Papers by Matthias Kieslich
Epilepsy & Behavior, 2019
The aim of this study was to describe the treatment pattern of patients with Dravet syndrome (DS)... more The aim of this study was to describe the treatment pattern of patients with Dravet syndrome (DS) in Germany with routine antiepileptic drugs (AEDs) and emergency medication, and to review the literature of realworld evidence on medicine utilization of patients with DS in Europe. Methods: Patient use of routine AEDs and emergency medications over 3-6 months was analyzed from a 2018 multicenter survey of 93 caregivers of patients with DS throughout Germany. Results were contextualized in a review of real-world evidence on medicine utilization of patients with DS in Europe. Results: The variety of medications and the most frequent combinations routinely used by patients with DS (AEDs and others) are described. Patients use a large number of pharmaceutical treatments to manage seizures. The five most commonly used AEDs were sodium valproate (66% of the patients; mean daily dose: 660 mg; 24.5 mg per kg bodyweight), bromide (44%; 1462 mg; 51.2 mg per kg), clobazam (41%; 10.4 mg; 0.32 mg per kg), stiripentol (35%; 797 mg; 27.6 mg per kg), and topiramate (24%; 107 mg; 3.5 mg per kg). Ninety percent had reported using emergency medications in the last 3 months;, with the most common medications being Buccolam (40%, an oromucosal form of midazolam) and diazepam (20%, mostly rectal application). No discernable relationships between current medication and age or seizure frequency were observed. Significance: This is the first comprehensive report of routine AEDs and emergency medication use in a large sample of patients with DS in Germany over a period of 3-6 months and shows that despite the most common
Seizure, 2019
To identify factors correlating with poorer quality of life (QoL) in children and adolescents wit... more To identify factors correlating with poorer quality of life (QoL) in children and adolescents with epilepsy and regarding QoL and depression of their caregivers in Germany. Method: A cross-sectional multicenter study on QoL and depression was performed in two representative German states. Variance analysis, linear regression, and bivariate correlation were used to identify correlating factors for poorer QoL and symptoms of depression. Results: Data from 489 children and adolescents (mean age: 10.4±4.2 years, range: 0.5-17.8; 54.0% male) and their caregivers were collected. We identified missing seizure freedom (p=0.046), concomitant diseases (p=0.007), hospitalization (p=0.049), recent status epilepticus (p=0.035), living in a nursing home or with foster parents (p=0.049), and relevant degree of disability (p=0.007) to correlate with poorer QoL in children and adolescents with epilepsy. Poorer QoL of caregivers was associated with longer disease duration (p=0.004), focal epilepsy (p=0.003), ongoing seizures (p=0.003), concomitant diseases (p=0.003), relevant disability (p=0.003), or status epilepticus (p=0.003) as well as with unemployment of the primary caretaker (p=0.010). Symptoms of depression of caregivers were associated with focal epilepsy (p=0.003), concomitant diseases (p=0.003), missing seizure freedom (p=0.007), status epilepticus (p=0.004), or a relevant disability (p=0.004) of their ward. A poorer QoL value of the children and adolescents correlated with a poorer QoL value of the caregivers (p<0.001). Conclusions: Epilepsy shows a considerable impact on QoL and depression. Early and effective therapy should focus on reduction of seizure frequency and the probability for developing status epilepticus. Furthermore, comprehensive care should pay attention at comorbidities, consequences of disability and dependency on others.
European Journal of Paediatric Neurology, 2019
Introduction: Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. This stu... more Introduction: Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. This study estimated cost, cost-driving factors and quality of life (QoL) in patients with Dravet syndrome and their caregivers in a prospective, multicenter study in Germany. Methods: A validated 3e12-month retrospective questionnaire and a prospective 3-month diary assessing clinical characteristics, QoL, and direct, indirect and out-of-pocket (OOP) costs were administered to caregivers of patients with DS throughout Germany. Results: Caregivers of 93 patients (mean age 10.1 years, ±7.1, range 15 monthse33.7 years) submitted questionnaires and 77 prospective diaries. The majority of patients (95%) experienced at least one seizure during the previous 12 months and 77% a status epilepticus (SE) at least once in their lives. Over 70% of patients had behavioural problems and delayed speech development and over 80% attention deficit symptoms and disturbance of motor skills and movement coordination. Patient QoL was lower than in the general population and 45% of caregivers had some form of depressive symptoms. Direct health care costs per three months were a mean of V6,043 ± V5,825 (median V4054, CI V4935-V7350) per patient. Inpatient costs formed the single most important cost category (28%, V1,702 ± V4,315), followed by care grade benefits (19%, V1,130 ± V805), anti-epileptic drug (AED) costs (15%, V892 ± V1,017) and ancillary treatments (9%, V559 ± V503). Total indirect costs were V4,399 ±V 4,989 (median V0, CI V3466-V5551) in mothers and V391 ± V1,352 (median V0, CI V195-V841) in fathers. In univariate analysis seizure frequency, experience of SE, nursing care level and severe additional symptoms were found to be associated with total direct healthcare costs. Severe additional symptoms was the single independently significant explanatory factor in a multivariate analysis. Conclusions: This study over a period up to 15 months revealed substantial direct and indirect healthcare costs of DS in Germany and highlights the relatively low patient and caregiver QoL compared with the general population.
