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Biomedical subjects

Reetta Kälviäinen

Publications and source records attributed to Reetta Kälviäinen.

At least 19 recordsLinked to original sources
PubMed2006

Optimizing treatment of epilepsy during pregnancy.

Freedom from seizures is the ultimate goal in treatment of patients with epilepsy. At the same time, the side effects of antiepileptic drugs (AEDs) should not outweigh the benefits of treatment. This is particularly important in women with epilepsy who wish to become pregnant. These women and their partners should be made aware of the risks associated with uncontrolled seizures as well as the teratogenicity of some AEDs. Recent studies have indicated a higher risk for birth defects and possibly also adverse cognitive effects associated with exposure to valproate compared with carbamazepine. Although further studies are needed, it appears reasonable to use valproate with caution in women with epilepsy who are planning to become pregnant and to consider whether other equally effective and safer AEDs are available. However, women who need valproate to control their seizures should continue the drug and not be discouraged from pregnancy, provided that they receive counseling with the best available knowledge. With proper management before conception, during pregnancy, and after birth, the vast majority of pregnancies in women with active epilepsy will have a favorable outcome.

Abnormalities, Drug-Induced↗
PubMed2006

More severe epilepsy and cognitive impairment in the offspring of a mother with mosaicism for the ring 20 chromosome.

PURPOSE: Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder. Cases tend to be sporadic. We elucidate the characteristics of an inherited r(20) mosaicism by describing the clinical features of three family members: a mother and her two children. RESULTS: The mosaicism rate of the mother was 10% and that of the children 40%. The mother experienced her first epileptic seizures at 24 years of age. Epilepsy was diagnosed two years later. After an unstable period lasting 3 years, she has been seizure-free for 13 years on a combination of valproate and lamotrigine. She has normal intelligence with full working capacity. The daughter exhibited her first epileptic seizures at the age of 7 years and she continues to have seizures weekly. The first epileptic seizures in the son were observed at 5 years of age. The son's epilepsy has been drug resistant from the onset, and a vagal nerve stimulator (VNS) has been ineffective. Psychomotor development was normal in both children up to the onset of epilepsy. Learning difficulties increased throughout school age and both children needed special educational programs. Neuropsychological evaluations have shown deterioration of cognitive levels. Both children had behavioural problems during school age but no longer in adolescence. All three subjects are nondysmophic, normocephalic and of normal growth. CONCLUSION: In this family the phenotype of r(20) mosaicism seems to be more severe in the successive generation along with a greater level of mosaicism. The aggravated clinical picture in inherited r(20) mosaicism concerned the onset of epilepsy, drug responsiveness, the cognitive level and behavioural features.

Adolescent↗
PubMed2006

The effects of valproate exposure in utero on behavior and the need for educational support in school-aged children.

Children exposed to valproate monotherapy in utero were evaluated with respect to neurological functioning, behavior, and additional educational needs, and the results were compared with those for age- and gender-matched controls exposed to carbamazepine and children with no prenatal exposure to antiepileptic drugs. We identified from the community-based pregnancy registry of Kuopio University Hospital area (1989-2000) all first-born and school-aged children exposed to valproate (N=13). Neurological and neuropsychological assessments were made clinically, and behavioral problems were assessed with the Conners' Teacher Rating Scale (CTRS). Eight children (62%) exposed to valproate and two (15%) each in the carbamazepine-exposed and nonexposed groups (P=0.022) required educational support. Minor dysmorphic features were noted in eight children (62%) exposed to valproate and in three children (23%) each in the carbamazepine-exposed and nonexposed groups. On CTRS, children exposed to valproate received higher scores, indicating behavioral problems. In our small but population-based study, all children exposed to valproate had minor, and some of them major, cognitive or neurological problems. This difference is clearly observed when assessing each child individually, but the many confounding factors explaining at least part of this difference are difficult to control and avoid in clinical practice. Larger studies with a prospective design are needed to confirm these findings.

Anticonvulsants↗
PubMed2006

Temporal changes in the incidence of epilepsy in Finland: nationwide study.

