PubMed Health⌕ Search

Biomedical subjects

T Keränen

Publications and source records attributed to T Keränen.

At least 19 recordsLinked to original sources
PubMed2004

Regulation of IL-6 system in cerebrospinal fluid and serum compartments by seizures: the effect of seizure type and duration.

Experimental studies suggest that cytokine production may be triggered by seizure activity. Here we determined the levels of interleukin-6 (IL-6) and its soluble receptor components (sIL-6R and sGp130) in CSF and serum from control subjects and patients after different types of seizures. IL-6 levels were increased after seizures, whereas sIL-6R levels were decreased. Interestingly, the levels of IL-6 were strongly increased after recurrent generalized tonic-clonic seizures (GTCS), whereas after single tonic-clonic or prolonged partial seizures IL-6 levels were increased to lesser extent. These results provide further support for a hypothesis of cytokine production induced by seizure activity per se.

Antigens, CD↗
PubMed2003

Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures.

We have previously shown that IL-6 protein levels are increased in cerebrospinal fluid in humans after recent tonic-clonic seizures with unchanged levels of IL-1beta and TNFalpha. Here we studied the expression of cytokines IL-6, LIF, IL-1beta and TNFalpha and cytokine receptors IL-6R, LIFR and Gp130 in the rat brain after kainic acid-induced status epilepticus using Northern blot analysis and in situ hybridization histochemistry. After seizures, IL-6 mRNA was induced in the hippocampus, cortex, amygdala and meninges, and IL-6R was up-regulated in the hippocampus. LIF was up-regulated in the hippocampus, cortex and meninges after seizures, and LIFR mRNA was induced in the hippocampus and cortex. Gp130 was constitutively expressed in the brain. After seizures, Gp130 transcription was rapidly induced in the meninges. In thalamus, cortex, amygdala and hippocampus Gp130 mRNA was induced in a delayed fashion. IL-1beta transcription was induced in the temporal lobe cortex and thalamus, and TNFalpha in the hippocampus. In general, the cytokine and their receptor mRNA levels were low in intact rat brain, but were induced by seizures. Since IL-6 and LIF transcripts were induced in the meninges after seizures, the protein products of these transcripts may be more readily released in cerebrospinal fluid after seizures. In addition, the activity of IL-6 and LIF signaling pathways may be influenced by increased expression of their receptors after seizures.

Animals↗
PubMed2003

Economic burden and quality of life impairment increase with severity of PD.

PURPOSE: To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson's disease (PD) severity in a common patient management setting in Finland.Scope. Two hundred and sixty consecutive outpatients with idiopathic PD participated. UPDRS, motor fluctuations, QoL, and the use of health care resources were measured. Direct and indirect costs were calculated. CONCLUSIONS: There is a strong relationship between QoL or cost-of-illness on the one hand, and severity of PD on the other. Treatment policies capable of reducing or delaying motor fluctuations would be expected to increase QoL and reduce some of the economic burden of PD.

Aged↗
PubMed2002

Indicators of inflammation after recent tonic-clonic epileptic seizures correlate with plasma interleukin-6 levels.

Cerebrospinal fluid (CSF) and peripheral blood pleocytosis have been observed after epileptic seizures without any evidence of infections, but no systematic studies on the acute phase reaction in such patients have been performed. We have previously reported increased levels of interleukin-6 (IL-6) in patients with recent tonic--clonic seizures. Because IL-6 is a major inducer of the systemic acute phase reaction, we decided to study various indicators of inflammation in the blood as well as their correlation with plasma and CSF IL-6 levels. CSF and blood samples were studied from 37 patients with previously undiagnosed and untreated tonic-clonic seizures without any clinical evidence of systemic or central nervous system infections as well as from 40 controls. The mean peripheral blood and CSF-leukocyte counts were significantly higher in patients compared with controls ( 7.9 x 10(9)vs. 6.1 x 10(9), P= 0.002 and 1.9 x 10(6)vs. 1.1 x 10(6), P= 0.032, respectively). There was some indication of increased concentration of C-reactive protein (CRP) and no difference in haptoglobin levels. There was a significant correlation between plasma but not CSF IL-6 concentration and those of both B-leukocyte count ( r= 0.051, P= 0.009) and CRP ( r= 0.42, P= 0.009). Epileptic seizures provoke a production of cytokines such as IL-6 that may in turn cause an activation of the acute phase reaction. Thus, CSF pleocytosis and increase in some indicators of inflammation should not automatically be attributed to systemic or CNS infections in patients with acute seizures.

Acute-Phase Reaction↗
PubMed2001

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures.

