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Biomedical subjects

Kai Eriksson

Publications and source records attributed to Kai Eriksson.

13 recordsLinked to original sources
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

Cystatin B: mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients.

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessive neurodegenerative disorder caused by mutations in the cystatin B gene (CSTB) that encodes an inhibitor of several lysosomal cathepsins. An unstable expansion of a dodecamer repeat in the CSTB promoter accounts for the majority of EPM1 disease alleles worldwide. We here describe a novel PCR protocol for detection of the dodecamer repeat expansion. We describe two novel EPM1-associated mutations, c.149G > A leading to the p.G50E missense change and an intronic 18-bp deletion (c.168+1_18del), which affects splicing of CSTB. The p.G50E mutation that affects the conserved QVVAG amino acid sequence critical for cathepsin binding fails to associate with lysosomes. This further supports the previously implicated physiological importance of the CSTB-lysosome association. Expression of CSTB mRNA and protein was markedly reduced in lymphoblastoid cells of the patients irrespective of the mutation type. Patients homozygous for the dodecamer expansion mutation showed 5-10% expression compared to controls. By combining database searches with RT-PCR we identified several alternatively spliced CSTB isoforms. One of these, CSTB2, was also present in mouse and was analyzed in more detail. In real-time PCR quantification, CSTB2 expression was less than 5% of total CSTB expression in all human adult and fetal tissues analyzed. In patients homozygous for the minisatellite mutation, the level of CSTB2 was reduced similarly to that of CSTB implicating regulation from the same promoter. The physiological significance of CSTB2 remains to be determined.

Alternative Splicing↗
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↗
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

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↗
PubMed2004

Outcome after prolonged convulsive seizures in 186 children: low morbidity, no mortality.

Prolonged convulsive seizures are a common neurological emergency and a potential cause of neuronal damage and functional sequelae. We explored the role of seizure duration and various background factors for neurological sequelae in children with prolonged convulsive seizures. The population-base of this study was all children (age < 16 years) who had been admitted to the Tampere University Hospital, Finland between 1993 and 1999 with convulsive seizures lasting more than 5 minutes. Patients were followed up individually (mean length of follow-up 2 years 1 month, range 0 to 7 years 8 months). All available data on the prolonged seizure episodes and clinical follow-up were analyzed retrospectively by a detailed review of all medical charts and records. In 186 children (94 males, 92 females; mean age 4 years 5 months, SD 3 years 10 months, range 1 month to 15 years 4 months) there were 279 separate convulsive seizure episodes lasting over 5 minutes, yielding an annual incidence of 47.5 out of every 100000 episodes. Seizure aetiology was idiopathic in 26.2% of episodes, febrile in 41.9%, remote symptomatic in 28%, and acute symptomatic in 3.9% of episodes. Mean duration of all seizure episodes was 42.5 minutes (SD 46.1 minutes) and was significantly correlated with the aetiology: shortest in the febrile group (mean 35.4 minutes) and longest in the acute symptomatic group (mean 88.6 minutes; p < 0.001). There was no mortality related directly to these acute seizure episodes. The most common sequela was an onset of epilepsy in 40 children (22%). Permanent neurological sequelae were noted in only four patients (2.2%; mean seizure duration 16 minutes) and non-permanent sequelae in six patients (3.2%; mean seizure duration 38 minutes). Neurological sequelae of prolonged convulsive seizures in children are rare and are related to aetiological factors rather than the duration of a single seizure. The role of acute seizures in the evolution of epilepsy in children remains obscure.

Adolescent↗
PubMed2004

Uptake of GABA and activity of GABA transaminase in blood platelets from children with absence epilepsy.

Childhood absence epilepsy (CAE) is a well-defined generalized epilepsy syndrome clinically characterized by frequent absence seizures. The aim of this study was to assess the activity of GABA transaminase (GABA-T) and the kinetic parameters of GABA uptake in platelets from patients with CAE. We studied 13 patients with CAE and eight sex- and age-matched controls. The mean activity of GABA-T was lower in patients with CAE than in controls (1.22+/-0.05 vs. 1.75+/-0.10 micromol/min/kg protein). The capacity of GABA uptake into the platelets was higher in patients using valproate (0.66+/-0.09 micromol/min/kg protein), but not in those using ethosuximide (0.34+/-0.05 micromol/min/kg protein), when compared to controls (0.26+/-0.06 micromol/min/kg protein). The affinity of the transporters was not altered. The observed peripheral alterations may indicate impaired function of brain GABAergic systems in children with absence epilepsy.

4-Aminobutyrate Transaminase↗
PubMed2003

Visual agnosia in a child with non-lesional occipito-temporal CSWS.

