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Lieven Lagae

Publications and source records attributed to Lieven Lagae.

17 recordsLinked to original sources
PubMed2006

Long-term cognitive sequelae of antenatal maternal anxiety: involvement of the orbitofrontal cortex.

Anxiety and stress experienced by the mother during pregnancy are reported to have a negative association with the cognitive development of the child. An integration of recent evidence from cognitive reaction time tasks pointed to a deficit in endogenous response inhibition, a function ascribed to prefrontal cortex. To further delineate the cognitive sequelae associated with antenatal maternal anxiety, we reviewed recent neuro-imaging literature to create a cortical map of regions commonly and selectively activated by well-known cognitive tasks. The pragmatic value of this cortical map was tested in a follow-up sample of 49 17-year old adolescents. Adolescents of mothers with high levels of anxiety during week 12-22 of their pregnancy performed significantly lower in tasks which required integration and control of different task parameters. Working memory, inhibition of a prepotent response, and visual orienting of attention were not impaired. Based on the established cortical map, these results were related to subtle developmental aberrations in a part of, or in cortical and sub-cortical regions linked to, the orbitofrontal cortex.

Animals↗
PubMed2006

Cognitive side effects of anti-epileptic drugs. The relevance in childhood epilepsy.

In recent years several new anti-epileptic drugs have been introduced, also for the treatment of childhood epilepsy. A major concern is their effect on learning and cognitive development. Testing the genuine effects on cognition of the anti-epileptic drugs is methodologically not easy. At this moment there are very few controlled trials that systematically examine the cognitive side effects of anti-epileptic drugs in childhood epilepsy. The available data indicate that the newer anti-epileptic drugs have a safe cognitive profile when prescribed correctly at the right dose and in monotherapy. Possible negative effects are mainly found for speed of processing and attention processes. As these processes are important instruments in every day learning and cognition, it is necessary to test these newer anti-epileptic drugs in well designed studies and in specific childhood epilepsy syndromes.

Anticonvulsants↗
PubMed2006

A novel mitochondrial transfer RNA(Asn) mutation causing multiorgan failure.

BACKGROUND: Mitochondrial cytopathies are a heterogeneous group of disorders with a broad spectrum of clinical symptoms. OBJECTIVE: To characterize a novel mutation in the transfer RNA(Asn) (m.5728A>G) identified in a 13-year-old boy with multiorgan failure. DESIGN: Biochemical and immunocytochemical studies were performed in combination with transmitochondrial cybrid analysis. SETTING: A university hospital. Molecular and biochemical analyses were performed in collaboration between 2 other university hospitals. PATIENT: Thirteen-year-old boy with multiorgan failure. RESULTS: In the patient's muscle tissue and cultured skin fibroblasts, a combined deficiency of complexes I and IV was found, using spectrophotometric analysis and activity staining in the gel following blue native polyacrylamide gel electrophoresis. An identical biochemical profile was seen in transmitochondrial cybrids carrying more than 55% mutant mitochondrial DNA. CONCLUSION: These data suggest that the m.5728A>G transition is a pathogenic mutation and is the cause of the respiratory chain dysfunction in the propositus.

Adolescent↗
PubMed2006

Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients.

Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a rare epilepsy syndrome. In 30 to 70% of SMEI patients, truncating and missense mutations in the neuronal voltage-gated sodium-channel alpha-subunit gene (SCN1A) have been identified. The majority of patients have truncating mutations that are predicted to be loss-of-function alleles. Because mutation detection studies use PCR-based sequencing or conformation sensitive gel electrophoresis (CSGE), microdeletions, which are also predicted to be loss-of-function alleles, can easily escape detection. We selected 11 SMEI patients with or without additional features who had no SCN1A mutation detectable with sequencing analysis. In addition, none of the patients was heterozygous for any of the SNPs in SCN1A, indicating that they were either homozygous for all SNPs or hemizygous due to a microdeletion of the gene. We subsequently analyzed these patients for the presence of microdeletions in SCN1A using a quantitative PCR method named multiplex amplicon quantification (MAQ), and observed three patients missing one copy of the SCN1A gene. All three microdeletions were confirmed by fluorescence in situ hybridization (FISH). These findings demonstrate that a substantial percentage of SCN1A-mutation-negative SMEI patients with or without additional features carry a chromosomal microdeletion comprising the SCN1A gene and that haploinsufficiency of the SCN1A gene is a cause of SMEI.

