Status epilepticuksen hoidon viiveet : vaikutus ennusteeseen

Status epilepticus (SE), i.e. prolonged epileptic seizure, is a life-threatening medical emergency, which is associated with high mortality and morbidity. International guidelines suggest early and efficient treatment. Thus, long duration of SE is one of the main predictors of poor prognosis and the only prognostic factor that can be affected by shortening the delays in the treatment. However, studies on delays, implementation of treatment guidelines and the effect of delays on outcome are scarce. The aim of this thesis was to systematically investigate delays in the treatment of SE and factors related to the delays along the whole treatment chain. We also aimed at clarifying the effect of delays on the outcome and at identifying the significant delays related to outcome in order to propose evidence-based targets for streamlining the SE treatment protocol. The material of this retrospective study consists of 82 consecutive SE patients treated in a tertiary hospital emergency department over two years. Delays, patient characteristics and parameters related to treatment chain were identified and their relations, correlations and effects were investigated. The results of this thesis reveal that the delays in the treatment of SE are unacceptably long and exceed markedly the suggested time frames in the guidelines. Fulfilment of the suggested SE treatment algorithm is frequently hampered by failing recognition of SE at onset, also by professionals, which may increase the delays in consecutive parts of the treatment chain. Delays seem to be more significant determinants of SE duration than previously established outcome predictors. Additionally, various long delays in the treatment (second- and third-stage medication, diagnostic and tertiary hospital delays) increase the risk of mortality and poor functional outcome at hospital discharge and since the predictive cut-off point of these delays lies under 2,5 hours, the focus of protocol streamlining should be in the pre-hospital phase of the treatment. However, none of the delays are independent risk factors for poor outcome, which reflects the dynamism of SE, but also demonstrates that every step of the treatment chain needs to be optimized. In conclusion, we propose that generation of simplified criteria for suspicion of an imminent SE and streamlining pre-hospital treatment chain are advocated. We suggest amendments to the protocol, such as triaging suspected SE patients with highest priority, recruiting physician-based EMS units upon primary alarm, administration of second-stage medication out-of-hospital and transportation of SE patients exclusively to hospitals with neurological expertise. Also improvement of diagnostic possibilities on emergency site should be considered.Status epilepticus (SE), eli pitkittynyt epileptinen kohtaus, on hengenvaarallinen hätätila, johon tehokkaastikin hoidettuna liittyy kuolleisuutta ja sairastavuutta. Kohtauksen pitkä kesto on yksi merkittävimmistä huonoon ennusteeseen liittyvistä tekijöistä. Kansainväliset hoitosuositukset suosittavat nopeaa ja tehokasta hoitoa SE:n lopettamiseksi. Tutkimustieto hoidon viiveistä, hoitosuositusten toteutumisesta ja näiden vaikutuksista ennusteeseen on kuitenkin erittäin vähäistä. Väitöstutkimuksen tavoitteena oli selvittää status epilepticuksen hoitoon liittyviä viiveitä ja viiveisiin vaikuttavia tekijöitä hoitoketjun eri vaiheissa. Lisäksi tavoitteena oli tutkia viiveiden vaikutusta SE-potilaiden ennusteeseen ja tunnistaa sen kannalta merkittävimmät viiveet ja tekijät, jotta hoitoketjun toiminnan tehostaminen tulevaisuudessa olisi mahdollista. Tavoitteiden saavuttamiseksi tarkasteltiin Helsingin Yliopistollisen Keskussairaalan päivystyksessä kahden vuoden aikana hoidettujen aikuisten SE-potilaiden asiakirjamerkinnät. Tutkimustulosten perusteella viiveet status epilepticuksen hoidossa ovat pitkiä ja ylittävät kestoltaan selvästi kansainvälisten hoitosuositusten viiterajat. Hoidon viiveet näyttävät vaikuttavan SE:n kestoon enemmän kuin muut aiemmin tunnistetut ennustetekijät. Lääkehoitoihin, diagnostiikkaan ja hoitopaikan valintaan liittyvillä viiveillä on merkittävä vaikutus SE-potilaiden kuolleisuuteen ja toipumisennusteeseen: mitä lyhyemmät viiveet, sitä parempi ennuste akuuttivaiheen sairaalahoidon päättyessä. Useat eri viiveet, erityisesti hoitoketjun alkupäässä, vaikuttavat merkittävästi ennusteeseen, mikä korostaa hoitoketjun jokaisen vaiheen mahdollisimman hyvän onnistumisen tärkeyttä ennusteen parantamiseksi. Status epilepticuksen hoidon viiveet eivät tutkimuksen perusteella olleet hyväksyttävällä tasolla ja niiden lyhentämiseksi tulisi pyrkiä hoitoketjun virtaviivaistamiseen. Epäiltäessä potilaalla SE:tä lääkäriyksikön tai koulutetun hoitoyksikön hälyttäminen olisi suositeltavaa heti ensivaiheessa, jotta viiveiden lyhentämiseksi kaikki olennaiset lääkkeet ja hoitotoimenpiteet olisi mahdollista toteuttaa jo ennen sairaalaan saapumista. Erityisesti toisen linjan lääkehoidon annostelun mahdollistaminen ensihoidossa olisi suositeltavaa. SE-potilaat tulisi kuljettaa jatkohoitoon sellaiseen sairaalaan, jossa neurologinen erityisosaaminen ja riittävät diagnostiset tutkimusmahdollisuudet ovat ympärivuorokautisessa käytössä

