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R Korinthenberg

Publications and source records attributed to R Korinthenberg.

At least 19 recordsLinked to original sources
PubMed2006

Prospective study on anti-ganglioside antibodies in childhood Guillain-Barré syndrome.

BACKGROUND: Antiganglioside antibodies have been reported to play a part in the pathophysiology of Guillain-Barré syndrome (GBS). AIMS: To investigate the prevalence and correlation of anti-ganglioside antibodies with clinical data in children with GBS in a multicentre clinical trial. METHODS: Immunoglobin (Ig)G and IgM to GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, and GQ1b were measured by ELISA in sera obtained before treatment. In addition, serological testing for Campylobacter jejuni was carried out. In parallel, a group of adults with GBS and a control group of children without GBS or other inflammatory diseases were evaluated. RESULTS: Sera from 63 children with GBS, 36 adults with GBS and 41 children without GBS were evaluated. Four of the children with GBS showed positive IgG to GM1, in one case combined with anti-GalNAc-GD1a and in one with anti-GD1b. Two others showed isolated positive IgG to GD1b and GT1a. One showed increased anti-GalNAc-GD1a IgM. In 5 of the 63 children, serological evidence of a recent infection with C jejuni was found, and this correlated significantly with the raised antibodies (p = 0.001). In the control group without GBS, no child showed positive IgG, but one showed anti-GalNAc-GD1a IgM. Compared with the adults with GBS, the frequency of antibodies in children was insignificantly lower. In our study, patients with positive antibodies did not show a more severe GBS course or worse outcome than those who were seronegative, and we could not show an increased incidence of axonal dysfunction. CONCLUSIONS: In some children with GBS, one can detect raised IgG against various gangliosides, similar to that in adults. A recent infection with C jejuni is markedly associated with the presence of these antibodies. However, in contrast with what has been reported in adults, in this study we were unable to show a negative effect of these findings on the clinical course.

Adolescent↗
PubMed2005

Facing the genetic heterogeneity in neuromuscular disorders: linkage analysis as an economic diagnostic approach towards the molecular diagnosis.

The identification of an ever increasing number of gene defects in patients with neuromuscular disorders has disclosed both marked phenotype and genotype variability and considerable disease overlap. In order to offer an economic strategy to characterise the molecular defect in patients with unclassified neuromuscular disorders, we designed DNA marker sets for linkage analysis of 62 distinct neuromuscular disorders gene loci, including all known muscular dystrophies, congenital myopathies, congenital myasthenic syndromes and myotonias. Genotyping of marker loci of 140 clinically well-characterised families with unclassified neuromuscular disorders reduced the number of candidates to one or two genes in 49 % of the families. Subsequent mutation analysis and genome-wide scans enabled the determination of the genetic defect in 31 % of the families including the identification of a new gene and a new mutation in an unexpected candidate gene. This highlights the effective application of this approach both for diagnostic strategies as well as for the identification of new loci and genes.

DNA Mutational Analysis↗
PubMed2005

Recruitment of the sensorimotor cortex--a developmental FMRI study.

INTRODUCTION: The growing mastery of motor tasks is one of the most visible changes in the developing child. The cortex is known to play a central role in learning, planning, and performance of motor tasks. We investigated the age dependency of motor cortex activation using functional magnetic resonance imaging (fMRI). METHODS: Thirty-two right-handed subjects were studied: 11 children (median age 9 years, range 6 - 10 years), 10 adolescents (median age 13 years, range 11 - 15 years), and 11 adults (median age 27 years, range 23 - 42 years). The subjects performed a simple, paced unilateral motor task (repetitive squeezing of a ball with the right hand). Also, we set up a control experiment (visual stimulation using an alternating checkerboard pattern) in which no age-related differences were expected. RESULTS: Compared to children, adults showed significantly increased activation of the bilateral sensorimotor cortex, parietal areas, the supplementary motor area, and the cerebellum. In the visual stimulation experiment there were no age-related differences. CONCLUSION: Children show a significant difference in the degree of cortical activation compared to adults when performing a simple motor task. The change in fMRI activation patterns may reflect a maturation process of primary and secondary motor areas.

