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Biomedical subjects

Ulrich Stephani

Publications and source records attributed to Ulrich Stephani.

At least 19 recordsLinked to original sources
PubMed2007

Lack of evidence of an allelic association of a functional GABRB3 exon 1a promoter polymorphism with idiopathic generalized epilepsy.

PURPOSE: Mutation screening and linkage disequilibrium mapping of the gene encoding the GABA(A) beta(3) subunit (GABRB3) identified a common genetic variant in the exon 1a promoter region (C-allele of rs4906902) which displayed a reduced transcriptional activity and showed a strong allelic association with childhood absence epilepsy (CAE). The present population-based association study tested whether the C-allele of rs4906902 confers susceptibility to CAE or other common syndromes of idiopathic generalized epilepsy (IGE) in a German sample. METHODS: Seven hundred and eighty unrelated German IGE patients (250 CAE, 123 juvenile absence epilepsy, 303 juvenile myoclonic epilepsy (JME), 104 epilepsy with generalized tonic-clonic seizures on awakening) and 559 healthy population controls were genotyped for the single nucleotide polymorphism (SNP) rs4906902. RESULTS: The frequency of the risk-conferring C-allele did not differ significantly between CAE patients (f(C)=0.190) and controls (f(C)=0.183; P=0.376, one-tailed). Similarly, no evidence for an allelic association was found for 373 patients with idiopathic absence epilepsy, 303 JME patients, and the entire IGE sample (P>0.77, two-tailed). CONCLUSION: Our study failed to replicate an association of the common GABRB3 exon 1a promoter SNP rs4906902 with CAE. Moreover, the present results do not provide evidence that the common functional C-variant confers a substantial epileptogenic effect to a broad spectrum of IGE syndromes in the German population.

Alleles↗
PubMed2006

Spreading photoparoxysmal EEG response is associated with an abnormal cortical excitability pattern.

Photosensitivity or photoparoxysmal response (PPR) is a highly heritable electroencephalographic trait characterized by an abnormal cortical response to intermittent photic stimulation (IPS). In PPR-positive individuals, IPS induces spikes, spike-waves or intermittent slow waves. The PPR may be restricted to posterior visual areas (i.e. local PPR with occipital spikes only) or spread to anterior non-visual cortical regions (i.e. PPR with propagation). The mechanisms underlying the PPR and causing its spread remain to be clarified. In unmedicated PPR-positive individuals and PPR-negative control participants without any history of previous seizures, we used focal transcranial magnetic stimulation (TMS) to investigate the excitability of the visual or primary motor cortex (M1). In the first experiment [18 healthy control subjects (i.e. without PPR in electroencephalography: 6 females, mean age 26.5 +/- 7.34 years) and 17 healthy participants with PPR (7 females, mean age 25.18 +/- 12.2 years) were studied], occipital TMS was used to elicit phosphenes or to suppress the visual perception of letter trigrams. PPR-positive individuals with propagation had lower phosphene thresholds and steeper stimulus-response curves than individuals without PPR or with occipital spikes only. Occipital TMS also induced a stronger suppression of visual perception in PPR-positive subjects with propagation relative to subjects without PPR or with occipital spikes. In the second experiment, we applied TMS over the right M1 without concurrent IPS and measured the motor threshold, the stimulus response curve, and the duration of the cortical silent period (CSP) in PPR positive individuals with propagation and in PPR-negative control participants [15 right-handed healthy subjects without PPR (3 males, mean age 17.7 +/- 3.6 years) and 14 right-handed healthy individuals showing a PPR with propagation (3 males, mean age 17.4 +/- 3.9 years)]. PPR-positive individuals showed no changes in these excitability measures relative to the PPR-negative control participants. We also measured the modifiability of the CSP by continuous IPS at a frequency of 18 or 50 Hz. While IPS reduced the duration of the CSP in PPR-negative control subjects, IPS had no effect on the duration of the CSP in PPR-positive individuals. Our results provide first time evidence that the propagation of the PPR is associated with increased excitability of the occipital but not the motor cortex. The stronger inhibitory effect of TMS on visual perception and the failure of IPS to shorten the CSP in PPR-positive participants may possibly reflect adaptive changes that prevent the provocation of seizures during the PPR.

