Rare and Complex Epilepsies from Childhood to Adulthood: Requirements for Separate Management or Scope for a Lifespan Holistic Approach?

Purpose: In this descriptive review, we describe current models of transition in rare and complex epilepsy syndromes and propose alternative approaches for more holistic management based on disease biology. // Recent Findings: Previously published guidance and recommendations on transition strategies in individuals with epilepsy have not been systematically and uniformly applied. There is significant heterogeneity in models of transition/transfer of care across countries and even within the same country. // Summary: We provide examples of the most severe epilepsy and related syndromes and emphasise the limited data on their outcome in adulthood. Rare and complex epilepsy syndromes have unique presentations and require high levels of expertise and multidisciplinary approach. Lifespan clinics, with no transition, but instead continuity of care from childhood to adulthood with highly specialised input from healthcare providers, may represent an alternative effective approach. Effectiveness should be measured by evaluation of quality of life for both patients and their families/caregivers

Climate control on sulphate and nitrate concentrations in alpine streams of Northern Italy along a nitrogen saturation gradient

International audienceThe role of meteorology, hydrology and atmospheric deposition on the temporal pattern of SO4 and NO3 concentrations was investigated for three streams draining alpine catchments in Northern Italy. The study sites lie on a gradient of atmospheric fluxes of SO4 and NO3 (from about 50 to 80 meq m?2 y?1, and from 40 to 90 meq m?2 y?1, respectively). As a consequence of the increasing N input, the three catchments are also representative of aggrading levels of N saturation. Different methods of statistical analysis were applied to monthly data for the period 1997?2005 to identify which variables (temperature, precipitation, hydrology, SO4 and NO3 deposition) were the main predictors of water chemistry and its change in time. Hydrological changes and snow cover proved to be the main confounding factors in the response to atmospheric deposition in the River Masino catchment. Its particular characteristics (small catchment area, rapid flushing during runoff and thin soil cover) meant that this site responded without a significant delay to SO4 deposition decrease. It also showed a clear seasonal pattern of NO3 concentration, in response to hydrology and biological uptake in the growing season. The selected driving variables failed to model the water chemistry at the other study sites. Nevertheless, temperature, especially extreme values, turned out to be important in both SO4 and NO3 export from the catchments. This result might be largely explained by the effect of warm periods on temperature-dependent processes such as mineralization, nitrification and S desorption. Our findings suggest that surface waters in the alpine area will be extremely sensitive to a climate warming scenario: higher temperatures and increasing frequency of drought could exacerbate the effects of high chronic N deposition

Monogenic Epilepsies: Disease Mechanisms, Clinical Phenotypes, and Targeted Therapies

A monogenic aetiology can be identified in up to 40% of people with severe epilepsy. To address earlier and more appropriate treatment strategies, clinicians are required to know the implications that specific genetic causes might have on pathophysiology, natural history, comorbidities and treatment choices. In this narrative review, we summarise concepts on the genetic epilepsies based on the underlying pathophysiological mechanisms and present the current knowledge on treatment options based on evidence provided by controlled trials or studies with lower classification of evidence. Overall, evidence robust enough to guide antiseizure medication (ASM) choices in genetic epilepsies remains limited to the more frequent conditions for which controlled trials and observational studies have been possible. Most monogenic disorders are very rare and ASM choices for them are still based on inferences drawn from observational studies and early, often anecdotal, experiences with precision therapies. Precision medicine remains applicable to only a narrow number of patients with monogenic epilepsies and may target only part of the actual functional defects. Phenotypic heterogeneity is remarkable, and some genetic mutations activate epileptogenesis through their developmental effects, which may not be reversed postnatally. Other genes seem to have pure functional consequences on excitability, acting through either loss- or gain-of-function effects, and these may have opposite treatment implications. In addition, the functional consequences of missense mutations may be difficult to predict, making precision treatment approaches considerably more complex than estimated by deterministic interpretations. Knowledge of genetic aetiologies can influence the approach to surgical treatment of focal epilepsies. Identification of germline mutations in specific genes contraindicates surgery while mutations in other genes do not. Identification, quantification and functional characterization of specific somatic mutations before surgery using cerebrospinal fluid liquid biopsy or after surgery in brain specimens, will likely be integrated in planning surgical strategies and re-intervention after a first unsuccessful surgery as initial evidence suggests that mutational load may correlate with the epileptogenic zone. Promising future directions include gene manipulation by DNA or mRNA targeting; although most are still far from clinical use, some are in early phase clinical development

Applying a perceptions and practicalities approach to understanding nonadherence to antiepileptic drugs

