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1.
Neuropediatrics ; 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31541997

RESUMO

Metabolic myopathies are heterogeneous hereditary diseases affecting skeletal muscle energy supply. Symptoms usually comprise pain, cramps, hypotonia, weakness, and myoglobinuria.We present a boy with recurrent myalgia and weakness after some minutes of exercise or during febrile infections since early infancy. First laboratory workup at the age of 9 years showed no abnormalities, apart from a slightly elevated creatine kinase. After exclusion of common structural and metabolic myopathies, next generation sequencing panel (4 years after the initial diagnostic metabolic workup) revealed two potentially pathogenic missense mutations in the CPT2 gene (c.149C > A (p.P50H) and c.1459G > A (p.E487K)).Our case underscores the clinical variability of muscle carnitine palmitoyltransferase II (CPT II) deficiency and illustrates a pitfall of diagnostic algorithms for metabolic myopathies. Myalgia following exercise of a few minutes duration would have argued for a carbohydrate and against a fatty acid metabolic defect. However, CPT II deficiency is the most common disorder of muscle fatty acid metabolism and should be considered even in atypical scenarios. Analyses of plasma acyl carnitine profile during acute metabolic crises may help to unmask biochemical markers which are often overlooked in dried-blood analyses.

2.
Neuropediatrics ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31505688

RESUMO

INTRODUCTION: Beta-propeller protein-associated neurodegeneration (BPAN) is a very rare, X-linked dominant (XLD) inherited member of the neurodegeneration with brain iron accumulation (NBIA) disease family. CASE REPORT: We present a female case of BPAN with infantile spasms in the first year, Rett-like symptomatology, focal epilepsy, and loss of motor skills in childhood. Menarche occurred at the age of 9, after precocious pubarche and puberty.Dystonia-parkinsonism as extrapyramidal sign at the age of 10 years resulted in radiological and genetic work-up. RESULTS: Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) measured 66/120 points in body part-related dystonia symptoms. Cerebrospinal fluid examination showed dopamine depletion.T2 and B0 sequences of the diffusion-weighted magnetic resonance imaging showed susceptibility artifacts with NBIA-typical hypointense globus pallidus (GP) and substantia nigra (SN). Next-generation sequencing revealed a BPAN-causing pathogenic variant in WDR45 (WD repeat-containing protein 45) gene (c.830 + 1G > A, XLD, heterozygous, de novo). Skewed X-inactivation was measured (2:98). CONCLUSIONS: Autophagy-related X-linked BPAN disease might still be underdiagnosed in female cases of infantile spasms.Skewed X-inactivation will have mainly influenced the uncommon, very early childhood neurodegenerative symptomatology in the present BPAN case. Oral levodopa substitution led to improvement in sleep disorder, hypersalivation, and swallowing.Reduced white matter and hypointense signals in SN and GP on susceptibility sequences in magnetic resonance imaging are characteristic radiological findings of advanced disease in NBIA. No BPAN-typical halo sign in T1-weighted scan at midbrain level was seen at the age of 11 years. NBIA panel is recommended for early diagnosis.

3.
Orphanet J Rare Dis ; 14(1): 96, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053163

RESUMO

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years. RESULTS: A total of 17 children (median age at study inclusion 2.4 years, range 0-6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0-19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1-2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3-4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction. CONCLUSION: This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy.


Assuntos
Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/tratamento farmacológico , Transtorno do Espectro Autista/tratamento farmacológico , Criança , Pré-Escolar , Colesterol/sangue , Colinesterases/sangue , Epilepsia/tratamento farmacológico , Everolimo/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Masculino , Estudos Multicêntricos como Assunto , Fosfatos/sangue , Estudos Retrospectivos , Triglicerídeos/sangue
4.
Epileptic Disord ; 21(2): 197-205, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31010799