PURPOSE: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS: 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS: The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.

Adolescent↗
PubMed2001

High prevalence of antiphospholipid antibodies in children with epilepsy: a controlled study of 50 cases.

Evidence of immune system aberrations in patients with epilepsy includes antiphospholipid antibody positivity in adult patients with epilepsy with a prevalence of 19-26% and in 13% of children with partial epilepsy. Also immunoglobulin A deficiency has been reported to exist in up to 25% of epilepsy patients. The possible role of immune mechanisms in the pathogenesis of childhood epilepsy is clinically supported by the effectiveness of immunomodulatory treatments in cases with catastrophic childhood epilepsies. We analyzed a set of various autoantibodies in 50 consecutive children with epilepsy and in 20 healthy control subjects. None of the children had any clinical signs of immune system disorders. The main result was a significantly (P=0.011) higher prevalence of antiphospholipid antibodies in the study group (44%) compared with controls (10%). These antibodies were unexpectedly common (71-80%) in children with multiple seizure types associated often with symptomatic etiology, early onset and high frequency of seizures. There was no evidence of the antiphospholipid positivity being induced by certain AEDs (e.g. phenytoin or carbamazepine). Even though the significance of these autoantibodies remains unknown, their increased prevalence indicates that immune system mediated mechanisms may have a role in the manifestation of epilepsy in some children.

Adolescent↗
PubMed2000

Antiphospholipid and antinuclear antibodies in patients with epilepsy or new-onset seizure disorders.

PURPOSE: The increased prevalence of autoantibodies in patients with epilepsy has been traditionally regarded to be a consequence of antiepileptic drugs. The purpose of this study was to measure autoantibodies in well-defined groups of patients with seizures to determine the effects of epilepsy and antiepileptic medications on the presence of autoantibodies. PATIENTS AND METHODS: We studied the frequency of antinuclear antibodies, anti-beta2-glycoprotein I antibodies, and anticardiolipin antibodies in 50 patients with therapy-resistant localization-related epilepsy, 50 patients with generalized epilepsy syndromes, 52 patients with a newly diagnosed seizure disorder but no antiepileptic medication, and 83 healthy controls. RESULTS: Compared with controls, newly diagnosed patients had a significantly greater prevalence of immunoglobulin (Ig) G class anticardiolipin antibodies (21% versus 7%); the prevalence was 14% in patients with localization-related epilepsy and 8% in patients with generalized epilepsy. The prevalence of IgM class anticardiolipin antibodies was significantly greater in all seizure groups (60% in localization-related epilepsy, 42% in generalized epilepsies, and 33% in newly diagnosed patients) compared with controls (7%). Antinuclear antibodies were significantly more common in newly diagnosed patients (21%) and localization-related epilepsy (24%) compared with controls (12%). When patients with generalized epilepsy (8%) were used as the reference group, antinuclear antibodies were also significantly more frequent in localization-related epilepsy (relative risk [RR] = 2.9, 95% confidence interval [CI]: 1.1 to 8.2) and newly diagnosed seizures (RR = 3.4, 95% CI: 1.2 to 9.3). There were no consistent associations between autoantibodies and specific antiepileptic medications. CONCLUSIONS: The prevalence of autoantibodies is greater in patients with epilepsy, including newly diagnosed seizure disorder. The increased prevalence of autoantibodies is more strongly associated with epilepsy than with antiepileptic drugs, perhaps indicating that immune dysregulation may be commonly associated with epilepsy.

Adult↗
PubMed2000

Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy.

BACKGROUND: Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in type 1 diabetes and stiff man syndrome (SMS), and have also been reported in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A, implying that epilepsy sometimes is associated with anti-GAD autoimmunity. METHODS: The authors investigated the prevalence of GAD-A in patients with therapy-resistant localization-related epilepsy (n = 51) and generalized epilepsy (n = 49) by a radiobinding assay. The positive samples were confirmed by immunohistochemistry and immunoblotting of recombinant human GAD65. RESULTS: GAD-A were found in eight patients with localization-related epilepsy, whereas none of the patients with generalized epilepsy, other neurologic disorders (n = 38), or the control subjects (n = 48) had GAD-A. Two patients had high levels of GAD-A, similar to SMS, whereas six patients had significantly lower titers, characteristic of type 1 diabetes. The two patients with high levels of GAD-A had GAD-A both in serum and CSF by immunohistochemistry and immunoblotting. Both of them had longstanding therapy-resistant temporal lobe epilepsy but did not have diabetes. One had a history of autoimmune disease, whereas the other had serologic evidence of multiple autoantibodies without any clinical signs of autoimmune disease. CONCLUSIONS: GAD autoimmunity may be associated with refractory localization-related epilepsy.