Adolescent↗
PubMed2004

Low level of intracortical inhibition in children shown by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to evaluate the integrity and maturation of the corticospinal tract. TMS was used in this study to compare intracortical inhibition (ICI) in children, adolescents, and adults. The paired-pulse technique of TMS with interstimulus intervals of 2 ms was used to determine the ratio of conditioned (cMEP) and unconditioned amplitudes (ucMEP) that measures ICI. In experiment 1 (Exp 1) stimulus intensity was adapted to motor threshold (50 healthy subjects; 24 male, 26 female, median age 13.5 years, range 6.3 - 34 years) and in experiment 2 (Exp 2) stimulus intensity was adapted to the ucMEP (200 - 400 microV). Children (quotient of cMEP and ucMEP: Exp. 1: 0.71 +/- 0.41, Exp. 2: 0.82 +/- 0.25) had significantly less ICI compared to adults (Exp. 1: 0.21 +/- 0.19, mean +/- STD, Exp. 2: 0.35 +/- 0.22, in both experiments p < 0.001). Recently, ICI has been linked to the regulating function of GABAergic cortical interneurons on practice-dependent neuronal plasticity. Therefore, the lower ICI in children points to maturation processes that may have implications for the greater capacity of practice-dependent neuronal plasticity in children.

Adolescent↗
PubMed2003

Classical infantile spinal muscular atrophy with SMN deficiency causes sensory neuronopathy.

OBJECTIVE: Classic infantile spinal muscular atrophy (SMA) is believed to be a purely motor disorder, affecting neurons of the spinal anterior horn and nuclei of the lower cranial nerves. Other organ malformations or peripheral nerve involvement have been regarded as exclusion criteria for infantile SMA. Whether SMN protein deficiency can also lead to loss of sensory neurons has not been systematically addressed. METHODS: The authors evaluated the sural nerve biopsies of 19 patients with infantile SMA of varying severity. The diagnosis of SMA was confirmed by the presence of a homozygous deletion of the SMN1 gene in all patients. RESULTS: In seven unrelated infants with SMA type I, axonal degeneration of the sural nerve was noted. Five patients showed abnormal sensory conduction, thus prompting sural nerve biopsy. Sural nerves showed different degrees of axonal loss: fiber density ranged from 3.482 to 22.076/mm2 and was markedly reduced in four patients. There was no evidence of primary demyelination: the ratio of total myelinated fiber thickness to axon diameter (g-ratio) was normal in the patients examined. In seven patients with SMA II and five patients with SMA III, no sural nerve alterations were seen, and conduction velocity was normal. In addition to SMN1 gene deletions, homozygous NAIP gene deletions were detected in six out of seven infants with peripheral neuropathy, whereas there was no evidence of a large deletion including the multicopy markers C212 and Ag1-CA in two out of three families tested. CONCLUSIONS: In this series of patients with SMA I through III who underwent sural nerve biopsy, there was significant sensory nerve pathology in severely affected patients with SMA type I, whereas there were no sensory nerve alterations clinically or morphologically in patients with milder SMA type II or III.

Axons↗
PubMed2003

Identification of seven novel mutations in the GAN gene.

Giant axonal neuropathy (GAN) is a severe early onset neurodegenerative disorder affecting both the peripheral nerves and the central nervous system. The diagnosis is based on the presence of characteristic giant axons on nerve biopsy. In GAN, the integrity of the intermediate filament network is altered. Indeed, abnormal accumulation of the intermediate filaments has been reported in different cell types, including in the swollen axons, which are filled with neurofilaments. We identified the defective protein, gigaxonin, of unknown function, and reported fourteen distinct mutations in twelve families of various origins. Two additional mutations have been recently reported. In the present study, we analysed the GAN gene in 6 families, and identified seven novel mutations: three nonsense and two missense mutations and two deletions. In addition, the molecular result for an already reported family was re-evaluated. In this family, the R269Q "polymorphism" is in fact the pathogenic mutation.

Age of Onset↗
PubMed2003

Identification of a novel LAMP2 mutation responsible for X-chromosomal dominant Danon disease.

