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Biomedical subjects

P Uldall

Publications and source records attributed to P Uldall.

At least 19 recordsLinked to original sources
PubMed2006

The misdiagnosis of epilepsy in children admitted to a tertiary epilepsy centre with paroxysmal events.

AIMS: To determine the proportion of children admitted with difficult to treat paroxysmal events to a tertiary epilepsy centre who did not have epilepsy. METHODS: In an observational retrospective study, all case notes of 223 children admitted in 1997 were examined. The referral was made from the local paediatric department in 51% of cases, other departments in 27%, and from general or specialist practitioners in 22%. Doubt regarding the diagnosis of epilepsy was expressed in the referral note in 17%. On admission, 86% were on antiepileptic drug treatment. During admission all children were subjected to a comprehensive intensive observation and 62% had EEG monitoring. RESULTS: In total, 39% (87/223) were found not to have epilepsy. In 30% of children (55/184) referred without any doubts about the epilepsy diagnosis, the diagnosis was disproved. Of the 159 children admitted for the first time, 75 (47%) were discharged with a diagnosis of non-epileptic seizures. Of 125 children admitted for the first time with no doubts about the diagnosis of epilepsy, 44 (35%) did not have epilepsy. Staring episodes were the most frequently encountered non-epileptic paroxysmal event. Psychogenic non-epileptic seizures were found in 12 children. A total of 34 (15%) had their medication tapered off; a further 22 (10%) had tapered off medication before admission. CONCLUSION: The present study supports the view that misdiagnosis of epilepsy is common. The treating physician should be cautious in diagnosis, especially of staring episodes. A diagnostic re-evaluation should be undertaken in difficult cases with continuing paroxysmal events in order to avoid unnecessary drug treatment and restrictions on the child's lifestyle.

Adolescent↗
PubMed2004

Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?

AIM: To investigate risk factors of adverse outcome in a cohort of very preterm children treated mainly with nasal continuous positive airway pressure (CPAP) during the neonatal course. METHODS: In Denmark, preterm children are treated with nasal CPAP as a first approach to respiratory support. A national prospective study of all infants with a birthweight below 1000 g or a gestational age below 28 wk born in 1994-1995 was initiated to evaluate this approach. Of the 269 surviving children 164 (61%) were not treated with mechanical ventilation in the neonatal period. A follow-up of the children at 5 y of age was conducted. Data from the neonatal period and the 5-y follow-up were analysed. RESULTS: In multivariate analyses including 250 children, a severely abnormal neonatal brain ultrasound scan was predictive of cerebral palsy (OR = 19.9, CI 95%: 6.1-64.8) and intellectual disability (OR = 6.2, CI 95%: 2.3-16.5). A high Clinical Risk Index for Babies (CRIB) score (OR = 2.4, CI 95%: 1.1-5.5) and chronic lung disease (OR = 2.8, CI 95%: 1.2-6.9) were predictive of intellectual disability. In univariate analyses mechanical ventilation was associated with cerebral palsy (OR=4.3, CI 95%: 1.7-10.8) and intellectual disability (OR = 2.2, CI 95%: 1.2-4.2), but the associations became insignificant in multivariate analyses including chronic lung disease and a severely abnormal ultrasound scan. CONCLUSION: The associations between neonatal risk factors and adverse outcome in our cohort were very similar to those found in other cohorts with another initial treatment of respiratory insufficiency. We found no significant adverse effects of mechanical ventilation beyond what could be explained by associations with chronic lung disease and IVH 3-4/PVL.

Cerebral Palsy↗
PubMed2001

Lamotrigine plasma levels reduced by oral contraceptives.

Although it is known that the use of oral contraceptives (OC's) can induce glucuronide conjugating enzymes, currently no data exists as to the potential that the elimination of the glucuronidated drug lamotrigine (LTG) is increased by OC's. We present seven cases in whom the plasma levels of LTG were significantly decreased by OC's (mean 49%, range 41-64%). The interaction was of clinical relevance in most of the patients who either experienced increased seizure frequency/recurrence of seizures after OC's had been added, or adverse effects following withdrawal of OC's.

Adolescent↗
PubMed2001

Cerebral palsy births in eastern Denmark, 1987--90: implications for neonatal care.

