A study of the significance of photoparoxysmal responses and spontaneous epileptiform discharges in the EEG in childhood epilepsy.

AIM: In clinical practice, there is a prevailing notion that photosensitivity mostly occurs in children with epilepsy (CWE) with idiopathic generalized epilepsy. We investigated the distribution of epilepsy types and etiology in photosensitive children and the associations with specific clinical and electroencephalogram (EEG) variables. METHODS: In this retrospective cohort study, clinical data were acquired from all children that showed photosensitivity during systematic intermittent photic stimulation (IPS), over a 10-year interval at a tertiary level Children's Hospital, Winnipeg. Patient demographics, EEG findings, and clinical data and symptoms during IPS were abstracted. Classification of diagnoses using the International League Against Epilepsy (ILAE) 2017 guidelines was done by an expert panel. RESULTS: Seventy-eight photosensitive children were identified. Forty (51.3%) had generalized epilepsy (idiopathic: 27, structural: 2, other: 11) compared with 19 (24.4%) focal (idiopathic: 1, structural: 2, other: 16), 8 (10.3%) combined focal and generalized (structural: 4, other: 4), and 11 (14.1%) unknown epilepsy (other: 11); (χ2 (3) = 32.1, p = .000). Self-sustaining or outlasting photoparoxysmal responses (PPRs) occurred in association with all epilepsy types; however, the EEGs of focal CWE without treatment comprised almost solely of PPRs which outlasted the stimulus (8/10), in contrast to only 8/17 of focal CWE with treatment and to 13/26 of generalized epilepsy without treatment. Most frequency intervals in individual patients were less under treatment: a decrease in standardized photosensitivity range (SPR) was seen in 5 CWE, an increase in 2, and no change in 1 during treatment. Both CWE with focal and generalized epilepsy showed abnormal activity on EEG during hyperventilation (40% vs 65.7%). Thirteen out of 14 CWE with clinical signs during IPS had independent spontaneous epileptiform discharges (SEDs) in the EEG recording. CONCLUSION: Photosensitivity occurs in all types of epilepsy rather than in idiopathic generalized epilepsy alone. Surprisingly, there is a tendency for focal epilepsy to be associated with self-sustaining PPRs, especially when no treatment is used. Treatment tends to make the PPR more self-limiting and decrease the SPR. There is a tendency that clinical signs during IPS occur in EEGs in individuals with SEDs.

A randomized controlled trial of an internal family systems-based psychotherapeutic intervention on outcomes in rheumatoid arthritis: a proof-of-concept study.

OBJECTIVE: To conduct a proof-of-concept randomized trial of an Internal Family Systems (IFS) psychotherapeutic intervention on rheumatoid arthritis (RA) disease activity and psychological status. METHODS: Patients with RA were randomized to either an IFS group for 9 months (n = 39) or an education (control) group (n = 40) that received mailed materials on RA symptoms and management. The groups were evaluated every 3 months until intervention end and 1 year later. Self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory) were assessed. The 28-joint Disease Activity Score-C-reactive Protein 4 was determined by rheumatologists blinded to group assignment. Treatment effects were estimated by between-group differences, and mixed model repeated measures compared trends between study arms at 9 months and 1 year after intervention end. RESULTS: Of 79 participants randomized, 68 completed the study assessments and 82% of the IFS group completed the protocol. Posttreatment improvements favoring the IFS group occurred in overall pain [mean treatment effects -14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Posttreatment improvements were sustained 1 year later in self-assessed joint pain [-0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [-3.2 (5.0); p =0.01]. There were no sustained improvements in anxiety, self-efficacy, or disease activity. CONCLUSION: An IFS-based intervention is feasible and acceptable to patients with RA and may complement medical management of the disease. Future efficacy trials are warranted. ClinicalTrials.gov identifier: NCT00869349.

Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study.

