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Biomedical subjects

J Lycke

Publications and source records attributed to J Lycke.

At least 19 recordsLinked to original sources
PubMed2006

IL-6 and CCL2 levels in CSF are associated with the clinical course of MS: implications for their possible immunopathogenic roles.

Biological markers would provide valuable tools for tracking disease activity, immunopathological processes or therapeutic efficacy in MS. In this study we analysed a panel of Th(1)/Th(2) cytokines and the chemokine CCL2 in serum and CSF from MS patients and healthy controls. Increased levels of IL-6 (p<0.05) and decreased levels of CCL2 (p<0.001), with the lowest levels during acute relapses, was found in CSF from patients with relapsing-remitting MS. CSF levels of CCL2 correlated with indices for intrathecal IgG production and the CSF level of the neurofilament light protein, a marker for axonal damage, indicating a immunopathogenic role for CCL2.

Adolescent↗
PubMed2003

Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS.

OBJECTIVE: To determine if CNS-derived proteins present in the CSF of multiple sclerosis (MS) patients reflect different pathologic processes of MS and if these proteins could be useful as biologic markers of disease activity. METHODS: Concentrations of the neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), S100B, and the neuron-specific enolase protein (NSE) were determined in the CSF of 66 MS patients and 50 healthy control subjects with immunoassays. RESULTS: The mean levels of the NFL were increased during all stages of MS compared with controls (p < 0.001), peaking almost 10 times higher during acute relapses. The highest levels of GFAP were found during the secondary progressive course (p < 0.001) with a strong correlation with neurologic deficits (Expanded Disability Status Scale score, r = 0.73, p < 0.001). No increase of S100B or NSE protein was found in the CSF of MS patients compared with control subjects. CONCLUSIONS: Increased level of NFL is a general feature of MS, indicating continuous axonal damage during the entire course of the disease with the most profound damage during acute relapses. GFAP may serve as a biomarker for disease progression, probably reflecting the increasing rate of astrogliosis.

Acute Disease↗
PubMed2002

A randomized, double-blind, placebo-controlled MRI study of anti-herpes virus therapy in MS.

OBJECTIVE: To evaluate the effect of treatment with the antiherpes drug valacyclovir on MRI-evident lesions in patients with relapsing-remitting MS in a phase 2, randomized, double-blind, placebo-controlled study. BACKGROUND: It has been postulated from virologic studies that herpesvirus infection could play a role in the progression of MS. METHODS: Patients were eligible for the study if they had had two or more MS relapses in the 2-year period before enrollment. Seventy patients with Expanded Disability Status Scale scores of 0 to 5.5 were randomly assigned to receive 1 gram of valacyclovir (n = 36) or placebo (n = 34) three times daily for 24 weeks. Patients underwent MRI every fourth week for 32 weeks: twice during pretreatment, six times during treatment, and once after treatment. Scoring of neurologic disability was performed at the start and end of the treatment period. The primary endpoint was the number of new active MRI-evident lesions over 24 weeks of treatment. Secondary endpoints included other MRI measures and clinical endpoints. RESULTS: The mean number of new active lesions +/- SD per patient during 24 weeks of treatment with valacyclovir was 11.9 +/- 17.6 and that during placebo treatment was 14.5 +/- 21.4. A protocol-planned exploratory analysis stratified patients according to baseline activity; this analysis showed that patients with high levels of disease activity in the valacyclovir treatment group (n = 17) developed fewer new active lesions per scan than did those in the placebo treatment group (n = 11). The median number (Q(1), Q(3) range) of active lesions was 2.0 (1.38, 3.96) in the valacyclovir treatment group and 6.5 (2.63, 9.0) in the placebo treatment group. CONCLUSIONS: Valacyclovir treatment did not reduce the formation of active lesions in patients with relapsing-remitting MS who had two or more relapses during the previous 2-year period. In a subgroup of patients with high levels of disease activity who had more than one active MRI-evident lesion during 4 weeks, valacyclovir treatment was associated with a reduced number of new active MRI-evident lesions and with an increase in the number of scans free of new active lesions. The results of the exploratory subgroup analysis provide support for further studies of antiherpes therapy for patients with MS and high levels of MRI-evident disease activity.

Acyclovir↗
PubMed2001

IL-10 and IFN-gamma in Guillain-Barré syndrome. Network Members of the Swedish Epidemiological Study Group.

