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Janbernd Kirschner,
Joachim Schessl,
Ulrike Schara,
Bernd Reitter,
Georg M Stettner,
Elke Hobbiebrunken,
Ekkehard Wilichowski,
Günther Bernert,
Simone Weiss,
Florian Stehling,
Gert Wiegand,
Wolfgang Müller-Felber,
Simone Thiele,
Ulrike Grieben,
Maja von der Hagen, Jürg Lütschg,
Claudia Schmoor,
Gabriele Ihorst,
Rudolf Korinthenberg
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ABSTRACT: Duchenne muscular dystrophy is a rare X-linked progressive disease characterised by loss of ambulation at about age 10 years, with death in early adulthood due to respiratory and cardiac insufficiency. Steroids are effective at slowing the progression of muscle weakness; however, their use is limited by side-effects, prompting the search for alternatives. We assessed the effect of ciclosporin A as monotherapy and in combination with intermittent prednisone for the treatment of ambulant patients with this disorder.
Our study was a parallel-group, placebo-controlled, double-blind, multicentre trial at trial sites of the German muscular dystrophy network, MD-NET, over 36 months. Ambulant patients with Duchenne muscular dystrophy who were aged 5 years or older were randomly assigned to receive either ciclosporin A (3·5-4·0 mg/kg per day) or matching placebo. Allocation was done centrally with computer-generated random numbers. Patients and investigators were masked to the allocated treatment. After 3 months of treatment, both groups were also given intermittent prednisone for a further 12 months (0·75 mg/kg, alternating 10 days on with 10 days off). All patients who received at least one dose of study drug or placebo were included in the primary analysis. The primary outcome measure was manual muscle strength measured on the Medical Research Council (MRC) scale. This trial is registered with the German clinical trial register DRKS, number DRKS00000445.
77 patients were randomly assigned to the ciclosporin A group and 76 to the placebo group; 73 patients on ciclosporin A and 73 on placebo received at least one dose and were available for efficacy analyses. 3 months of treatment with ciclosporin A alone did not show any significant improvement in primary outcome measures (mean change in the proportion of a possible total MRC score [%MRC] was -2·6 [SD 6·0] for patients on ciclosporin A and -0·8 [4·9] for patients on placebo; adjusted group difference estimate -0·88, 97·5% CI -2·6 to 0·9; p=0·26). The combination of ciclosporin A with intermittent steroids was not better than intermittent steroids alone over 12 months (mean change in %MRC was 0·7 [7·1] for patients on ciclosporin A and -0·3 [7·9] for patients on placebo; adjusted group difference estimate -0·85, -3·6 to 1·9; p=0·48). Numbers of adverse events (75 in patients on ciclosporin A and 74 on placebo) and serious adverse events (four with ciclosporin A and four with placebo) did not differ significantly between groups.
Ciclosporin A alone or in combination with intermittent prednisone does not improve muscle strength or functional abilities in ambulant boys with Duchenne muscular dystrophy, but is safe and well tolerated.
German Federal Ministry of Education and Research, Action Benni and co eV, Novartis Pharma AG, and Deutsche Gesellschaft für Muskelkranke eV.
The Lancet Neurology 11/2010; 9(11):1053-9. · 23.46 Impact Factor
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ABSTRACT: Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disease due to a mutation in the ROBO3 gene. This rare disease is of particular interest because the absence, or at least reduction, of crossing of the ascending lemniscal and descending corticospinal tracts in the medulla predicts abnormal ipsilateral sensory and motor systems.
We evaluated the use of functional magnetic resonance imaging (fMRI) for the first time in this disease and compared it to diffusion tensor imaging (DTI) tractography and neurophysiological findings in the same patient with genetically confirmed ROBO3 mutation.
As expected, motor fMRI, somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) were dominantly ipsilateral to the stimulation side. DTI tractography revealed ipsilateral ascending and descending connectivity in the brainstem yet normal interhemispheric connections in the corpus callosum. Auditory fMRI revealed bilateral auditory activation to monaural left-sided auditory stimulation. No significant cortical activation was observed after monaural right-sided stimulation, a hearing defect having been excluded. Prosaccades fMRI showed no activations in the eye-movement network.