Summary Objective Nonadherence to antiepileptic drugs (AEDs) is a common cause of poor seizure control. This study examines whether reported adherence to AEDs is related to variables identified in the National Institute for Health and Clinical Excellence (NICE) Medicines Adherence Guidelines as being important to adherence: perceptual factors (AED necessity beliefs and concerns), practical factors (limitations in capability and resources), and perceptions of involvement in treatment decisions. Methods This was a cross-sectional study of people with epilepsy receiving AEDs. Participants completed an online survey hosted by the Epilepsy Society (n = 1,010), or as an audit during inpatient admission (n = 118). Validated questionnaires, adapted for epilepsy, assessed reported adherence to AEDs (Medication Adherence Report Scale [MARS]), perceptions of AEDs (Beliefs about Medicines Questionnaire [BMQ]), and patient perceptions of involvement in treatment decisions (Treatment Empowerment Scale [TES]). Results Low adherence was related to AED beliefs (doubts about necessity: t(577) = 3.90, p < 0.001; and concerns: t(995) = 3.45, p = 0.001), reported limitations in capability and resources (t(589) = 7.78, p < 0.001), and to perceptions of a lack of involvement in treatment decisions (t(623) = 4.48, p < 0.001). In multiple logistic regression analyses, these factors significantly (p < 0.001) increased variance in reported adherence, above that which could be explained by age and clinical variables (seizure frequency, type, epilepsy duration, number of AEDs prescribed). Significance Variables identified in the NICE Medicines Adherence Guidelines as potentially important factors for adherence were found to be related to adherence to AEDs. These factors are potentially modifiable. Interventions to support optimal adherence to AEDs should be tailored to address doubts about AED necessity and concerns about harm, and to overcome practical difficulties, while engaging patients in treatment decisions

Climatic and pedoclimatic factors driving C and N dynamics in soil and surface water in the alpine tundra (NW-Italian Alps)

In alpine tundra the interannual and seasonal variability of C and N forms in soil and lake water during the short snow-free season could be significant and related to climatic and pedoclimatic variables. The hypothesis that not only the climatic and pedoclimatic parameters recorded during the summer season but also the ones measured during the previous snow-covered season could contribute to explaining the C and N dynamics in soil and surface water was tested along 10 snow-free seasons in 3 sites in the alpine tundra in the north-western Italian Alps (LTER site Istituto Mosso). Among the considered parameters, the snow cover duration (SCD) exerted a primary control on soil N-NH4+, DOC, Cmicr, Nmicr and DOC:DON ratio, with an inverse relationship. A long SCD might cause the consumption of all the subnival substrata by the soil microorganisms, determining a C starvation during the subsequent snow-free season. An opposite trend was observed for the lake water, where a longer SCD corresponded to a higher content of inorganic N forms. Among the pedoclimatic indices, the number of soil freeze/thaw cycles (FTC) recorded during the snow-covered season had a positive relation with most of soil C and N forms and N-NO3− in lake water. Only the soil DON showed an inverse pattern, and this result is consistent with the hypothesis that FTC released soil DON, subsequently decomposed and mineralized. Only N-NO3− had a significant intraseasonal variability, reaching the highest values in September both in soil and water, revealing a significant slowdown of the contribution of soil N immobilization processes

Ammonia: what adult neurologists need to know

Hyperammonaemia is often encountered in acute neurology and can be the cause of acute or chronic neurological symptoms. Patients with hyperammonaemia may present with seizures or encephalopathy, or may be entirely asymptomatic. The underlying causes are diverse but often straightforward to diagnose, although sometimes require specialist investigations. Haemodialysis or haemo(dia)filtration is the first-line treatment for acute severe hyperammonaemia (of any cause) in an adult. Here we discuss our approach to adult patients with hyperammonaemia identified by a neurologist

Application of laser microdissection to identify the mycorrhizal fungi that establish arbuscules inside root cells.

Obligate symbiotic fungi that form arbuscular mycorrhizae (AMF; belonging to the Glomeromycota phylum) are some of the most important soil microorganisms. AMFs facilitate mineral nutrient uptake from the soil, in exchange for plant-assimilated carbon, and promote water-stress tolerance and resistance to certain diseases. AMFs colonize the root by producing inter- and intra-cellular hyphae. When the fungus penetrates the inner cortical cells, it produces a complex ramified structure called arbuscule, which is considered the preferential site for nutrient exchange. Direct DNA extraction from the whole root and sequencing of ribosomal gene regions are commonly carried out to investigate intraradical AMF communities. Nevertheless, this protocol cannot discriminate between the AMFs that actively produce arbuscules and those that do not. To solve this issue, the authors have characterized the AMF community of arbusculated cells (AC) through a laser microdissection (LMD) approach, combined with sequencing-based taxa identification. The results were then compared with the AMF community that was found from whole root DNA extraction. The AMF communities originating from the LMD samples and the whole root samples differed remarkably. Five taxa were involved in the production of arbuscules, while two taxa were retrieved inside the root but not in the AC. Unexpectedly, one taxon was found in the AC, but its detection was not possible when extracting from the whole root. Thus, the LMD technique can be considered a powerful tool to obtain more precise knowledge on the symbiotically active intraradical AMF community