Guillain-Barré syndrome (GBS) is an acute inflammatory disease affecting myelin and axons of the peripheral nervous system (PNS). GBS is considered to be caused by breakdown of tolerance to autoantigens of the PNS. The involvement of cytokines in GBS and in relation to treatment with high dose intravenous immunoglobulin (IvIg) is incompletely known. We studied the temporal profiles of IL-10 and IFN-gamma-secreting blood mononuclear cells (MNC) over the course of GBS, using enzyme-linked immunospot (ELISPOT) assays. Pretreatment levels of blood MNC spontaneously secreting IL-10 were higher in the acute phase of GBS than in control patients with aseptic meningitis, other neurological diseases, diabetic neuropathy and healthy subjects. Levels of IFN-gamma-secreting blood MNC were not increased over the course of GBS. Patients treated with IvIg had lower numbers of IL-10-secreting MNC compared to untreated patients. High levels of IL-10-secreting MNC correlated with serum anti-ganglioside IgM antibody levels, and with neurophysiological signs of axonal damage. The present data suggests that IFN-gamma is not involved in GBS pathogenesis, and IL-10 being up-regulated in the early phase of GBS and associated with axonal damage, may have a pathogenetic role in GBS.

Adult↗
PubMed2001

Asymptomatic visual loss in multiple sclerosis.

Visual disturbances are common in multiple sclerosis (MS) and often a result of acute demyelinating optic neuropathy. Careful examination of MS patients, who have never suffered optic neuritis, may also reveal asymptomatic visual loss. This type of silent disease activity was investigated by computerised resolution perimetry, which has the potential to reflect the percentage of functional retino-cortical neural channels. The time of onset and the evolution of asymptomatic visual loss was investigated. One approach was to retrospectively select patients who never had suffered acute optic neuritis from a closely monitored MS population and re-examine them again. Sixteen patients were identified and vision was evaluated during a period of 5.5-9 years of follow-up and compared with that in 14 healthy controls. The mean channel percentage of the MS group was 89 +/- 19 % (SD) on entry into the study, compared with 110 +/- 15% (SD) of controls (p < 0.003). At termination of the study the mean percentage was essentially unchanged both in MS patients (87 +/- 21%, SD) and controls (110 +/- 19%, SD). The second approach was to test a group of 7 patients with MS or strongly suspected MS, with the same method, in close connection with their first clinical exacerbation. All cases lacked visual symptoms and none had previously had acute visual loss. Again, virtually all performed subnormally in the vision tests, and to the same degree as in the first group of patients. Results were compared with those obtained from 25 MS patients who had experienced one or more attacks of optic neuritis. Compared with controls the loss of functional retino-cortical neural channels was 20% in patients without a previous history of optic neuritis and 30 % in patients who previously had experienced optic neuritis. We conclude that asymptomatic visual loss seems to be a universal feature of MS and has a substantial impact on the visual pathways, that it is present already at the time of clinical onset of the disease, and that any progression thereafter is slow enough to elude detection during several years of follow-up.

Adult↗
PubMed2000

Weaning from mechanical support in a patient with acute heart failure and multiple sclerosis.

We describe a 19-year-old woman developing acute left ventricular heart failure during her first exacerbation of multiple sclerosis. Histopathologic examination of myocardial tissue showed extensive myocytolysis. A left ventricular assist device was implanted. Three months later the cardiac function was restored and the left ventricular assist device was explanted. After 1 year the patient still remains well and her cardiac function is normal.

Acute Disease↗
PubMed2000

Brain tumours in Sweden 1996: care and costs.

OBJECTIVES: Brain tumours cause considerable concern due to a high mortality and there are increasing efforts to provide adequate care, sometimes outside hospitals. Health care utilisation, direct costs of care, and the indirect social cost of morbidity and early mortality caused by brain tumours in Sweden in the year 1996 was analysed. METHODS: Quantification of ambulatory care, care in hospital, long term and palliative/terminal care, drug consumption, temporary as well as long term morbidity, and mortality from comprehensive national data sources. Direct costs were calculated using 1996 charges. Indirect costs were calculated by sex and age specific salaries. A sensitivity analysis considered the impact of alternative estimates of each item. RESULTS: Indirect costs were 75% of the total and were caused mainly by early mortality. Direct costs were predominantly for care in hospital, long term care, and home health care. Among direct costs, astrocytomas III-IV and meningiomas accounted for 42% and 30% respectively. CONCLUSIONS: The cost of illness from brain tumours reflects the characteristics of these malignancies. Despite their low incidence rate, the economic impact caused by high mortality among young persons is a predominant trait. Costs of acute hospital care and also long term care and home care are considerable.

