Expanding Phenotype of ATP1A3 - Related Disorders: A Case Series.

Neurologic disorders caused by mutations in the ATP1A3 gene were originally reported as three distinct rare clinical syndromes: Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and Cerebellar ataxia, Areflexia, Pes cavus, Opticus atrophy and Sensorineural hearing loss (CAPOS). In this case series, we describe 3 patients. A mother and her daughter showed an intermediate phenotype different from each other with the same heterozygous missense mutation (p.[R756C]), recently described in literature as Relapsing Encephalopathy With Cerebellar Ataxia (RECA). In addition, a third patient showed an intermediate AHC-RDP phenotype and had a likely pathogenic novel de novo missense mutation (p.[L100 V]). These patients support the growing evidence that AHC, RDP and RECA are part of a continuous ATP1A3 mutation spectrum that is still expanding. Three common features were a sudden onset, asymmetrical neurological symptoms, as well as the presence of triggering factors. When present, the authors argue to perform exome sequencing in an early stage.

Evaluation of management and guideline adherence in children with mild traumatic brain injury.

AIM: To evaluate the management and guideline adherence in children with mild traumatic brain injury (MTBI) in emergency departments (ED) in the Netherlands. METHODS: A multicentre cohort study was conducted, including children younger than 18 years with MTBI who presented within 24 hours after trauma in the ED of hospitals in the southwest region of the Netherlands, in 2014. Primary outcome measures for management were percentages of performed computed tomography (CT) scans and hospital admissions. Guideline adherence was defined as percentages of correctly following the guideline. Secondary outcome measures were differences in management and guideline adherence between hospitals. RESULTS: About 563 patients were analysed. Hospital admission was the most frequently performed management type (49.2% hospital admission vs. 30.9% CT). In only 49.7% of patients, the guideline was followed correctly. A substantial overuse of hospital admission (35%) and underuse of CT (40.1%) were found. Percentages of hospital admission and CT varied between 39.4-55.6% and 23.3-44.1%, respectively, across hospitals. Percentages of correctly following the guideline varied between 39.2-64.9% across hospitals. CONCLUSION: These findings suggest that physicians in the participating hospitals prefer hospital admission of children with MTBI instead of CT despite the current recommendations of the national MTBI guideline in the Netherlands.

A cost-effectiveness decision model for antiepileptic drug treatment in newly diagnosed epilepsy patients.

OBJECTIVE: To establish cost-effectiveness of antiepileptic drug (AED) treatment strategies of newly diagnosed patients with epilepsy. METHODS: A decision analysis was carried out comparing effectiveness and treatment cost of six treatment strategies comprising carbamazepine (CBZ), lamotrigine (LTG), and valproate (VPA) as first-line and second-line drugs. Three outcome groups were defined: complete success, partial success, and failure. Data on seizure control and failure due to adverse effects were derived from the literature. Data on resource use and costs were collected for each outcome group by means of a patient survey. RESULTS: Cost data were obtained from 71 patients. Cost increased from complete success to failure outcome groups. The probability of obtaining complete success varied from 64% (VPA-CBZ strategy) to 74% (LTG-VPA strategy). The strategy LTG-VPA was more effective than the least expensive strategy CBZ-VPA, but at higher costs per additional effectively treated patient. Probabilistic sensitivity analysis confirmed these findings to be robust. Subsequent analysis showed that changing inclusion criteria used in the selection of the studies from the literature had a major effect on cost-effectiveness ratios of the various strategies. The probability that LTG first-line therapy is the most cost-effective option remains small, even defining a high cost-effectiveness threshold. Nevertheless, LTG second-line strategies can be cost-effective depending on the willingness to pay for patient improvement. CONCLUSIONS: Only a few studies satisfied our inclusion criteria for employment in our decision model. Our model supports the use of conventional AEDs as first-line options for patients with newly diagnosed epilepsy. LTG second-line therapy is likely to be the most cost-effective option in case society is willing to pay more than Euro 6000 for an additional successfully treated patient. This study also illustrates that, with the data presently available, the outcome of decision analysis for AED treatment choice depends on the inclusion criteria used to select trials. Prospective real-life studies are needed in which first- and second-line treatment strategies are compared with respect to both effectiveness and costs.