The Cerebral Palsy Register in eastern Denmark has collected cases using a uniform data sampling procedure since birth year 1979. We have investigated changes in the rate of cerebral palsy, related to gestational age, mortality and perinatal risk factors in children born 1983--90. The total cerebral palsy birth prevalence decreased from 3.0 in the birth year period 1983--86 to 2.4 per 1000 live births (P < 0.01) in 1987--90, owing to a decrease among all preterm infants (29--19 per 1000, P < 0.001). The perinatal and early neonatal mortality in preterm infants was unchanged from 1983--86 to 1987--90. The rate of cerebral palsy in term infants was 1.5 per 1000 in all birth-year periods from 1979--90. Among the cerebral palsy infants, the proportion of very preterm babies treated with mechanical ventilation in the neonatal period decreased from 95% in 1983--86 to 61% in 1987--90 (P < 0.001), while the group treated with CPAP among the moderately preterm babies increased from 61% to 78% (P < 0.05). The significant decline in cerebral palsy rate in preterm infants born 1987--90 may be due to a change in treatment at the neonatal intensive care units using less mechanical ventilation, a hypothesis which needs further investigation.

Cerebral Palsy↗
PubMed2001

The Danish Cerebral Palsy Registry. A registry on a specific impairment.

Cerebral palsy (CP) is the commonest disabling impairment in childhood, with a prevalence of 2-3 per 1000 live births. The Danish Cerebral Palsy Registry is a research registry that contains cases of CP from birth year 1925 and has estimated the birth prevalence since 1950. Data on children with CP are collected from paediatric departments and one special institution for disabled children. The children are included by a child neurologist and an obstetrician, and information on pregnancy, birth, neonatal period, impairments and demographic data on the child and mother are registered in a standard form. The uptake area is eastern Denmark, covering about 50% of the population, but the rest of Denmark is planned to be included from 2001. The Registry is large, well established and validated, and the definitions and collection procedures have not changed through several decades. It therefore has great research potential. Birth prevalence is estimated continuously, and changes over time are analysed and correlated with pre- and perinatal conditions. A correlation between increased survival of preterm babies and an increased prevalence was found previously, and a decreased prevalence in very preterm infants was later associated with less use of mechanical ventilation. A study correlating CP and maternal infection is ongoing. Collaboration between 14 European CP registries allows the true differences in prevalence between different countries to be studied. Linkage to other individually based registries in Denmark will allow the social consequences of CP to be described.

Cerebral Palsy↗
PubMed2000

Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study.

Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.

Adolescent↗
PubMed2000

Landau-Kleffner syndrome with onset at 18 months and an initial diagnosis of pervasive developmental disorder.

We report one of the youngest and most intensively studied cases of Landau-Kleffner syndrome, with a follow-up of 5 years. The boy developed normally until the age of 18 months when he had two attacks, possibly epileptic. Electroencephalogram (EEG) was normal. Over the next 5 months he lost his six to ten words, did not engage with other children and became mute. When he was 34 months old a child-psychiatrist suggested a diagnosis of pervasive developmental disorder or developmental dysphasia. An EEG 3 months later showed abnormalities typical of Landau-Kleffner syndrome. His non-verbal abilities were normal as well as his neurological examination and brain magnetic resonance imaging (MRI). A trial of clobazam and vigabatrin was unsuccessful. When he was 4 years and 9 months old he was treated with corticosteroids and within 3 months his vocabulary increased from the standard for 1 1/2 years of age to that for 2 1/2 years of age. His language abilities continued to improve slowly until a stagnation period at the age of 6 years and 9 months. A second course of corticosteroids improved his comprehension and vocabulary to an almost normal level, and his EEG normalized. A total of 11 EEGs were obtained; all included sleep, but continuous spike and wave during slow sleep was never documented. This report illustrates that Landau-Kleffner syndrome should be considered as an alternative diagnosis in children diagnosed with developmental dysphasia. An EEG including sleep should be considered, and in the presence of abnormalities a trial of anti-epileptic drugs or corticosteroids should be undertaken.

Brain↗
PubMed2000

Provocation of non-convulsive status epilepticus by tiagabine in three adolescent patients.

