Biomedical subjects

J L Frederiksen

Publications and source records attributed to J L Frederiksen.

At least 19 recordsLinked to original sources

PubMed2006

CD8+ T cell activation correlates with disease activity in clinically isolated syndromes and is regulated by interferon-beta treatment.

An increased percentage of blood CD8+ T cells from patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) was found to express CD26 and CD69. The percentage of CD26 or CD69 positive CD8+ T cells was higher in patients with MRI evidence of disease dissemination in space or with active MRI lesions than in the remaining patients. Treatment of MS with interferon (IFN)-beta resulted in a decrease in the percentage of CD26 and CD71 positive CD8+ T cells and an increase in the percentage of CD8+ T cells that expressed interleukin (IL)-10 and IL-13. CD8+ T cell activation in MS may be linked to disease activity already at disease onset, and is regulated by treatment with IFN-beta.

Adult↗

PubMed2006

The association between apolipoprotein E and multiple sclerosis.

The article is a complete literature study that investigates the association between apolipoprotein E (Apo E) and multiple sclerosis (MS). Apo E is an important factor in transport, uptake, and redistribution of cholesterol, which is significant to remodelling and repair of nerve tissue. Apo E is involved in neurodegenerative diseases and the most well known association is between Apo epsilon4 and Alzheimer's disease. Only one study found that homozygosity for Apo epsilon4 does cause an increased risk of developing MS. No results indicate that heterozygosity for Apo epsilon4 causes a greater risk of developing MS. No association between the Apo epsilon4 allele and MS subgroups, age of onset, and gender has been found. The association between Apo epsilon4 and relapse rate is contradictory. Most results confirm the hypothesis about an association between the Apo epsilon4 allele and increased disease progression. Two longitudinal studies found an association between Apo epsilon4 and increased disease progression. Half of the cross-sectional studies found the same association. Four of seven published studies examining the association between Apo epsilon4 and increased disease progression using magnetic resonance imaging (MRI) found a significant association. Apo epsilon4 appears to be a predisposing factor to a faster disease progression in MS.

Apolipoproteins E↗

PubMed2005

A double-blind, randomized trial of IV immunoglobulin treatment in acute optic neuritis.

OBJECTIVE: To investigate if IV immunoglobulin (IVIG) treatment in the acute phase of optic neuritis (ON) could improve visual outcome and reduce MRI disease activity 6 months after onset of ON. METHODS: Sixty-eight patients with ON were randomized within 4 weeks from onset of symptoms. Thirty-four patients were randomized to IVIG 0.4 g/kg body wt, and 34 patients were randomized to placebo. Infusions were given at days 0, 1, 2, 30, and 60. Contrast sensitivity, visual acuity, and color vision were measured at baseline and after 1 week, 1 month, and 6 months. Pattern reversal visual evoked potential studies and gadolinium-enhanced MRI were performed at baseline and after 1 and 6 months. Clinical relapses during follow-up were recorded. RESULTS: There was no difference in the primary outcome, contrast sensitivity after 6 months, between patients randomized to treatment with IVIG or placebo. In addition, there was no significant difference in the secondary outcome measures, improvement in the visual function measures and MRI, at any time during follow-up. At baseline, a significantly higher number of patients in the IVIG group had one or more enhancing lesions on MRI and IVIG-treated patients had a significantly higher number of enhancing lesions on MRI than patients treated with placebo. No difference was found in number of patients with one or more enhancing lesions or number of enhancing lesions in subsequent scans between treatment groups. Number of relapses was equal in the two treatment groups during follow-up. CONCLUSIONS: There was no effect of IV immunoglobulin (IVIG) on long-term visual function following acute optic neuritis, nor was there an effect of IVIG treatment in reducing latency on visual evoked potentials and thus preserving function of axons of the optic nerve.

Acute Disease↗

PubMed2005

Apo E in multiple sclerosis and optic neuritis: the apo E-epsilon4 allele is associated with progression of multiple sclerosis.