RESUMO

Epilepsy is a life-changing disease, and patients with epilepsy may face a number of issues. Paediatricians and general practitioners are often the first to be asked for advice. This cross-sectional study was performed to gain information on the knowledge and experiences of paediatricians and general practitioners on epilepsy. From September 2015 to July 2017, paediatricians and general practitioners in Leipzig, Germany, were asked to take part in a face-to-face interview. Overall, 40 paediatricians and 60 general practitioners participated in the study. A total of 99/100 (99%) kept emergency medication available and 96/100 (96%) would administer it during a seizure. Also, 40/40 (100%) of the paediatricians and 34/60 (57%) of the general practitioners recommended that non-professionals should administer emergency medication, and 18/40 (45%) of the paediatricians and 35/60 (58%) of the general practitioners would put an object in the patient's mouth during a seizure. With regards to safety precautions, paediatricians mentioned the risks associated with swimming (30/40; 75%) and the potential of falling from a height (23/40; 58%), whereas general practitioners focused on being around vehicles including driving regulations (43/60; 72%). Only 5/60 (8%) of the general practitioners advised that precautions should be taken during swimming. Fatigue/exhaustion was the most common adverse drug event associated with long-term anticonvulsive therapy mentioned by paediatricians (13/40; 33%) and general practitioners (27/60; 45%). Of all the participants, 23/100 (23%) recommended epilepsy training programmes for patients and families, however, none were able to name a specific programme. Nearly half of the general practitioners did not recommend the use of rescue medication by non-professionals. This measure, however, can prevent the occurrence of prolonged non-treatable seizures. Both paediatricians and general practitioners should bear in mind that placing an object in the mouth during a seizure should be avoided due to the risk of additional injury. To reduce the risk of drowning, physicians should recommend safety precautions during swimming. Information on epilepsy training programmes for patients and families should be diffused to all physicians taking care of patients with epilepsy.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/terapia , Clínicos Gerais , Conhecimentos, Atitudes e Prática em Saúde , Pediatras , Adulto , Estudos Transversais , Epilepsia/tratamento farmacológico , Feminino , Clínicos Gerais/estatística & dados numéricos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Pediatras/estatística & dados numéricos
5.
Neurology ; 91(22): e2078-e2088, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30413629

RESUMO

OBJECTIVE: To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype-phenotype correlation. METHODS: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations. RESULTS: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype-phenotype correlation did not emerge. CONCLUSION: COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.

6.
Eur J Pediatr ; 177(10): 1451-1457, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29967923

RESUMO

Epilepsy and bronchial asthma are frequent in adolescents. Data on adolescents' experiences with their disease and on their expectations for the future, however, is scarce. Patients of a university hospital aged 12 to 17 with epilepsy or bronchial asthma were interviewed based on a questionnaire. Forty-five patients with epilepsy and 47 with bronchial asthma were interviewed. Adolescents with epilepsy felt more impaired by their disease (median 2.5; Q25/Q75 0.75/3.0; 6-level Likert scales: 0 = not at all, 5 = very strong) than those with asthma (1.0; 0/3.0; p = 0.017). Seventy-nine patients (85.9%) had never used the Internet to gain information about their disease. Adolescents with epilepsy felt more limited in their career possibilities by their disease (2.0; 0/4.0) than those with asthma (0; 0/2.0; p = 0.001) and had a higher level of concern about passing their disease on to their children (3.0; 0/4.0) than their peers with asthma (1.5; 1.5/3.0; p = 0.016). Girls with epilepsy were more anxious (4.0; 0.5/5.0) than girls with asthma (0; 0/4.0) about complications of the disease regarding pregnancy (p = 0.019). CONCLUSION: As well adolescents with epilepsy as with asthma described limitations of their daily life and concerns about the future. What is Known: • Epilepsy and bronchial asthma are frequent chronic diseases in adolescents. • Those diseases can affect psychosocial development. What is New: • Adolescents with epilepsy and bronchial asthma described a high burden of their disease, and most adolescents had not used the Internet to inform themselves on their disease. • Especially adolescents with epilepsy fear limitations in their job possibilities, inheritance of their disease and complications in their prospective pregnancy.