PURPOSE: To examine possible changes over time in the incidence of epilepsy in different age groups. METHODS: Based on the nationwide full-refundable antiepileptic drug register and population register, incidence of newly diagnosed epilepsy was measured by granted full-refundable antiepileptic drugs for epilepsy. RESULTS: The incidence was throughout all age groups higher in men than in women. The incidence in the total population had significantly declined in 1986-2002, from 71.6/100,000 to 52.9/100,000. The incidence significantly decreased in children (0.77; 0.71-0.84, p<0.0001) and adults (0.83; 0.77-0.89, p<0.0001) but increased in the elderly (1.18; 1.10-1.26, p<0.0001). The increased incidence in the elderly over the time period was primarily seen in women. CONCLUSION: The incidence of epilepsy has significantly declined in both children and adults with a concurrent increase in the incidence among the elderly. Further studies are needed to elucidate the precise cause of these temporal changes.

Adult↗
PubMed2006

Propofol in the treatment of refractory status epilepticus.

OBJECTIVES: To study prospectively the effects of propofol anesthesia on seizure control, hemodynamics and course of intensive care in patients with refractory status epilepticus. DESIGN AND SETTING: Prospective observational study in the general intensive care unit in a tertiary university hospital. PATIENTS: Ten patients with refractory status epilepticus. INTERVENTIONS: Patients received propofol anesthesia aiming to burst suppression EEG pattern for 12 h. MEASUREMENTS AND RESULTS: Dose of propofol, quality of burst suppression EEG, hemodynamics and the course of intensive care were recorded. Clinical and electrophysiological seizures terminated quickly, but maintaining burst suppression EEG pattern required incremental doses of propofol. Despite high doses of propofol, recovery from anesthesia was fast. CONCLUSIONS: High doses of propofol are needed in the treatment of refractory status epilepticus. The maintenance of continuous-burst suppression is difficult, and vigilant titrating of dosage of propofol is necessary under continuous EEG monitoring.

Adult↗
PubMed2006

Long-term effects of tiagabine monotherapy on cognition and mood in adult patients with chronic partial epilepsy.

The long-term effects of tiagabine monotherapy on cognition and mood were evaluated in adult patients with chronic partial epilepsy in a 48-week, open-label extension period that followed an 8-week, double-blind, titration study. Cognitive function was evaluated using neuropsychological evaluations that measured learning and memory, general intellectual ability, attention and mental speed, and reaction speed. Mood was assessed using a Finnish modification of the Profile of Mood States. Of the 34 patients who entered the open-label extension period, 18 successfully continued long-term monotherapy and underwent neuropsychological evaluation at 48 weeks of tiagabine monotherapy. The mean daily dose of tiagabine monotherapy at the end of open-label treatment was 19.7 mg/day (range, 5-35 mg/day). Tiagabine monotherapy did not adversely affect cognitive function. No significant changes in mood were observed. The median number of seizures was 2 (range, 0-71), and 8 patients (44%) were seizure-free during the 48 weeks of open-label tiagabine treatment. The results of this small open-label extension study indicate that patients with chronic partial epilepsy who were successfully converted to long-term tiagabine monotherapy demonstrated no adverse effects on cognitive function or mood.

Adolescent↗
PubMed2006

Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy.

PURPOSE: This study evaluated obstetric and neonatal outcome in a community-based cohort of women with active epilepsy (WWAE) compared with the general pregnant population receiving modern obstetric care. METHODS: We reviewed the total population who gave birth between January 1989 and October 2000 at Kuopio University Hospital. Obstetric, demographic, and epilepsy data were collected prospectively from 179 singleton pregnancies of women with epilepsy and from 24,778 singleton pregnancies of unaffected controls. The obstetric data from the pregnancy register was supplemented with detailed neurologic data retrieved from the medical records. The data retrieved were comprehensive because of a follow-up strategy according to a predecided protocol. RESULTS: During pregnancy, the seizure frequency was unchanged, or the change was for the better in the majority (83%) of the patients. We found no significant differences between WWAE and controls in the incidence of preeclampsia, preterm labor, or in the rates of caesarean sections, perinatal mortality, or low birth weight. However, the rate of small-for-gestational-age infants was significantly higher, and the head circumference was significantly smaller in WWAE. Apgar score at 1 min was lower in children of WWAE, and the need for care in the neonatal ward and neonatal intensive care were increased as compared with controls. The frequency of major malformations was 4.8% (-0.6-10.2%; 95% confidence interval) in the 127 children of WWAE. CONCLUSIONS: Pregnancy course is uncomplicated and neonatal outcome is good in the majority of cases when a predecided protocol is used for the follow-up of WWAE in antenatal and neurologic care. Long-term follow-up of the neurologic and cognitive development of the children of WWAE is still needed.