Adolescent↗
PubMed2006

Flexible and floating choroid plexus cyst of the third ventricle: an ultrasonographic video documentation.

INTRODUCTION: Choroid plexus cysts can lead to isolation of the lateral ventricles and distension of the third ventricle. We present an ultrasonographic video documentation of an infant with variably shaped and localized choroid plexus cyst of the third ventricle. CASE REPORT: An infant had periods of increased intracranial pressure with changing dilatation of the first to third ventricle. Cerebral ultrasonography of the not crying boy demonstrated a choroid plexus cyst limply hanging down from the roof of the third ventricle to the beginning of the aqueduct of Sylvius. During crying, the cyst prolapsed from the third into left lateral ventricle and was strangled by the foramen of Monro. Endoscopic cyst fenestration and third ventriculostomy continuously solved the problem of intermittent hydrocephalus occlusus. CONCLUSION: Depending not only on localization and size but also on cyst form and cerebrospinal fluid pressure, a single choroid plexus cyst can cause various obstructions of cerebrospinal fluid pathways.

Choroid Plexus↗
PubMed2006

Localized short-range correlations in the spectrum of the equal-time correlation matrix.

We suggest a procedure to identify those parts of the spectrum of the equal-time correlation matrix C where relevant information about correlations of a multivariate time series is induced. Using an ensemble average over each of the distances between eigenvalues, all nearest-neighbor distributions can be calculated individually. We present numerical examples, where (a) information about cross correlations is found in the so-called "bulk" of eigenvalues (which generally is thought to contain only random correlations) and where (b) the information extracted from the lower edge of the spectrum of C is statistically more significant than that extracted from the upper edge. We apply the analysis to electroencephalographic recordings with epileptic events.

Journal Article↗
PubMed2006

A single dose of sulthiame induces a selective increase in resting motor threshold in human motor cortex: A transcranial magnetic stimulation study.

Sulthiame is a carbonic anhydrase inhibitor that is widely used to treat partial and myoclonic seizures. In 11 healthy adults, we applied transcranial magnetic stimulation (TMS) to the primary motor cortex. Using a cross-over study design, we found that a single oral dose of sulthiame (5 mg/kg) produced a significant increase of resting motor threshold relative to placebo. No other TMS measure of corticomotor excitability was altered after a single dose of sulthiame. The selective increase in motor threshold suggests that sulthiame produces its antiepileptic effect by reducing the axonal excitability of cortical neurons.

Administration, Oral↗
PubMed2006

Neurophysiological reactivity before a migraine attack.

Migraine patients are characterized by increased amplitudes and reduced habituation of the contingent negative variation (CNV) response, especially before a migraine attack. As shown previously, migraine provoking and precipitating agents can cause CNV abnormalities. However, it is unclear whether the temporal relation to the migraine attack determines how the brain reacts to a migraine precipitant. In this study, experimentally-induced achievement stress, one of the typical precipitants for migraine, was examined for its effects upon the CNV response. CNV was recorded during conditions of rest and stress, both before and after a migraine attack, as well as during a headache-free interval. The neurophysiological reactivity to stress in migraineurs was compared with those of healthy subjects. Before a migraine attack, migraine patients demonstrated significantly more pronounced neurophysiological reactivity to stress: the amplitude of the early CNV component was more increased and its habituation was more reduced in the stress condition, especially 1-3 days before an attack compared with changes of CNV amplitudes and habituation under stress obtained after an attack, during the headache-free interval, or in healthy controls. The study demonstrates that the brain of migraine patients is characterized by increased susceptibility to migraine provoking agents before an actual attack.

Adult↗
PubMed2006

Association of BRD2 polymorphisms with photoparoxysmal response.

