Pseudoresistance in idiopathic/genetic generalized epilepsies - Definitions, risk factors, and outcome.

OBJECTIVE: The aim of the study was to determine risk factors associated with pseudoresistance in a large, representative cohort of patients with Idiopathic/Genetic Generalized Epilepsy (IGE) and the impact of pseudoresistance on socioeconomic parameters. METHODS: We performed a literature review on definitions of pseudoresistance in IGE. In an established cohort of patients with IGE from Funen, patients with current or previous pseudoresistant seizures were retrospectively identified based on a comprehensive evaluation of the patients' medical records and direct patient contact, if required. In addition, clinical characteristics, socioeconomic, and demographic data were assessed. Personal interviews were used to determine the brief version of Barratts (BIS-8) impulsivity score. RESULTS: The literature review provided the following definition of pseudoresistance: Seizures due to (I) lacking adherence to antiseizure medication (ASM), (II) incompliance to general rule of conduct, (III) psychogenic nonepileptic seizures (PNES), (IV) inadequate choice of ASM/dosage, and (V) incorrect classification of epilepsy. Applying criteria I-III to a cohort of patients with IGE (n = 499), 73 patients (14.6%) were currently pseudoresistant and 62 (12.4%) were previously pseudoresistant, but currently seizure free. Current pseudoresistance was associated with younger age, drug/alcohol abuse, lower rate of full-time employment, and higher BIS-8 scores. We found no associations of pseudoresistance with juvenile myoclonic epilepsy, psychiatric disease, specific seizure types, or number of seizure types. Patients with previously pseudoresistant seizures have tried more ASMs and were characterized by male preponderance, higher BIS-8, and higher rates of abuse. Surrogate markers for social outcome did not differ. SIGNIFICANCE: In IGE, pseudoresistance may be defined as PNES or insufficient adherence to medication/conduct and is associated with younger age, drug/alcohol abuse, and higher scores for impulsivity. If transient, its impact on socioeconomic status remains limited but may be associated with a risk of overtreatment with ASM.

The burden of disease of idiopathic/genetic generalized epilepsy - A nationwide online survey.

The aim of the study was to assess the self-reported burden of disease in people with idiopathic/genetic generalized epilepsy and risk factors associated with high disease burden. We performed a nationwide online survey on epilepsy characteristics/treatment, quality of life/daily living followed by Standardized Assessment of Personality-Abbreviated Scale, Major Depression Inventory, Barratt Impulsiveness Scale (brief) and the brief Epilepsy Anxiety Survey Instrument. The survey was sent to 275 representative patients with IGE ('Funen cohort') and later publicly distributed via the Danish Epilepsy Association. The characteristics of the responders of the 'Funen cohort' (n = 119) did not differ from non-responders and previously assessed data. Out of 753 persons accessing the public survey, 167 had probable IGE. As compared to the 'Funen cohort', patients from the public survey reported similar age, time since last seizure, years with disease, seizure types, and IGE syndromes but more current and previously tried anti-seizure medications (ASMs). In both cohorts, patients had higher scores for depression, impulsivity, and personality disorders as compared to Danish normal values irrespective of seizure control or medication. Higher depression and anxiety scores but neither impulsivity nor personality disorders were associated with ongoing seizures. Overall health condition was estimated as bad by 28%. In the last four weeks, 20.4% reported limitations of activities of daily living due to epilepsy; 27.8% felt fed up because of their epilepsy. Patients with high subjective disease burden had more current ASMs, shorter time since last seizure and increased scores for depression, anxiety, impulsivity, and personality disorders. In conclusion, having IGE was associated with higher scores for impulsivity, depression, and personality disorders irrespective of seizure control and current treatment. High subjective disease burden was common and associated with ongoing seizures, absence/myoclonic seizures and high scores for impulsivity, depression, anxiety, and personality disorders.

Oligonucleotides containing 2'-O-methyl-5-(1-phenyl-1,2,3-triazol-4-yl)uridines demonstrate increased affinity for RNA and induce exon-skipping in vitro.

The nucleotide monomer containing the 1-phenyl-1,2,3-triazole group attached to the 5-position of 2'-O-methyluridine is hereby presented together with a derivative further substituted with a p-sulfonamide group on the phenyl ring. Both were conveniently synthesised, and synergistic effect of the modifications were demonstrated when introduced into oligonucleotides and hybridised to complementary RNA. The combination of stacking of the phenyltriazoles and the conformational steering from the 2'-OMe group gave thermally very stable duplexes. Exon skipping in the distrophin transcript using 20-mer 2'-OMePS sequences with two phenyltriazoles introduced in different positions with and without the sulfonamide demonstrated efficient exon skipping but at the same level as the 2'-OMePS reference ASO.