Stroke of the Visual Cortex

Stroke is the leading cause of homonymous visual field defect (VFD), resulting from irreversible damage of the post-chiasmatic visual pathway. From 6 to 13% of ischaemic strokes affect the supply area of the posterior cerebral artery, including the visual cortex in the occipital lobe. Besides ischaemic injury, the visual cortex can be damaged by intracerebral haemorrhage (ICH), 10% of which reside in the occipital lobe. Since occipital stroke almost always disturbs vision but can leave motor and language functions untouched, it may remain unrecognised in the acute phase, withholding the patients from receiving recanalisation treatments. Moreover, only up to 25% of stroke-related VFD recover spontaneously, whereas the rest continue to hinder patients’ independence in daily living and quality of life. Despite rigorous efforts, no evidence-based rehabilitation method to restore vision after stroke has been established. The aim of this thesis was to study the recognition, clinical characteristics, rehabilitation, neural mechanisms, and outcome of occipital stroke patients with VFD. The retrospective part of the thesis consists of two cohorts. The first cohort comprised 245 occipital ischaemic stroke patients admitted to the neurological emergency department of Helsinki University Hospital due to visual symptoms in 2010‒2015. We investigated their prehospital recognition and diagnostic delays and analysed the obstacles in their access to acute stroke treatment. The second retrospective cohort was the Helsinki ICH Study registry of 1013 consecutive non-traumatic ICH patients treated at Helsinki University Hospital in 2005‒2010, among whom we searched for isolated occipital ICH patients and analysed their clinical characteristics, aetiology, outcome, and incidence of post-stroke epilepsy in comparison to ICHs of other location. The prospective part of the thesis was based on the multicentre, randomised, sham-controlled exploratory REVIS (Restoration of Vision after Stroke) trial that studied rehabilitation of persistent VFD after chronic occipital stroke with different methods of non-invasive electrical brain stimulation. Altogether 56 patients were included in three 10-day experiments in three centres. The centres examined: 1) repetitive transorbital alternating current stimulation (rtACS) vs transcranial direct current stimulation preceding rtACS (tDCS/rtACS) vs sham in Germany, 2) rtACS vs sham in Finland, and 3) tDCS vs sham in Italy. In a functional magnetic resonance imaging spin-off study, resting-state functional connectivity of occipital stroke patients receiving rtACS or sham was compared to healthy control subjects at baseline and to each other after intervention. We found out that the prehospital delay of occipital stroke patients ranged between 20 minutes and 5 weeks and only 20% were admitted within the 4.5-hour time window of intravenous thrombolysis. Consequently, only 6.5% received thrombolysis, which is the mainstay of acute stroke treatment. One fourth of the patients arrived through at least two points of care and as many were assessed by an ophthalmologist before entering the neurological care, even though acute stroke patients should be transported directly to the neurological emergency department. The diagnostic delay was primarily caused by the patients’ late contact to health care but was also attributed to poor recognition and misdiagnosis by health-care professionals. The incidence of isolated occipital ICH was 1.9% of all non-traumatic ICHs and 5.3% of lobar ICHs. The patients with occipital ICH were younger and had more often vascular malformations as an aetiology of the bleeding than the non-occipital lobar ICH patients. They presented with milder symptoms and longer delay, and over 60% of the patients suffered solely from visual focal symptom. The haematoma volume in the occipital lobe was smaller and grew less compared to the non-occipital lobar haemorrhages. All in all, the occipital location of ICH was independently associated with favourable outcome at discharge among the patients with lobar ICH. The majority of the occipital ICH patients were able to return to independent activities of daily living, including driving a car and working, within a follow-up of a year. However, post-stroke epilepsy was as frequent as after non-occipital lobar ICH. In the prospective REVIS