Abnormalities, Drug-Induced↗
PubMed2006

Comparison of the cognitive effects of tiagabine and carbamazepine as monotherapy in newly diagnosed adult patients with partial epilepsy: pooled analysis of two long-term, randomized, follow-up studies.

PURPOSE: Patients with epilepsy are at greater risk for cognitive impairment than are age- and education-matched controls. Cognitive decline is a significant adverse event associated with many first-generation anticonvulsant drugs (AEDs); however, the past decade has seen the introduction of several new AEDs with more-favorable cognitive profiles. Tiagabine (TGB) is indicated as adjunctive therapy for the treatment of partial seizures. The cognitive effects of TGB and carbamazepine (CBZ) monotherapy were evaluated in adult epilepsy patients with partial seizures. METHODS: This analysis pooled data from two randomized studies with similar populations, dosing, and cognitive assessments. TGB was titrated to 20-30 mg/day and CBZ to 400-800 mg/day over a 6-week period. A control or no-drug group of untreated patients with a single epileptic seizure was included for comparison. Cognitive function was assessed at baseline and 52 weeks. RESULTS: Of the 105 epilepsy patients enrolled, 79 completed the 52 weeks of monotherapy (TGB, 74%; CBZ, 77%). Altogether, 19 untreated patients composed the no-drug group. During the 52-week follow-up, only one statistically significant difference was found between the treatment groups and the no-drug group [verbal fluency task: F(2, 92) = 3.16; p = 0.047]. On further analysis, it was determined that this statistical difference was solely based on the patients receiving CBZ performing worse than the control group (p = 0.048). Statistically significant improvements (p < 0.05) were found on six (26%) of 23 variables with TGB and CBZ, as well as the no-drug group, although the variables differed between the groups. Significant worsening in the test scores was not seen in any of the study groups. CONCLUSIONS: The results of this 52-week, follow-up study show that successful TGB monotherapy with 20-30 mg/day has a cognitive profile similar to that of successful long-term CBZ monotherapy with 400-800 mg/day in newly diagnosed patients with epilepsy and to that of untreated patients with a single seizure. We observed no significant decline in cognitive scores associated with TGB monotherapy.

Adolescent↗
PubMed2005

Color vision and contrast sensitivity in epilepsy patients treated with initial tiagabine monotherapy.

The purpose of the study was to determine whether the use of a GABAergic antiepileptic drug (AED), tiagabine, affects color vision and contrast sensitivity. Twenty newly diagnosed patients with partial epilepsy (aged 19-72 years), receiving tiagabine as their initial monotherapy for 5-41 months were examined. Color vision was examined with the Standard Pseudoisochromatic Plates 2 (SPP2), with the Farnsworth-Munsell 100 Hue Test (FM100) and with the Color Vision Meter 712 (CVM) anomaloscope. Contrast sensitivity was measured with the Pelli-Robson letter chart. Three patients excluded from the color vision evaluation for congenital red-green color vision defects. Seven out of 17 patients (41%) had acquired color vision deficit examined with the FM100. The CVM anomaloscope revealed minor defects in two patients. Contrast sensitivity function was within normal ranges. The present study suggests that AED therapy with tiagabine, like with other established and newer AEDs may interfere with color perception.

Adult↗
PubMed2005

Carotid stenosis degree in CT angiography: assessment based on luminal area versus luminal diameter measurements.

