Biomedical subjects

U Stephani

Publications and source records attributed to U Stephani.

At least 19 recordsLinked to original sources

PubMed2003

Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects.

We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the biotin-dependent mitochondrial carboxylases in lymphocytes remained below 50% of the mean control values. Not only urinary 3-hydroxyisovaleric acid excretion has been persistently elevated, but also plasma and, with even higher concentrations, cerebrospinal fluid 3-hydroxyisovaleric acid have not normalized. The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g>a on one chromosome and a truncating mutation on the other. This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency.

Age of Onset↗

PubMed2003

Grip force parameters in precision grip of individuals with myelomeningocele.

The aim of this study was to characterize impairments of hand function in individuals with myelomeningocele (MMC) using a quantitative method. A grip-lift task was studied in 29 individuals with MMC (17 females, 12 males; mean age 12 years 4 months, SD 5 years 6 months; range 4 to 28 years) and 29 age- and sex-matched control participants. A small object (weight 200 g) was grasped and lifted with a precision grip of the dominant hand and grip forces (GF) and time intervals were measured. Sensibility was examined with a two-point discrimination test. In those with MMC, the latency between GF onset of the thumb and index finger and ensuing preload duration were both significantly prolonged (p<0.01). Fingertip forces were excessively high and variable. Several parameters differed significantly between those with MMC and control individuals: GF peak, GF at start of loading, mean GF, and the SDs of the GF during static holding. Although the two-point discrimination task indicated deficits of sensibility, these did not correlate with grip force parameters. Results demonstrate that fine motor skills in patients with MMC are impeded by slowness and inadequate adjustments of manipulative forces.

Adolescent↗

PubMed2002

Guidelines for the use of EEG methodology in the diagnosis of epilepsy. International League Against Epilepsy: commission report. Commission on European Affairs: Subcommission on European Guidelines.

The Commission of European Affairs of the International League Against Epilepsy published 'Appropriate Standards for Epilepsy Care Across Europe' which contained recommendations for the use of electroencephalography (EEG) in the diagnosis of epilepsy (Brodie et al. Epilepsia 1997; 38:1245). The need for a more specific basic document of EEG methodology was recognized and the Subcommission on European Affairs was asked to produce more detailed guidelines to be used across Europe recognizing the range of practices in EEG laboratories. There are many general guidelines published on EEG methodology but this document focuses on the diagnosis of epilepsy. Details from previously published guidelines are included in references and in an appendix. These guidelines are not meant to be used as minimal standards but recommendations that can be applied to all EEG laboratories despite variations in equipment.

Adult↗

PubMed2002

Infantile Alexander disease: a GFAP mutation in monozygotic twins and novel mutations in two other patients.

Alexander disease (AD) is a rare disorder of cerebral white matter due to a dysfunction of astrocytes. The most common infantile form presents as a megalencephalic leukodystrophy. Recently, heterozygous de novo mutations in the glial fibrillary acidic protein gene (GFAP) have been demonstrated to be associated with AD. We report heterozygous mutations in GFAP in 5 patients, including a pair of monozygotic twins, with clinical and neuroradiological features of infantile AD. Novel mutations were detected affecting nucleotides 304 T --> C (L97 P) and 730 G --> C (R239 P) in two other patients. None of the parents of our patients carried the mutations stressing dominant de novo mutations as the cause of AD. The presence of an identical mutation 250 G --> A (R79 H) in both monozygotic twins with infantile AD points to the origin of these GFAP mutations in germ cells or very early postzygotic stages.

Alexander Disease↗

PubMed2001

Atypical "benign" partial epilepsy of childhood or pseudo-lennox syndrome. Part II: family study.

Atypical benign partial epilepsy of childhood (ABPE = Pseudo-Lennox syndrome) shows semiologic parallels to Lennox-Gastaut syndrome, however--besides the lack of tonic seizures--it has an entirely different etiology and prognosis. Recently Hahn et al [17] investigated the long-term evolution of 43 cases with ABPE. Symptomatology, EEG findings, and course were found to overlap with Rolandic epilepsy, Landau-Kleffner syndrome and ESES. The incidence of seizures in relatives was determined in the whole series investigated by Hahn et al [17]. Five of 56 siblings suffered from seizures (3 Rolandic seizures; one febrile convulsions; one unclassified). Three fathers reported grand mal. In 29 families of the series of Hahn et al EEG recordings were performed: 22 brothers, 19 sisters and 16 pairs of parents. In 29% of the siblings a sharp wave focus was demonstrable. The rate rose to 40% when only siblings investigated at the age of maximum expression (3 to 10 years) were considered. Sharp wave foci were mostly multifocal and indistinguishable from those observed in siblings of children with Rolandic epilepsy. Photoparoxysmal response and generalized spikes and waves during rest and hyperventilation were also found to be significantly elevated (26% and 13% respectively). We conclude that ABPE is a subgroup of idiopathic partial epilepsy of childhood (representing a less benign part of a spectrum) that has to be ranked in a continuum with Rolandic epilepsy. The different clinical phenotype might be caused by a higher expressivity of the identical genetic trait, possibly facilitated by other genetic or acquired factors. Genetic heterogeneity represents another possibility.