trial, rtACS was mostly ineffective in vision rehabilitation according to behavioural vision tests. Neither did it affect resting-state functional connectivity in comparison to sham. Transcranial DCS alone increased the monocular visual field measured with standard automated perimetry. The combined tDCS/rtACS propelled some improvements in the secondary visual outcome measures but did not differ from the sham stimulation. All the stimulation modalities were tolerated well. The functional connectivity of the chronic occipital stroke patients with VFD did not differ from the healthy control subjects when the whole brain network was considered in the analyses. However, a few occipital regions close to the infarct expressed lower local connectivity to the highly connected regions of the network according to the network graph metrics, whereas a lateral occipital region in the damaged hemisphere had higher network connectivity. These findings support the view that chronic ischaemic damage of the visual cortex affects functional connectivity within the visual network but leaves global connectivity unchanged. In conclusion, occipital stroke patients are insufficiently recognised, and thus the awareness of visual stroke symptoms should be raised especially among the public but also among health-care professionals to provide the patients with timely acute treatment and to prevent permanent disability. Occipital ICH patients have relatively favourable outcomes, but a structural cause of bleeding should be searched. Non-invasive electrical brain stimulation with the examined modalities does not cause robust improvement in vision or functional connectivity of the brain networks after a 10-day treatment, but further experiments with tDCS-based methods, potentially in combination with vision training, may be worth pursuing.Ihmisen näköaivokuori sijaitsee pääosin takaraivolohkossa ja sen vaurio johtaa tyypillisesti molempien silmien toispuoleiseen näkökenttäpuutokseen. Yleisin syy vaurioon on aivoverenkiertohäiriö: joko aivovaltimon tukoksesta johtuva infarkti tai verisuonen repeämästä aiheutuva aivoverenvuoto. Näkökenttäpuutos alentaa toiminta-, työ- ja ajokykyä ja heikentää elämänlaatua. Alle neljäsosa näkökenttäpuutoksista paranee täysin, eikä niiden kuntouttamiseksi ole kliiniseen käyttöön vakiintunutta menetelmää. Väitöskirjatyössä tutkittiin näköaivokuoren aivoverenkiertohäiriöiden tunnistamista, kliinistä kuvaa, kuntoutusta ja ennustetta. Tutkimuksessa selvisi, että ainoastaan 20,8 % HUS:in neurologian päivystyksessä vuosina 2010–2015 hoidetuista, näköoirein ilmenneen takaraivolohkon infarktin saaneista potilaista tuli hoitoon liuotushoidon mahdollistavassa aikaikkunassa ja vain 6,5 % sai liuotuksen. Viiveen yleisin syy oli potilaiden hidas hakeutuminen hoitoon, mutta kolmasosassa tapauksista myöskään terveydenhuoltohenkilökunta ei aluksi tunnistanut oireiden johtuvan aivoverenkiertohäiriöstä. Takaraivolohkoon rajautuvia aivoverenvuotoja esiintyi 1,9 %:lla HUS:issa 2005–2010 hoidetusta 1013 aivoverenvuotopotilaasta. Potilaat olivat nuorempia ja lieväoireisempia kuin muut vuotopotilaat, ja heidän vuotonsa johtuivat useammin verisuoniepämuodostumista. Vuodon sijainti takaraivolohkossa ennusti parempaa toimintakykyä sairaalasta kotiutuessa, ja suurin osa potilaista toipui vuoden sisällä päivittäistoiminnoissa itsenäisiksi. Epilepsian ilmaantuvuus ei eronnut pitkäaikaisseurannassa muista aivoverenvuotopotilaista. Satunnaistetussa, lumekontrolloidussa REVIS-monikeskustutkimuksessa selvitettiin kajoamattomien, heikkoa sähkövirtaa hyödyntävien stimulaatiomenetelmien tehoa takaraivolohkon aivoinfarktin aiheuttaman kroonisen näkökenttäpuutoksen kuntoutuksessa. Hoitokokeessa tasavirtastimulaatio (tDCS) pienensi vaurion vastapuoleisen silmän näkökenttäpuutosta verrattuna lumehoitoon, kun taas vaihtovirtastimulaatio (rtACS) oli tehotonta. Myöskään näiden yhdistelmällä (tDCS/rtACS) tulokset eivät eronneet lumeesta. Lisäksi toiminnallisella magneettikuvauksella tutkittiin 16 takaraivolohkon aivoinfarktipotilaan lepohermoverkostojen toiminnallista kytkeytyvyyttä verrattuna terveisiin koehenkilöihin. Tutkimus paljasti paikallisia muutoksia kytkeytyvyydessä potilaiden näköinformaation käsittelyyn osallistuvilla aivoalueilla, mutta laajemmin verkostojen toiminta ei eronnut verrokeista. Vaihtovirtastimulaatio ei muuttanut toiminnallista kytkeytyvyyttä