The essence of the first 2.5 h in the treatment of generalized convulsive status epilepticus

Purpose: This study was designed to find realistic cut-offs of the delays predicting outcome after generalized convulsive status epilepticus (GCSE) and serving protocol streamlining of GCSE patients. Method: This retrospective study includes all consecutive adult (>16 years) patients (N = 70) diagnosed with GCSE in Helsinki University Central Hospital emergency department over 2 years. We defined ten specific delay parameters in the management of GCSE and determined functional outcome and mortality at hospital discharge. Functional outcome was assessed with Glasgow Outcome Scale (GOS1-3 for poor outcome, GOS > 3 for good outcome) and also defined as condition relative to baseline (worse-than baseline vs. baseline). Univariate and multivariate regression models were used to analyze the relations between delays and outcome. Delay cut-offs predicting outcome were determined using ROC-Curves. Results: In univariate analysis long onset-to-tertiary-hospital time (p = 0.034) was a significant risk factor for worse-than-baseline condition. Long delays in onset-to-diagnosis (p = 0.032), onset-to-second-stage medication (p = 0.023), onset-to-consciousness (p = 0.027) and long total-anesthesia-time (0 = 0.043) were risk factors for low GOS score (1-3). Short delay in onset-to-initial-treatment (p = 0.047), long onset-to-anesthesia (p = 0.003) and onset-to-consciousness (p = 0.008) times were risk factors for in hospital mortality. Multivariate analysis showed no significant factors. Cut-offs for increased risk of poor outcome were onset-to-diagnosis 2.4 h (p = 0.011), onset-to-second stage-medication 2.5 h (p = 0.001), onset-to-consciousness 41.5 h (p = 0.009) times and total-anesthesia time 45.5 h (p = 0.003). The delay over 2.1 h in onset-to-tertiary-hospital time increased the risk of worse than-baseline condition (p = 0.028). Conclusions: GCSE treatment is a dynamic process, where every delay component needs to be optimized. We suggest that GCSE patients should be handled with high priority and transported directly to hospital ED with neurological expertise. Critical steps in the treatment, such as diagnosing GCSE and starting progressive antiepileptic medication on stages 1 through 3, if needed, should be accomplished within 2.5 h. (C) 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Epilepsiapotilas päivystyksessä

Vertaisarvioitu. English summaryEpilepsiapotilaat ohjautuvat päivystykseen ensimmäisen, pitkittyneen, tiheästi toistuvan tai komplisoituneen kohtauksensa vuoksi. Nopea ja oikein kohdennettu hoito parhaassa tapauksessa estää kohtauksen vaikeutumisen status epilepticukseksi. Hoitoketjun eri vaiheiden saumaton eteneminen selkeän hoitoprotokollan mukaan on pitkittyneen epilepsiakohtauksen saaneen potilaan ennusteen kannalta keskeistä. Viiveettömän hoidon toteutuksen lisäksi lääkehoidon valinnassa tulisi huomioida epilepsian ja pitkittyneen kohtauksen tyyppi, etiologia ja niihin liittyvät epävarmuustekijät. Aikuispotilaiden osalta korostuvat liitännäissairaudet, niihin liittyvät hoidot ja kohtaustilanteen vaikeutumisen muut syyt. Vaikeassa kohtaustilanteessa epileptologisen yksikön konsultoiminen on tarpeen. Jos potilaan status epilepticus on vaikeahoitoinen, konsultaation tulisi toteutua kiireellisesti. Päivystyspisteiden osuus on merkittävä paitsi viiveettömässä kohtausten hoidossa myös jatkohoidon toteutuksessa ja ohjauksessa.Peer reviewe

Delays and Factors Related to Cessation of Generalized Convulsive Status Epilepticus

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Predictors of mortality at one year after generalized convulsive status epilepticus