Assuntos
Asma/psicologia , Atitude Frente a Saúde , Epilepsia/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Qualidade de Vida/psicologia , Adolescente , Criança , Medo , Feminino , Humanos , Masculino , Inquéritos e Questionários
7.
Epilepsy Behav ; 84: 37-43, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29747033

RESUMO

OBJECTIVE: Parents of children with epilepsy are at risk of committing high-risk handling errors with a high potential to harm the patient when administering anticonvulsant rescue medication. We developed a training concept addressing identified high-risk handling errors and investigated its effects on parents' skills. STUDY DESIGN: In a controlled prospective intervention study, parents of children with epilepsy were asked to demonstrate their administration of rescue medication by using dummy dolls. A clinical pharmacist monitored rectal or buccal administration and addressed errors in the intervention group with training and information sheets. Three to 6weeks later, intervention's sustainability was assessed at a home visit. RESULTS: One hundred sixty-one parents completed full study assessment: 92 in the intervention group and 69 in the control group. The number of processes with at least one handling error was reduced from 96.4% to 56.7% in rectal tube administration and from 66.7% to 13.5% in buccal administration (both p<0.001). CONCLUSION: A one-time intervention for parents significantly and sustainably reduced high-risk handling errors. Dummy dolls and information sheet were adequate for an effective and feasible training to support the correct administration of anticonvulsant rescue medication.

8.
Pediatr Radiol ; 48(6): 858-864, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29623352

RESUMO

BACKGROUND: Brain imaging is the most common examination in pediatric magnetic resonance imaging (MRI), often combined with the use of a gadolinium-based contrast medium. The application of gadolinium-based contrast medium poses some risk. There is limited evidence of the benefits of contrast medium in pediatric brain imaging. OBJECTIVE: To assess the diagnostic gain of contrast-enhanced sequences in brain MRI when the unenhanced sequences are normal. MATERIALS AND METHODS: We retrospectively assessed 6,683 brain MR examinations using contrast medium in children younger than 16 years in the pediatric radiology department of the University Hospital Leipzig to determine whether contrast-enhanced sequences delivered additional, clinically relevant information to pre-contrast sequences. All examinations were executed using a 1.5-T or a 3-T system. RESULTS: In 8 of 3,003 (95% confidence interval 0.12-0.52%) unenhanced normal brain examinations, a relevant additional finding was detected when contrast medium was administered. Contrast enhancement led to a change in diagnosis in only one of these cases. CONCLUSION: Children with a normal pre-contrast brain MRI rarely benefit from contrast medium application. Comparing these results to the risks and disadvantages of a routine gadolinium application, there is substantiated numerical evidence for avoiding routine administration of gadolinium in a pre-contrast normal MRI examination.

9.
BMC Anesthesiol ; 18(1): 25, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29458333

RESUMO

BACKGROUND: Children with obstructive sleep apnea are at high risk for perioperative airway obstruction. Many "at risk" children may remain unrecognized. The aim of this study is to find a clinically practicable test to identify obstructive sleep apnea in childhood. METHODS: In this pilot study, we prospectively compared four parental questionnaires with the respective findings of subsequent sleep laboratory testing in children. Right before sleep laboratory testing, children's parents answered both the Pediatric Sleep Questionnaire, a subscale of the Sleep Related Breathing Disorder questionnaire (PSQ-SRBD-Subscale), and an eight-item questionnaire derived from it. Finally, we condensed the eight-item questionnaire to three core issues: Does your child regularly snore at night? Does your child demonstrate labored breathing during sleep? Does your child have breathing pauses during sleep? With it, two similar questionnaires were generated that differed in the formation of the resulting score. One questionnaire was built by a quotient comparable to the abovementioned questionnaires and a second as quick test that functioned as a simple sum score. Both sensitivity and specificity were determined by using a Receiver Operating Characteristic analysis. RESULTS: In total, 53 children were included in the study. Both the PSQ-SRBD-questionnaire and self-derived eight-item questionnaire failed to reach statistically significant results in detecting obstructive sleep apnea. The set of three core questions with a score built by a quotient was statistically significant and provided sensitivity and a moderate specificity of 0.944 and 0.543, respectively. This could be slightly optimized by creating a simple sum-score (specificity of 0.571). CONCLUSIONS: The use of three core-questions may facilitate the detection of pediatric obstructive sleep apnea within the scope of the anesthesia survey. While the study has some limitations, future studies with both unselective collectives and older children might prove this ultra-short questionnaire to be advantageous in detecting pediatric OSA in clinical practices. TRIAL REGISTRATION: German Clinical Trial Register ( DRKS00010408 , https://www.drks.de ); date of registration 26.07.2016.