Prehospital pathways of occipital stroke patients with mainly visual symptoms

ObjectivesOccipital ischemic strokes typically cause homonymous visual field defects, for which means of rehabilitation are limited. Intravenous thrombolysis is increasingly and successfully used for their acute treatment. However, recognition of strokes presenting with mainly visual field defects is challenging for both patients and healthcare professionals. We studied prehospital pathways of occipital stroke patients with mainly visual symptoms to define obstacles in their early recognition. Materials & methodsThis observational, retrospective, registry-based study comprises occipital stroke patients with isolated visual symptoms treated at the neurological emergency department of Helsinki University Central Hospital in 2010-2015. We analyzed their prehospital pathways, including time from symptom onset to admission at the neurological emergency department (ODT), the number of points of care, the percentage of patients with ODT4.5hours, and factors associated with delay. ResultsAmong 245 patients, only 20.8% arrived within 4.5hours and 6.5% received IV thrombolysis. Delayed arrival was most often due to patients' late contact to health care. Of the patients, 27.3% arrived through at least two points of care, and differential diagnostics to ophthalmologic disorders proved particularly challenging. ODT4.5hours was associated with EMS utilization, direct arrival, and atrial fibrillation; a visit at an ophthalmologist and initial misdiagnosis were associated with ODT>4.5hours. After multivariable analysis, only direct arrival predicted ODT4.5hours. ConclusionsOccipital stroke patients with visual symptoms contact health care late, are inadequately recognized, and present with complex prehospital pathways. Consequently, they are often ineligible for IV thrombolysis. This presents a missed opportunity for preventing permanent visual field defects.Peer reviewe

Clinical frailty and outcome after mechanical thrombectomy for stroke in patients aged > 80 years

Objectives: Data concerning the results of endovascular thrombectomy (EVT) in old patients is still limited. We aimed to investigate the outcomes in thrombectomytreated ischemic stroke patients aged > 80 years, focusing on frailty as a contributing factor. Patients and methods: We performed a single-centre retrospective cohort study with 159 consecutive patients aged > 80 years and treated with EVT for acute ischemic stroke between January 1st 2016 and December 31st 2019. Pre-admission frailty was assessed with the Clinical Frailty Scale (CFS). Patients with CFS > 5 were defined as frail. The main outcome was very poor outcome defined as mRS 46 at three months after EVT. Secondary outcomes were recanalization status, symptomatic intracerebral haemorrhage (sICH), and one-year survival. Finally, we recorded if the patient returned home within 12 months. Results: Very poor outcome was observed in 57.9% of all patients (52.4% in non-frail and 79.4% in frail patients). Rates of recanalization and sICH were comparable in frail and non-frail patients. Of all patients, 46.5% were able to live at home within 1 year after stroke. One-year survival was 59.1% (65.6% in non-frail and 35.3% in frail patients). In logistic regression analysis higher admission NIHSS, not performing thrombolysis, lack of recanalization and higher frailty status were all independently associated with very poor three-month outcome. Factors associated with one-year mortality were male gender, not performing thrombolysis, sICH, and higher frailty status. Conclusion: Almost 60% of studied patients had very poor outcome. Frailty significantly increases the likelihood of very poor outcome and death after EVT-treated stroke.(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

Hemicraniectomy for Dominant vs Nondominant Middle Cerebral Artery Infarction : A Systematic Review and Meta- Analysis