Motor fMRI confirmed the established findings of DTI and neurophysiology in the same patient. In suspected HGPPS, any technique appears appropriate for further investigation. Auditory fMRI suggests that a monaural auditory system with bilateral auditory activations might be a physiological advantage as compared to a binaural yet only unilateral auditory system, in analogy to anisometropic amblyopia. Moving-head fMRI studies in the future might show whether the compensatory head movements instead of normal eye movements activate the eye-movement network.
Neuroradiology 02/2008; 50(5):453-9. · 2.82 Impact Factor
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ABSTRACT: The aim of the present preliminary study was to evaluate the feasibility of measuring cerebral hemodynamic effects of a clinical dose of methylphenidate by near-infrared spectroscopy in 10 boys (median age, 10.7 years; range, 8.6-11.8 years) with developmental attention-deficit/hyperactivity disorder (ADHD). Using a Trail Making Test known to activate the left dorsolateral prefrontal cortex, cerebral hemodynamic changes show a lower increase of cerebral blood volume in the right prefrontal cortex (P = .033) and a lower increase of the tissue oxygenation index in the left prefrontal cortex (P = .015) in the condition after intake of methylphenidate compared with a drug-naive situation. A lower increase of the tissue oxygenation index indicates a changing regional oxygen metabolism and consumption induced by methylphenidate. Near-infrared spectroscopy is a sensitive tool for measuring pharmacological effects of methylphenidate on the cerebral hemodynamics.
Journal of Child Neurology 08/2007; 22(7):812-7. · 1.75 Impact Factor
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ABSTRACT: A 7-y-old, right-handed girl presented at our clinic with complex partial seizures, behavioural problems and word-finding difficulties. Clinical examination was normal, but electroencephalogram revealed bilateral epileptic discharges in the temporal and paracentral leads. Magnetic resonance imaging showed an intracerebral mass in the left mesial temporal lobe in the areas of the gyrus temporooccipitalis medialis and gyrus parahippocampalis. Neuropsychological testing brought to light an above-average general intelligence, but the girl performed below average in verbal memory tests and average in figural memory tests.
The tumour was completely removed by surgery. Neuropsychological testing 3 and 11 wk after tumour resection demonstrated above-average verbal learning and memory abilities and improved visual memory. The emotional disturbances, seizures and electroencephalogram abnormalities disappeared completely during the postoperative follow-up.
After resection of a left temporal brain tumour, the patient was free of seizures, and neuropsychological functions recovered completely within weeks.
Acta Paediatrica 11/2006; 95(10):1306-9. · 2.07 Impact Factor
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ABSTRACT: Sudden unexplained death is a significant cause of mortality in adults with epilepsy. Only a few data exist about this risk in childhood.
Cases of sudden unexplained death in epilepsy (SUDEP) up to the age of 18 y occurring at our hospital between 1984 and 2001 were identified. The incidence rate was calculated on the basis of diagnosed epileptics registered with a statutory disability insurance scheme. Results: Four cases of SUDEP were identified during the 18-y period. The incidence of SUDEP was 4.3 per 10,000 patient-years. All children showed polytherapy-refractory epilepsy, developmental retardation and early-onset epilepsy. Two witnessed cases had shown no previous signs of seizure.
SUDEP is rare in childhood. Children with uncomplicated epilepsy seem not to be at risk.
Acta Paediatrica 06/2005; 94(5):564-7. · 2.07 Impact Factor
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ABSTRACT: There are no special recommendations for basic vaccinations in patients with chronic neurological deficits distinct from the nationwide advocated schedule in Switzerland. Reports describing adverse neurological events possibly related to vaccinations have attracted public attention. It is unclear if patients with chronic neurological deficits are more reluctantly vaccinated compared to healthy children. We therefore investigated the acceptance of vaccinations in such patients and healthy controls in a retrospective case-control study. At the University Children's Hospital, Basel, Switzerland we investigated 100 patients with chronic neurological deficits and 200 age-matched healthy controls regarding the issue of vaccination rates and ages. The total number of administered vaccinations against diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), mumps, measles, rubella and hepatitis B were significantly lower in patients compared to healthy controls ( P < 0.01 for each of the respective vaccines). Patients had an increased risk to receive the third pertussis, diphtheria, and tetanus vaccinations (relative risks (RR) for late vaccination 1.53, 1.53, and 1.54 respectively, P < 0.01 for all comparisons), the second (RR = 1.60, P < 0.05) and third Hib vaccinations (RR = 1.52, P < 0.05), and the third polio vaccination (RR = 1.43, P < 0.05) later than controls. CONCLUSION: Children with chronic neurological deficits received fewer vaccinations than healthy controls. In addition, patients received vaccinations later than healthy children. Hence, it may be assumed that children with chronic neurological deficits are at an increased risk to acquire preventable infections. Therefore, vaccination should be promoted as part of the consultation during a routine appointment with the specialist.