Danon disease (DD) is a rare lysosomal glycogen storage disease with normal acid maltase activity, which is characterised clinically by cardiomyopathy and myopathy, and a variable degree of mental retardation. The causative gene, LAMP2, has been mapped to chromosome Xq24-q25. LAMP2 encodes a lysosome-associated membrane glycoprotein. We identified a novel LAMP2 mutation of the exon 8 splice acceptor site (IVS7-1G --> A) in an affected male and female, which predicts abnormal splicing. Both affected individuals presented solely with hypertrophic cardiomyopathy. Muscle weakness and mental impairment were absent. Diagnosis of Danon disease was established by muscle biopsy, when the male index patient developed transient severe muscle weakness following heart transplantation. Typical biopsy findings were also found in a heart muscle specimen. Demonstration of the LAMP2 mutation in affected male and female siblings is compatible with X-linked dominant inheritance. Danon disease should be actively looked for in cardiomyopathy patients.

Adult↗
PubMed2002

Hashimoto encephalopathy - is it underdiagnosed in pediatric patients?

Hashimoto encephalopathy (HE) is associated with Hashimoto thyroiditis. Clinically it presents with variable symptoms like seizures, neuropsychiatric changes or focal neurological deficits. Autoimmune phenomena are hypothesized for the pathogenesis. HE has mainly been described in the adult population. We present two 14-year-old patients who presented with recurrent seizures and mental decline. SPECT and PET scans showed distinctly pathological changes. Both patients were diagnosed with HE and improved dramatically on steroids. We feel that HE is a rare but important differential diagnosis of encephalopathy also in the pediatric population. As this disease responds well to steroids, we recommend to obtain basic thyroid function tests as well as thyroid antibodies in all cases of unexplained encephalopathy or unexplained status epilepticus.

Adolescent↗
PubMed2002

Polyradiculoneuritis with myelitis: a rare differential diagnosis of Guillain-Barré syndrome.

AIM: To describe the symptoms, signs, findings and prognosis in children suffering simultaneously from polyradiculoneuritis and myelitis. METHODS: Retrospective review of eight patients aged 2 to 13 years out of 210 patients with polyradiculoneuritis reported from 70 hospitals. Diagnostic criteria for polyradiculoneuritis were: flaccid paresis with loss of tendon reflexes, increased CSF protein and slowing of nerve conduction velocity. Criteria for myelitis were: severe and persistent bladder dysfunction, a sharply defined sensory level and/or evolving spastic paresis, with or without myelitic changes in spinal MRI. RESULTS: In the disease's earliest stage it was difficult to differentiate polyradiculoneuritis with myelitis from classical GBS. However, onset was often unusually rapid compared to GBS. Five patients developed a sensory level and seven suffered from severe bladder dysfunction. Four of the six children studied showed focal myelitic changes in MRI. All seven children with sufficient follow-up remained with residual paresis and significant long-term motor deficits. CONCLUSION: Due to its severe long-term prognosis, polyradiculoneuritis with myelitis must be differentiated from classical GBS. In the disease's early stage, the detection of a sensory level, severe bladder dysfunction and an unusually rapid onset can be helpful. The effect of high-dose corticosteroids is not yet clear. After the acute phase, most children require extended rehabilitation.

Adolescent↗
PubMed2002

Pro- and anticoagulatory factors under sodium valproate-therapy in children.

OBJECTIVE: To evaluate sodium valproate-induced hemostatic side effects in children. METHODS: A variety of both pro- and anticoagulatory parameters were longitudinally investigated in 80 children before therapy and up to 720 days after initiation of sodium valproate (VPA) therapy. RESULTS: VPA caused a significant reduction in platelet count (309,000/ micro l +/- 122,000 before treatment to 261,000/ micro l +/- 150,000 under VPA therapy, p = 0.007). However platelet function was not impaired. While vWF antigen was reduced during VPA therapy (1.05 U/ml +/- 0.4 U/ml before therapy, 0.95 +/- 0.4 U/ml under VPA therapy), the in vivo activity of vWF (ratio between function and antigen concentration) increased significantly (1.06 +/- 0.2 before therapy, 1.36 +/- 0.3 under VPA therapy, p = 0.01). Both procoagulatory and anticoagulatory factors were significantly reduced (fibrinogen: 264.5 +/- 64.5 mg/dl before therapy, 221.4 +/- 47.5 mg/dl under therapy, p = 0.001; protein C: 81.3 % +/- 18 before therapy, 65.6 % +/- 21.4 under VPA therapy, p = 0.005, antithrombin: 122.7 % +/- 23.7 before therapy, 101.7 % +/- 18 under VPA therapy, p = 0.04). With the exception of fibrinogen, these effects were identical in children treated either with monotherapy or with polytherapy. CONCLUSIONS: Besides already known alterations of a variety of procoagulatory parameters, a relevant influence of VPA on the anticoagulatory system is demonstrated. We hypothesize that this additional alteration of anticoagulatory parameters might reduce the absolute bleeding risk of children treated with VPA.