Child↗
PubMed2006

Specific memory impairment in a multiple disabled male with fragile X syndrome and temporal lobe epilepsy.

Evaluation of the cognitive repercussions of an epileptic disorder and its treatment are important issues in clinical follow-up. This especially holds true for temporal lobe epilepsy (TLE) where resective surgery can be a valid treatment option. However, in patients where TLE coexists with another neurocognitive disorder, questions can arise about the precise nature of the neuropsychological deficits. The aim of the present study was to evaluate memory impairments, found in a male aged 12 years who had the dual pathology of fragile X syndrome and refractory TLE. Memory functions of this child were compared with those of a male aged 11 years 7 months with fragile X syndrome matched for intellectual functioning as indicated by highly comparable verbal (5 y 5 mo vs 5 y 9 mo) and non-verbal (7 y 2 mo vs 6 y 1 mo) cognitive age equivalents. Performance on each neuropsychological measure was evaluated twice, separately with normative data based on chronological age and on verbal or non-verbal cognitive level. A specific, distinguishable profile of task performance could be found only when controlling for general level of cognitive functioning. This made it possible to accurately evaluate neuropsychological abilities before and 6 months after anterior temporal lobe resection even in this male with a complex neurological pathology.

Abnormalities, Multiple↗
PubMed2005

Novel frameshift and splice site mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with hereditary sensory neuropathy type IV.

Congenital insensitivity to pain with anhidrosis or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is the first human genetic disorder implicated in the neurotrophin signal transduction pathway. HSAN IV is characterized by absence of reaction to noxious stimuli, recurrent episodes of fever, anhidrosis, self-mutilating behavior and often mental retardation. Mutations in the neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) are associated with this disorder. Here we report four homozygous mutations, two frameshift (p.Gln626fsX6 and p.Gly181fsX58), one missense (p.Arg761Trp) and one splice site (c.359+5G>T) mutation in four HSAN IV patients. The splice site mutation caused skipping of exons 2 and 3 in patient's mRNA resulting in an in-frame deletion of the second leucine-rich motif. NTRK1 mutations are only rarely reported in the European population. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with HSAN IV.

Case-Control Studies↗
PubMed2005

ADHD deficit as measured in adolescent boys with a continuous performance task is related to antenatal maternal anxiety.

Antenatal maternal anxiety has been shown to be related to infant temperament, childhood disorders, and impulsivity in adolescence. This study prospectively investigated whether antenatal maternal anxiety is associated with performance on a continuous performance task. Sixty-four adolescents (mean age, 15 y; 34 boys, 30 girls) were examined with a computerized continuous performance task (CPT) measuring sustained attention. Results showed that the CPT performance of boys of mothers with high levels of state anxiety during the 12th to 22nd postmenstrual week of pregnancy declined as the task progressed: their processing speed became slower and the variability in their reaction times increased. The study controlled for the possible confounding influences of postnatal maternal anxiety, the parents' educational level, and intelligence. Establishing a link between antenatal maternal anxiety and an objective measure of sustained attention/self-regulation, our results extend the growing evidence for an association between antenatal maternal anxiety and the neurobehavioral development of the offspring up into adolescence.

Adolescent↗
PubMed2005

Mapping multiple visual areas in the human brain with a short fMRI sequence.