European Journal of Pediatrics 06/2005; 164(5):320-5. · 1.88 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate the hemodynamic changes in both prefrontal regions induced by a cognitive task in children with a developmental attention-deficit disorder in comparison to normal controls using near-infrared spectroscopy (NIRS). A total of 11 boys with a mean age of 10.4 (+/-1.2) years that met the DSM-IV criteria for attention-deficit hyperactivity disorder (ADHD) participated in the study and were compared with 9 healthy age- and sex-matched controls. Using a trail-making test designed for the task of connecting numbers from 1-90 in four sets, changes in oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin, tissue oxygenation index (TOI), and cerebral blood volume (CBV) were measured by near-infrared spectroscopy. During the first test set, designed as a short-attention task, the children with ADHD showed significant increases in O2Hb and CBV, whereas the controls showed no significant changes. During the 4 task cycles in which extended attention was demanded, both groups showed increases in O2Hb and CBV, but only the controls showed an additional increase in HHb in the left prefrontal region. In the ADHD group only, TOI showed an increase mainly on the left side. NIRS is a sensitive tool for measuring differences in hemodynamic changes between boys with ADHD and normal controls. Overall, the normal controls showed lateralized oxygen consumption in the left prefrontal cortex during an extended-attention task, whereas the boys with ADHD showed an imbalance between oxygenated and deoxygenated hemoglobin during the short- and extended-attention tasks.
Journal of Developmental & Behavioral Pediatrics 05/2005; 26(2):105-11. · 2.13 Impact Factor
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ABSTRACT: In eight right-handed healthy males aged 9.6-12.9 years, changes in the frontal cerebral concentrations of oxygenated, deoxygenated, and total hemoglobin, as well as in tissue oxygenation index and cytochrome oxidase aa(3) were measured by near-infrared spectroscopy. The males were evaluated using a trail-making test with four test cycles interrupted by relax breaks. During the first cycle of this task, a significant increase in deoxygenated hemoglobin was documented in the left frontal region. In the extended course of the test, a significant increase in oxygenated and total hemoglobin was observed on both sides, indicating an increase in cerebral blood volume. However, only on the left side was an increase in deoxygenated hemoglobin documented. In children, changes in cerebral oxygenation induced by a cognitive task could be measured by near-infrared spectroscopy. In a short and extended attention task, a lateralized increase in oxygen consumption was documented by an increase in deoxygenated hemoglobin. In an extended attention task, an increase in oxygenated and total hemoglobin was recorded additionally in both frontal brain regions, indicating a compensatory increase in cerebral perfusion. Further studies are required to examine the significance of this technique in testing differences in children with neurobehavioral disabilities.
Pediatric Neurology 09/2004; 31(2):96-100. · 1.52 Impact Factor
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ABSTRACT: Methylphenidate is the psychotropic drug most commonly used to treat individuals suffering from developmental attention-deficit-hyperactivity disorder. Additional attention deficit is part of numerous neurologic diseases in childhood. Despite the vast extent of scientific research on methylphenidate, the use of this stimulant in the treatment of cognitive and behavioral dysfunction in children with epilepsy, brain tumor, leukemia, closed brain injury, encephalitis, meningitis, or mental retardation continues to be controversial. Only few data exist about the efficacy and side effects of methylphenidate treatment in children with this neurologic illness or history. The aim of the present study is to provide a review of this important clinical topic and perhaps to stimulate further controlled investigations.
Pediatric Neurology 05/2002; 26(4):261-6. · 1.52 Impact Factor
