Clinical significance of treatment delay in status epilepticus

BACKGROUND: Status epilepticus (SE) is a medical emergency that requires immediate action. The clinical and demographic features of SE are known to be highly variable. The objective of this study was to analyze the effect of treatment delays on patient recovery and different clinical factors that are important in the determination of the acute prognosis in SE. METHODS: This population-based study included 109 consecutive visits of patients with the diagnosis of SE in the emergency department (ED) of Tampere University Hospital. The clinical features of SE were compared with the discharge condition. RESULTS: The treatment delays were long; in half of the patients, the delay for paramedic arrival was over 30 min, and in one-third of the cases, the delay was over 24 h. ED patients who had less than 1 h of delay before the administration of an antiepileptic drug (AED) had better outcomes compared to patients with a greater than 1 h delay (p < 0.05). The two major etiologies for the SE were cerebrovascular disease and alcohol misuse. A good immediate outcome was found in 46% of the patients. Epileptiform activity on the EEG, a history of epilepsy or SE, presence of cardiovascular disease, and alcohol misuse were associated with a poor outcome. CONCLUSIONS: The results of this study emphasize the importance of an urgent response by emergency services and proper recognition of atypical phenotypes of SE

Impedance Characteristics of Stimulation Contacts in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus and Its Relationship to Seizure Outcome in Patients With Refractory Epilepsy

Background: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an emerging form of adjunctive therapy in focal refractory epilepsy. Unlike conventional DBS targets, the ANT is both encapsulated by white matter layers and located immediately adjacent to the cerebrospinal fluid (CSF) space. Owing to the location of the ANT, implantation has most commonly been performed using a transventricular trajectory. Previous studies suggest different electrical conductivity between gray matter, white matter, and CSF. Objectives: In this study, we asked whether therapeutic impedance values from a fully implanted DBS device could be used to deduce the actual location of the active contact to optimize the stimulation site. Secondly, we tested whether impedance values correlate with patient outcomes. Materials and Methods: A total of 16 patients with ANT-DBS for refractory epilepsy were evaluated in this prospective study. Therapeutic impedance values were recorded on regular outpatient clinic visits. Contact locations were analyzed using delayed contrast-enhanced postoperative computed tomography–3T magnetic resonance imaging short tau inversion recovery fusion images previously shown to demonstrate anatomical details around the ANT. Results: Transventricularly implanted contacts immediately below the CSF surface showed overall lower and slightly decreasing impedances over time compared with higher and more stable impedances in contacts with deeper parenchymal location. Impedance values in transventricularly implanted contacts in the ANT were significantly lower than those in transventricularly implanted contacts outside the ANT or extraventricularly implanted contacts that were typically at the posterior/inferior/lateral border of the ANT. Increasing contact distance from the CSF surface was associated with a linear increase in therapeutic impedance. We also found that therapeutic impedance values were significantly lower in contacts with favorable therapy response than in nonresponding contacts. Finally, we observed a significant correlation between the left- and right-side averaged impedance and the reduction of the total number of seizures. Conclusions: Valuable information can be obtained from the noninvasive measurement of therapeutic impedances. The selection of active contacts to target stimulation to the anterior nucleus may be guided by therapeutic impedance measurements to optimize outcome.publishedVersionPeer reviewe

Structural connectivity of the ANT region based on human ex-vivo and HCP data. : Relevance for DBS in ANT for epilepsy

Objective: Deep Brain Stimulation (DBS) in the Anterior Nucleus of the Thalamus (ANT) has been shown to be a safe and efficacious treatment option for patients with Drug-Resitant focal Epilepsy (DRE). The ANT has been selected frequently in open and controlled studies for bilateral DBS. There is a substantial variability in ANT-DBS outcomes which is not fully understood. These outcomes might not be explained by the target location alone but potentially depend on the connectivity of the mere stimulation site with the epilepsy onset-associated brain regions. The likely sub-components of this anatomy are fiber pathways which penetrate or touch the ANT region and constitute a complex and dense fiber network which has not been described so far. A detailed characterization of this ANT associated fiber anatomy may therefore help to identify which areas are associated with positive or negative outcomes of ANT-DBS. Furthermore, prediction properties in individual ANT-DBS cases might be tested. In this work we aim to generate an anatomically detailed map of candidate fiber structures which might in the future lead to a holistic image of structural connectivity of the ANT region. Methods: To resolve the various components of the complex fiber network connected to the ANT we used a synthetic pathway reconstruction method that combines anatomical fiber tracking with dMRI-based tractography and iteratively created an anatomical high-resolution fiber map representing the most important bundles related to the ANT. Results: The anatomically detailed 3D representation of the fibers in the ANT region generated with the synthetic pathway reconstruction method incorporates multiple anatomically defined fiber bundles with their course, orientation, connectivity and relative strength. Distinctive positions within the ANT region have a different hierarchical profile with respect to the stimulation-activated fiber bundles. This detailed connectivity map, which is embedded into the topographic map of the MNI brain, provides novel opportunities to analyze the outcomes of the ANT-DBS studies. Conclusion: Our synthetic reconstruction method provides the first anatomically realistic fiber pathway map in the human ANT region incorporating histological and structural MRI data. We propose that this complex ANT fiber network can be used for detailed analysis of the outcomes of DBS studies and potentially for visualization during the stimulation planning procedures. The connectivity map might also facilitate surgical planning and will help to simulate the complex ANT connectivity. Possible activation patterns that may be elicited by electrodes in different positions in the ANT region will help to understand clinically diverse outcomes based on this new dense fiber network map. As a consequence this work might in the future help to improve individual outcomes in ANT-DBS.publishedVersionPeer reviewe

Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion-attention interaction in humans