It is a fundamental insight of neuroscience that the cerebral cortex is divided into spatially separated and functionally distinct areas. In this study, we tried to map a large number of visual areas in individual subjects passively viewing a simple stimulus sequence during functional magnetic resonance imaging (fMRI) at 1.5 T. The blocked stimulus sequence contrasted static object photographs with video takes of movement through natural indoor and outdoor scenes, alternated with a control fixation task. Two runs of the 5-min sequence sufficed to invoke 29 distinguishable activations, 16 (13 bilateral) of which were observed in all 10 participants. At the ventral side, object responsive activations were organized along the lateral occipital-temporal surface and near the collateral and occipital-temporal sulci. The latter activations, corresponding to the lateral occipital complex, showed a different activation profile from those near the collateral sulcus, most likely corresponding to the color constancy areas V4/V8-V4alpha. A potentially new fusiform object area was seen in 6 subjects, even more anterior than the parahippocampal place area. At the dorsal side, consistent activations were mainly related to motion stimuli and included the well-known areas V3a, VIPS, POIPS, hV5+, STS and the cingulate sulcus. There was consistent activation in the parietal-occipital sulcus, containing the areas V6a and V6. In addition, all subjects showed activation in the superior-anterior precuneus. Thus, the short stimulus sequence robustly invoked multiple visual areas and can be used to map the organization of the visual system in normal and brain-damaged individuals.

Adult↗
PubMed2005

Steroids in intractable childhood epilepsy: clinical experience and review of the literature.

Steroids and adrenocorticotrophic hormone (ACTH) have been used for the treatment of infantile spasms for several years. However, the use of steroids in the treatment of epilepsy beyond infantile spasms has been limited to only a few studies. We report the experience with steroids in 32 children with intractable epilepsy, not including West syndrome. In 47% there was a decrease in seizure frequency, 25% became seizure free, 11% had a seizure reduction of >50% and 11% had a seizure reduction of <50%. Our study confirms the conclusions of few previous reports of effective adjunctive steroid treatment for children with intractable epilepsy. The possible side effects, however, especially during prolonged therapy remain an important concern.

Administration, Oral↗
PubMed2005

Atypical neuropsychological profile in a boy with 22q11.2 Deletion Syndrome.

In this article the general and specific cognitive impairments of the boy R.H. with a de novo deletion 22q11.2 are described. His full-scale IQ was 73, and he obtained only slightly better verbal than non-verbal subtest scores. Neuropsychological assessment revealed specific impairments in perceptual categorization of objects presented suboptimal, matching of unfamiliar faces, and verbal learning and memory. In contrast, he performed in accordance with his intelligence level on other visual perceptual tasks, on non-verbal learning and memory tasks, and on attention tasks. Voxel-wise statistical comparison of a high-resolution T1-weighted magnetic resonance image of R.H's brain with similar images obtained from 14 normal control children revealed as major abnormalities a reduction of the right inferior parietal and superior occipital lobe, and a bilateral reduction of deep white matter behind the inferior frontal gyrus. These cognitive impairments and MRI abnormalities are not commonly described in 22q11.2 Deletion Syndrome and may indicate a larger heterogeneity in the neurocognitive phenotype than currently evidenced. At least in this boy the microdeletion seems to have interfered with the development and functioning of particular neural subsystems, while the structure and functioning of other subsystems was left intact.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Thalamic stimulation as a treatment for primary erythromelalgia: technical case report.

OBJECTIVE AND IMPORTANCE: We report the use of bilateral thalamic stimulation in a case of primary erythromelalgia with immediate and important pain relief for 3 years. CLINICAL PRESENTATION: A 12-year-old boy experiencing primary erythromelalgia had a 4-year history of recurrent attacks of severe burning pain in both feet, accompanied by local reddening, swelling, and heating of the skin. The attacks were triggered by warmth and exercise. The pain was relieved only by elevation and cooling of the lower limbs, which he achieved by immersing his legs in a bucket of ice water, resulting in severe ulceration of the skin. INTERVENTION: Because of the gradual aggravation of the signs and symptoms and resistance of the patient's condition to several medical therapies, the patient received spinal cord stimulation. The implants were removed twice because of recurrent infection. Finally, the patient was treated with bilateral electrical stimulation of the ventral posterolateral thalamic nucleus, which resulted in important pain control until 3 years later. The patient was able to avoid water immersions, and all ulcerations disappeared. CONCLUSION: We conclude that thalamic stimulation was successful in this case of primary erythromelalgia.

Child↗
PubMed2004

High antenatal maternal anxiety is related to impulsivity during performance on cognitive tasks in 14- and 15-year-olds.

