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.

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.

The difference between 90 patients reported worldwide from 1979 to 2005 and the 16 new documented cases from only Germany over 10 years corroborates that the occurrence of this severe side effect is under reported.

LEV is a well-tolerated new AED that may effectively improve seizure control as an add-on drug in resistant epilepsy in childhood with good tolerability. However, neurologically handicapped children appear at increased risk for reversible neurocognitive side effects and have a poorer treatment response.

There are conflicting results concerning bone metabolism in children receiving antiepileptic medication, with data concentrating on neurologically impaired patients. We performed a multicenter cross-sectional study in otherwise healthy children who received monotherapy with valproic acid, oxcarbazepine, lamotrigine, sulthiame, levetiracetam, or topiramate for at least 6 months. Data on calcium, phosphorus, alkaline phosphatase, 25-OH vitamin D, and parathormone were collected. Among 128 patients, 24.4% had hypocalcemia, 25.4% hypophosphatemia, and 13.3% (n = 17) 25-OH vitamin D levels <10 ng/mL. All patients were clinically asymptomatic. Mean calcium concentrations were found to be significantly lower among the study population (2.41 mmol/L) compared with healthy controls (2.53 mmol/L). Lowest mean concentration was observed in patients treated with sulthiame followed by oxcarbazepine and valproic acid. No influence of calcium intake or therapy on bone metabolism was noted. Effects on bone metabolism of anticonvulsive monotherapy are not restricted to neurologically impaired children but also affect otherwise healthy children.