BACKGROUND: Deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) is a novel promising therapeutic method for treating refractory epilepsy. Despite reports of subjective memory impairments and mood disturbances in patients with ANT-DBS, little is known of its effects on cognitive and affective processes. HYPOTHESIS: The anterior thalamus has connections to prefrontal and limbic networks important for cognitive control and emotional reactivity. More specifically, anterior cingulate cortex (ACC), linked with ANT, has been assigned roles related to response inhibition and attention allocation to threat. Thus, we hypothesized ANT-DBS to influence executive functions, particularly response inhibition, and modulate emotional reactivity to threat. METHOD: Twelve patients having undergone ANT-DBS for intractable epilepsy participated in the study. Patients performed a computer-based executive reaction time (RT) test—that is, a go/ no-go visual discrimination task with threat-related emotional distractors and rule switching, while the DBS was switched ON (5/5 mA constant current) and OFF every few minutes. RESULTS: ANT-DBS increased the amount of commission errors—that is, errors where subjects failed to withhold from responding. Furthermore, ANT-DBS slowed RTs in context of threat-related distractors. When stimulation was turned off, threat-related distractors had no distinct effect on RTs. CONCLUSION: We found immediate objective effects of ANT-DBS on human cognitive control and emotion-attention interaction. We suggest that ANT-DBS compromised response inhibition and enhanced attention allocation to threat due to altered functioning of neural networks that involve the DBS-target, ANT, and the regions connected to it such as ACC. The results highlight the need to consider affective and cognitive side-effects in addition to the therapeutic effect when adjusting stimulation parameters. Furthermore, this study introduces a novel window into cognitive and affective processes by modulating the associative and limbic networks with direct stimulation of key nodes in the thalamus

Kulttuurihyvinvointitoiminnan taloudellinen arviointi : Arviointimenetelmien jatkokehitystarpeet Suomessa

Hankkeen tavoitteena oli 1) kehittää kulttuurihyvinvointitoimien ennakoivassa taloudellisessa arvioinnissa tarvittavia menetelmiä ja laskentamalleja, 2) kehittää arvioinnin kriteeristöjä, 3) tunnistaa arviointia tukevan tietotuotannon tarpeita sekä 4) tehdä näiden pohjalta toimenpidesuosituksia kulttuurihyvinvointitoimien taloudellisen arvioinnin kehittämiseksi Suomessa. Hankkeessa tunnistettiin sidosryhmähaastatteluiden avulla kulttuurihyvinvointitoiminnan taloudellisen arvioinnin mahdollisuuksia ja haasteita Suomessa sekä kartoitettiin kirjallisuuskatsauksella kulttuurihyvinvointitoiminnan vaikuttavuustutkimuksen nykytilaa kansainvälisesti. Lisäksi hankkeessa pilotoitiin kirjallisuudesta tunnistettuja koetun hyvinvoinnin mittareita kulttuurihyvinvointitoiminnan vaikuttavuuden arvioinnissa. Viimeisessä osahankkeessa sovellettiin terveystaloudellisen mallinnuksen menetelmiä esimerkinomaisesti osallisuutta tukevan kulttuurihyvinvointitoiminnan taloudellisessa arvioinnissa. Tällä hetkellä kulttuurihyvinvointitoiminnan vaikuttavuustutkimus on sekä kansallisesti että kansainvälisesti tarkastellen vähäistä ja pistemäistä. Alan toimijat ja organisaatiot ovat kuitenkin valmiita vaikuttavuusperustaiseen yhteistyöhön. Tämä edellyttää kuitenkin konkreettisia tekoja ja tarvittavan tietopohjan rakentamista, mikä vahvistaa kulttuurihyvinvointitoiminnan vaikuttavuuden arviointia ja mittaamista.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa. (tietokayttoon.fi) Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

Complex executive functions assessed by the trail making test (TMT) part B improve more than those assessed by the TMT part A or digit span backward task during vagus nerve stimulation in patients with drug-resistant epilepsy

IntroductionThere is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years.MethodsThe study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes.ResultsOn average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p &lt; 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p = 0.036 and 0.028 units/month, p = 0.003, respectively). TMT-A z scores improved the most in patients taking 1–2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p = 0.002 and p = 0.003, respectively).ConclusionPerformance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities

Genetics of osteopontin in patients with chronic kidney disease: The German chronic kidney disease study

Osteopontin (OPN), encoded by SPP1, is a phosphorylated glycoprotein predominantly synthesized in kidney tissue. Increased OPN mRNA and protein expression correlates with proteinuria, reduced creatinine clearance, and kidney fibrosis in animal models of kidney disease. But its genetic underpinnings are incompletely understood. We therefore conducted a genome-wide association study (GWAS) of OPN in a European chronic kidney disease (CKD) population. Using data from participants of the German Chronic Kidney Disease (GCKD) study (N = 4,897), a GWAS (minor allele frequency [MAF]>= 1%) and aggregated variant testing (AVT, MAFAuthor summaryOsteopontin (OPN) is involved in many (patho)physiological processes of the human body. Among others, it is known to be associated with adverse kidney outcomes. Since its genetic underpinnings are incompletely understood, we conducted a genome-wide association study of OPN in a European chronic kidney disease (CKD) population (N = 4,897). Of the three detected signals, two could be replicated within a population-based study of Finns. One locus is located upstream of SPP1 which encodes the OPN protein and is related to OPN production. This gene was also disclosed by an analysis of rare variants, all presumably effecting the gene product. Another locus maps into KLKB1 encoding prekallikrein (PK) that after processing to kallikrein (KAL) is implicated in blood pressure control and inflammation among others. Overall, our results highlight the multi-functional role of OPN and its possible pathological role in CKD. Further studies are needed to elucidate the complex role of OPN in humans.</p