Brain Neoplasms↗
PubMed1997

Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis.

Several members of the herpesvirus family have been implicated in the pathogenesis of multiple sclerosis (MS). Recently, HHV-6 viral antigen has been demonstrated in association to MS plaques, as well as DNA from human herpesvirus 6 (HHV-6) in cerebrospinal fluid from a few MS patients by polymerase chain reaction (PCR). In the present study, CSF from patients with MS, optic neuritis and other neurological diseases, as well as consecutive CSF and serum samples from MS patients included in a clinical trial with acyclovir, were analysed by nested PCR for the presence of DNA from herpes simplex virus 1 and 2, Epstein-Barr virus, varicella zoster virus, cytomegalovirus, human herpesvirus 6 and 7. No virus DNA was found in any CSF (n = 115) or serum (n = 116) sample. These findings argue against a continuous disseminated herpesvirus infection in MS, but do not rule out a lesion-associated, low-grade herpesvirus infection within the MS brain.

Adolescent↗
PubMed1996

Acyclovir treatment of relapsing-remitting multiple sclerosis. A randomized, placebo-controlled, double-blind study.

Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on "intent-to-treat" data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0-2), medium (3-5) and high (6-8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.

Acyclovir↗
PubMed1996

Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis.

The synthetic immunomodulator Linomide, a quinoline-3-carboxamide, has a profound inhibitory influence in several experimental autoimmune diseases, including acute and chronic experimental allergic encephalomyelitis. In a double-blind trial, 31 patients with relapsing-remitting multiple sclerosis were randomized to oral doses of 2.5 mg Linomide or placebo once a day for six months. Fourteen patients receiving Linomide and 14 receiving placebo completed the trial, and the results were based on this population. The mean number of active (new and enlarged T2 weighted) lesions per monthly MRI scan was 1.37 in the patients receiving Linomide and 4.22 in the patients receiving placebo (p = 0.043). The percentage of scans with active MRI lesions was lower in the Linomide-treated group (p = 0.0064). When neurologic deficit was assessed by the Regional Functional Scoring System (RFSS), the Linomide group showed an improvement of 1% of the maximal RFSS range and the placebo group a deterioration of 0.2% (p = 0.14). There were three patients with relapses in the Linomide-treated group and six in the placebo group (p = 0.22). A slightly decreased proportion of natural killer cells in cerebrospinal fluid and peripheral blood was noted in the Linomide group. A severe adverse event of pleuropericarditis occurred in one of the Linomide-treated patients. The most frequent adverse event was musculoskeletal pain, of mild to severe degree, which tended to diminish after three months on Linomide therapy.

Adjuvants, Immunologic↗
PubMed1995

Glial fibrillary acidic protein in CSF of multiple sclerosis patients: relation to neurological deficit.

Glial fibrillary acidic protein (GFAp) was analysed in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and healthy controls. Patients with relapsing-remitting course (n = 13) were followed with quantitative neurological examinations and lumbar punctures during a 24-month period. The patient group was a subsample from a randomised, double-blind clinical trial of acyclovir on MS: 7 patients were treated with acyclovir and 6 were placebo controls. CSF was also collected from 5 age-matched healthy individuals with normal quantitative neurological examinations. The CSF assays disclosed increased concentrations of GFAp in MS patients compared to controls (p < 0.01). Furthermore, the GFAp levels correlated significantly with the deficit score (p < 0.01) but not with exacerbation frequency. When the group treated with acyclovir was compared with the placebo group, no significant change of CSF GFAp was observed. In the present study we show that GFAp is increased in CSF of patients with MS and that the levels correlate with the neurological dysfunction. Further work is needed to ascertain whether determinations of CSF GFAp can be used to monitor disease progression in MS or whether the assay may be useful to evaluate therapeutic intervention.

Acyclovir↗
PubMed1994

Human spumaretrovirus antibody reactivity in multiple sclerosis.

The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS.

Adolescent↗
PubMed1993

Peripheral neuropathy associated with monoclonal IgM antibody to glycolipids with a terminal glucuronyl-3-sulfate epitope.