Adolescent↗
PubMed2001

Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option.

Intramuscular injections of botulinum toxin type A (BTX-A) have increasingly been used to reduce spasticity in specific muscle groups in children with cerebral palsy. Targets of therapeutic efforts are improvement of gross motor function, alleviation of pain or facilitation of hygienic care. Placebo-controlled studies have shown the local and functional effectiveness of BTX-A for the treatment of dynamic pes equinus. Whether long-term treatment with BTX-A improves motor development and delays contractures is still under investigation.

Animals↗
PubMed2001

Inhibitory conditioning stimulus in transcranial magnetic stimulation reduces the number of excited spinal motor neurons.

OBJECTIVE: To study the mechanisms of amplitude attenuation caused by a transcranial magnetic conditioning stimulus. Both conventional MEPs and the recently described triple stimulation technique (TST) were applied; the latter to improve the quantification of the response size decrease. METHODS: TST uses a peripheral collision method to eliminate the effects of desynchronization of the transcranial magnetic stimulation (TMS) induced spinal motor neuron discharges. The attenuation of motor evoked potentials (MEPs) and responses to TST was studied in 10 healthy volunteers using the conditioning-test paradigm with 2 ms interstimulus intervals. RESULTS: Conventional MEPs and responses to TST demonstrated a marked attenuation by the preceding conditioning stimulus in all subjects. The ratio of MEP to TST amplitudes was the same in conditioned and unconditioned responses. CONCLUSIONS: Our findings suggest that the transcranial conditioning stimulus does not change the degrees of desynchronization of spinal motor neuron discharges, but results in a reduced number of excited alpha motor neurons. This reduction can be estimated by both MEPs and TST.

Adult↗
PubMed2001

Medium-term functional benefits in children with cerebral palsy treated with botulinum toxin type A: 1-year follow-up using gross motor function measure.

One of the main goals when treating spasticity is to relieve pain and improve function. Intramuscular injection of botulinum toxin type A (BTX-A) has gained widespread acceptance in the treatment of spastic cerebral palsy. Several studies have clearly shown the short-term functional benefit of BTX-A treatment. Information is limited, however, on the efficacy of medium and long-term regimens, using repeated injection of BTX-A. The aim of the present open-label, prospective study was to evaluate functional outcome in children with spastic cerebral palsy after 1 year of treatment with BTX-A, using the Gross Motor Function Measure (GMFM) as a validated outcome measure. Patients (n=25, age 1.5--15.5 years) were treated with BTX-A for adductor spasm (n=12) or pes equinus (n=13). The local effect was evaluated using passive range of motion and modified Ashworth Scale. Apart from a significant improvement in joint mobility and reduction of spasticity compared to pretreatment values (P < 0.01), we demonstrated a significant improvement of gross motor function after 12 months of treatment, with a median gain of 6% in total and goal scores (P < 0.001). An increase in GMFM scores was particularly evident in younger and moderately impaired children (Gross Motor Function Classification System level III). Whether the observed improvement in gross motor function in children with cerebral palsy is specifically related to therapy with BTX-A or represents at least in part the natural course of motor development still needs clarification.

Adolescent↗
PubMed2001

Neurosurgical interventions in children with Maroteaux-Lamy syndrome. Case report and review of the literature.

This paper reports the case of a 14-year-old child with Maroteaux-Lamy syndrome (mucopolysaccharidosis type 6) who was treated consecutively for compressive damage of the optic nerves, hydrocephalus communicans and progressive spastic tetraparesis within 2 years. The clinical course of the patient is presented and the pathophysiologic mechanisms of disease progression in patients with Maroteaux-Lamy syndrome are discussed and reviewed.

Adolescent↗