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Mikko Kallela

Publications and source records attributed to Mikko Kallela.

11 recordsLinked to original sources
PubMed2005

Chromosome 19p13 loci in Finnish migraine with aura families.

Chromosomal area 19p13 contains two migraine associated genes: a Ca(v)2.1 (P/Q-type) calcium channel alpha(1) subunit gene, CACNA1A, and an insulin receptor gene, INSR. Missense mutations in CACNA1A cause a rare Mendelian form of migraine, familial hemiplegic migraine type 1 (FHM1). Contribution of CACNA1A locus has also been studied in the common forms of migraine, migraine with (MA) and without aura (MO), but the results have been contradictory. The role of INSR is less well established: A region on 19p13 separate from CACNA1A was recently reported to be a major locus for migraine and subsequently, the INSR gene was associated with MA and MO. Our aim was to clarify the role of these loci in MA families by analyzing 72 multigenerational Finnish MA families, the largest family sample so far. We hypothesized that the potential major contribution of the 19p13 loci should be detected in a family sample of this size, and this was confirmed by simulations. We genotyped eight polymorphic microsatellite markers surrounding the INSR and CACNA1A genes on 757 individuals. Using parametric and non-parametric linkage analysis, none of the studied markers showed any evidence of linkage to MA either under locus homogeneity or heterogeneity. However, marginally positive lod scores were observed in three families, and thus for these families the results remain inconclusive. The overall conclusion is that our study did not provide evidence of a major MA susceptibility region on 19p13 and thus we were not able to replicate the INSR locus finding.

Antigens, CD↗
PubMed2005

Eletriptan review.

Eletriptan is a selective, high affinity serotonin 5-HT(1B/1D)-receptor agonist which is rapidly absorbed and has a long half-life in plasma. Eletriptan has been shown to be effective and well tolerated in randomised, double-blind, placebo-controlled acute migraine trials and long-term open-label trials. Eletriptan maintains a consistency of response across three attacks and patients continue to respond to eletriptan for at least up to 1 year. Eletriptan has been compared with sumatriptan, zolmitriptan, naratriptan and ergotamine/caffeine in placebo-controlled, randomised, head-to-head trials, and has shown better efficacy with similar adverse events. In a large triptan meta-analysis, including 53 trials and > 24,000 patients, eletriptan 80 mg showed better efficacy, similar consistency but lower tolerability compared with sumatriptan 100 mg. Eletriptan has also shown efficacy in difficult-to-treat patients who were dissatisfied with their previous treatment with sumatriptan, rizatriptan, nonsteroidal anti-inflammatory drugs or Excedrin.

Clinical Trials as Topic↗
PubMed2004

Long-term outcome after intravenous thrombolysis of basilar artery occlusion.

CONTEXT: Basilar artery occlusion (BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. OBJECTIVE: To evaluate outcomes for patients with BAO treated with intravenous thrombolytic therapy. DESIGN, SETTING, AND PARTICIPANTS: During 1995 to 2003, 50 consecutive patients with angiographically proven BAO were treated according to an institutional therapy protocol based on intravenous thrombolysis with recombinant tissue plasminogen activator (alteplase). Patients were treated at an urban university teaching hospital receiving all patients with ischemic stroke who were considered for thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland. INTERVENTION: Intravenous administration of alteplase (0.9 mg/kg) during a 1-hour infusion. MAIN OUTCOME MEASURES: Basilar artery recanalization determined by magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or longer determined by modified Rankin Scale and Barthel Index scores. RESULTS: Recanalization was studied in 43 patients and verified in 26 (52%) of all patients. By 3 months, 20 patients (40%) had died while 11 had good outcomes (modified Rankin Scale score, 0-2); 12 (24%) reached independence in activities of daily living (Barthel Index score, 95-100), and 6 (16%) were severely disabled (Barthel Index score, 0-50). In the long term (median follow-up 2.8 years), 15 patients (30%) reached good outcomes (modified Rankin Scale score, 0-2) while 23 (46%) died. CONCLUSIONS: Intravenous administration of alteplase for patients with BAO appears to be associated with rates of survival, recanalization, and independent functional outcome comparable with those reported with endovascular approaches. These data suggest that a randomized trial is needed to compare these approaches for treatment of BAO.