In this paper we describe a case of severe visual agnosia in a child with an electrophysiological pattern of continuous spike-wave discharges in slow sleep (CSWS) in the occipito-temporal regions. The neuropsychological spectrum related to this phenomenon is discussed. Published paediatric reports associate visual agnosia (i.e. an inability to recognize objects without impairment of visual acuity) mainly with symptomatic occipito-temporal aetiology (e.g. cortical dysplasia, vascular insults) and other neurological symptoms (e.g. autism). We describe a detailed 2 year electrophysiological and neuropsychological follow-up of an 8-year-old boy with sporadic seizures, occipito-temporal CSWS and visual agnosia. The growth and neurological development of the child had been considered as normal, neurological examination did not reveal any focal signs, visual acuity was intact and MRI was normal. First EEG and six consecutive 24 h video EEG recordings during the follow-up of 22 months showed continuous spike-and-wave activity covering over 85% of the non-REM sleep. According to structured neuropsychological tests (Wechsler Intelligence Scale for Children--Third Edition, A Developmental Neuropsychological Assessment (NEPSY), Test of Visual-Perceptual Skills, Corsi block, Hooper Visual Organization Test) the boy had normal verbal intelligence but major deficits in visual perception, especially in object recognition, impaired shape discrimination and detection, and poor copying skills. Attention and executive functions were intact. There were no difficulties in short- or long-term memory. Verbal cues and naming the objects improved visual memory. Tracing the objects with a finger or by moving the head improved object recognition. Currently the boy attends a special school with a rehabilitation plan including neuropsychological and occupational therapies. This case adds a new facet to the spectrum of neuropsychological deficits in children with CSWS. Sleep EEG should be included in the etiological studies of children with specific neuropsychological problems and detailed neuropsychological assessment is needed for diagnostic and rehabilitation purposes.

Agnosia↗
PubMed2002

Visual field constriction in 91 Finnish children treated with vigabatrin.

PURPOSE: To study the prevalence and features of visual field constrictions (VFCs) associated with vigabatrin (VGB) in children. METHODS: A systematic collection of all children with any history of VGB treatment in fifteen Finnish neuropediatric units was performed, and children were included after being able to cooperate reliably in repeated visual field tests by Goldmann kinetic perimetry. This inclusion criterion yielded 91 children (45 boys; 46 girls) between ages 5.6 and 17.9 years. Visual field extent <70 degrees in the temporal meridian was considered abnormal VFC. RESULTS: There was a notable variation in visual field extents between successive test sessions and between different individuals. VFCs <70 degrees were found in repeated test sessions in 17 (18.7%) of 91 children. There was no difference in the ages at the study, the ages at the beginning of treatment, the total duration of the treatment, general cognitive performance, or neuroradiologic findings between the patients with normal visual fields and those with VFC, but the patients with VFC had received a higher total dose of VGB. In linear regression analysis, there were statistically significant inverse correlations between the temporal extent of the visual fields and the total dose and the duration of VGB treatment. The shortest duration of VGB treatment associated with VFC was 15 months, and the lowest total dose 914 g. CONCLUSIONS: Because of a wide variation in normal visual-field test results in children, the prevalence figures of VFCs are highly dependent on the definition of normality. Although our results confirm the previous findings that VFC may occur in children treated with VGB, our study points out the need to reevaluate critically any suspected VFC to avoid misdiagnosis. Nevertheless, our study suggests that the prevalence of VFC may be lower in children than in adults, and that the cumulative dose of VGB or length of VGB therapy may add to the personal predisposition for developing VFC.

Adolescent↗
PubMed2002

Idiopathic generalised epilepsies with 3 Hz and faster spike wave discharges: a population-based study with evaluation and long-term follow-up in 71 patients.

For several years we have been following patients with intractable, childhood-onset idiopathic generalised epilepsies with > or = 3 Hz spike-wave discharges. Our need to find explanations for their intractability was the starting point for this study. We were interested in identifying characteristics, which would predict intractability; evaluating how these patients were treated and whether polytherapy was useful. We identified patients with > or = 3 Hz spike-wave discharges by reviewing EEG reports recorded between 1983 and 1992. Data were collected from medical records and through personal interviews. We identified 82 patients with tentative idiopathic generalised epilepsy. Eleven were excluded. Thirty-eight patients had childhood absence epilepsy, 18 had juvenile absence epilepsy, 13 had juvenile myoclonic epilepsy and two had eyelid myoclonia with absences: 89.5, 78, 38 and 0% of the patients in each group, respectively, had been seizure free for more than 2 years. Twenty percent of the patients had intractable seizures. All intractable patients with juvenile absence epilepsy had rhythmic, random eyelid blinking and generalised tonic-clonic seizures. A history of more than ten generalised tonic-clonic seizures was associated with intractability in juvenile myoclonic patients. Monotherapy with ethosuximide or valproate resulted in seizure control in 65% of patients. Seventeen patients (24%) were treated with polytherapy, six achieved remission. These six patients had childhood absence epilepsy and juvenile absence epilepsy. Positive outcome was found in childhood absence epilepsy and juvenile absence epilepsy. Intractable seizures were more frequent among patients with juvenile myoclonic epilepsy. None of them benefited from polytherapy with conventional anti-epileptic drugs.

Adolescent↗