OBJECTIVE: To investigate the association between apolipoprotein E (Apo E) genotype in multiple sclerosis (MS) and acute monosymptomatic optic neuritis (ON) in a genetically homogeneous population with a high frequency of the Apo epsilon4 allele. BACKGROUND: The association between heterozygosity of Apo epsilon4 and the development of MS is thoroughly investigated, while the association between homozygosity of Apo epsilon4 and the development of MS is insufficiently studied. The association between Apo E genotype and disease progression remains controversial. METHODS: 475 patients were included, 385 with MS and 90 with ON, consecutively seen in the MS clinic in the County of Copenhagen. Clinical data were obtained from medical records and degree of disability was determined prospectively using the Kurtzke expanded disability status scale (EDSS). Blood samples were used for Apo E genotyping. Disease progression was evaluated by the progression index (PI = EDSS/disease duration). Apo E genotype distribution was compared with 361 healthy controls. RESULTS: The Apo epsilon genotype distribution in the MS and ON groups was similar to the controls. The rate of disease progression in the group of MS patients with a disease duration of 10 years or less was significantly faster in the Apo epsilon4 positive group (heterozygosity and homozygosity for Apo epsilon4) (PI = 1.41) compared to the Apo epsilon4 negative group (PI =0.92) (P =0.009). Observing the MS subgroups, we found that the group of patients with RRMS had a faster rate of disease progression in the Apo epsilon4 positive group (PI =1.12) compared to the Apo epsilon4 negative group (P =0.77) (P =0.024). CONCLUSIONS: Apo E genotypes do not influence the development of MS and ON. The Apo epsilon4 allele seems to predispose carriers with MS to a faster progression of disease.

Adult↗

PubMed2005

CD26 + CD4 + T cell counts and attack risk in interferon-treated multiple sclerosis.

Biomarkers that allow the identification of patients with multiple sclerosis (MS) with an insufficient response to immunomodulatory treatment would be desirable, as currently available treatments are only incompletely efficacious. Previous studies have shown that the expression of CD25, CD26 and CCR5 on T cells is altered in patients with active MS. We studied the expression of these molecules by flow cytometry in patients followed for six months during immunomodulatory treatment. In interferon (IFN)-beta-treated patients, we found that the hazard ratio for developing an attack was 28 in patients with CD26 + CD4 + T cell counts above median, and this risk was independent of the risk conferred by neutralizing anti-IFN-beta antibodies. CD26 + CD4 + T cell counts may identify patients with MS at increased risk of attack during treatment with IFN-beta.

Adjuvants, Immunologic↗

PubMed2004

Role of magnetic resonance imaging within diagnostic criteria for multiple sclerosis.

The diagnosis of multiple sclerosis (MS) has been improved in recent decades with the incorporation of paraclinical investigations in diagnostic workup. In the last 15 years, magnetic resonance imaging (MRI) has become an especially valuable tool for supporting MS diagnosis, and specific imaging criteria became fundamental to the guidelines for the diagnosis of MS published in 2001 by an international panel (IP). The new IP criteria include MRI evidence of dissemination in space and time, making it possible to diagnose MS after a single clinical episode. This review considers current evidence concerning the reliability of the new IP criteria for the diagnosis of relapsing-onset MS, discusses strengths and weaknesses of the criteria, and outlines areas which may need modification or should be the focus of future research directed toward improving diagnostic accuracy. It also makes practical recommendations when using MRI and the IP criteria in MS diagnosis, especially in patients with clinically isolated syndromes or atypical presentations. The IP criteria are timely and concrete and introduce an important concept to MS diagnosis. Future modifications, based on emerging evidence, should further facilitate their implementation and improve their accuracy.

Humans↗

PubMed2004

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI.

Adult↗

PubMed2003

Motor evoked potentials from the pelvic floor in patients with multiple sclerosis.

