To provide first data on the cost of epilepsy and cost-driving factors in children, adolescents, and their caregivers in Germany.A population-based, cross-sectional sample of consecutive children and adolescents with epilepsy was evaluated in the states of Hessen and Schleswig-Holstein (total of 8.796 million inhabitants) in all health care sectors in 2011. Data on socioeconomic status, course of epilepsy, and direct and indirect costs were recorded using patient questionnaires.We collected data from 489 children and adolescents (mean age ± SD 10.4 ± 4.2 years, range 0.5-17.8 years; 264 [54.0%] male) who were treated by neuropediatricians (n = 253; 51.7%), at centers for social pediatrics ("Sozialpaediatrische Zentren," n = 110, 22.5%) and epilepsy centers (n = 126; 25.8%). Total direct costs summed up to €1,619 ± €4,375 per participant and 3-month period. Direct medical costs were due mainly to hospitalization (47.8%, €774 ± €3,595 per 3 months), anticonvulsants (13.2%, €213 ± €363), and ancillary treatment (9.1%, €147 ± €344). The total indirect costs amounted to €1,231 ± €2,830 in mothers and to €83 ± €593 in fathers; 17.4% (n = 85) of mothers and 0.6% (n = 3) of fathers reduced their working hours or quit work because of their child's epilepsy. Independent cost-driving factors were younger age, symptomatic cause, and polytherapy with anticonvulsants. Older age, active epilepsy, symptomatic cause, and polytherapy were independent predictors of higher antiepileptic drug (AED) costs, whereas younger age, longer epilepsy duration, symptomatic cause, disability, and parental depression were independent predictors for higher indirect costs.Treatment of children and adolescents with epilepsy is associated with high direct costs due to frequent inpatient admissions and high indirect costs due to productivity losses in mothers. Direct costs are age-dependent and higher in patients with symptomatic epilepsy and polytherapy. Indirect costs are higher in the presence of a child's disability and parental depression.
After atraumatic birth, three neonates presented with muscle hypotonia and weakness. Flaccid paresis of the upper extremities, spasticity of the lower extremities, dissociate sensory loss and autonomic dysfunction developed later. This ruled out the initial, tentative diagnoses of cerebral palsy, spinal muscular atrophy or hereditary neuropathy. Diagnostic imaging revealed marked thinning of the cervical spinal cord in all patients. The possible aetiology of these lesions is considered. In all cases, an antenatal or perinatal infarction is thought to be the most probable cause. Different clinical pictures following intrauterine spinal cord ischemia are discussed. Spinal cord lesion must be considered even after atraumatic birth.
The size of the distal femoral epiphysis is an important criterion for determining the maturity of a neonate. The distal femoral epiphysis has been demonstrated and measured sonographically in two planes during the first month of life in 174 neonates. The sum of the epiphyseal diameters has been related to gestational age. The average sum of the sagittal and transverse diameter of both distal femoral epiphysis was 10.9 mm in the 35th week (standard deviation 7.6 mm) and increases to 38.4 mm at 43 weeks (standard deviation 6.3 mm). Linear regression of the mean values of the sum of the epiphyseal diameters y against gestational age x shows a correlation coefficient of 0.95 (regression gradient y = -117.7 + 3.7 x). Sonographic demonstration and measurements of the distal femoral epiphyses is a valid alternative to radiological examination.
To report the first prenatal dopaminergic replacement therapy in autosomal recessive (AR) guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency without hyperphenylalaninemia.Case reports, literature review, and video presentation.University of Lübeck, Lübeck, Germany.Two boys from a consanguineous family.Physical and mental development as a function of replacement initiation.The older sibling presented with typical features of AR GTPCH deficiency due to a homozygous mutation in the GCH1 gene with proven pathogenicity. Levodopa treatment was initiated at age 10 months and resulted in a distinct motor improvement. However, mental development was delayed. In the younger sibling, prenatal replacement therapy was initiated after a prenatal diagnosis of AR GTPCH deficiency was made. At age 17 months, both motor and mental development were normal for his age.This report highlights the importance of an early diagnosis, including prenatal diagnosis, of complex dopa-responsive extrapyramidal syndromes. Prenatally initiated dopaminergic replacement therapy is beneficial and thus justified in AR GTPCH deficiency, allowing prevention of significant impairment of mental abilities.