A trait locus for electroencephalographic photoparoxysmal response (PPR) has been mapped to the chromosomal region 6p21 near a susceptibility locus for juvenile myoclonic epilepsy (JME). Linkage disequilibrium mapping revealed strong associations between JME and polymorphisms of the gene encoding the bromodomain-containing protein 2 (BRD2). The present association study tested whether genetic variation of BRD2 confers also susceptibility to PPR. All study participants were of German descent, comprising 187 subjects exhibiting PPR (types I-IV) and 666 healthy controls. Genotypes of each study participant were assessed for seven single nucleotide polymorphisms and one dinucleotide repeat polymorphism, covering the genomic BRD2 sequence. Allelic and haplotypic associations were found between PPR and six BRD2 polymorphisms (P: 0.0075-0.035). Considering the strong neurobiological association of JME and PPR, the present results support evidence that PPR and JME share epileptogenic pathways, for which BRD2 might be an underlying susceptibility gene.

Chromosome Mapping↗
PubMed2006

Satoyoshi syndrome: a rare multisystemic disorder requiring systemic and symptomatic treatment.

Satoyoshi syndrome is a rare multisystemic disorder with assumed autoimmune pathogenesis. Typical clinical features are progressive painful muscle spasms, alopecia, diarrhoea, and skeletal and endocrine abnormalities often resulting in early invalidism and death. Patients have been treated with immunoglobulins and glucocorticoids with varying outcome. We report on a 19-year-old German adolescent who has been successfully treated with a new combination of carbamazepine to reduce the severity and frequency of painful nocturnal muscle spasms, prednisolone, methotrexate and sex-steroids. Prednisolone treatment alone was not successful. After introduction of low-dose of methotrexate to the therapy the patient recovered from muscle spasms, alopecia and diarrhoea. Initiation of sex-steroid treatment resulted in pubertal development, regular menstrual cycles and improved quality of life.

Adult↗
PubMed2006

Candidate gene analysis of the succinic semialdehyde dehydrogenase gene (ALDH5A1) in patients with idiopathic generalized epilepsy and photosensitivity.

Succinic semialdehyde dehydrogenase (SSADH) is involved in the degradation of the inhibitory neurotransmitter GABA and about 50% of patients with SSADH deficiency suffer from seizures. The gene encoding SSADH (gene symbol: ALDH5A1) maps in proximity to susceptibility loci for juvenile myoclonic epilepsy (JME) and photosensitivity on chromosome 6p22. The present study tested whether variation of the ALDH5A1 gene confers susceptibility to common syndromes of idiopathic generalized epilepsy (IGE) and an abnormal photoparoxysmal response (PPR). Mutation screening of the ALDH5A1 coding sequence of 35IGE/PPR patients and four healthy control subjects identified 17 sequence variants, of which three resulted in an exchange of amino acids (H180Y, P182L, A237S). Association analysis was carried out for six single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (TNR, intron 1), covering the genomic ALDH5A1 sequence. The study sample comprised 566 unrelated German IGE patients, including 218 JME and 95 photosensitive IGE patients, 78 PPR probands without IGE, and 662 German population controls. None of the investigated ALDH5H1 polymorphisms showed evidence for an allelic or genotypic association with either IGE, JME, or PPR, when corrected for multiple tests. A tentative haplotypic association of the two-marker haplotype (rs1883415-TNR) covering the 5'-regulatory region in IGE patients (chi2=11.65, d.f.=3, P=0.009) warrants further replication studies. The present results do not provide evidence that any ALDH5A1 missense variant itself contributes a common and substantial susceptibility effect (RR>2) to IGE syndromes or an increased liability to visually-induced cortical synchronization.

Epilepsy, Generalized↗
PubMed2006

Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancy.

Mutations in the voltage-gated sodium channel gene SCN1A are a major cause of severe myoclonic epilepsy of infancy (Dravet syndrome) and generalized epilepsy with febrile seizures plus. This study reports the identification of six de novo SCN1A mutations in patients with severe myoclonic epilepsy of infancy, including a tetranucleotide deletion in exon 26. The same deletion was previously observed in two unrelated patients and appears to result from slipped-strand mispairing of a direct repeat during deoxyribonucleic acid replication. Review of the literature indicates that recurrent mutations account for 25% of SCN1A mutations in severe myoclonic epilepsy of infancy, including six sites of deamination at CpG dinucleotides.