The aim of this study was to investigate CT angiography (CTA) luminal area measurements in the assessment of carotid artery stenosis compared with the current clinically used criteria based on lumen diameter measurements. Seventy-two vessels in 36 patients were evaluated by CTA and digital subtraction angiography (DSA). Two observers measured area and diameter stenosis degrees using automated 3D CTA analysis software. The ratio of the largest/smallest luminal diameter at the level of maximal stenosis (L/S ratio) was used to describe lumen morphology. Diagnostic agreement between CTA and DSA was calculated. For the assessment of area stenosis, interobserver and intraobserver correlation coefficients were 0.898 and 0.906 (p<0.001). The correlation coefficient between the diameter stenosis and area stenosis was lower in stenoses with extremely noncircular lumen (L/S ratio>or=1.5) (r=0.797, p<0.001) compared with stenoses with circular lumen (LS ratio<1.2) (r=0.978, p<0.001). Only satisfactory agreement (kappa 0.54-0.77, p<0.001) was obtained between area stenosis on CTA and diameter stenosis on DSA. Assessment of stenosis degree with area measurements on 3D CTA proved to be reproducible. Area stenosis provides a less-severe estimate of the degree of carotid stenosis but might theoretically express the real hemodynamic significance of the lesion better than diameter stenosis, especially in stenoses with noncircular lumen.

Aged↗
PubMed2005

Cystatin C expression is associated with granule cell dispersion in epilepsy.

Human temporal lobe epilepsy (TLE) is associated with cellular alterations (eg, hilar cell death, neurogenesis, and granule cell dispersion) in the dentate gyrus but their underlying molecular mechanism are not known. We previously demonstrated increased expression of cystatin C, a protease inhibitor linked to both neurodegeneration and neurogenesis, during epileptogenesis in the rat hippocampus. Here, we investigated cystatin C expression in the dentate gyrus in chronic epilepsy and its association with neuronal loss and neurogenesis. In both rats with epilepsy and human patients with TLE, cystatin C expression was increased in glial cells in the molecular layer of the dentate gyrus, being most prominent in cases with granule cell dispersion. In patients with TLE, high cystatin C expression associated with greater numbers of polysialylated neural cell adhesion molecule-positive newborn cells in the molecular layer, although the overall number was decreased, indicating that the newborn cells migrate to abnormal locations in the epileptic dentate gyrus. These data thus demonstrate that cystatin C expression is altered during the chronic phase of epilepsy and suggest that cystatin C plays a role in network reorganization in the epileptic dentate gyrus, especially in granule cell dispersion and guidance of migrating newborn granule cells.

Adolescent↗
PubMed2005

Ophthalmologic and neurologic findings in two children exposed to vigabatrin in utero.

Vigabatrin (VGB) is an important treatment option for infantile spasms. Vigabatrin-induced visual field defects are at present the most important safety issue in the use of the drug. The knowledge concerning VGB-associated visual dysfunction in pediatric patients, particularly in those who have been exposed to VGB in utero is limited. We explored ophthalmic and neurologic findings in two children who have been exposed prenatally to VGB.

Adult↗
PubMed2005

Children exposed to valproate in utero--population based evaluation of risks and confounding factors for long-term neurocognitive development.

PURPOSE: To evaluate neurological and cognitive functioning of school-aged (> or =6 years) children exposed to valproate monotherapy in utero in a population based, evaluator-blinded, controlled study. METHODS: Studied children (N=39, aged 6.6-13.4 years) and their mothers were identified through a population based pregnancy registry. Mothers with carbamazepine monotherapy and mothers with epilepsy but without antiepileptic drug (AED) treatment during pregnancy and their age and gender matched children served as controls. Hospital records were reviewed and neurological examination (Touwens test), intelligent quotients (IQ) of mothers (WAIS), and children (WISC-III) and neuropsychological assessment of children (NEPSY) were performed evaluator-blinded. RESULTS: The prevalence of low intelligence (FIQ<80) was 19% (4/21) and the prevalence of exceptionally low intelligence (FIQ<70) 10% (2/21) in valproate (VPA) monotherapy exposed children. Children exposed to carbamazepine (CBZ) and children of women with epilepsy but without AED exposure during pregnancy had all at least low average intelligence. The mothers using valproate scored significantly lower (p<0.05) in FIQ, VIQ and PIQ tests and had also significantly lower (p=0.035) educational level. Altogether 21% (8/39) of the children had minor neurological dysfunctions. CONCLUSIONS: In a population based setting inheritance and cumulating environmental factors may partly explain the increased prevalence of neurocognitive symptoms in children exposed to valproate in utero although concern about the possible long-term effects of intrauterine valproate exposure does exist.