Adult↗

PubMed2001

Atypical "benign" partial epilepsy or pseudo-Lennox syndrome. Part I: symptomatology and long-term prognosis.

PURPOSE: Atypical benign partial epilepsy (ABPE) or pseudo-Lennox syndrome (PLS) is characterised by generalised minor seizures and focal sharp slow waves and spikes (SHW) as observed in Rolandic epilepsy (RE), but with exceptional pronounced activation during sleep. The aim of this study was to describe the full spectrum of ABPE in the hitherto largest group of patients. METHODS: We retrospectively analysed the clinical and EEG data of 43 children who fulfilled the following criteria: occurrence of generalised minor seizures as described for ABPE (i.e., atonicastatic seizures, myoclonic seizures, atypical absences) and focal SHW identical to those observed in RE, but with generalisation during sleep. RESULTS: Language development prior to onset of epilepsy was retarded in 26% of patients. In 74%, age at onset of epilepsy ranged from 2 to 6 years. Manifestation occurred earlier in boys than in girls. Generalised minor seizures constituted the predominating seizure type in 67% of patients. Twenty-eight percent of patients suffered from simple partial seizures of the oro-facial region or generalised tonic-clonic seizures originating from the oro-facial region. Additionally, generalised tonic-clonic (44%), unilateral (21%), partial motor (44%), versive (12%), focal atonic (9%), and complex-partial seizures (2%) were observed. A bioelectrical status was recorded in 56% of patients during sleep. No tonic seizures and no fast spike series (bursts of 10-20 Hz rhythms) were observed. At last follow-up, 84% of patients were in clinical remission. All subjects older than age 15 were seizure-free. However, 56% of patients attended a school for mentally handicapped children. CONCLUSIONS: ABPE or PLS broadly overlaps with RE, electrical status epilepticus during sleep, and Landau-Kleffner syndrome. Regarding the epilepsy, the prognosis is excellent, mental deficit, however, seems to be frequent. The differentiation from Lennox-Gastaut syndrome and myoclonic astatic epilepsy is essential. Instead of ABPE, the term pseudo-Lennox syndrome is proposed.

Cerebral Cortex↗

PubMed2001

Holoprosencephaly and low molecular weight proteinuria: the human homologue of murine megalin deficiency.

We encountered a child with holoprosencephaly, pulmonary insufficiency, absent circulating vitamin D metabolites, mild albuminuria, and urinary excretion of vitamin D-binding protein. The child displayed a phenotype highly reminiscent of that observed in mice genetically deficient for megalin, a member of the low-density lipoprotein receptor superfamily. Only the Guthrie card was available from the child; the DNA sufficed for a limited haplotype analysis. We were not able to implicate the megalin gene locus directly; however, the possibility of a functional megalin defect in this child remains. To the best of our knowledge, this patient represents the first report that pathologic abnormalities consistent with megalin deficiency are present in humans.

Animals↗

PubMed2000

Migraine in childhood--are periodically occurring migraine attacks related to dynamic changes of cortical information processing?

Amplitudes and habituation of contingent negative variation (CNV) were analyzed in relation to spontaneously occurring migraine attacks in ten children suffering from migraine without aura. Recording took place during feedback training and instrumental conditioning of slow brain potentials. Both the amplitude of the early CNV component and its habituation deficit increase during the 5 days prior to a migraine attack, with maximum abnormalities the day before the ictal episode. Abrupt reduction of the amplitude and normalization of the CNV habituation were observed during the attack. This study provides evidence for neurophysiological periodicity in young migraineurs and emphasizes that the time relative to the migraine attacks must be considered in studies of juvenile migraine during the headache-free period.

Cerebral Cortex↗

PubMed2000

Intensity dependence of auditory evoked cortical potentials in migraine families.

Intensity dependence of auditory evoked cortical potentials is abnormal in migraine. This study investigated intensity dependence in migraine and healthy families using group comparisons and analysis of individual differences. Migraineurs were characterized by a steeper amplitude/stimulus function slope and more pronounced difference between the amplitudes of N1-P2 on the more and the less intensive tones than healthy age matched subjects. Apart from migraine, the age of the participants was an important predictive variable of intensity dependence. Analysis of individual differences revealed low sensitivity and moderate specificity of intensity dependence for migraine. Familial prevalence of intensity dependence among first-degree relatives in migraine families was equal to that in healthy families. These findings support the assumption that high-intensity dependence reflects a functional CNS trait which is more pronounced and prevalent in migraine, but may also be found in healthy individuals and in other neuropsychiatric disorders. Increased intensity dependence is only one of several factors contributing to the risk for this form of headache.