Summary: Purpose: Topiramate (TPM) inhibits carbonic anhydrase, with metabolic acidosis as a possible side effect, although this has been reported in only two adult cases. We investigated the acid–base metabolism in infants and toddlers treated with TPM. Methods: Nine infants and toddlers aged 5 months to 2.3 years (median, 6 months) were treated with TPM at maximal doses of 8.2–26 mg/kg/day (median, 11 mg/kg/day). The maximal TPM dose was achieved after 8–35 days (median, 17 days). TPM was given in addition to other antiepileptic drugs (AEDs) in five cases and as a sole AED in four patients with refractory epilepsy resistant to multiple AEDs. The diagnoses were infantile spasms (n = 5), epilepsia partialis continua (n = 1), infantile epileptic encephalopathy (n = 1), and Lennox–Gastaut syndrome (n = 2). Results: The blood gases were normal before treatment with TPM in all nine children. Metabolic acidosis developed in eight children after 8–26 days (median, 14 days) of TPM treatment with a minimum of serum bicarbonate between 15 to 18 m M (median, 17 m M ), a minimal base excess between –6.2 and –11.2 m M (median, –7.9 m M ), and pH between 7.22 and 7.40 (median, 7.35). Four of nine children showed clinical signs of hyperventilation and received oral sodium bicarbonate (1–2 mmol/kg), while TPM was still effective. Conclusions: Because metabolic acidosis developed in eight of the nine infants and toddlers taking TPM, we would suggest that the acid–base metabolism be monitored in young children who receive TPM.
Introduction: Simultaneous interictal EEG and MEG sleep recordings were compared as to their sensitivity in the visual detection of focal epileptiform activity. Because MEG is indifferent to radial activity, i.e., sleep changes, a higher ratio of epileptic discharges (ED) unique to MEG compared to EEG was presumed in the case of overlapping sleep changes. Patients: We studied 14 children and adolescents aged 3.5–17 years with localization-related epilepsy. Methods: The 122-channel whole-head MEGs and 33-channel EEGs were recorded simultaneously for 20–40min, most of them in segments of 5–20min. Segments of artefacts or bilateral polyspikes (>2 ED/200 ms) were excluded from the evaluation. The EEG and MEG data were separated and a blinded independent review of the 28 data segments was performed by 4 raters for the presence oEf D. EEG and MEG data were matched and ED identified by 3 reviewers were classified in three categories: 1. EEG=MEG (3 raters each), 2. EEG >MEG (difference of 3 raters) and 3. MEG > EEG (dto). The presence of simultaneous sleep changes (spindles, vertex waves, K-complexes, slow wave sleep) was visually determined for every single ED segment (±500 ms). Results: Out of 4704 detected ED, 1387 spikes fulfilled the above criteria; 689 spikes unique to MEG (54% within EEG sleep changes) and 136 spikes unique to EEG (21% sleep changes). 562 spikes were identified by 3 raters in both EEG and MEG (42% sleep changes). The presence of vertex waves alone led to a significantly higher number of spikes unique to MEG. Conclusion: A higher number of spikes was detected by MEG compared to EEG. Beside various factors such as focus localization and source orientation, overlapping sleep changes contribute to the differences observed.
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life-threatening cardiomyopathy with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify a common phenotype among the patients with skeletal muscle involvement, consisting of humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and elbow and Achilles tendon contractures. The disease course was generally slow, but we observed either a milder phenotype characterized by late onset and a mild degree of weakness and contractures or a more severe phenotype with early presentation and a rapidly progressive course in a few cases. Mutation analysis identified 18 mutations in LMNA (i.e., 1 nonsense mutation, 2 deletions of a codon, and 15 missense mutations). All the mutations were distributed between exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA mutations arose de novo in 76% of the cases; 2 of these de novo mutations were typical hot spots, and 2 others were identified in 2 unrelated cases. There was no clear correlation between the phenotype and type or localization of the mutations within the gene. Moreover, a marked inter- and intra-familial variability in the clinical expression of LMNA mutations exists, ranging from patients expressing the full clinical picture of EDMD to those characterized only by cardiac involvement, which points toward a significant role of possible modifier genes in the course of this disease. In conclusion, the high proportion of de novo mutations together with the large spectrum of both LMNA mutations and the expression of the disease should now prompt screening for LMNA in familial and sporadic cases of both EDMD and dilated cardiomyopathy associated with conduction system disease.
Epileptic encephalopathies are a devastating group of severe childhood onset epilepsies with medication-resistant seizures and poor developmental outcomes. Many epileptic encephalopathies have a genetic aetiology and are often associated with de novo mutations in genes mediating synaptic transmission, including GABA