BACKGROUND: HLA-DRB1*15 genotype, previous infection with Epstein-Barr virus, and vitamin D insufficiency are susceptibility factors for multiple sclerosis, but whether they act synergistically to increase risk is unknown. We aimed to assess the contributions of these risk factors and the effect of established precursors of multiple sclerosis, such as brain lesions on MRI and oligoclonal bands in CSF at the time of incident demyelination, on development of multiple sclerosis in children. METHODS: In our prospective national cohort study, we assessed children who presented with incident CNS demyelination to any of the 16 paediatric health-care facilities or seven regional health-care facilities in Canada. We did univariate and multivariable analyses to assess contributions of HLA-DRB1*15, Epstein-Barr virus, vitamin D status, MRI evidence of brain lesions, and CSF oligoclonal bands as determinants of multiple sclerosis. We used classification and regression tree analyses to generate a risk stratification algorithm for clinical use. FINDINGS: Between Sept 1, 2004, and June 30, 2010, we screened 332 children of whom 302 (91%) were eligible and followed-up for a median of 3·14 years (IQR 1·61-4·51). 63 (21%) children were diagnosed with multiple sclerosis after a median of 127 days (99-222). Although the risk of multiple sclerosis was increased with presence of one or more HLA-DRB1*15 alleles (hazard ratio [HR] 2·32, 95% CI 1·25-4·30), reduced serum 25-hydroxyvitamin D concentration (HR per 10 nmol/L decrease 1·11, 1·00-1·25), and previous Epstein-Barr-virus infection (HR 2·04, 0·99-4·20), no interactions between these variables were detected on multivariate analysis. Multiple sclerosis was strongly associated with baseline MRI evidence of one or more brain lesion (HR 37·9, 5·26-273·85) or CSF oligoclonal bands (6·33, 3·35-11·96), suggesting established disease. One patient diagnosed with multiple sclerosis had a normal MRI scan, and therefore sensitivity of an abnormal MRI scan for multiple sclerosis diagnosis was 98·4%. INTERPRETATION: Risk of multiple sclerosis in children can be stratified by presence of HLA-DRB1*15 alleles, remote Epstein-Barr virus infection, and low serum 25-hydroxyvitamin D concentrations. Similar to previous studies in adults, brain lesions detected on MRI and CSF oligoclonal bands in children are probable precursors to the clinical onset of multiple sclerosis. Children with a normal MRI are very likely to have a monophasic illness. FUNDING: Canadian Multiple Sclerosis Scientific Research Foundation.

Subcortical band heterotopia (SBH) in males: clinical, imaging and genetic findings in comparison with females.

Subcortical band heterotopia (SBH) or double cortex syndrome is a neuronal migration disorder, which occurs very rarely in males: to date, at least 110 females but only 11 in males have been reported. The syndrome is usually associated with mutations in the doublecortin (DCX) (Xq22.3-q23) gene, and much less frequently in the LIS1 (17p13.3) gene. To determine whether the phenotypic spectrum, the genetic basis and genotype-phenotype correlations of SBH in males are similar to those in females, we compared the clinical, imaging and molecular features in 30 personally evaluated males and 60 previously reported females with SBH. Based on the MRI findings, we defined the following band subtypes: partial, involving one or two cerebral lobes; intermediate, involving two lobes and a portion of a third; diffuse, with substantial involvement of three or more lobes; and pachygyria-SBH, in which posterior SBH merges with anterior pachygyria. Karyo typing and mutation analysis of DCX and/or LIS1 were performed in 23 and 24 patients, respectively. The range of clinical phenotypes in males with SBH greatly overlapped that in females. MRI studies revealed that some anatomical subtypes of SBH, such as partial and intermediate posterior, pachygyria-SBH and diffuse bands with posterior predominance, were more frequently or exclusively present in males. Conversely, classical diffuse SBH and diffuse bands with anterior predominance were more frequent in females. Males had either mild or the most severe band subtypes, and these correlated with the over-representation of normal/borderline intelligence and severe mental retardation, respectively. Conversely, females who had predominantly diffuse bands exhibited mostly mild or moderate mental retardation. Seven patients (29%) had missense mutations in DCX; in four, these were germline mutations, whereas in three there was evidence for somatic mosaicism. A germline missense mutation of LIS1 and a partial trisomy of chromosome 9p were identified in one patient (4%) each. One male each had a possible pathogenic intronic base change in both DCX and LIS1 genes. Our study shows that SBH in males is a clinically heterogeneous syndrome, mostly occurring sporadically. The clinical spectrum is similar to that of females with SBH. However, the greater cognitive and neuroradiological heterogeneity and the small number of mutations identified to date in the coding sequences of the DCX and LIS1 genes in males differ from the findings in females. This suggests other genetic mechanisms such as mutations in the non-coding regions of the DCX or LIS1 genes, gonadal or somatic mosaicism, and finally mutations of other genes.