Remission in epilepsy: How long is enough?

Objective: The International League Against Epilepsy (ILAE) has proposed to expand the definition of remission to 10 years seizure-free with the last 5years off antiepileptic drugs (AEDs). We examined if a 10-year remission is needed to predict the lowest recurrence risk.Methods: The population-based study cohort consisted of 148 patients with new-onset childhood epilepsy living in the catchment area of Turku University Hospital. They were prospectively followed for 44years (median). Patients in first remission were prospectively followed for the duration of remission or possible relapse at 2years in remission with the last year without antiepileptic drugs (AEDs), at 5years in remission with the last 2years without AEDs, and at 10years with the last 5years without AEDs. For comparison of the proportions of relapsed patients within each remission category exact Clopper Pearson 95% confidence intervals were used.Results: The magnitude of the relapse rate estimates off AEDs did not significantly improve when remission increased from 2 years (2YR) to 5 years (5YR) and further to 10 years (10YR). However, 10YR was a more sensitive measure of no relapse than 2YR. Among patients with remission on or off AEDs, the ability to predict lower relapse rate increased markedly from 2 to 5years, and again from 5 to 10years. The risk of relapse was virtually the same estimated after 2YR off AEDs as after 10YR on or off AEDs, except for patients with generalized epilepsy whose 2YR off AEDs was a weaker predictor than 10YR on or off AEDs.Significance: Given the modest differences in relapse rates between the 5years seizure-free with last 2years off medications definition and the 10years seizure-free with last 5years off medications, and the adverse impact of not being considered in remission, we propose that a return to the 5-year definition may be warranted.</p

Association of blood pressure variability and neurocognition in children with chronic kidney disease

Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV). Increased BPV has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine if children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV

Cerebrospinal metastases in malignant childhood astrocytomas

Over a period of five years, antemortem diagnosis of leptomeningeal spread was made in six of thirteen children with high grade astrocytomas. These included four of seven children with hemispheral tumors and two of six children with malignant brainstem gliomas. Leptomeningeal spread was diagnosed by the clinical picture and CSF profile. Meningeal spread occurred an average of 5 months (range 0–16) after initial diagnosis of tumor was made. Several patients responded well to local radiation and/ or chemotherapy. Mean survival after evidence of meningeal spread was 7 months (range 2–16) with one patient still alive.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45379/1/11060_2004_Article_BF00177897.pd

The Established Status Epilepticus Trial 2013

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99653/1/epi12288.pd

Treatment of infantile spasms: emerging insights from clinical and basic science perspectives.

Infantile spasms is an epileptic encephalopathy of early infancy with specific clinical and electroencephalographic (EEG) features, limited treatment options, and a poor prognosis. Efforts to develop improved treatment options have been hindered by the lack of experimental models in which to test prospective therapies. The neuropeptide adrenocorticotropic hormone (ACTH) is effective in many cases of infantile spasms, although its mechanism(s) of action is unknown. This review describes the emerging candidate mechanisms that can underlie the therapeutic effects of ACTH in infantile spasms. These mechanisms can ultimately help to improve understanding and treatment of the disease. An overview of current treatments of infantile spasms, novel conceptual and experimental approaches to infantile spasms treatment, and a perspective on remaining clinical challenges and current research questions are presented here. This summary derives from a meeting of specialists in infantile spasms clinical care and research held in New York City on June 14, 2010

Neurocognitive, Social-Behavioral, and Adaptive Functioning in Preschool Children with Mild to Moderate Kidney Disease

The negative impact of End Stage Kidney Disease on cognitive function in children is well established, but no studies have examined the neurocognitive, social-behavioral, and adaptive behavior skills of preschool children with mild to moderate chronic kidney disease (CKD)

Differences in brain changes between adults with childhood-onset epilepsy and controls: A prospective population-based study

PurposeTo determine the impact of childhood-onset uncomplicated epilepsy (COE) on brain aging over 50-year prospective follow-up.MethodsA population-based cohort of 41 aging subjects with COE and their 46 matched controls participated in a detailed in-person prospective assessment in 2012 and 2017 to characterize ongoing changes in the aging brain.ResultsThe mean age of the COE participants was 63.2 years (SD 4.14, median 63.2, range 55.8–70.6) and 63.0 years (mean, SD 4.13, median 63.3, range 56.0–69.9) years for controls. Neurologic signs were significantly more common in COE participants not in remission (p = .015), and the most frequent abnormalities were cerebellar signs (p p = .008) and cerebellar signs in particular (p = .018) were significantly more common in focal than in generalized epilepsies. MRI white matter abnormalities were significantly associated with absence of vocational education (p = .011), and MRI hippocampal atrophy in COE subjects was associated with arterial hypertension versus normal blood pressure (p = .017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and in the controls from the 2012 to 2017 study.ConclusionsAt ultra-long-term follow-up, clinical and neuroimaging findings show tendencies to brain aging that is more accelerated in COE participants with active adult childhood-onset epilepsy, and particularly in focal epilepsy.</div

Duration of chronic kidney disease reduces attention and executive function in pediatric patients

Chronic kidney disease (CKD) in childhood is associated with neurocognitive deficits. Affected children show worse performance on tests of intelligence than their unaffected siblings and skew toward the lower end of the normal range. Here we further assessed this association in 340 pediatric patients (ages 6 to 21) with mild-moderate CKD in The Chronic Kidney Disease in Childhood cohort from 48 pediatric centers in North America. Participants underwent a battery of age-appropriate tests including Conner’s Continuous Performance Test-II (CPT-II), Delis- Kaplan Executive Function System Tower task, and the Digit Span Backwards task from the age-appropriate Wechsler Intelligence Scale. Test performance was compared across the range of estimated GFR and duration of CKD with relevant covariates including maternal education, household income, IQ, blood pressure and preterm birth. Among the 340 patients, 35% had poor performance (below the mean by1.5 or more standard deviations) on at least one test of executive function. By univariate nonparametric comparison and multiple logistic regression, longer duration of CKD was associated with increased odds ratio for poor performance on the CPT-II Errors of Commission, a test of attention regulation and inhibitory control. Thus, in a population with mild to moderate CKD, the duration of disease rather than estimated GFR was associated with impaired attention regulation and inhibitory control

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK