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

Kinetics of fragmentation-annihilation processes

We investigate the kinetics of systems in which particles of one species undergo binary fragmentation and pair annihilation. In the latter, nonlinear process, fragments react at collision to produce an inert species, causing loss of mass. We analyse these systems in the reaction-limited regime by solving a continuous model within the mean-field approximation. The rate of fragmentation, for a particle of mass $x$ to break into fragments of masses $y$ and $x-y$, has the form $x^{\lambda-1}$ ($\lambda>0$), and the annihilation rate is constant and independent of the masses of the reactants. We find that the asymptotic regime is characterized by the annihilation of small-mass clusters. The results are compared with those for a model with linear mass-loss (i.e.\ with a sink). We also study more complex models, in which the processes of fragmentation and annihilation are controlled by mutually-reacting catalysts. Both pair- and linear-annihilation are considered. Depending on the specific model and initial densities of the catalysts, the time-decay of the cluster-density can now be very unconventional and even non-universal. The interplay between the intervening processes and the existence of a scaling regime are determined by the asymptotic behaviour of the average-mass and of the mass-density, which may either decay indefinitely or tend to a constant value. We discuss further developments of this class of models and their potential applications.Comment: 16 pages(LaTeX), submitted to Phys. Rev.

Cognitive Outcome in Childhood-Onset Epilepsy: A Five-Decade Prospective Cohort Study

Objectives: Little is known about the very long-term cognitive outcome in patients with childhood-onset epilepsy. The aim of this unique prospective population-based cohort study was to examine cognitive outcomes in aging participants with childhood-onset epilepsy (mean onset age = 5.3 years) five decades later (mean age at follow-up = 56.5 years). Methods: The sample consisted of 48 participants with childhood-onset epilepsy and 48 age-matched healthy controls aged 48-63 years. Thirty-six epilepsy participants were in remission and 12 continued to have seizures. Cognitive function was examined with 11 neuropsychological tests measuring language and semantic function, episodic memory, and learning, visuomotor function, executive function, and working memory. Results: The risk of cognitive impairment was very high in participants with continuing seizures; odds ratio (OR) = 11.7 (95% confidence interval [CI] (2.8, 49.6), p = .0008). They exhibited worse performances across measures of language and semantic function, and visuomotor function compared to participants with remitted epilepsy and healthy controls. In the participants with remitted epilepsy, the risk of cognitive impairment was somewhat elevated, but not statistically significant; OR = 2.6 (95% CI [0.9, 7.5], p = .08).Conclusions: Our results showed that the distinction of continued versus discontinued seizures was critical for determining long-term cognitive outcome in childhood-onset epilepsy. Few participants in remission exhibited marked cognitive impairment compared to age-matched peers. However, a subgroup of participants with decades long active epilepsy, continuous seizure activity and anti-epileptic drug (AED) medication, showed clinically significant cognitive impairment and are thus in a more precarious position when entering older age.</div

Towards 1H-MRSI of the human brain at 7T with slice-selective adiabatic refocusing pulses

Contains fulltext : 70576.pdf (publisher's version ) (Closed access)OBJECTIVE: To explore the possibilities of proton spectroscopic imaging (1H-MRSI) of the human brain at 7 Tesla with adiabatic refocusing pulses. MATERIALS AND METHODS: A combination of conventional slice selective excitation and two pairs of slice selective adiabatic refocusing pulses (semi-LASER) results in the formation of an echo from a localized volume. Depending on the used radio frequency (rf) coil efficiency and available rf power, the duration of the adiabatic full passage pulses (AFPs) is adapted to enable echo times down to 50 ms (head coil) or 30 ms (local surface coil). RESULTS: An AFP duration of 5 ms with a corresponding bandwidth of 5.1 kHz resulted in a chemical shift displacement error of 23% over 3.8 ppm at 7T. Using a local surface coil and an echo time down to 30 ms, we detected not only the three main metabolites (NAA, Cr and Cho), but also coupled signals from myo-inositol and glutamate/glutamine in spectra from 0.14 cc voxels with linewidths down to 10 Hz in 10 min measurement time. CONCLUSIONS: The semi-LASER pulse sequence enables 1H-MRSI of the human brain at 7T for larger parts of the brain as well as small localized areas with both a high spectral and spatial resolution

Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems

Stable Distributions in Stochastic Fragmentation

We investigate a class of stochastic fragmentation processes involving stable and unstable fragments. We solve analytically for the fragment length density and find that a generic algebraic divergence characterizes its small-size tail. Furthermore, the entire range of acceptable values of decay exponent consistent with the length conservation can be realized. We show that the stochastic fragmentation process is non-self-averaging as moments exhibit significant sample-to-sample fluctuations. Additionally, we find that the distributions of the moments and of extremal characteristics possess an infinite set of progressively weaker singularities.Comment: 11 pages, 5 figure

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

Epileptogenesis after prolonged febrile seizures: mechanisms, biomarkers and therapeutic opportunities.

Epidemiological and recent prospective analyses of long febrile seizures (FS) and febrile status epilepticus (FSE) support the idea that in some children, such seizures can provoke temporal lobe epilepsy (TLE). Because of the high prevalence of these seizures, if epilepsy was to arise as their direct consequence, this would constitute a significant clinical problem. Here we discuss these issues, and describe the use of animal models of prolonged FS and of FSE to address the following questions: Are long FS epileptogenic? What governs this epileptogenesis? What are the mechanisms? Are there any predictive biomarkers of the epileptogenic process, and can these be utilized, together with information about the mechanisms of epileptogenesis, for eventual prevention of the TLE that results from long FS and FSE