Background: Status epilepticus (SE) is a life-threatening neurologic emergency, which requires prompt medical treatment. Little is known of the long-term survival of SE. The aim of this study was to investigate which factors influence 90 days and 1-year mortality after SE. Materials and methods: This retrospective study includes all consecutive adult (>16 years) patients (N = 70) diagnosed with generalized convulsive SE (GCSE) in Helsinki University Central Hospital (HUCH) emergency department (ED) over 2 years. We defined specific factors including patient demographics, GCSE characteristics, treatment, complications, delays in treatment, and outcome at hospital discharge and determined their relation to 90 days and 1-year mortality after GCSE by using logistic regression models. Survival analyses at 1 year after GCSE were performed with Cox proportional hazards regression analysis. Results: In-hospital mortality was 7.1%. Mortality rate was 14.3% at 90 days and 24.3% at 1 year after GCSE. In the univariate logistic regression analysis, Status Epilepticus Severity Score > 4 (STESS) (ODDS = 7.30, p = 0.012), worse-than-baseline condition at hospital discharge (ODDS = 3.5, p = 0.006), long delays in attaining seizure freedom (ODDS = 2.2, p = 0.041), and consciousness (ODDS = 3.4, p = 0.014) were risk factors for mortality at 90 days whereas epilepsy (ODDS = 0.2, p = 0.014) and Glasgow Outcome Scale (GOS) > 3 at hospital discharge (ODDS = 0.05, p = 0.006) were protective factors. Risk factors for mortality at 1 year were STESS >4 (ODDS = 5.1, p = 0.028), use of vasopressors (ODDS = 8.2, p = 0.049), and worse-than-baseline condition at discharge (ODDS = 7.8, p = 0.010) while GOS >3 (ODDS = 0.2, p = 0.005) was protective. The univariate survival analysis at 1 year confirmed the significant findings regarding parameters STESS >4 (Hazard ratio (HR) = 4.1, p = 0.009), worse-than-baseline condition (HR = 6.2, p = 0.015), GOS >3 (HR = 0.2, p = 0.004) at hospital discharge and epilepsy (HR = 0.4, p = 0.044). Additionally, diagnostic delay over 6 h (HR = 3.8, p = 0.022) and Complication Burden Index (CBI) as an ordinal variable (0-2, 3-6, >6) (HR = 2.7, p = 0.027) were predictive for mortality. In the multivariate survival analysis, STESS > 4 ( HR = 5.1, p = 0.007), CBI (HR = 3.2, p = 0.025, ordinal variable), diagnostic delay over 6 h (HR = 7.2, p = 0.003), and worse-than-baseline condition at hospital discharge (HR = 5.8, p = 0.027) were all independent risk factors for mortality at 1 year. Conclusions: Severe form of SE, delayed recognition of GCSE, high number of complications during treatment period, and poor condition at hospital discharge are all independent predictors of long-term mortality. Most of these factors are also associated with mortality at 90 days, though at that point, delays in treatment seem to have a greater impact on prognosis than at 1 year. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures (c) 2019 Elsevier Inc. All rights reserved.Peer reviewe

Early clinical features of new-onset refractory status epilepticus (NORSE) in adults

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Associations between cognition and employment outcomes after epilepsy surgery

Objectives: Previous studies have shown that younger age, higher education, and seizure freedom after epilepsy surgery are associated with employment. However, very few studies have investigated associations with cognition and employment status in epilepsy surgery patients.Methods: This retrospective study consists of 46 adult patients, who underwent resective epilepsy surgery in the Helsinki University Hospital between 2010 and 2018 and who had been assessed by a neuropsychologist prior to surgery and 6 months after surgery using a systematic test battery. In addition to neuropsychological evaluation, neurologists assessed the patients prior to surgery and followed up the patients up to 24 months after the surgery and evaluated work status of the patients. Logistic regression models were used to assess the effects of cognition on changes in employment status, while controlling for age and education. Results: Out of the 46 patients 38 (82.6%) were seizure free and 7 (15.2%) had their seizures reduced 2 years postsurgically. From prior to surgery to 2 years postsurgery, use of antiseizure medication was reduced in most of the patients, mean reduction of the dosage being 26.9%. Employment status improved in 10 (21.7%) patients, remained unchanged in 27 (58.7%) and worsened in 3 (6.5%). An additional 6 patients were already not working prior to surgery. Subsequent analyses are based on the subsample of 37 patients whose employment status improved or remained unchanged. Mistakes in executive function tasks (p = 0.048) and working memory performance (p = 0.020) differentiated between the group whose employment status remained similar and those who were able to improve their employment status. Epilepsy surgery outcome or changes in antiseizure medication (ASM) use were not associated with changes in employment status.Conclusions: In the subsample of 37 patients, errors in executive function tasks and poorer working memory differentiated patients whose employment status did not change from those patients who could improve their employment status. Problems in executive function and working memory tasks might hinder performance in a complex work environment. When assessing the risks and opportunities in returning to work after surgery, difficulties in working memory and executive function performance should be taken into consideration as they may predispose the patient to challenges at work.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Fatal Tick-Borne Encephalitis Virus Infections Caused by Siberian and European Subtypes, Finland, 2015

In most locations except for Russia, tick-borne encephalitis is mainly caused by the European virus subtype. In 2015, fatal infections caused by European and Siberian tick-borne encephalitis virus subtypes in the same Ixodes ricinus tick focus in Finland raised concern over further spread of the Siberian subtype among widespread tick species.Peer reviewe

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 < 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

Focal atrophy of the unilateral masticatory muscles caused by pure trigeminal motor neuropathy : case report

Key Clinical Message Patients with unknown clinical or radiological asymmetry in the face structures combined with atrophy and weakness of the masticatory muscles should be comprehensively examined clinically and with MRI, neurophysiological measurements, and serologically. Malignant lesions or benign idiopathic unilateral trigeminal motor neuropathy should be considered as an etiological explanation for the asymmetry.Peer reviewe