10.
J Neurol ; 265(4): 845-855, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29423614

RESUMO

Antibodies against the myelin oligodendrocyte glycoprotein (MOG-Ab) can be detected in various pediatric acquired demyelinating syndromes (ADS). Here, we analyze the spectrum of neuroradiologic findings in children with MOG-Ab and a first demyelinating event. The cerebral and spinal MRI of 69 children with different ADS was assessed in regard to the distribution and characteristics of lesions. Children with acute disseminated encephalomyelitis (n = 36) or neuromyelitis optica spectrum disorder (n = 5) presented an imaging pattern characterized predominantly by poorly demarcated lesions with a wide supra- and infratentorial distribution. Younger children also tended to have poorly defined and widespread lesions. The majority of patients with an isolated optic neuritis (n = 16) only presented small non-specific brain lesions or none at all. A longitudinally extensive transverse myelitis mainly affecting the cervical, and less often so the thoracic, lumbar, and conus regions, was detected in 31 children. The three children of our cohort who were then finally diagnosed with multiple sclerosis had at onset already demarcated white matter lesions as well as transverse myelitis. In conclusion, children with MOG seropositive ADS present disparate, yet characteristic imaging patterns. These patterns have been seen to correlate to the disease entity as well as to age of symptom onset.


Assuntos
Anticorpos/metabolismo , Encéfalo/diagnóstico por imagem , Doenças Desmielinizantes/diagnóstico por imagem , Glicoproteína Mielina-Oligodendrócito/imunologia , Medula Espinal/diagnóstico por imagem , Adolescente , Aquaporina 4/imunologia , Criança , Pré-Escolar , Doenças Desmielinizantes/imunologia , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos
11.
Childs Nerv Syst ; 34(1): 155-163, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28971247

RESUMO

INTRODUCTION: Fetofetal transfusion syndrome is a dreaded cause of morbidity and mortality in monochorionic pregnancies. CASE REPORTS: We present two pairs of twins one of which we have followed for more than 6 years. The donors suffer from cerebral palsy, orofacial, and motor problems, and both are significantly smaller than their recipient twins. Interestingly, cranial MRI revealed medial frontal lobe polymicrogyria, ventriculomegaly, and decreased thickness in both parietal lobes in both donors. We suggest this as a possible feature of fetofetal transfusion syndrome. REVIEW: A minireview of the literature on neuroimaging and neurodevelopmental outcome in fetofetal transfusion syndrome is presented. CONCLUSION: While the close resemblance of the imaging features of both cases is likely incidental further study of a connection between migration and gyration disorders and fetofetal transfusion syndrome is warranted.

12.
Klin Padiatr ; 230(1): 44-49, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29258157

RESUMO

BACKGROUND: A developmental disorder of a child has a major impact on the affected families' lives. However, data about the parents' perception of the revealing of the diagnosis is scarce. PATIENTS AND METHODS: Parents of children with developmental disorder treated as outpatients in a university hospital were interviewed about the initial medical consultation concerning the diagnosis of their child. RESULTS: Parents of 210 children agreed to take part in the study. 35/210 (17%) had to be excluded from the study as they were not able to remember the initial medical consultation, or claimed there was either no initial medical consultation or they did not attend it. The diagnosis of developmental disorder was made in median 4 months (Q25/Q75: 0/12; min/max: 0/63) after the parents had noticed the first symptoms. According to the parents, options to support the development of the child were the most frequently addressed topic in the initial medical consultation (119/175, 68%). Some parents wished more empathy (19/175, 11%), and less medical terminology (12/175, 7%). 114/175 (65%) of parents rated the initial medical consultation as "very good" or "good". After their initial medical consultation, 66/175 (38%) of the parents had open questions mainly concerning the prognosis of the disease. Sources of information that were used after the consultation were most often the treating physician (150/175, 86%) and the internet (133/175, 76%). CONCLUSION: Generally, parents perceive the initial medical consultation on the developmental disorder of their child well. Nevertheless, many parents state that they had unanswered questions after the consultation. The internet is one of the main sources parents use to answer those questions.