The costs of epilepsy in three different populations of patients with epilepsy.

The purpose of this study was to estimate the costs of care in three different populations of patients with epilepsy (general practices (GP), University Hospital (UH), and Epilepsy Center (EC)), and to analyse the distribution of costs by type of services for each patient group. A cost diary was developed to obtain prospective information on epilepsy-attributable service use over a period of 3 months. Similar information over the previous 3 months was obtained from a cost questionnaire. In addition, a quality of life inventory (QOLIE-31) was used. Standard cost lists were applied for the valuation of the direct cost items. A sensitivity analysis was performed for certain cost items for which no reliable data were available. One hundred and sixteen patients with established epilepsy were included, and the mean costs per patient per month (in Euros) ranged from 52.08 to 357.63. Patients from GP appeared to have lower direct costs, spent less time in seeking or undergoing a treatment, and reported lower seizure frequencies and less severe seizure types than the patients from the other patient groups. Patients from the EC reported the highest productivity changes and unemployment rates and also had the lowest scores on the QOLIE-31. The cost items anti-epileptic drugs, hospital services, unpaid care, and transportation accounted for the majority of the total direct costs.

The diagnosis of epileptic and non-epileptic seizures.

The aim of this prospective population-based study was to systematically define a cluster of diagnostic items which can assist in the early identification and classification of epileptic and non-epileptic seizures. A cohort of patients aged > or =14 years, suspected with a first epileptic seizure, were included in this study. A team of neurologists evaluated and classified all cases. Diagnostic items for epileptic and non-epileptic seizures were identified using logistic regression analysis. Three hundred and fifty cases entered this study. Distinctive features for epileptic seizures were postictal confusion (OR 0.09), an epileptiform EEG pattern (OR 0.02), and abnormal neuroimaging findings (OR 0.07), whereas for non-epileptic seizures of organic origin there was a history of hypertension (OR 7.5), and provoking factors (OR 13.4) such as exercise and warmth. Diagnostic items for seizures of non-organic origin were a history of febrile seizures (OR 5.8), treatment by a psychologist or psychiatrist (OR 9.1), and presentiment of the seizure (OR 3.7) such as a feeling of choking and palpitations. A separate analysis for the patients who were systematically investigated provided some additional diagnostic items for the different subgroups of patients. For instance, back arching during the seizure for the patients with seizures of non-organic origin and female sex for the patients with non-epileptic seizures of organic origin.

Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures.

PURPOSE: To evaluate the methodology of incidence studies of epilepsy and unprovoked seizures and to assess the value of their findings by summarizing their results. METHODS: A Medline literature search from January 1966 to December 1999 was conducted. In each selected study, key methodologic items such as case definition and study design were evaluated. Furthermore, a quantitative meta-analysis of the incidence data was performed. RESULTS: Forty incidence studies met the inclusion criteria. There was considerable heterogeneity in study methodology, and the methodologic quality score was generally low. The median incidence rate of epilepsy and unprovoked seizures was 47.4 and 56 per 100,000, respectively. The age-specific incidence of epilepsy was high in those aged 60 years or older, but was highest in childhood. Males had a slightly higher incidence of epilepsy (median, 50.7/100,000) than did females (median, 46.2/100,000), and partial seizures seemed to occur more often than generalized seizures. Developing countries had a higher incidence rate of epilepsy (median, 68.7/100,000) than did industrialized countries (median, 43.4/100,000). Similar results were found for unprovoked seizures. The incidence of epilepsy over time appears to decrease in children, whereas it increases in the elderly. CONCLUSIONS: The age-specific incidence of epilepsy showed a bimodal distribution with the highest peak in childhood. No definitive conclusions could be reached for the incidence of unprovoked seizures and other specific incidence rates of epilepsy. More incidence studies with an adequate study methodology are needed to explore geographic variations and time trends of the incidence of epilepsy and unprovoked seizures.