The use of motor evoked potentials (MEPs) to study the integrity of pelvic floor motor innervation is poorly described in the literature. This study evaluated the clinical use of pelvic floor MEPs in 16 women with multiple sclerosis. Lower urinary tract dysfunction was assessed with urodynamic investigations. Transcutaneous magnetic stimulation was applied over the motor cortex and spinal roots, and MEPs were recorded from the puborectalis, the external urethral sphincter, and the abductor hallucis muscles. In many patients, responses from the pelvic floor muscles could not be evoked, and central motor conduction times for the puborectalis motor pathways could only be calculated in 56%. There was a poor correlation of abnormal conduction to lower urinary tract dysfunction. It is concluded, that unevokable responses from pelvic floor muscles in a patient with multiple sclerosis should be interpreted with care, and that pelvic floor MEPs have a limited clinical value in the investigation of suspected demyelinating disease.

Adult↗

PubMed2003

Gadolinium-enhanced magnetic resonance imaging predicts response to methylprednisolone in multiple sclerosis.

Oral high-dose methylprednisolone treatment is efficacious in acute optic neuritis (ON) and attacks of multiple sclerosis (MS). The responses to treatment in subgroups of patients participating in two randomized, controlled trials were assessed. Fifty-eight patients with ON and 51 patients with attacks of MS were treated with placebo or oral methylprednisolone (500 mg daily for five days with a 10-day tapering period). A gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan was obtained at baseline in 66 patients, and 29 patients underwent repeated MRI studies. Seventy-four patients underwent lumbar puncture before treatment. The odds ratio (OR) of improvement after methylprednisolone treatment (a one point change in the visual function system score of the Kurtzke Expanded Disability Status Scale (EDSS) in ON or in the EDSS score in attacks of MS) was higher in patients with enhancing lesions on baseline MRI (one week: OR 15, P = 0.02; eight weeks: OR 4.6, P = 0.02). Methylprednisolone treatment suppressed Gd-enhancement after one week (P < 0.001) and three weeks (P = 0.001). Cerebrospinal fluid measures of intrathecal inflammation correlated with the area of Gd-enhancement but did not correlate as closely with the treatment response as did the results of Gd-enhanced MRI. These findings suggest that the resolution of intrathecal inflammation as assessed by Gd-enhanced MRI is a major effect of oral high-dose methylprednisolone.

Adult↗

PubMed2002

Functional MRI of the visual cortex and visual testing in patients with previous optic neuritis.

The volume of cortical activation as detected by functional magnetic resonance imaging (fMRI) in the visual cortex has previously been shown to be reduced following optic neuritis (ON). In order to understand the cause of this change, we studied the cortical activation, both the size of the activated area and the signal change following ON, and compared the results with results of neuroophthalmological testing. We studied nine patients with previous acute ON and 10 healthy persons served as controls using fMRI with visual stimulation. In addition to a reduced activated volume, patients showed a reduced blood oxygenation level dependent (BOLD) signal increase and a greater asymmetry in the visual cortex, compared with controls. The volume of visual cortical activation was significantly correlated to the result of the contrast sensitivity test. The BOLD signal increase correlated significantly to both the results of the contrast sensitivity test and to the Snellen visual acuity. Our results indicate that fMRI is a useful method for the study of ON, even in cases where the visual acuity is severely impaired. The reduction in activated volume could be explained as a reduced neuronal input; however, the greater asymmetry might point to a cortical reorganization as a consequence of neuronal damage. Future fMRI studies in ON will add to the understanding of the neural adaptive behaviour following ON.

Adult↗

PubMed2001

Coronaviruses in brain tissue from patients with multiple sclerosis.

Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E and three PCR assays with primers specific for the nucleocapsid protein of human coronavirus strain OC43 were performed. Sporadic positive PCR assays were observed in both patients and controls in some of the PCR assays. However, these results were not reproducible and there was no difference in the proportion of positive signals from the MS patients compared to controls. Evidence for a chronic infection with the human coronaviruses strain 229E or OC43 in brain tissue from patients with MS or controls has not been found in this study.

Adult↗

PubMed2000

Immunological effects of oral high-dose methylprednisolone in acute optic neuritis and multiple sclerosis.