13.
Klin Padiatr ; 230(1): 5-12, 2018 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-29258161

RESUMO

Expertise in a variety of fields is required for the diagnostic process of epilepsies in children and adolescents as well as for their treatment with anticonvulsants. Patients benefit in the process from the cooperation of different health care professionals. It is of critical importance for risks to be minimised and for the efficacy shown in controlled clinical trials to be maintained in routine conditions. In the first instance, drug prescription procedures, including the choice of anticonvulsants and combinations of drugs and dosing, have to be considered. The administration of drugs has, of course, also to be taken into account. Only if patients are given their anticonvulsants appropriately, the intended success of the therapy can be accomplished. Strategies aimed at improving drug administration have to be directed not only at nurses but also at parents, children and adolescents themselves, as well as caregivers in schools and children's day-care facilities. By providing theoretical teaching, practical training, and routinely including pharmacists in the therapeutic team, drug-related problems that may result in limited effectiveness and increased risks are prevented. As a result, drug (therapy) safety is not only qualitatively improved, but the degree of participation and quality of life of patients and families is improved as well.

15.
Klin Monbl Augenheilkd ; 234(10): 1243-1249, 2017 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-29025172

RESUMO

Background Myelin oligodendrocyte glycoprotein (MOG) is located on the surface of oligodendrocytes and myelin in the central nervous system. MOG-IgG is associated with acute disseminated encephalomyelitis (ADEM), relapsing and bilateral optic neuritis (NNO), and transverse myelitis (TM) in both paediatric and adult patients. The combination of NNO and TM or other inflammatory brain lesions is a typical feature of neuromyelitis optica spectrum disorders (NMO-SD) which are associated with specific pathogenic autoantibodies against the water channel aquaporin-4 (AQP4-IgG). However, children with NMO-SD are often seronegative for AQP4-IgG but seropositive for MOG-IgG. Therefore, the course and therapy of MOG-IgG positive NNO in children were of special interest. Patients The course of disease of two male patients with acute NNO is presented (bilateral NNO, age of onset 8 years each, AQP4-IgG negative, MOG-IgG positive). Several relapses of NNO occurred in patient 1 with persisting MOG-IgG in spite of immunsuppressive therapy. He suffered from increasing optic atrophy, considerable visual loss and transient brainstem affection. Patient 2 showed a monophasic course of disease with a rapid decline in MOG-IgG titre and only minor asymmetric optic atrophy. Conclusions MOG-IgG in children is associated with recurrent NNO and cerebral lesions characteristic of ADEM or NMO-SD. High titres of MOG-IgG are observed during the acute phase of clinical symptoms. Relapses of NNO lead to increasing loss of retinal nerve fibre layer. Diagnostic investigation includes the determination of AQP4-IgG and MOG-IgG as well as magnetic resonance imaging (MRI) of brain and spinal cord. The therapeutic consequence of this is consistent immunsuppressive treatment, starting with intravenous steroids and followed by second-line therapy with steroid sparing immunosuppressants, including mycophenolate or azathioprine, followed in refractory cases by rituximab. The therapeutic effect should be controlled by laboratory tests of MOG-IgG titre.

16.
Brain ; 140(9): 2322-2336, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29050398

RESUMO

De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutations. Using different molecular genetic techniques, we identified 20 patients with a pathogenic or likely pathogenic SPTAN1 variant and reviewed their clinical, genetic and imaging data. SPTAN1 de novo alterations included seven unique missense variants and nine in-frame deletions/duplications of which 12 were novel. The recurrent three-amino acid duplication p.(Asp2303_Leu2305dup) occurred in five patients. Our patient cohort exhibited a broad spectrum of neurodevelopmental phenotypes, comprising six patients with mild to moderate intellectual disability, with or without epilepsy and behavioural disorders, and 14 patients with infantile epileptic encephalopathy, of which 13 had severe neurodevelopmental impairment and four died in early childhood. Imaging studies suggested that the severity of neurological impairment and epilepsy correlates with that of structural abnormalities as well as the mutation type and location. Out of seven patients harbouring mutations outside the α/ß spectrin heterodimerization domain, four had normal brain imaging and three exhibited moderately progressive brain and/or cerebellar atrophy. Twelve of 13 patients with mutations located within the spectrin heterodimer contact site exhibited severe and progressive brain, brainstem and cerebellar atrophy, with hypomyelination in most. We used fibroblasts from five patients to study spectrin aggregate formation by Triton-X extraction and immunocytochemistry followed by fluorescence microscopy. αII/ßII aggregates and αII spectrin in the insoluble protein fraction were observed in fibroblasts derived from patients with the mutations p.(Glu2207del), p.(Asp2303_Leu2305dup) and p.(Arg2308_Met2309dup), all falling in the nucleation site of the α/ß spectrin heterodimer region. Molecular modelling of the seven SPTAN1 amino acid changes provided preliminary evidence for structural alterations of the A-, B- and/or C-helices within each of the mutated spectrin repeats. We conclude that SPTAN1-related disorders comprise a wide spectrum of neurodevelopmental phenotypes ranging from mild to severe and progressive. Spectrin aggregate formation in fibroblasts with mutations in the α/ß heterodimerization domain seems to be associated with a severe neurodegenerative course and suggests that the amino acid stretch from Asp2303 to Met2309 in the α20 repeat is important for α/ß spectrin heterodimer formation and/or αII spectrin function.