Adolescent↗
PubMed2005

Visual function in epilepsy patients treated with initial valproate monotherapy.

PURPOSE: To investigate whether initial valproate (VPA) monotherapy for the treatment of epilepsy causes visual field defects and visual dysfunction. METHODS: In a cross-sectional study, visual fields were examined with the kinetic Goldmann and automated Humphrey perimeters, contrast sensitivity function with the Pelli-Robson letter chart and colour vision with the Standard Pseudoisochromatic Plates Part 2 (SPP 2) and Farnsworth-Munsell 100 Hue test (FM 100) in eighteen epilepsy patients (aged 18--50 years, 30.2.+/-10 years, mean+/-S.D.) treated with initial valproate monotherapy for 2--20 years (8.4+/-5.1 years). RESULTS: None had vigabatrin-type, concentric visual field defect with the kinetic Goldmann or automated Humphrey perimetries. In the Humphrey perimetry, the mean deviation for the group was within normal limits varying from -2.53 to 0.59 dB (-0.74+/-0.80 dB) in the right eye and from -2.66 to 0.67 dB (-0.78+/-0.82 dB) in the left eye. In the FM 100 test, acquired colour vision deficiency was found in two out of 18 patients (11%, 95% CI: 0--25%). However, the mean total error score was lower in the patient group than in the control group. All patients had normal contrast sensitivity function. CONCLUSIONS: The use of VPA in the treatment of epilepsy is not associated with visual field defects similar to vigabatrin, but may induce abnormalities in colour vision.

Adult↗
PubMed2005

Pharmacologic management of convulsive status epilepticus in childhood.

The incidence of convulsive status epilepticus in children is approximately 20-50/100,000/year, and is an emergency requiring prompt medical intervention. Prolonged seizures lasting over 5 min are unlikely to stop spontaneously, and time-to-treatment influences treatment response. Prolonged seizures should thus be treated as early status epilepticus. Mortality and morbidity increase significantly with the length of ongoing seizure activity, especially after 60 min. Benzodiazepines remain the first-line drug therapy due to their rapid onset of action. Recent studies imply that buccal midazolam is more effective and easier to administer than rectal diazepam. Phenytoin/fosphenytoin and phenobarbital administered intravenously remain the second-line treatments of choice, whilst barbiturates and midazolam as intravenous anesthetics are used for third-line treatment. Electroencephalogram monitoring is essential to evaluate the electrophysiologic treatment response and depth of anesthesia, especially in refractory status epilepticus. In the future, more individualized protocols and pathways are needed in order to optimize treatment responses. Randomized clinical trials are needed to evaluate new treatment protocols, which should not only stop the seizures more effectively but also be safer and include some neuroprotective elements to halt the cascade of neuronal injury and minimize the risk for neurologic morbidity caused by the convulsive status epilepticus.

Child↗
PubMed2005

Refractory generalised convulsive status epilepticus : a guide to treatment.