Abstracts of the 44th Annual Meeting of the Society for Neuropediatrics, 2018
Growth Factors, 2017
Abstract Introduction: Ataxia telangiectasia (A-T) is a devastating autosomal recessive disorder ... more Abstract Introduction: Ataxia telangiectasia (A-T) is a devastating autosomal recessive disorder with chromosomal instability and growth failure. Low levels of growth hormone (GH) and growth factors may be related to advanced neurological deterioration, wasting syndrome and more pronounced immunodeficiency. Objective: The objective of this study is to study safety and effectiveness of GH therapy in patients with A-T and evaluate the effect of GH on ataxia and lymphocyte subsets. Methods: Three patients with classical A-T were treated with GH (0.3 mg/kg/d) for 1 year. Growth rate, ataxia score and lymphocyte subsets were monitored. Results: GH treatment was well tolerated. All patients showed a significant increase of height SDS of +1.3 (mean height SDS −1.994), a mean increase of 8 (6–11) cm/12 months. Lymphocytes subsets and ataxia were not altered before and after GH treatment. Conclusions: Treatment with GH is feasible and effective in A-T patients with severe growth arrest, but no effect on ataxia and lymphocytes could be recorded.
European Journal of Paediatric Neurology, 2016
Previous studies hypothesized that the analysis of magnetic resonance intensity of the solid port... more Previous studies hypothesized that the analysis of magnetic resonance intensity of the solid portion in paediatric tumours can provide pre-surgical information about the histopathology. Classically, high signal-intensity in T2weighted (T2w) images identifies low-grade tumours, while anaplasia is characterized by T2 hypointensity. We aimed to investigate if T2w signal intensities can pre-operatively distinguish between low-grade and high-grade brain tumours in paediatric patients. Two raters, blinded to the histological diagnosis, rated the signal intensity of MR images (T2w) from 36 children with newly diagnosed brain tumours, 17 children with low-grade brain tumours and 19 children with high-grade brain tumours were included in this study. Relative T2 values were obtained by dividing the T2w values of the solid portion of the tumour by the T2w values of the vitreous humour. The best cut-off point to distinguish low and high-grade paediatric brain tumours was 0.8. If the signal intensity was less than or equal to 0.8 the tumour was expected to be a high-grade tumour with a sensitivity of 100%. Prediction of a low-grade tumour was more uncertain with a sensitivity of 70.5%. Overall, 86% of the tumours would have been predicted correctly. Our data suggest that T2w signal intensities of the solid portion of brain tumours in paediatrics can pre-operatively differentiate between low-grade and high-grade tumours. In addition, T2 hypointensity may be helpful in targeting stereotactic biopsy.
Neuropediatrics, 2014
DESCRIPTION Second Part of Syllabus of the german-speaking Society of Neuropeditrics (GNP), descr... more DESCRIPTION Second Part of Syllabus of the german-speaking Society of Neuropeditrics (GNP), describing the different levels of neuropediatric care in outpatient, inpatient and rehabilitative institutions in Germany, it&#39;s needs and financial background
Paediatrics Today, 2014
Objective-To describe the magnetic resonance imaging (MRI) and time-of-flight (TOF)-magnetic reso... more Objective-To describe the magnetic resonance imaging (MRI) and time-of-flight (TOF)-magnetic resonance angiography (MRA) characteristics of children with arterial ischemic stroke and correlate them with the aetiology. Methods-We performed a retrospective review of clinical records and imaging (MRI and MRA) of 34 children (8 months to 17 years) with arterial ischemic stroke. Results-The group contained 14 females and 20 males. Risk factors were congenital heart disease (CHD) in 8, sickle cell disease in 2, prothrombotic abnormalities in 7, vasculitis in 5 (varicella in 2, neuroborreliosis in 1), trauma in 3, steno-occlusive cerebral arteriopathy, herniation due to intracranial bleeding, complication of aneurysmal subarachnoid haemorrhage with vasospasm, and arterial dissection with and without previous trauma. In 5 of the 34 patients the aetiology was undetermined. The most common infarctions were observed in the distribution of the middle cerebral artery, followed by the posterior circulation. The intracranial MRA was normal in 15 of the 34 children. In all but one patient with cryptogenic stroke MRA was normal. Conclusion-MRI is helpful to determine the exact location and limit of the infarct zone. The absence of cerebral arteriopathy on TOF-MRA in childhood stroke suggests a nonvascular cause; mainly cryptogenic stroke, but also prothrombotic abnormalities and CHD.