The immunological effects of high-dose methylprednisolone in attacks of multiple sclerosis and acute optic neuritis have only been examined in a few randomized, controlled trials. We studied immunological changes in 50 patients with optic neuritis or multiple sclerosis who underwent lumbar puncture before and 1 week after completing a 15-day course of oral high-dose methylprednisolone treatment. Treatment resulted in a decrease in the concentration of myelin basic protein, a decrease in the serum concentration of immunoglobulin G (IgG) and intrathecal IgG synthesis, an increase in the cerebrospinal fluid concentration of transforming growth factor-beta1, and changes in the expression of CD25, CD26, and human leukocyte antigen-DR (HLA-DR) on CD4 T-cells. No effect was seen on the cerebrospinal fluid leucocyte count or the cerebrospinal fluid activity of matrix metalloproteinase-9 (MMP-9). The lack of a persistent effect on cerebrospinal fluid leucocyte recruitment and MMP-9 activity, despite changes in IgG synthesis, T-cell activation, and cytokine production, suggests that modulation of the function of inflammatory cells may contribute to the clinical efficacy of oral high-dose methylprednisolone treatment in optic neuritis and multiple sclerosis.

Acute Disease↗

PubMed1999

[Randomized controlled trial of high-dose peroral methylprednisolone in attacks of multiple sclerosis].

The efficacy of glucocorticoid treatment in multiple sclerosis (MS) is uncertain. We assessed the effect of oral high-dose methylprednisolone in attacks of MS. Twenty-five patients with an attack of MS with a duration of less than four weeks were randomized to placebo, 26 patients received oral methylprednisolone (500 mg once daily for five days with a 10 days tapering period). Scripps Neurological rating scale scores differed significantly in methylprednisolone and placebo-treated patients the first three weeks (p = 0.005) and after eight weeks (p = 0.0007). Subjective symptom assessment on a visual analogue scale the first three weeks (p = 0.02) and the answers to an efficacy questionnaire administered after eight weeks (p = 0.05) also favoured a beneficial effect of methylprednisolone treatment. The risk of a new attack of MS was not influenced by the treatment at short-term follow up. No serious adverse events were seen. Oral high-dose methylprednisolone is recommended for treatment of attacks of MS.

Adult↗

PubMed1999

Optic neuritis as onset manifestation of multiple sclerosis: a nationwide, long-term survey.

OBJECTIVE: To determine the predictive value on survival of optic neuritis (ON) as onset manifestation of MS. METHODS: We used data obtained from the Danish Multiple Sclerosis Registry, which includes virtually all patients diagnosed with MS in Denmark. From 1949 to 1990, 7,548 unselected patients fulfilling standardized diagnostic criteria of MS were registered. RESULTS: The onset manifestation of MS was known in 6,923 patients, and was ON in 1,282 patients (19%). The mean age at onset was 31.1 years for these patients compared with 34.8 years for patients with another or unknown onset manifestation of MS (non-ON) (p < 0.001). The mean delay from the first known manifestation of MS to the final diagnosis of MS was 6.1 years (ON) and 4.2 years (non-ON). The median survival time from onset of ON was 30 years in men (compared with 41 years in the matched general male population) and 40 years in women (versus 47 years). The excess death rate increased with age at onset of MS in people of each sex. Excess death rate for women differed significantly between patients with ON as onset manifestation and patients with another or unknown onset manifestation of MS (8.3 versus 13.0). In patients with ON as onset manifestation of MS, the excess death rate was significantly higher in men (14.0) than in women (8.3). CONCLUSION: ON as onset manifestation of MS indicates a more favorable prognosis of survival of MS judged by excess death rate only in women.

Adolescent↗

PubMed1999

A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis.