This study prospectively investigated the influence of antenatal maternal anxiety, measured with the State Trait Anxiety Inventory at 12-22, 23-31 and 32-40 postmenstrual weeks of pregnancy, on cognitive functioning in 57 adolescents (mean age 15 years). ANCOVAs showed effects of State anxiety at 12-22 weeks, after controlling for influences of State anxiety in later pregnancy and postnatal maternal Trait anxiety. Adolescents of high anxious pregnant women reacted impulsively in the Encoding task; they responded faster but made more errors than adolescents of low anxious women. They also scored lower on two administered WISC-R subtests. In the Stop task no differences in inhibiting ongoing responses were found between adolescents of high and low anxious pregnant women. We suspect that high maternal anxiety in the first half of pregnancy may negatively affect brain development of the fetus, reflected by impulsivity and lower WISC-R scores at 14-15 years.

Adolescent↗
PubMed2004

Severe myoclonic epilepsy in infancy: toward an optimal treatment.

Severe myoclonic epilepsy in infancy, or Dravet syndrome, is one of the catastrophic epilepsy syndromes. In the past, treatment was mainly based on valproate and phenobarbital. Recently, some of the new antiepilepsy drugs, such as topiramate and stiripentol, have been shown to be promising in the treatment of this epilepsy syndrome. The treatment regimen of 12 children with Dravet syndrome and proven mutations in the alpha subunit of the sodium channel SCN1A is reported here. Five patients on the "traditional" treatment regimen are compared with seven children on an "optimal" treatment regimen based on a combination of valproate and topiramate. With respect to the literature and our own experience, we propose guidelines for "optimal" treatment of children with severe myoclonic epilepsy in infancy. This includes prevention of hyperthermia, rigorous treatment of fever, avoiding stressful situations, maintenance treatment based on a combination of only two antiepilepsy drugs (ie, valproate and topiramate), and a strict acute seizure treatment based on benzodiazepines. To prevent long-lasting periods of status epilepticus, this acute seizure treatment must be taught to parents and caregivers.

Adolescent↗
PubMed2004

Partial rhombencephalosynapsis.

We describe an infant in whom partial rhombencephalosynapsis was diagnosed by using MR imaging. The anterior vermis and nodulus were normally developed, but part of the posterior vermis was deficient. There was partial fusion of the hemispheres in the inferior part of the cerebellum. Partial rhombencephalosynapsis is described for the first time, and our findings support the recent embryologic observations.

Abnormalities, Multiple↗
PubMed2002

New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum.

BACKGROUND AND PURPOSE: Leukoencephalopathies of unknown origin constitute a considerable problem in child neurology. The purpose of our ongoing study of the subject was to define new disease entities among them by using primarily MR imaging pattern recognition. METHODS: We identified seven unrelated patients with a distinct MR imaging pattern consisting of hypomyelination and atrophy of the basal ganglia (neostriatum) and cerebellum (H-ABC). We reviewed the clinical, MR imaging, MR spectroscopic, and laboratory data. RESULTS: Clinically, the patients' diseases were characterized by variably disturbed early development followed by increasing extrapyramidal movement abnormalities, ataxia, and spasticity. Mental capacity was variably affected, but it appeared to be relatively preserved. Parents were not related, and none of their siblings were affected. No metabolic defect was found. Follow-up MR imaging demonstrated atrophy of the cerebral white matter, neostriatum, and cerebellum, which was most pronounced in the most clinically severe cases. Single-voxel proton MR spectroscopic results were normal in the parietal cortex. In the cerebral white matter, myo-inositol and creatine levels were elevated; this finding was compatible with gliosis. N-acetylaspartate and choline levels were normal, suggesting that neither axonal loss nor active demyelination occurred. Proton MR spectroscopic imaging revealed relatively decreased N-acetylaspartate levels in the frontal region. CONCLUSION: The uniform and highly characteristic MR imaging findings, in combination with the similarities in the clinical findings, provide evidence of a distinct nosologic entity. The acronym H-ABC is offered to indicate patients sharing these clinical and MR imaging features.

Atrophy↗