The patient with status epilepticus has continuous or rapidly repeating seizures. Generalised convulsive status epilepticus (GCSE) is the most common form of the disorder and is a life-threatening condition that requires prompt medical management. Status epilepticus that does not respond to first-line benzodiazepines (lorazepam or diazepam) or to second-line antiepileptic drugs (phenytoin/fosphenytoin, phenobarbital or valproate) is usually considered refractory and requires more aggressive treatment. The optimal treatment of refractory GCSE has not been defined, but patients should be treated in an intensive care unit, as artificial ventilation and haemodynamic support are required. Invasive haemodynamic monitoring is often necessary and EEG monitoring is essential. The drug treatment of refractory GCSE involves general anaesthesia with continuous intravenous anaesthetics given in doses that abolish all clinical and electrographic epileptic activity, often requiring sedation to the point of burst suppression on the EEG. Barbiturate anaesthetics, pentobarbital in the US and thiopental sodium in Europe and Australia, are the most frequently used agents and are highly effective for refractory GCSE both in children and adults. Indeed, they remain the only way to stop seizure activity with certainty in severely refractory cases. Other options are midazolam for adults and children and propofol for adults only.Regardless of the drug selected, intravenous fluids and vasopressors are usually required to treat hypotension. Once seizures have been controlled for 12-24 hours, continuous intravenous therapy should be gradually tapered off if the drug being administered is midazolam or propofol. Gradual tapering is probably not necessary with pentobarbital or thiopental sodium. Continuous EEG monitoring is required during high-dose treatment and while therapy is gradually withdrawn. During withdrawal of anaesthetic therapy, intravenous phenytoin/fosphenytoin or valproate should be continued (these agents having been administered during earlier phases of GCSE) to ensure an adequate baseline of antiepileptic medication so as to prevent the recurrence of status epilepticus. If additional medication is needed, the most appropriate antiepileptic drugs are gabapentin for focal seizures and levetiracetam and topiramate for all seizure types, as these drugs can be started at high doses with a low risk of idiosyncratic reactions. Even with current best practice, mortality in patients who experience refractory GCSE is about 50% and only the minority return to their premorbid functional baseline. Therefore, new treatment options are urgently needed. The ideal new drug for refractory GCSE would be one that has the ability to stop seizures more effectively and safely than current drugs, and that has neuroprotective properties to prevent the brain damage and neurological morbidity caused by GCSE.

Age Factors↗
PubMed2005

MR volumetric analysis of the piriform cortex and cortical amygdala in drug-refractory temporal lobe epilepsy.

BACKGROUND AND PURPOSE: The assessment of patients with temporal lobe epilepsy (TLE) traditionally focuses on the hippocampal formation. These patients, however, may present structural abnormalities in other brain areas. Our purpose was to develop a method to measure the combined volume of the human piriform cortex and cortical amygdala (PCA) by using MR imaging and to investigate PCA atrophy. METHODS: The definition of anatomic landmarks on MR images was based on histologic analysis of 23 autopsy control subjects. Thirty-nine adults with chronic TLE and 23 age-matched control subjects were studied. All underwent high-spatial-resolution MR imaging at 1.5T, including a tilted T1-weighted 3D dataset. The PCA volumes were compared with the control values and further correlated with hippocampal, amygdala, and entorhinal cortex volumes. RESULTS: The normal volume was 530 +/- 59 mm(3) (422-644) [mean +/- 1 SD (range)] on the right and 512 +/- 60 mm(3) (406-610) on the left PCA (no asymmetry, and no age or sex effect). The intraobserver and interobserver variability were 6% and 8%, respectively. In right TLE patients, the mean right PCA volume was 18% smaller than in control subjects (P < .001) and 15% smaller than in left TLE (P < .001). In left TLE, the mean left PCA volume was 16% smaller than in control subjects (P < .001) and 19% smaller than in right TLE (P < .001). Overall, 46% (18/39) of the patients had a greater than 20% volume reduction in the ipsilateral PCA. There was bilateral atrophy in 18% (7/39). Patients with hippocampal volumes of at least 2 SDs below the control mean had an 18% reduction in the mean PCA volume compared with patients without hippocampal atrophy (P < .001). Ipsilaterally, hippocampal (r = 0.756, P < .01), amygdaloid (r = 0.548, P < .01), and entorhinal (r = 0.500, P < .01) volumes correlated with the PCA volumes. CONCLUSION: The quantification of PCA volume with MR imaging showed that the PCA is extensively damaged in chronic TLE patients, particularly in those with hippocampal atrophy.

Adolescent↗