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Biomedical subjects

L Kappos

Publications and source records attributed to L Kappos.

At least 73 records · Page 4Linked to original sources
PubMed2000

A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine.

A multinational, multicentre, randomised, double-blind, double-dummy, crossover study (368 patients treating two attacks) was conducted to compare the efficacy and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60 minutes after dosing, significantly more patients obtained headache relief (change from moderate or severe to none or mild) after treatment with sumatriptan than with DHE (53% sumatriptan, 41% DHE, p < 0.001). Significantly more patients reported relief of nausea after sumatriptan than after DHE at 60 minutes (64% sumatriptan, 49% DHE, p = 0.006). A significant difference between the two treatments was first observed at 45 minutes with respect to both headache relief (38% sumatriptan, 31% DHE, p = 0.037) and relief of nausea (55% sumatriptan, 40% DHE, p = 0.014). There were no significant differences between the two treatments for other measures of efficacy. Both treatments were well tolerated, with only 10% of patients in each group reporting one or more adverse events. The most frequently reported adverse event after sumatriptan was a bad or bitter taste, which was reported by 5% of patients. After DHE, 4% of patients reported symptoms of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse events. It is concluded that sumatriptan nasal spray is superior to DHE nasal spray in the relief of pain and nausea associated with acute migraine headache.

Adult↗
PubMed1999

Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis Group.

BACKGROUND: Reliable prognostic factors are lacking for multiple sclerosis (MS). Gadolinium enhancement in magnetic resonance imaging (MRI) of the brain detects with high sensitivity disturbance of the blood-brain barrier, an early event in the development of inflammatory lesions in MS. To investigate the prognostic value of gadolinium-enhanced MRI, we did a meta-analysis of longitudinal MRI studies. METHODS: From the members of MAGNIMS (European Magnetic Resonance Network in Multiple Sclerosis) and additional centres in the USA, we collected data from five natural-course studies and four placebo groups of clinical trials completed between 1992 and 1995. We included a total of 307 patients, 237 with relapsing disease course and 70 with secondary progressive disease course. We investigated by regression analysis the relation between initial count of gadolinium-enhancing lesions and subsequent worsening of disability or impairment as measured by the expanded disability status scale (EDSS) and relapse rate. FINDINGS: The relapse rate in the first year was predicted with moderate ability by the mean number of gadolinium-enhancing lesions in monthly scans during the first 6 months (relative risk per five lesions 1.13, p=0.023). The predictive value of the number of gadolinium-enhancing lesions in one baseline scan was less strong. The best predictor for relapse rate was the variation (SD) of lesion counts in the first six monthly scans which allowed an estimate of relapse in the first year (relative risk 1.2, p=0.020) and in the second year (risk ratio=1.59, p=0.010). Neither the initial scan nor monthly scans over six months were predictive of change in the EDSS in the subsequent 12 months or 24 months. The mean of gadolinium-enhancing-lesion counts in the first six monthly scans was weakly predictive of EDSS change after 1 year (odds ratio=1.34, p=0.082) and 2 years (odds ratio=1.65, p=0.049). INTERPRETATION: Although disturbance of the blood-brain barrier as shown by gadolinium enhancement in MRI is a predictor of the occurrence of relapses, it is not a strong predictor of the development of cumulative impairment or disability. This discrepancy supports the idea that variant pathogenetic mechanisms are operative in the occurrence of relapses and in the development of long-term disability in MS.

Adolescent↗
PubMed1999

Self glycolipids as T-cell autoantigens.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by discrete areas of demyelination. An autoimmune response against components of myelin is thought to contribute to disease pathogenesis. Here we identify glycolipids as new targets recognized by T cells in multiple sclerosis patients. Circulating T cells reactive with glycolipids are more frequent in MS patients than in control donors as shown by enzyme-linked immunospot assay. They specifically recognize different types of glycolipids, such as gangliosides, sulfatide and galactosylceramide and release IFN-gamma and TNF-alpha. T cells specific for gangliosides were found to be CD8+, TCR alphabeta+, restricted by the MHC-like CD1b molecule and specific for epitopes residing in the carbohydrate moiety of gangliosides. Our findings suggest that in addition to self proteins, self glycolipids may represent potential source of autoantigens recognized by T cells in autoimmune diseases.

Adult↗
PubMed1999

[Interferon beta-1b for treatment of secondary chronic progressive multiple sclerosis].

