Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study.

BACKGROUND: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. METHODS: A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany. RESULTS: The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7-21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088-5863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027-1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221-3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193-586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs. CONCLUSIONS: This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting. TRIAL REGISTRATION: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

Health-related quality of life and the burden of prolonged seizures in noninstitutionalized children with epilepsy.

OBJECTIVE: This study aimed to provide information on the burden of illness and health-related quality of life (HRQoL) in children with epilepsy who experience prolonged acute convulsive seizures (PACS) in the community setting, and to investigate factors that may predict poor HRQoL in this population. METHODS: Noninstitutionalized children (aged 3-16 years) who had experienced at least one PACS within the past year and had currently prescribed PACS rescue medication were enrolled in a cross-sectional study in Germany, Italy, Spain, and the United Kingdom (Practices in Emergency and Rescue medication For Epilepsy managed with Community-administered Therapy 3 [PERFECT-3]). Clinicians, parents/guardians, and patients completed web-based questionnaires regarding clinical characteristics, PACS frequency, and day-to-day impairment. Patients' HRQoL was rated by clinicians, parents/guardians, and patients themselves using the 5-dimension EuroQol questionnaire (EQ-5D) and summarized as a utility score. Potential predictors of poor HRQoL were tested in individual univariate generalized linear models and a global multivariable model. RESULTS: Enrolled children (N = 286) had experienced 1-400 PACS (median: 4) in the past year. Clinicians reported that 216/281 patients (76.9%) had learning disabilities of varying severity. Mean EQ-5D utility scores rated by clinicians (n = 279), parents (n = 277), and patients (n = 85) were 0.52 (standard deviation: 0.41), 0.51 (0.39), and 0.74 (0.29), respectively. Increasing PACS frequency, increasing severity of learning disability, and specialist school attendance were significantly associated with decreasing EQ-5D utility score. In the multivariable model, having learning disabilities was the best predictor of poor HRQoL. SIGNIFICANCE: Health-related quality of life was very poor in many children with epilepsy whose PACS were managed with rescue medication in the community, with learning disability being the most powerful predictor of patients' HRQoL. Mean EQ-5D utility scores were lower (worse) than published values for many other chronic disorders, indicating that optimal treatment should involve helping children and their families to manage learning disabilities and day-to-day impairments, in addition to preventing seizures.

Assessment of myelination in hypomyelinating disorders by quantitative MRI.

PURPOSE: To apply myelin-sensitive quantitative magnetic resonance imaging (MRI) techniques in defined hypomyelinating conditions and to identify spatial patterns of myelination as criteria for characterization of undefined disorders. MATERIALS AND METHODS: Seven patients were included, based on the diagnosis of mitochondrial cytopathy, Pelizaeus-Merzbacher disease, GJA12/GJC2-related Pelizaeus-Merzbacher-like disease, hypomyelination with atrophy of the basal ganglia and cerebellum, and leukoencephalopathy with ataxia, delayed dentition, and hypomyelination. The control group comprised 23 children and adolescents (age range 2.6-22.4 years). The 3T MRI protocol consisted of high-resolution T1- and T2-weighted 3D MRI, diffusion tensor (DTI), and magnetization transfer (MT) imaging. Parameter maps of mean diffusivity, fractional anisotropy, and MT saturation were displayed as pseudocolor overlays and assessed by region-of-interest and histogram analysis. RESULTS: Structural MRI revealed widespread signal alterations in white matter, but were hampered by signal heterogeneity. Quantitative DTI and MT reflected the degree of hypomyelination and discriminative patterns of myelination emerged on MT saturation maps. CONCLUSION: The quantitative parameters in the defined hypomyelination conditions provide additional criteria to further classify undefined white matter disorders.