Acoustic Stimulation↗

PubMed2000

Self-regulation of slow cortical potentials in children with migraine: an exploratory study.

Migraine patients are characterized by increased amplitudes of slow cortical potentials (SCPs), representing pronounced excitability of cortical networks. The present study investigated the efficiency of biofeedback training of SCPs in young migraineurs. Ten children suffering from migraine without aura participated in 10 feedback sessions. They were compared with 10 healthy children for regulation abilities of cortical negativity and with 10 migraineurs from the waiting list for clinical efficacy. During the first two sessions, the migraine children were characterised by lacking ability to control cortical negativity, especially during transfer trials, compared with healthy controls. However, there was no difference following 10 sessions of training. Feedback training was accompanied by significant reduction of cortical excitability. This was probably responsible for the clinical efficacy of the training; a significant reduction of days with migraine and other headache parameters was observed. It is suggested that normalization of the threshold regulation of cortical excitability during feedback training may result in clinical improvement.

Analysis of Variance↗

PubMed2000

Slow cortical potentials in migraine families.

Amplitude and habituation of event-related potentials are abnormal in migraine. We investigated 43 migraine and 41 healthy families to evaluate the influences of age, sex and familial contribution on the variance of amplitude and habituation of the contingent negative variation (CNV). Analysis of individual differences in relation to the CNV habituation was performed. The study demonstrated that habituation of the early CNV component characterizes migraine considerably better than the CNV amplitudes. Habituation, however, is strongly influenced by age. Migraine adults and children generally showed reduced habituation. Surprisingly, more than 30% of the healthy adults demonstrated a marked loss of habituation. The reduced CNV habituation represented a high sensitivity but low specificity to migraine, especially in children. CNV amplitude and habituation parameters revealed a considerable familial contribution associated with migraine. No familial influence on either morphology or habituation of the CNV in healthy families or between healthy members of migraine families was observed. The low specificity and familial transmission of CNV parameters in members of migraine families suggest that increased amplitudes and reduced habituation of CNV do not constitute a primary risk factor for migraine, but rather represent a predisposition. Genetic components probably affect variation of the CNV amplitude and habituation.

Adolescent↗

PubMed2000

Paraneoplastic cerebellar degeneration in pediatric Hodgkin disease.

Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication in adults with extracerebral neoplasms. It is characterized by a diffuse cerebellar dysfunction, usually leading to severe neurological sequelae. In childhood, this complication is extremely rare. We report on PCD as primary manifestation of Hodgkin disease (HD) in a thirteen-year old boy. On magnetic resonance imaging, irreversible atrophy of the cerebellum developed within three months. Antibodies against Purkinje cells were detectable at diagnosis and normalised after successful treatment of the lymphoma. Cerebellar symptoms, however, only partially resolved. The necessity of a search for a malignant tumour is emphasised in the presence of an otherwise unexplained, subacutely developing, diffuse cerebellar dysfunction.

Adolescent↗

PubMed2000

Nonconvulsive status epilepticus--a possible cause of mental retardation in patients with Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is one of the most severe types of childhood epilepsy. It is usually resistant to treatment and associated with mental retardation. To delineate the risk factors associated with the outcome of LGS, we evaluated, in a retrospective and multicentre study, the course of the disease, EEG tracings, and intellectual function in 101 patients. Inclusion criteria were the presence of tonic seizures as well as slow spike and wave complexes in the EEG. The average documented observation period was 16 years (range 4-31 years). Overall, the intellectual and neurological outcome was poor. At the last follow-up, 38% of the patients could not speak, 21% were unable to walk and only 4% were free of seizures. Four independent risk factors for severe mental retardation were identified by multivariate analysis. These were in a decreasing order of importance: nonconvulsive status epilepticus (NCSE), odds ratio (OR) 25.2, a previous diagnosis of West syndrome (OR 11.6), a symptomatic etiology of epilepsy (OR 9.5), and an early age at onset of epilepsy (OR 4.7). The results highlight the association between NCSE and the severity of mental retardation in patients with LGS; this association appears to be independent of symptomatic etiology. Our data provide an indirect evidence that, at least in some of the patients, NCSE is not only a concomitant feature, but also a cause of severe mental retardation.

Adolescent↗

PubMed2000

Inheritance of photosensitivity.