Assuntos
Encefalopatias/genética , Encéfalo/patologia , Proteínas de Transporte/genética , Epilepsia/genética , Proteínas dos Microfilamentos/genética , Adolescente , Atrofia/complicações , Atrofia/patologia , Encéfalo/anormalidades , Encefalopatias/complicações , Proteínas de Transporte/metabolismo , Células Cultivadas , Criança , Pré-Escolar , Progressão da Doença , Epilepsia/complicações , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Proteínas dos Microfilamentos/metabolismo , Modelos Moleculares , Mutação , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Agregação Patológica de Proteínas/metabolismo , Adulto Jovem
17.
Seizure ; 51: 139-144, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28858641

RESUMO

PURPOSE: Attitudes concerning epilepsy improved over the last few decades, but children with epilepsy still suffer from stigmatisation. Data about unaffected children's knowledge of and attitudes about epilepsy is scarce. METHODS: We developed a questionnaire regarding epilepsy for high school students attending 8th-10th grade. The survey was performed from October 2015 to March 2016 in 5 different federal states of Germany. RESULTS: 1092 students [mean age (Q25/75): 14.5 (14/15) years] participated. 542/1092 (50%) of the respondents knew that people could die from a seizure. 216/1092 (20%) thought emotional strain could cause epilepsy. Asked for measures they would perform in case of a seizure, 235/1092 (24%) participants would hold the person to the ground, and 182/1092 (19%) would put a solid object into the person's mouth. 28/1092 (3%) would not like to be friends with a person with epilepsy, and 237/1092 (22%) would not like to go on a date with a person with epilepsy. Answers of 342/1092 (31%) students of a school located nearby a specialised epilepsy centre differed in some questions. The latter students were more familiar with epilepsy and showed better knowledge concerning causes, symptoms and treatment of epilepsy. In a question about special characteristics of people with epilepsy, 63/342 (18%) [other schools: 52/750 (11%)] answered people with epilepsy were friendlier and 76/342 (22%) [other schools: 49/750 (11%)] answered they were more sociable compared to people without epilepsy. CONCLUSION: To improve knowledge and attitudes and reduce misconceptions further education seems necessary.


Assuntos
Epilepsia , Conhecimentos, Atitudes e Prática em Saúde , Estudantes , Adolescente , Feminino , Alemanha , Humanos , Masculino , Inquéritos e Questionários
18.
Eur J Pediatr ; 176(8): 1121-1129, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28691134

RESUMO

Seizure disorder and developmental disorder are two of the most common chronic disorders in childhood. Data on perceived parental burden and specific effects on daily life is scarce. We performed a structured interview, consecutively talking to all parents of pediatric outpatients of our university hospital diagnosed with seizure or developmental disorder. Three hundred seven parents (of 317 affected children: 53 with seizure disorder, 44 with specific developmental disorder, 35 with learning disorder, 71 with intellectual disability, 15 with seizure + specific developmental disorder, 23 with seizure + learning disorder, 76 with seizure disorder + intellectual disability) were interviewed. Parents of children with both seizure disorder and intellectual disability stated the highest constraints in daily life, regarding friends, hobbies, emotional pressure, occupation, partnership, habitation, and financial burden. Due to diagnosis of seizure or developmental disorder, 155/307 (51%) parents reduced their working hours/stopped working, 62/307 (20%) changed their habitation, and 46/307 (15%) broke up. As judged by parents, 148/317 (47%) children are being discriminated against, even own family/friends and educators are held responsible. CONCLUSION: Parents perceive changes in their daily life and discrimination of their children due to their children's seizure and developmental disorders. An intellectual disability combined with seizure disorder caused the highest constraint. What is Known: • Seizure and/or developmental disorders of children may adversely influence quality of life for affected parents. • Caring for a child with special health care needs can take complete attention and own parental needs may therefore be difficult to meet. What is New: • Two out of three parents stated changes of their daily life such as quitting work, change of habitation, or breakup of partnership due to their child's diagnosis. • As judged by the parents, one in two children with developmental disorder of any kind is being discriminated against, even teachers and own family are held responsible.