Adolescent↗
PubMed2006

Exploration of the genetic architecture of idiopathic generalized epilepsies.

PURPOSE: Idiopathic generalized epilepsy (IGE) accounts for approximately 20% of all epilepsies and affects about 0.2% of the general population. The etiology of IGE is genetically determined, but the complex pattern of inheritance suggests an involvement of a large number of susceptibility genes. The objective of the present study was to explore the genetic architecture of common IGE syndromes and to dissect out susceptibility loci predisposing to absence or myoclonic seizures. METHODS: Genome-wide linkage scans were performed in 126 IGE-multiplex families of European origin ascertained through a proband with idiopathic absence epilepsy or juvenile myoclonic epilepsy. Each family had at least two siblings affected by IGE. To search for seizure type-related susceptibility loci, linkage analyses were carried out in family subgroups segregating either typical absence seizures or myoclonic and generalized tonic-clonic seizures on awakening. RESULTS: Nonparametric linkage scans revealed evidence for complex and heterogeneous genetic architectures involving linkage signals at 5q34, 6p12, 11q13, 13q22-q31, and 19q13. The signal patterns differed in their composition, depending on the predominant seizure type in the families. CONCLUSIONS: Our results are consistent with heterogeneous configurations of susceptibility loci associated with different IGE subtypes. Genetic determinants on 11q13 and 13q22-q31 seem to predispose preferentially to absence seizures, whereas loci on 5q34, 6p12, and 19q13 confer susceptibility to myoclonic and generalized tonic-clonic seizures on awakening.

Chromosome Mapping↗
PubMed2006

The natural history of myoclonic astatic epilepsy (Doose syndrome) and Lennox-Gastaut syndrome.

The purpose of this article is to present a short review of the natural history of myoclonic astatic epilepsy (MAE; Doose syndrome) and the Lennox-Gastaut syndrome (LGS). In the 1989 classification of the International League Against Epilepsy (ILAE, 1989), MAE and LGS were initially included in group 2.2: "Cryptogenic or symptomatic generalized epilepsies and syndromes." The subsequent classification of the Proposed Diagnostic Scheme for People with Epileptic Seizures and with Epilepsy (see Ref. 8) placed MAE in axis 3 in the "generalized epilepsy" group and LGS, severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and atypical benign partial epilepsy/pseudo-Lennox syndrome (ABPE/PLS) in the "epileptic encephalopathy" group. The semiology of MAE and LGS and their differential diagnosis from SMEI and ABPE/PLS are described. Before the onset of SMEI, MAE, and ABPE/PLS, the development of the child is usually normal. In contrast, in LGS, development is frequently retarded at the onset, depending on the etiopathogenesis of the underlying brain disease. The course of MAE is highly variable with regard to seizure outcome (complete remission in some cases, persistent epilepsy in others) and cognitive development (normal or delayed). The course of LGS and SMEI is generally poor, both with regard to the epilepsy and to the cognitive development whereas the course and seizure outcome of ABPE/PLS is favorable; the patients will be seizure-free at puberty. However, the neuropsychological outcome is less favorable; most patients remain mentally retarded.

Age of Onset↗
PubMed2006

The spectrum from BCECTS to LKS: The Rolandic EEG trait-impact on cognition.

The laboratory hallmark of BCECTS is the rolandic discharge (RD) in the EEG of patients, occurring in a characteristic topographical, vigilance-related, event-related, and age-related pattern, disappearing during puberty. RDs are present in 2% of healthy children. About 8% of children with RDs have epilepsy. An increased prevalence rate of RDs is found in children with cognitive and behavioral disorders, with headaches and some genetic syndromes. In some patients, the cognitive disorders are transient but in others they are progressive, resulting in stable mental retardation after puberty. A recent study of 36 BCECTS patients addressed the following questions. (1) the possible relationship between the severity of RDs and the neuropsychological deficits; (2) the profile of neuropsychological deficits; (3) changes of cognition related to EEG changes; and (4) effects of therapy. No correlation was found between global IQ and the severity of the RDs. All the children had at least one specific learning disorder (sometimes long-lasting). When the children were treated, a correlation between cognitive and EEG improvement could not be demonstrated. Recently, 21 patients without epilepsy but with attention deficit and hyperactivity and/or learning disorders were studied: an open treatment trial with sulthiame resulted in improved sustained and selective attention. The neurobiology of RDs and their relationship to cognitive dysfunction and epilepsy requires further study.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Detection and characterization of changes of the correlation structure in multivariate time series.