Twenty-nine patients with paraproteinaemia, 12 with neuropathy and 17 without a previous record of neurological symptoms were clinically characterized. All 12 neuropathy patients had a moderate to severe sensorimotor demyelinating neuropathy. The patients were examined with regard to serum antibodies to gangliosides, including GM1, GD1a, GD1b, GT1b, and LM1, and other acidic glycolipids, including LK1 and sulphatide, of human brain and peripheral nerve. Sera from 80 blood donors, 40 men and 40 women 20-60 years of age, were used as normal controls. The sera were analysed with an ELISA performed on thin-layer chromatography plates. At a dilution of 1/400 none of the control sera gave a detectable reaction and a titre of > or = 1:400 was considered as a positive test. In 11 of the 12 neuropathy patients the paraproteinaemia was of IgM type and 10 of them had a positive antibody titre against LK1 and Hex-LK1, acidic glycolipids with a terminal glucuronyl-3-sulphate group. The antibody titre against LK1 in 1 patient was 1:400 and varied between 1:5,000 and 1:3,200,000 in the other 9. One of the patients also had a positive titre, 1:64,000, to sulphatide. None of the sera from the 17 paraproteinaemia patients without a previous record of neurological symptoms contained antibodies to LK1 or to any glycolipid antigen examined, except for sulphatide. A positive titre (> or = 1:400) of antibodies to sulphatide was found in sera from 4 of these patients, the titres being < or = 3,200.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Possible association of HTLV-I infection and dementia.

We report a Swedish patient with progressive dementia possibly associated with human T cell-lymphotropic virus type I (HTLV-I) infection. The clinical investigation revealed no typical sings of other neurological disorders. The patient was probably infected in East-Asia 35 years before onset of the disease. High titers of specific HTLV-I antibodies were detectable with solid-phase peptide ELISA in serum (1:1.600) and cerebrospinal fluid (CSF) (1:20), and the CSF/serum anti-HTLV-I antibody ratio indicated intrathecal HTLV-I antibody synthesis. Western blot for HTLV-I and polymerase chain reaction with primers selected for the HTLV-I pol gene were positive in both peripheral blood and cerebrospinal fluid. HTLV-I antigen was also demonstrated after in vitro co-cultivation of mononuclear cells from peripheral blood. Thus, our findings indicate that HTLV-I infection also may be associated with dementia. In addition, this case report calls attention upon HTLV-I as a possible etiologic agent to neurological diseases in countries previously spared from the infection.

Blotting, Western↗
PubMed1993

Regional cerebral blood flow in multiple sclerosis measured by single photon emission tomography with technetium-99m hexamethylpropyleneamine oxime.

The regional cerebral blood flow (rCBF) in 19 patients with multiple sclerosis (MS), 10 with a relapsing remitting course and 9 with a progressive course, was examined by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ([99mTc]-d,l-HM-PAO) as flow tracer. Nine age-matched volunteers served as controls. Low rCBF in the frontal grey matter correlated with neurological disability (p < 0.01), low frontal grey and white matter perfusion correlated with impaired cognitive functions (p < 0.02), and low rCBF in the occipital regions correlated with impaired visual functions (p < 0.03) in the MS population. A relationship was also found between reduced parietal white matter perfusion and the duration of the disease (p < 0.005). Patients with progressive MS had significantly reduced rCBF in the frontal grey matter compared with relapsing remitting MS patients and controls (p < 0.05). No other rCBF differences were found. As a diagnostic tool in MS, SPECT-[99mTc]-d,l-HM-PAO was found to be insensitive.

Adult↗
PubMed1992

No evidence for spumavirus or oncovirus infection in relapsing-remitting multiple sclerosis.

Polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human T-cell lymphotropic virus types I [HTLV-I] and II [HTLV-II]) in multiple sclerosis. Eleven patients with relapsing-remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. Cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. Cultured cells were subjected to polymerase chain reaction analysis with primers selected for the pol and gag (human spumaretrovirus), pol and env (HTLV-I), and pol (HTLV-II) genes. Polymerase chain reaction was negative in all patient and blood donor control samples, whereas positive controls were consistently reactive with high sensitivity. No culture exhibited cytopathic effects and supernatants were negative for reverse transcriptase activity. Thus, our results do not support a role for these retroviruses in the pathogenesis of multiple sclerosis.

Adult↗