Assuntos
Efeitos Psicossociais da Doença , Deficiências do Desenvolvimento/psicologia , Epilepsia/psicologia , Pais/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Epilepsia/complicações , Feminino , Humanos , Lactente , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Discriminação Social/psicologia , Adulto Jovem
19.
Seizure ; 50: 38-42, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28605661

RESUMO

PURPOSE: Prolonged seizures can cause severe harm and even death. For seizures lasting longer than 5min, an administration of rescue medication is therefore recommended. Caregivers such as preschool teachers should be able to administer correctly anticonvulsive rescue medication to children. METHODS: A training concept for preschool teachers on seizure management focussing on practical skills was developed. To assess the success of the training, a structured interview on attitudes relating to rescue medication administration was conducted. The number of committed errors during administration of a rectal/buccal rescue medication to dummy dolls was compared before and after training. RESULTS: 210 teachers from 115 preschools participated while all teachers from 303 preschools had been invited. The self-reported level of confidence in their own skills to administer anticonvulsive rescue medication increased from 5 to 8 on a scale from 1 to 10 (p<0.001). The number of participants who agreed to administer rescue medication rose from 195/210 (92.8%) before training to 209/210 (99.5%, p<0.001) after training for the rectal route, and from 173/210 (82.4%) to 209/210 (99.5%, p<0.001) for the buccal route. For teachers who administered rescue medication before and after training, the number of administrations without any administration errors rose from 1/195 (0.5%) to 117/195 (60.0%, p<0.001) for the rectal route, and from 13/173 (7.5%) to 95/173 (54.9%, p<0.001) for the buccal route. CONCLUSION: A training for preschool teachers boosted the level of self-confidence relating to administration of anticonvulsive rescue medication. Teachers also committed fewer errors when administering rescue medication to dummy dolls.


Assuntos
Professores Escolares , Convulsões/terapia , Capacitação de Professores , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Atitude Frente a Saúde , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Professores Escolares/estatística & dados numéricos , Convulsões/tratamento farmacológico , Capacitação de Professores/métodos
20.
Acta Paediatr ; 106(11): 1811-1816, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28561263

RESUMO

AIM: In Germany, preschool teachers supervise children up to six years of age and are also responsible for supervising older pupils after school. This study explored the impact of a teaching session on epilepsy for teachers in charge of children from 1 to 10 years of age. METHODS: We evaluated the benefit of a teaching session offered to all preschool teachers in Leipzig, Germany, in 2014-2015, by asking them to complete the same questionnaire 12-24 months pre-intervention, and 12 months postintervention. RESULTS: Both questionnaires were completed by 123 teachers. The number of teachers who felt they were prepared to handle an acute seizure rose from 36 (29%) pre-intervention to 65 (53%) post-intervention (p < 0.001) and their willingness to administer a prescribed rescue medication rose from 66 (54%) to 93 (76%, p < 0.001). The session also increased the number of teachers who were prepared to take children with epilepsy on excursions under any circumstance from 38 (31%) to 52 (42%, p < 0.05). In addition, the number of teachers who would place a solid object in the child's mouth during an attack fell from 16 (13%) to seven (6%) (p < 0.05). CONCLUSION: Providing a teaching session on epilepsy increased the teachers' knowledge and willingness to act and reduced obsolete, counterproductive measures.


Assuntos
Epilepsia , Conhecimentos, Atitudes e Prática em Saúde , Professores Escolares/estatística & dados numéricos , Capacitação de Professores , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
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