerosis, 55 had secondary progressive multiple sclerosis (SPMS), 38 primary progressive multiple sclerosis (PPMS), and 12 TPMS. Retrospective analysis of the clinical data of these patients shows that TPMS is very similar to SPMS at the beginning of the disease (age at onset, time before progression, clinical symptoms at onset, progression index). In addition a cohort of patients was prospectively followed up clinically and by MRI for one year. CONCLUSIONS: The results did not show any significant differences between the three forms during this follow up. However, all data showed a concordant trend suggesting that at this progressive stage, TPMS is closer to PPMS in terms of progression of disability and new MRI lesions.

Brain↗

PubMed1995

Dementia of frontal lobe type due to adult polyglucosan body disease.

We describe a patient with adult polyglucosan body disease (APBD) who presented with a dementia of frontal lobe type (FLD), with a neurogenic bladder but no symptoms of sensory motor peripheral neuropathy. Diagnosis was made from a cerebral biopsy specimen which showed an accumulation of intra-axonal polyglucosan bodies in the central nervous system. This case differs from the usual presentation, in which gait disturbance is the main symptom and diagnosis is possible by sural nerve biopsy. Little is known about the neuropsychological pattern of APBD dementia but FLD has not previously been described. APBD is a heterogeneous clinical entity of unknown cause. This diagnosis must be considered in elderly patients with dementia.

Aged↗

PubMed1995

Double blind placebo controlled multicentre study of ginkgolide B in treatment of acute exacerbations of multiple sclerosis. The Ginkgolide Study Group in multiple sclerosis.

After an open labelled pilot study of ginkgolide B, a potent inhibitor of platelet activating factor, in the treatment of acute exacerbations of multiple sclerosis, a randomised double blind placebo controlled study was undertaken. One hundred and four patients were enrolled in the study: for seven days 43 received placebo, 29 received 240 mg/day ginkgolide B and 32 received 360 mg/day ginkgolide B. There was no statistical difference between the three groups for changes in Rankin, Kurtzke expanded disability status scale (EDSS), and Hauser ambulation index (AI) scores. Although there was a trend in favour of groups treated with ginkgolide for a change of Rankin and AI scores, it is concluded that ginkgolide B is not an effective treatment of exacerbations of multiple sclerosis.

Activities of Daily Living↗