PURPOSE: To investigate the mode of inheritance of the photoparoxysmal response (PPR) and to obtain more information about the influence of photosensitivity on the seizure risk in siblings of patients with epilepsy. METHODS: Examination of the records of families with one photosensitive parent (Group I, n = 54) and of families with a photosensitive proband, neither of whose parents was photosensitive (Group II, n = 72). RESULTS: At the age of maximum penetrance, between 5 and 15 years of age, 50% of the siblings in Group I were photosensitive, compared to only 15% in Group II. Siblings in Group I showed a higher seizure rate (19%) than siblings in Group II (4%, p < 0.005). The majority of photosensitive siblings had no seizures, but photosensitive siblings had a higher seizure risk than non-photosensitive siblings. The highest seizure risk was found in photosensitive siblings of Group I (33%) compared to 9% in non-photosensitive siblings (p < 0.05). CONCLUSION: Our findings show that a PPR in parents is a major determinant for the risk of a PPR in offspring. The results may indicate an autosomal-dominant transmission with age-dependent penetrance of the PPR. Photosensitivity is an important factor in the pathogenesis of seizure disorders in childhood.

Adolescent↗

PubMed2000

Typical semiology of benign childhood epilepsy with centrotemporal spikes (BCECTS).

The ILAE (1989) has defined benign childhood epilepsy with centro-temporal spikes (BCECTS) as follows: BCECTS is a syndrome of brief, simple, partial, hemifacial motor seizures, frequently having associated somatosensory symptoms which have a tendency to evolve into generalised tonic clonic seizures (GTCS) [1]. Both seizure types are often related to sleep. Onset occurs between the ages of 3 and 13 years (peak 9-10 years) and recovery occurs before the age of 15-16 years. Genetic predisposition is frequent, and there is a male predominance. The EEG has blunt high-voltage centrotemporal spikes, often followed by slow waves that are activated by sleep and tend to shift or spread from side to side.

Adolescent↗

PubMed2000

Neuropsychological long-term outcome of rolandic EEG traits.

BACKGROUND: Long-term outcome of rolandic epilepsy (RE) is associated with a diversity of neuropsychological deficits in childhood, although RE is historically considered as a benign epileptic disorder. Dyslexia and other developmental disorders are associated with rolandic EEG traits. AIM: To investigate if there is an association between the manifestation of a specific EEG trait of RE and dyslexia. If the EEG traits are causing dyslexia, the cognitive deficits are supposed to be normalised after the EEG trait have resolved. METHOD: Thirty adolescents and young adults, who had previously received a diagnosis of dyslexia by standard criteria, were included. Fifteen probands (mean age = 15.9) with dyslexia and rolandic EEG traits were compared with 15 age- and sex-matched controls (mean age = 16.0) with normal EEG. RESULTS: There were no statistical differences between the groups according to intelligence (Verbal IQ, Performance IQ and Arithmetical IQ) or spelling ability. However, there was a significant difference between the groups in reading ability of non-related words with the group without RE performing better than the group with RE (p < 0.01). Attentional shifts in dichotic listening with forced or directed attention are generally found in 50-60% in normative samples. However, the present date suggest an impaired attentional shift in dichotic listening test for both groups. Only one third was able to modulate their ear-preference. There were no group differences. CONCLUSION: In general, both dyslectic groups did not show significant neuropsychological deficits as compared to standard controls. However, there were more reading errors and a tendency to attention impairments in the group with rolandic EEG trait as compared to the dyslectic group with normal EEG. Possible pathogenic factors are discussed.

Adolescent↗

PubMed1999

Migraine--evidence for a disturbance of cerebral maturation in man?

The contingent negative variation (CNV), a slow cortical potential between two defined stimuli, was used to record the effect of age in 162 migraine patients and 320 healthy controls aged between 8 and 59 years. The early component (iCNV) and habituation slope of 32 GO-trials are presented. There were no significant differences between healthy controls and migraine patients in iCNV amplitudes or habituation slope up to the age of 19 years. In the age groups from 20-59 years the healthy controls showed a significantly reduced iCNV compared with migraine patients and healthy controls below 20 years of age. While the habituation slope increased in healthy controls, there was no habituation of iCNV in migraine patients. It is suggested that reduced iCNV amplitudes in healthy controls indicate a state of cerebral maturation. This maturation effect is missing in adult migraine patients, leading to pronounced attentional effort in these patients.

Adolescent↗

PubMed1999

Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase.

Type IV of the carbohydrate deficient glycoprotein syndromes (CDGS) is characterized by microcephaly, severe epilepsy, minimal psychomotor development and partial deficiency of sialic acids in serum glycoproteins. Here we show that the molecular defect in the index patient is a missense mutation in the gene encoding the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol. The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs. N-glycosylation is abnormal because of the transfer of truncated oligosaccharides in addition to that of full-length oligosaccharides and because of the incomplete utilization of N-glycosylation sites. The mannosyltransferase is the structural and functional orthologue of the Saccharomyces cerevisiae ALG3 gene.

Amino Acid Sequence↗