Several phase III studies have proven that the beta-interferons have positive effects on the number and severity of acute exacerbations of relapsing remitting multiple sclerosis. Recently the first study on the effectiveness of interferon beta-1b in secondary progressive multiple sclerosis was published. In a multicenter, double-blind, randomized, Placebo-controlled study 718 patients with secondary progressive multiple sclerosis and an expanded disability status scale (EDSS) value between 3.0 and 6.5 were treated with either 8 Mio.interferon beta-1b or Placebo subcutaneously every second day for two to three years. The primary study end-point was the time until confirmed progression of the disease as signified by a one point increase of the EDSS value (for initial EDSS values between 3.0 and 5.5) or 0.5 point increase when the initial EDSS value was between 6.0 and 6.5. After two years an interim analysis showed a highly significant difference in delay of disease progression by nine to twelve months for the treatment group (p = 0.0008). This means that interferon beta-1b is the first recombinant beta-interferon to be shown effective in the treatment of secondary progressive multiple sclerosis.

Adjuvants, Immunologic↗
PubMed1999

[MRI follow-up in multiple sclerosis. A guideline for quality assurance].

Magnetic resonance imaging (MRI) is highly sensitive to pathological tissue changes in multiple sclerosis (MS) patients. It demonstrates the frequently subclinical disease activity and follow-up examinations regularly show the accumulation of new lesions and the development of atrophy. The increasing importance of follow-up examinations in MS patients makes it necessary to provide comparable MRI data even over long observation periods. This review article focusses on critical variables in this regard and technical issues; practical guidelines for MRI protocols in MS patients are presented. The influence of field strength, MR systems from different manufacturers, and new software releases is described. Guidelines concerning the graphic planning of the examination, sequence protocols, documentation and reporting of cranial MR studies in MS patients are presented.

Atrophy↗
PubMed1998

[Reversible dementia].

A 65 year old woman, referred for differential diagnosis of dementia, presented with cognitive and mnestic deficits. Typical signs and symptoms of hypothyroidism led to the diagnosis of severe autoimmune thyroiditis. After six months of treatment with thyroid hormone, dementia, myopathy and ataxia had disappeared. The neurologic and neuropsychologic manifestations of hypothyroidism are discussed. In dementia the diagnosis of secondary and reversible forms is of great importance with regard to prognosis and treatment. Hypothyroidism is known to be a common and treatable cause of pseudodementia. Early diagnosis and adequate treatment are important to prevent further permanent deterioration of cerebral function.

Aged↗
PubMed1998

Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis.

Matrix metalloproteinases (MMPs) are a family of endopeptidases capable of enzymatic digestion of subendothelial basement membrane and other components of the extracellular matrix. Expression of MMP-2, -3, -7 and -9 is increased around multiple sclerosis plaques and in brain tissue in experimental allergic encephalomyelitis. To measure quantitatively the expression of these MMPs and their endogenous inhibitors (TIMP-1 and -2), we analysed samples from 52 patients with relapsing-remitting and primary progressive multiple sclerosis by ELISA (enzyme-linked immunosorbent assay) and substrate-gel electrophoresis (zymography). MMP-9 was increased over controls in 100% of relapsing-remitting multiple sclerosis cases, with similar levels detected in relapses and clinically stable phases of disease. In primary progressive multiple sclerosis, MMP-9 was increased in 57% of CSF samples, but concentrations were below those encountered in the relapsing-remitting form. The selective upregulation of MMP-9 suggests that T-cells and macrophages invading the brain parenchyma and the CSF space are the predominant source of MMP-9 in multiple sclerosis. TIMPs and other MMPs (MMP-2 and -3) were not upregulated or not detectable (MMP-7) in CSF of patients with relapsing-remitting and primary progressive multiple sclerosis. The sustained increase of MMP-9 in clinically stable multiple sclerosis supports the concept that multiple sclerosis is associated with ongoing proteolysis that may result in progressive tissue damage. The selective inhibition of MMP-9 could be a useful approach for the prevention of disease progression in multiple sclerosis.

Cerebrospinal Fluid↗
PubMed1998

Computer assisted retraining of attentional impairments in patients with multiple sclerosis.

OBJECTIVE: To evaluate the efficacy of a computer based retraining of specific impairments of four different attentional domains in patients with multiple sclerosis. METHODS: Twenty two outpatients with multiple sclerosis received consecutively a specific training comprising 12 sessions in each of the two most impaired attention functions. The baseline of attentional deficits, the performance after each training period, and the course of performance in the next nine weeks was assessed by a computerised attention test battery. Additionally, the impact of the training on daily functioning was evaluated with a self rating inventory. RESULTS: Subgroups of patients with multiple sclerosis showing different patterns of attentional impairment could be separated. Significant improvements of performance could almost exclusively be achieved by the specific training programmes. The increase of performance remained stable for at least nine weeks. For quality of life patients reported less attention related problems in everyday situations. CONCLUSIONS: In patients with multiple sclerosis it seems worthwhile to assess attentional functions in detail and to train specific attention impairments selectively.

Activities of Daily Living↗
PubMed1998

Body fluid markers to monitor multiple sclerosis: the assays and the challenges.