Adult↗
PubMed2004

The molecular genetics of migraine.

Within the past decade it has been possible to identify susceptibility gene loci that predispose to migraine using genetic markers distributed across the human genome. Five new loci with significant linkage to common types of migraine--migraine with or without aura--have been identified on four different chromosomes using a genome-wide screen approach. So far, only the locus on 4q has been replicated but no specific, disease-causing mutations have been described in these common forms of migraine. The best genetic evidence providing molecular insight into migraine still comes from the mutations detected in a rare Mendelian form of migraine with aura--familial hemiplegic migraine (FHM). In 50%-70% of FHM families, mutations in the calcium channel gene CACNA1A in chromosome 19p13 have been identified. In some families, mutations in the ATP1A2 gene encoding the alpha2 subunit of the Na+, K+-ATPase are associated with FHM, linked to 1q23. Here we discuss the current knowledge of the heritability of migraine and rare migraine variants as models for understanding the pathophysiology of common migraine and animal models that might contribute to understanding common forms of migraine.

Animals↗
PubMed2003

Community-based thrombolytic therapy of acute ischemic stroke in Helsinki.

BACKGROUND AND PURPOSE: Thrombolysis with alteplase is used in acute ischemic stroke within 3 hours after symptom onset in many stroke centers, but experience remains limited in Europe. METHODS: Using eligibility and management criteria similar to those published by the American Heart Association, we treated 75 consecutive patients aged 21 to 83 years (mean age, 63.6 years; median Scandinavian Stroke Scale score, 32/58) with hemispheric infarction with alteplase in 1998-2001. Their neuroradiological findings (ischemic and hemorrhagic changes) and functional outcome at 3 months were evaluated. RESULTS: Sixty-one percent of the patients had recovered functional independence (Barthel Index 95 to 100) at the 3-month follow-up. On the modified Rankin Scale (mRS), 37% (28/75) of patients had no or minimal symptoms (mRS 0 to 1), while 17% (13/75) remained dependent (mRS 4 to 5) and 5% (4/75) died. Cerebral parenchymal hematomas occurred in 8% (6/75) and hemorrhagic transformation in 8% (6/75) of the patients. Low initial diastolic blood pressure and administration of intravenous antihypertensive medication were associated with unfavorable outcome (mRS 3 to 6). CONCLUSIONS: We conclude that our management protocol for thrombolytic therapy is safe. These rates of functional outcome, case fatality, and hemorrhagic cerebral events compare favorably with those of other published series of stroke thrombolysis with similar time windows and management guidelines. Associations between blood pressure and its treatment during thrombolysis with functional outcome deserve further analysis.

Academic Medical Centers↗
PubMed2003

Genetic and environmental influences on migraine: a twin study across six countries.

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.

Adolescent↗
PubMed2002

A susceptibility locus for migraine with aura, on chromosome 4q24.

Migraine is a complex neurovascular disorder with substantial evidence supporting a genetic contribution. Prior attempts to localize susceptibility loci for common forms of migraine have not produced conclusive evidence of linkage or association. To date, no genomewide screen for migraine has been published. We report results from a genomewide screen of 50 multigenerational, clinically well-defined Finnish families showing intergenerational transmission of migraine with aura (MA). The families were screened using 350 polymorphic microsatellite markers, with an average intermarker distance of 11 cM. Significant evidence of linkage was found between the MA phenotype and marker D4S1647 on 4q24. Using parametric two-point linkage analysis and assuming a dominant mode of inheritance, we found for this marker a maximum LOD score of 4.20 under locus homogeneity (P=.000006) or locus heterogeneity (P=.000011). Multipoint parametric (HLOD = 4.45; P=.0000058) and nonparametric (NPL(all) = 3.43; P=.0007) analyses support linkage in this region. Statistically significant linkage was not observed in any other chromosomal region.

Chromosome Mapping↗