Pediatrics International, 2010
Background: Detection of leptomeningeal metastases is fundamental to a complete evaluation of cen... more Background: Detection of leptomeningeal metastases is fundamental to a complete evaluation of central nervous system (CNS) or non-CNS tumor with suspected involvement of the neuroaxis. Our purpose was to assess the appearances of different magnetic resonance (MR) sequences in the diagnosis of leptomeningeal metastases and correlate those positive findings with the cerebral spinal fluid (CSF) cytology results. Methods: The authors reviewed the medical records and MR image manifestations of leptomeningeal metastases from 18 children who had positive MR findings and retrospectively correlated them with CSF cytologic results. There was a uniform MR protocol and the patients were examined with the same sequences. Results: The abnormalities included pial-arachnoid disease (n = 16), disease coating the nerves (n = 12), hydrocephalus (n = 3) and subependymal metastases (n = 2). Enhanced T1 images were better than unenhanced fluid attenuated inversion recovery (FLAIR) and T2 to delineate cranial and spinal leptomeningeal metastases. In our sample, seven out of 18 cases were cytologically negative on a single lumbar puncture. Conclusions: Contrast-enhanced MR imaging can be invaluable, detecting the false-negative lumbar punctures. FLAIR and diffusion images can be helpful in diagnosing leptomeningeal metastases of non-enhancing primary tumors. Prognosis was more related to the primary tumor type than to the leptomeningeal enhancement MR pattern.
Epilepsia, 2014
SummaryObjectiveJuvenile myoclonic epilepsy (JME) has been considered to be a frontal variant of ... more SummaryObjectiveJuvenile myoclonic epilepsy (JME) has been considered to be a frontal variant of thalamocortical network dysfunction in epilepsy. Changes of γ‐aminobutyric acid (GABA)ergic neurotransmission may play a key role in this dysfunction. Magnetic resonance spectroscopy (MRS) is the only noninvasive method to measure GABA concentrations in different brain regions. We measured GABA and other metabolite concentrations in the thalamus and frontal lobe of patients with JME.MethodsA specific protocol was used for determining GABA concentrations in the thalamus, frontal lobe, and motor cortex contralateral to the handedness in 15 patients with JME and 15 age‐matched controls. In addition, we measured concentrations of glutamate and glutamine, N‐acetyl‐aspartate (NAA), myoinositol, creatine, and choline using MRS with short echo time. JME‐related concentration changes were analyzed comparing patients to controls, also considering potential effects of antiepileptic drugs.ResultsIn ...
Pediatric Neurology, 2014
Pediatric cerebrocerebellar neurodegenerative disorders such as ataxia-telangiectasia (AT) have n... more Pediatric cerebrocerebellar neurodegenerative disorders such as ataxia-telangiectasia (AT) have not been examined in detail for neuropsychologic changes. Such studies may contribute to the further understanding of ataxia-telangiectasia and to the role of the cerebrocerebellar system in the development of cognitive function in childhood. Twenty-two patients with the classic phenotype of ataxia-telangiectasia were grouped into early stage cerebellar disease (group AT-I) versus late stage cerebrocerebellar disease (group AT-II) and examined for neurocognitive features. Results were compared with those of healthy control subjects and with standard norms. Patients in AT-I group scored low average compared with standard norms on all tests and were impaired compared with healthy control subjects for verbal intelligence quotient (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), vocabulary and comprehension (P = 0.007), processing speed (P = 0.005), visuospatial processing (P = 0.020), and working memory (P = 0.046). Patients in AT-II group scored below average compared with standard norms on all tests and were impaired compared with control subjects for attention (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), working memory (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and abstract reasoning (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Comprehension scores were lower for patients in AT-II than in AT-I group (P = 0.002), whereas vocabulary scores showed no difference between groups (P = 0.480). Cognitive impairments in ataxia-telangiectasia present early, coinciding with cerebellar pathology and are characteristic of the cerebellar cognitive affective syndrome. Widespread and deeper cognitive deficits manifest in later stages of ataxia-telangiectasia when additional noncerebellar pathology develops. These results are the first indications of distinct cerebellar and extracerebellar and/or subcortical contributions to the range of cognitive domains affected in ataxia-telangiectasia and need to be confirmed in future studies.
Uploads
Papers by Matthias Kieslich