The need for reliable markers of disease activity in multiple sclerosis (MS) to better guide basic research, diagnosis, treatment, and monitoring of therapy is well-recognized. A recent European Charcot Foundation Symposium (Body fluid markers for course and activity of disease in multiple sclerosis (Madrid, Spain, October 2-4, 1997) organized by the European Charcot Foundation and the Fundación Española de Esclerosis Múltiple (the Spanish Multiple Sclerosis Foundation) brought together experts in the field to review the state of the art for the technology measuring markers in body fluids. An array of different approaches was presented to measure a wide diversity of classic and novel marker molecules, including cytokines, adhesion molecules, myelin compounds, and free antibody light chains, in either blood, urine, or cerebrospinal fluid. Here, recent progress in these approaches is assessed in the context of distinct pathophysiological stages of the disease, the requirements which such molecules and assays should ideally meet, and the practical and conceptual challenges which they face. Recommendations for further improvements are described.

Body Fluids↗
PubMed1997

[Diagnosis and differential diagnosis in multiple sclerosis].

The diagnosis of multiple sclerosis (MS) relies on the occurrence of characteristic symptoms, on the patient's history and on the correct interpretation of nowadays very sensitive but not very specific auxillary examinations. This paper reviews the diagnostic criteria and typical signs and symptoms of the disease. The significance of cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI) and evoked potentials is discussed, with emphasis on their predictive value concerning the development of MS after a first episode with symptoms suggestive of MS. A wide range of other diseases mimicking MS, like infectious, autoimmune, granulomatous, metabolic and hereditary diseases is reviewed. A checklist for important points in patient history and further investigations is proposed.

Adult↗
PubMed1997

Strategies for optimizing MRI techniques aimed at monitoring disease activity in multiple sclerosis treatment trials.

Serial magnetic resonance imaging (MRI) detects substantial subclinical disease activity in multiple sclerosis (MS) and is presently included in most treatment trials as an objective outcome measure. Our current knowledge of the role of MRI in MS treatment trials is derived from very limited patient studies, and the aim of this paper is to identify strategies to optimize the use of MRI in monitoring disease activity in treatment trials. The number of active lesions revealed by MRI can be used as the primary outcome measure in exploratory treatment trials. With monthly scanning, the majority of active lesions will be seen by virtue of a limited number of new areas of gadolinium enhancement. The contrast between enhancing lesions and background could be increased by: (1) using higher doses of gadolinium, (2) suppressing the background signal with magnetization transfer, (3) delayed scanning, or (4) a combination of these. Following a systematic comparison of those approaches, the effect on the sensitivity in detecting active lesions should be analysed with reference to the power of treatment trials. We present preliminary results showing marked agreement between observers in reporting enhancing lesions; however, with new acquisition strategies, the observer variation should be re-established in a multicentre fashion. In definitive trials, the increase in total lesion load serves as a secondary outcome measure. Since the majority of lesions making up the total lesion load are inactive during the study, spatial resolution should be maximized in order to preclude any artificial changes in lesion load to be superimposed (noise) upon the relatively small actual change (information). Reduction in measurement error can be attempted by improved acquisition techniques with increased lesion to background contrast. More importantly, improvement in quantitation techniques is warranted. With a 6% coefficient of variation in measuring a baseline lesion load, we calculate the standard error of the mean yearly increase in T2 lesion load (typically 10% in untreated patients) in a treatment arm of 124 patients to be 7.5%. A comparison of several quantitation techniques should be performed in a multicentre longitudinal fashion in order to include variation caused by both scanner and segmentation technique, in addition to biological activity.

Clinical Trials as Topic↗
PubMed1997

Intravenous immunoglobulin (IVIG) treatment for patients with primary or secondary progressive multiple sclerosis -- outline of a double-blind randomized, placebo-controlled trial.

We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.

Adult↗
PubMed1997

Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study.

To investigate the pathophysiology of fatigue in MS, we assessed cerebral glucose metabolism (CMR-Glu) in 47 MS patients using PET and 18F-fluorodeoxyglucose. Applying the Fatigue Severity Scale (FSS), we first compared MS patients with severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In addition, we determined global CMRGlu by region-of-interest analysis. Sixteen healthy subjects served as control subjects (CON). Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9 mumol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) but was not related to fatigue severity. Comparing the two MS groups, SPM95 analysis revealed predominant CMRGlu reductions bilaterally in a prefrontal area involving the lateral and medial prefrontal cortex and adjacent white matter, in the premotor cortex, putamen, and in the right supplementary motor area of MS-FAT. In addition, there were CMRGlu reductions in the white matter extending from the rostral putamen toward the lateral head of the caudate nucleus. FSS values were inversely related to CMRGlu in the right prefrontal cortex. CMRGlu in the cerebellar vermis and anterior cingulate was relatively higher in MS-FAT than in MS-NOF patients. CMRGlu of both regions showed positive correlations with FSS values. Our data suggest that fatigue in MS is associated with frontal cortex and basal ganglia dysfunction that could result from demyelination of the frontal white matter.

Adult↗