Adolescent↗
PubMed2000

Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures.

We have previously reported increased concentrations of interleukin (1L)-6 in CSF from patients with tonic-clonic seizures, where increased cytokine production most likely is a consequence of neuronal epileptic activity associated with seizures. The biological effects of IL-6 are mediated by other cytokines, which are studied here in addition to IL-6. The purpose of this study was to analyze levels of soluble cytokines from plasma and CSF from patients with newly developed tonic-clonic seizures. The concentrations of IL-6, IL-1 receptor antagonist (IL-1RA), IL-1beta, tumor necrosis factor (TNFalpha) and nerve growth factor (NGF) were measured from plasma and CSF from 22 patients with newly developed tonic-clonic seizures within 24 h from the seizure and 18 controls. The mean concentrations of IL-6 were significantly increased in CSF (P<0.001) and plasma (P<0.01) after tonic-clonic seizures, there was some indication of increased concentrations of IL-1RA and no significant change in NGF, IL-1beta or TNFalpha. Our study shows that cytokine network is activated in patients after recent tonic-clonic seizures. We provide evidence of intrathecal production of IL-6 associated with electrical seizure activity.

Adolescent↗
PubMed2000

Modified-release formulation of tizanidine in chronic tension-type headache.

The efficacy of the modified-release formulation of tizanidine (Sirdalud) was compared with placebo in a randomized, double-blind, parallel-group study of 138 women and 47 men, aged 18 to 79 years, with a history of chronic tension-type headache (IHS categories 2.2 and 2.3). The treatment period was 6 weeks preceded by a 2-week prerandomization period. The patients were randomly assigned to receive 6-mg Sirdalud, 12-mg Sirdalud MR, or placebo. The study medication was taken once per day, orally in the evening. Efficacy was measured by visual analog scale, the number of headache-free days, the daily duration of headache, and the use of paracetamol. The primary end point was the severity of daily headache derived from visual analog scale scores covering the last 2 treatment weeks. One hundred sixty patients (56 in the 6-mg group, 49 in the 12-mg group, and 55 in the placebo group) completed the study. The severity of the headache decreased similarly in the treatment groups and the placebo group. The visual analog scale values decreased from the prerandomization values by 53% in the 6-mg group, 48% in the 12-mg group, and 52% in the placebo group. The modified-release formulation of tizanidine in doses up to 12 mg taken in the evening is not superior to placebo in the treatment of chronic tension-type headache. The placebo effect was unexpectedly strong in the present study, supporting the view that psychophysiological mechanisms are of considerable importance in sustaining chronic tension-type headache.

Adrenergic alpha-Agonists↗
PubMed2000

Effects of short-term lamotrigine treatment on pharmacokinetics of carbamazepine.

AIM AND METHOD: The effects of short-term treatment with lamotrigine (LTG) (100 mg twice daily for one week) on single dose pharmacokinetics of carbamazepine (CBZ, 200 mg) were investigated in a randomized, double-blinded, placebo-controlled cross-over study with 10 healthy volunteers. RESULTS: Pharmacokinetic parameters for CBZ or for CBZ-10,11-epoxide, the main metabolite of CBZ, were not significantly affected by LTG pretreatment. The mean (+/- SEM) elimination half-life of CBZ was 33.0+/-1.8 h after pretreatment with placebo and 30.1+/-2.0 h after a one-week-pretreatment with LTG (NS). The area under the serum concentration curve to infinity (AUC) of CBZ was 638+/-45 micromol/l after placebo and 624+/-53 micromol/l after LTG (NS). Changes in the peak serum concentration, from 9.0+/-0.3 micromol/l to 9.2+/-0.4 micromol/l (LTG), and in the time to peak serum concentration, from 9.3+/-1.1 h to 9.1+/-1.2 h (LTG), were also not significant. CONCLUSION: These data support the earlier findings that LTG does not significantly affect the rate or extent of absorption, or elimination of CBZ.

Adult↗
PubMed1998

Elevated levels of interleukin-6 may occur in cerebrospinal fluid from patients with recent epileptic seizures.

Experimental animal studies suggest the involvement of cytokines in epilepsy. We measured increased concentrations of interleukin-6 in four out of 15 cerebrospinal fluid samples from unmedicated patients with newly developed tonic-clonic seizures; plasma levels were also increased but to a lesser extent. Although the significance of cytokine production in relation to epileptic seizures is not known, it might be important for neuronal survival.

Adolescent↗