Three girls, two aged 12 years and one aged 17 years with refractory localization-related epilepsy were treated on an add-on basis with tiagabine. At dosages 22.5-30 mg/day (0.45-0.57 mg/kg/day) longstanding non-convulsive status epilepticus was noted in all three patients. The events of non-convulsive status epilepticus subsided following reduction in tiagabine dosages. In two cases, tiagabine was withdrawn, whereas it was continued at a lower dosage in one case. This is the first report of non-convulsive status epilepticus provoked by tiagabine in adolescent patients.

Adolescent↗
PubMed1999

Clinical experiences with topiramate in children with intractable epilepsy.

At a tertial referral epilepsy centre 39 children were consecutively enrolled in an open add-on study with topiramate (TPM). All children had intractable epilepsy; the mean seizure frequency was 36 per month, and 31 children were treated with polypharmacy. All but five children were mentally retarded. The initial dose of TPM was 0.5-1 mg/kg daily, slowly titrated with 1-3 mg/kg daily every second week with an estimated target dose of 10 mg/kg daily. At latest follow-up 19 children continued on TPM, three (8%) were seizure-free, eight (21%) had a seizure reduction of more than 50% and eight (21%) improved their general condition. Mean follow-up was 13 months (range 9-36 months). Seizure reduction was seen in focal as well as generalized epilepsies. Adverse effects were reported in 21 cases (54%), weight loss and sedation being most frequent. The mean steady state dose in the children continuing on TPM was at latest follow-up: 14 mg/kg daily (< 5 years), 10 mg/kg daily (5-7 years), 5.8 mg/kg daily (8-17 years). The corresponding plasma level varied from 3 to 45 mumol/litre, and a significant correlation between the daily dose in mg/kg and the plasma level was found. Two patients with progressive myoclonus epilepsy are described separately; one had a dramatic general improvement. It is concluded that TPM seems to be a promising new broad-spectrum anti-epileptic drug, which is efficacious even in epilepsy syndromes, intractable to other new anti-epileptic drugs such as vigabatrin and lamotrigine.

Adolescent↗
PubMed1999

Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.

The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a progressive and ultimately fatal neurodegenerative disease of childhood. The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease. To better understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. Two mutations were particularly common: an intronic G-->C transversion in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a C-->T transition in 32 of 115 alleles, which prematurely terminates translation at amino acid 208 of 563. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL.

Amino Acid Sequence↗
PubMed1997

Validation of a cerebral palsy register.

OBJECTIVES: To analyse completeness and validity of data in the Cerebral Palsy Register in Denmark, 1979-1982. METHODS: Completeness has been assessed by comparing data from The Danish National Patient Register (DNPR) with the cases included in the Cerebral Palsy Register (CPR). Agreement between 12 variables in the CPR and obstetrical medical records has been analysed using kappa-statistics. RESULTS: Of 468 children in the DNPR, only 237 fulfilled the inclusion criteria of the CPR; and 35 (15%) of these cases had not been reported to the CPR. Data agreement was generally good, but gestational age was subject to a systematic error, and urinary infections in pregnancy (kappa = 0.43) and placental abruption (kappa = 0.52) were seriously under-reported in the CPR. CONCLUSIONS: Completeness of the Cerebral Palsy Register in Denmark, 1979-1982, has been assessed to maximal 85%, emphasizing the impact of using supplementary case ascertainment sources in the future. Validity of data varied according to definition and significance of the specific variable.

Bias↗
PubMed1997

Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1.

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.

Base Sequence↗
PubMed1997

Trend in cerebral palsy birth prevalence in eastern Denmark: birth-year period 1979-86.

To investigate changes in cerebral palsy birth prevalence and perinatal mortality rate by different gestational age groups, 1979-86, cerebral palsy cases in eastern Denmark were identified from the Danish Cerebral Palsy Register, and information on birth and mortality rates was sought in the Danish Medical Birth Register. From 1979-82 to 1983-86, the birth prevalence of cerebral palsy increased from 2.6 to 3.0 per 1000 (P < 0.05). The rate for infants of 31 weeks' gestation or more did not change, whereas a significant increase was observed in infants below 31 weeks (85-123 per 1000, P < 0.05). In the same periods, perinatal mortality in eastern Denmark decreased significantly from 8.6 to 7.8 per 1000. The decrease in stillbirth rate was significant in all subgroups of gestational ages except in those of 28-30 weeks' gestation. The early neonatal mortality rate decreased significantly only in infants below 31 weeks (282-239 per 1000, P < 0.05). Thus, in eastern Denmark, cerebral palsy birth prevalence has increased from birth-year period 1979-82 to 1983-86 because of an increased rate in preterm infants below 31 weeks, who at the same time had a reduced risk of early neonatal death.

