Seizure CostsQuality of life Depression a b s t r a c t 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.

Background: Traumatic stroke usually occurs after dissection of large extracranial or intracranial vessels, leading to disseminated cerebral embolism. Stretching and distorting forces in cerebral intraparenchymal end arteries can cause intimal lesions followed by an occluding thrombus. Objective: To investigate the importance of traumatic endothelial lesions in intraparenchymal end arteries after minor head injuries. Methods: The cases of eight children are reported. They were aged between two and seven years (mean 6.2 years), and they developed significant neurological deficits at 15 minutes to 72 hours (mean 16.3 hours) after minor head injuries. Results: The the patients all had hemiparesis combined with other signs, including central facial paralysis, dysphasia, dysphagia, and extrapyramidal signs. Computed tomography or magnetic resonance imaging showed cerebral infarctions affecting branches of the middle cerebral artery (n = 3), anterior cerebral artery (n = 1), posterior cerebral artery (n = 1), and basilar artery (n = 3). These lesions affected the basal ganglia, the internal capsule, and the brain stem. Neither heart disease nor dissections of large vessels were present. Two children had prothrombotic risk factors (an increase in lipoprotein (a) and a factor V Leiden mutation). The follow up period was between three months and 13 years (mean 3.9 years). Outcome was classified according to the Glasgow outcome scale as moderate disability (n = 4), severe disability (n = 2), non-disabling sequelae (n = 1), and total recovery (n = 1). Conclusions: Minor head injuries can be cause and co-factor in the aetiology of stroke. The frequency of this may be underestimated, and detailed medical history of the days before stroke manifestation may identify more traumatic events, especially in the group of so called "idiopathic" strokes.

ABSTRACT. Objective. Celiac disease (CD), or gluten sensitivity, is considered to be a state of heightened immunologic responsiveness to ingested gluten proteins in genetically predisposed individuals. The gastrointestinal manifestation suggests a severe enteropathy of the small intestine with malabsorption, steatorrhea, and weight loss because of a deranged mucosal immune response. Neurologic complications occur, especially epilepsy, possibly associated with occipital calcifications or folate deficiency and cerebellar ataxia. There have been reports of brain white-matter lesions as an extraintestinal manifestation in Crohn disease and ulcerative colitis but not in CD.Methods. In this study, 75 diet-treated mainly pediatric patients with biopsy-proven CD underwent prospectively clinical neurologic examinations, laboratory investigations, electroencephalography, computed tomography, and magnetic resonance imaging. The age range was 2.8 to 24.2 years with a mean of 11.6 years. The mean period of gluten exposure was 2.4 years.Results. Ten patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development. No folate deficiency was found. The hippocampal regions showed no abnormalities. Computed tomography did not reveal any cerebral calcifications, but magnetic resonance imaging detected unilateral and bilateral T2-hyperintensive white-matter lesions in 15 patients (20%). There was no correlation between these lesions and dietary compliance or neurologic or electroencephalographic abnormalities. The mean gluten exposure time of these patients was slightly increased (not significant).Conclusions. Focal white-matter lesions in the brain may represent an extraintestinal manifestation of CD. They may be ischemic in origin as a result of a vasculitis or caused by inflammatory demyelination. They seem to be more typical of pediatric CD than cerebral calcifications. Their prognostic value is unclear and needs to be elucidated in additional studies. CD should be suggested as a differential diagnosis in children with unclear white-matter lesions even without intestinal symptoms. Pediatrics 2001;108(2). URL: http://www.pediatrics.org/ cgi/content/full/108/2/e21; celiac disease, neurologic complications, brain white-matter lesions, child.ABBREVIATIONS. CD, celiac disease; EEG, electroencephalography; CT, computed tomography; MRI, magnetic resonance imaging; AU, arbitrary units. C eliac disease (CD), or gluten sensitivity, is considered to be a state of heightened immunologic responsiveness to ingested gluten proteins in genetically predisposed individuals. The gastrointestinal manifestation implies a severe enteropathy of the small intestine with malabsorption, steatorrhea, and weight loss associated with characteristic lesions of the small bowel mucosa, which improve after withdrawal of gluten from the diet. It often is associated with the presence of antiendomysial and antigliadin antibodies. The pathologic mucosal immune response has a ...

This article summarizes evident and recent findings on the characteristics of the neurological phenotype in ataxia telangiectasia (AT), reviews neuropathological and neuroradiological findings, and outlines therapeutic treatment options. In addition, this review offers an overview of current hypotheses on mechanisms of neurodegeneration in AT and discusses their relevance in clinical neurology. The obvious features of neurodegeneration in AT-cerebellar ataxia and dysarthia-are accompanied by a variety of further disabling disease symptoms. Review of the literature outlines a complex pattern of central nervous degeneration in AT that might have been underestimated so far. Neurodegeneration in AT is closely related to the absence or partial lack of the ataxia telangiectasia-mutated (ATM) kinase. ATM is a central player in maintaining cellular homeostasis. Systemic review of the literature reveals a subset of cellular targets hypothesized to count responsible for degeneration in ATM-deficient neurons. Further systematic cliniconeurological, pathoanatomical, and neuroradiological studies are required to understand the structural basis of this neurodegenerative disease. This better understanding has implications for the treatment of AT patients. Second, biochemical and molecular biological studies aimed at deciphering the pathomechanisms of this progressive disorder are necessary for the development of promising future therapies.

Objective To compare direct and indirect costs and quality of life (QoL) of pediatric and adult patients with Dravet syndrome (DS), with drug‐resistant epilepsy (DRE) and in seizure remission (SR), and their caregivers, in Germany. Methods Questionnaire responses from 93 DS patients and their caregivers were matched by age and gender with responses from 93 DRE and 93 SR patients collected in independent studies, and were compared across main components of QoL, direct costs (patient visits, medication use, care level, medical equipment, and ancillary treatments), and indirect costs (quitting job, reduced working hours, missed days). Results Mean total direct costs were highest for DS patients (€4864 [median €3564] vs €3049 [median €1506] for DRE [excluding outliers], P = 0.01; and €1007 [median €311], P < 0.001 for SR). Total lost productivity over 3 months was highest among caregivers of pediatric DS (€4757, median €2841), compared with those of DRE (€1541, P < 0.001; median €0) and SR patients (€891, P < 0.001; median €0). The proportions of caregivers in employment were similar across groups (62% DS, 63% DRE, and 63% SR) but DS caregivers were more likely to experience changes to their working situation, such as quitting their job (40% DS vs 16% DRE and 9% SR, P < 0.001 in both comparisons). KINDL scores were significantly lower for DS patients (62 vs 74 and 72, P < 0.001 in both comparisons), and lower than for the average German population (77). Pediatric caregiver EQ‐5D scores across all cohorts were comparable with population norms, but more DS caregivers experienced moderate to severe depressive symptoms (24% vs 11% and 5%). Mean Beck Depression Inventory (BDI‐II) score was significantly higher in DS caregivers than either of the other groups (P < 0.001). Significance This first comparative study of Dravet syndrome to difficult‐to‐treat epilepsy and to epilepsy patients in seizure remission emphasizes the excess burden of DS in components of QoL and direct costs. The caregivers of DS patients have a greater impairment of their working lives (indirect costs) and increased depression symptoms.