OBJECTIVE: To assess the efficacy of oral high-dose methylprednisolone in acute optic neuritis (ON). BACKGROUND: It has been determined that oral high-dose methylprednisolone is efficacious in attacks of MS. METHODS: A total of 60 patients with symptoms and signs of ON with a duration of less than 4 weeks and a visual acuity of 0.7 or less were randomized to treatment with placebo (n = 30) or oral methylprednisolone (n = 30; 500 mg daily for 5 days, with a 10-day tapering period). Visual function was measured and symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks. Primary efficacy measures were spatial vision and VAS scores the first 3 weeks (analysis of variance with baseline values as the covariate), and changes in spatial vision and VAS scores after 8 weeks. A significance level of p < 0.0125 was employed. RESULTS: The VAS score (p = 0.008) but not the spatial visual function (p = 0.03) differed in methylprednisolone- and placebo-treated patients during the first 3 weeks. After 8 weeks the improvement in VAS scores (p = 0.8) and spatial visual function (p = 0.5) was comparable with methylprednisolone- and placebo-treated patients. A post hoc subgroup analysis suggested that patients with more severe baseline visual deficit and patients treated early after onset of symptoms had a more pronounced response to treatment. The risk of a new demyelinating attack within 1 year was unaffected by treatment. No serious adverse events were seen. CONCLUSION: Oral high-dose methylprednisolone treatment improves recovery from ON at 1 and 3 weeks, but no effect could be demonstrated at 8 weeks or on subsequent attack frequency.

Acute Disease↗

PubMed1999

Serial visual evoked potentials in 90 untreated patients with acute optic neuritis.

To establish the value of visual evoked potentials (VEPs) for monitoring disease evolution, we undertook a population-based study of 90 untreated patients 12 to 57 years of age (median, 32 years) at the onset of optic neuritis (ON) and after 2, 4, 12, and 52 weeks. Optic neuritis was monosymptomatic (AMON) in 58 patients and part of the clinically definite multiple sclerosis (CDMS) in 32 patients. The VEP was abnormal in eyes with acute ON in 69 (77%) of 90 patients at onset and in 80 (89%) of 90 patients at one or more of the follow-up sessions. In eyes with acute ON, normalization of an initially abnormal VEP was observed during 1-year follow-up in 13 (19%) of 69 patients. At onset of ON, VEP was abnormal in 35% of the clinically unaffected eyes. By parametric analysis of variance, the latencies (P = 0.0058), the amplitudes (P = 0.0298), and the combined VEP scores (P = 0.0345) in the eyes with acute ON were significantly associated with the time after onset. The latencies were influenced by the presence of CDMS (P = 0.0033), whereas the amplitudes were influenced by visual acuity (P = 0.0000). When visual acuity was included in a multifactor model, the time after onset was, however, not significantly associated with the amplitude (P = 0.8826). The mean latency of the VEPs in eyes with acute ON was significantly shorter in AMON than in ON as part of CDMS. This study provides evidence that VEP abnormality is often transitory, and that VEP often normalizes during follow-up. The diagnostic yield is increased by repeating VEP in the spontaneous course of acute ON. Visual evoked potential is a sensitive tool for revealing subclinical lesions.

Acute Disease↗

PubMed1999

Coronaviruses in spinal fluid of patients with acute monosymptomatic optic neuritis.

UNLABELLED: Acute monosymptomatic optic neuritis (AMON) may be an initial symptom of multiple sclerosis (MS). Coronaviruses have been implicated in the etiology of MS. The objective of the present study was to look for coronaviral RNA in AMON, which could be present in the initial stages of the development of MS. MATERIAL AND METHODS: Spinal fluids from 37 patients with AMON and 15 surgical control patients with protrusion of the intervertebral disk were assayed with a nested multiplex polymerase chain reaction with primers specific for human coronaviruses strain (HCV) 229E and OC43. RESULTS: Four patients and 1 control were positive for HCV-229E. No evidence of HCV-OC43 was found. The frequency of positive samples was low and there was no statistical difference between AMON and controls. CONCLUSION: This study does not provide evidence for an etiological role of human coronaviruses in acute monosymptomatic optic neuritis.

Acute Disease↗

PubMed1999

Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients.

Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether specific chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of three chemokines that act toward T cells and mononuclear phagocytes: interferon-gamma-inducible protein of 10 kDa (IP-10); monokine induced by interferon-gamma (Mig); and regulated on activation, normal T-cell expressed and secreted (RANTES). We then investigated whether specific chemokine receptors were expressed by infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results imply pathogenic roles for specific chemokine-chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.

Acute Disease↗