Cerebral Palsy↗
PubMed1997

Preterm birth and cerebral palsy. Predictive value of pregnancy complications, mode of delivery, and Apgar scores.

BACKGROUND: Preterm infants are at 8 times higher risk than term infants for pre- and perinatal brain damage, resulting in cerebral palsy. In this paper we have analysed the influence of prenatal and birth-related risk factors on cerebral palsy in preterm infants. METHODS: In a register-based study, 175 preterm singleton infants with cerebral palsy, born in 1982-86, were compared with 687 controls matched by gestational age and year of birth. RESULTS: Statistically significant higher rates in cases were found in parity > or = 3 (22% vs. 16%, p < 0.05), Cesarean section (67% vs. 56%, p < 0.01), and low Apgar scores at 1 minute (45% vs. 36%, p < 0.05). By multivariate analyses, two variables remained statistically significant: parity > or = 3 (adjusted OR = 1.53 (95% CI 1.00-2.34), p < 0.05) and Cesarean section (adjusted OR = 1.57 (95% CI 1.07-2.32), p < 0.05). CONCLUSIONS: Pregnancy complications preceding preterm birth did not imply a higher risk of cerebral palsy. Delivery by Cesarean section was a prognostic factor for developing cerebral palsy, and the predictive value of Apgar scores was highly limited.

Adult↗
PubMed1996

Intrauterine growth and gestational age in preterm infants with cerebral palsy.

In a case-control study, gestational age and intrauterine growth of 191 preterm singleton infants 1971-82 with cerebral palsy were compared to all preterm live-born singletons in Denmark in 1982 (N = 2203). The distribution of gestational age among preterm cases was slightly bimodal with maximum values at 29 and 32 weeks. The risk for cerebral palsy was highest in the infants with gestational age 28-30 weeks (OR = 5.6 (4.0-7.8), 95% confidence interval). Birth weight deviation, in the 34-36 weeks infants, expressed as the number of standard deviations from the mean birth weight for gestational age, was more negative in cases than in controls (P < 0.001). The frequency of small for gestational age (SGA) was 13% in cases and 9% in controls (OR = 1.5 (0.96-2.3), 95% confidence interval). The odds for cerebral palsy being SGA, was lower in 28-30 weeks (OR = 0.22 (0.06-0.86), 95% confidence interval), the same in 31-33 weeks (OR = 0.83 (0.35-2.0), 95% confidence interval) and higher in 34-36 weeks (OR = 5.2 (2.9-9.5), 95% confidence interval). In conclusion, preterm infants with cerebral palsy are born earlier than other preterm infants. Small for gestational age is associated with cerebral palsy in preterm infants only above 33 weeks.

Case-Control Studies↗
PubMed1995

Vigabatrin in childhood epilepsy: a 5-year follow-up study.

In an retrospective uncontrolled long-term study in 30 children with intractable epilepsy, it was found that treatment with vigabatrin resulted in a seizure reduction of more than 50% at 1-year follow-up in 40% of the children. The responders were all children with partial seizures. Side effects were mild and did not lead to discontinuation of the drug. Increased numbers of seizures were seen in three cases. A moderate weight increase was seen in 27% of the children. At 5-year follow-up 7 children (23%) still maintained a seizure reduction of more than 50%. Trials of monotherapy in three seizure-free patients were unsuccessful. No further side effects were observed. A study of evoked potentials in 12 children showed no alteration in latency and amplitudes of VEP following treatment with vigabatrin. Our results show that in children vigabatrin seems to have a stable effect even though a few children may experience a breakthrough of seizures. The presented results together with previous reports on MRI-scans seem to indicate that even in children with a still maturing CNS vigabatrin is a safe drug.

Adolescent↗