We propose a method based on the equal-time correlation matrix as a sensitive detector for phase-shape correlations in multivariate data sets. The key point of the method is that changes of the degree of synchronization between time series provoke level repulsions between eigenstates at both edges of the spectrum of the correlation matrix. Consequently, detailed information about the correlation structure of the multivariate data set is imprinted into the dynamics of the eigenvalues and into the structure of the corresponding eigenvectors. The performance of the technique is demonstrated by application to N(f)-tori, autoregressive models, and coupled chaotic systems. The high sensitivity, the comparatively small computational effort, and the excellent time resolution of the method recommend it for application to the analysis of complex, spatially extended, nonstationary systems.

Journal Article↗
PubMed2005

Genetic dissection of photosensitivity and its relation to idiopathic generalized epilepsy.

Photosensitivity or photoparoxysmal response (PPR) is a common and highly heritable electroencephalographic trait characterized by an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. PPR occurs frequently associated with idiopathic generalized epilepsies (IGEs). The present genomewide linkage scan was designed to map susceptibility loci for PPR and to explore their genetic relationship with IGE. The study included 60 families with at least two siblings displaying PPR. To dissect PPR-specific and IGE-related susceptibility loci, we defined two distinct family subgroups, comprising 19 families with predominantly pure PPR and photosensitive seizures (PPR-families) and 25 families, in which PPR was strongly associated with IGE (PPR/IGE-families). MOD score analyses provided significant evidence for linkage to the region 6p21.2 in the PPR-families (empirical p = 0.00004) and suggestive evidence for linkage to the region 13q31.3 in the PPR/IGE families (p = 0.00015), both with a best-fitting recessive mode of inheritance. In the PPR/IGE-families, linkage evidence was even stronger (p = 0.00003) when the trait definition was broadened by IGE traits. Our study shows two PPR-related susceptibility loci, depending on the familial background of IGE. The locus on 6p21.2 seems to predispose to PPR itself, whereas the locus on 13q31.3 also confers susceptibility to IGE.

Chromosomes, Human, Pair 13↗
PubMed2005

Living a normal life with the nondominant hemisphere: magnetic resonance imaging findings and clinical outcome for a patient with left-hemispheric hydranencephaly.

In hemihydranencephaly, the human brain lacks 1 complete hemisphere. An occlusion of the carotid artery, affecting all supplied territories, is thought to be the underlying mechanism. This extremely rare disorder, of which only 7 cases have been reported to date, is thought to occur before the last trimester of gestation (20th to 27th week), after neural migration but before synaptogenesis. We report on a 36-year-old man born at term, with no complications, from nonconsanguineous healthy parents. Cranial computed tomography had been performed because of left-sided headaches. Because of the imaging findings, the patient presented at our institution for additional MRI and clinical testing (including the Motor Activity Log, Wolf motor function test, 2-point discrimination test, Purdue pegboard test, gross motor function test, Physician Rating Scale, and Aachener aphasia test, including patterns for spontaneous speech, repetition, naming, comprehension, written language, and the token test). The patient's disabilities were related to deficits in fine motor control and reduced precision. Therefore, the patient was unable to perform the Purdue pegboard test with his affected hand. According to the Aachener aphasia test, no aphasia could be demonstrated for this strongly left-handed patient. Strong mirror movements were found. Cortical reorganization is possible if damage occurs in very early childhood. Motor function and speech were controlled by the remaining, nonaffected hemisphere, with a remarkable outcome. Because the damage is thought to occur before synaptogenesis, existing or prepared cortical areas and pathways have the potential to execute the lacking functions of the destroyed hemisphere.

Adult↗