Objectives: Decompressive hemicraniectomy decreases mortality and severe disabil-ity from space-occupying middle cerebral artery infarction in selected patients. However, attitudes towards hemicraniectomy for dominant-hemispheric stroke have been hesitant. This systematic review and meta-analysis examines the associa-tion of stroke laterality with outcome after hemicraniectomy. Materials and methods: We performed a systematic literature search up to 6th February 2020 to retrieve original articles about hemicraniectomy for space-occupying middle cere-bral artery infarction that reported outcome in relation to laterality. The primary outcome was severe disability (modified Rankin Scale 4-6 or 5-6 or Glasgow Out -come Scale 1-3) or death. A two-stage combined individual patient and aggregate data meta-analysis evaluated the association between dominant-lateralized stroke and (a) short-term ( 3 months) outcome. We per -formed sensitivity analyses excluding studies with sheer mortality outcome, sec -ond-look strokectomy, low quality, or small sample size, and comparing populations from North America/Europe vs Asia/South America. Results: The analysis included 51 studies (46 observational studies, one nonrandomized trial, and four randomized controlled trials) comprising 2361 patients. We found no asso-ciation between dominant laterality and unfavorable short-term (OR 1.00, 95% CI 0.69-1.45) or long-term (OR 1.01, 95% CI 0.76-1.33) outcome. The results were unchanged in all sensitivity analyses. The grade of evidence was very low for short -term and low for long-term outcome. Conclusions: This meta-analysis suggests that patients with dominant-hemispheric stroke have equal outcome after hemicraniec-tomy compared to patients with nondominant stroke. Despite the shortcomings of the available evidence, our results do not support withholding hemicraniectomy based on stroke laterality.Peer reviewe

Recanalization treatment for acute ischemic stroke: 3-month outcome before and after implementation of routine endovascular treatment

Peer reviewe

Is the weekend effect true in acute stroke patients at tertiary stroke center?

Background: There is contradicting evidence on the outcome of emergency patients treated during weekends versus weekdays. We studied if outcome of ischemic stroke patients receiving intravenous thrombolysis (IVT) differs according to the treatment time. Methods: Our retrospective study included consecutive patients receiving IVT within 4.5 h of stroke onset between June 1995 and December 2018 at the Helsinki University Hospital. The patients were compared based on the treatment initiation either during weekdays (Monday to Friday) or weekend (Saturday and Sunday). The primary outcome was 3-month mortality and secondary outcomes comprised 3-month modified Rankin Scale (mRS) and incidence of symptomatic intracerebral hemorrhage (sICH). Additional analyses studied the effect of IVT treatment according to non-office hours, time of day, and season. Results: Of the 3980 IVT-treated patients, 28.0% received treatment during weekends. Mortality was similar after weekend (10.0%) and weekday (10.6%) admissions in the multivariable regression analysis (OR 0.78; 95% CI 0.59-1.03). Neither 3-month mRS (OR 0.98; 95% CI 0.86-1.12), nor the occurrence of sICH (4.2% vs 4.6%; OR 0.87; 95% CI 0.60-1.26) differed between the groups. No outcome difference was observed between the office vs non-office hours or by the time of day. However, odds for worse outcome were higher during autumn (OR 1.19; 95% CI 1.04-1.35) and winter (OR 1.15; 95% CI 1.01-1.30). Conclusion: We did not discover any weekend effect for IVT-treated stroke patients. This confirms that with standardized procedures, an equal quality of care can be provided to patients requiring urgent treatment irrespective of time.Peer reviewe

Effect of haemoglobin levels on outcome in intravenous thrombolysis-treated stroke patients

Introduction Alterations in haemoglobin levels are frequent in stroke patients. The prognostic meaning of anaemia and polyglobulia on outcomes in patients treated with intravenous thrombolysis is ambiguous. Patients and methods In this prospective multicentre, intravenous thrombolysis register-based study, we compared haemoglobin levels on hospital admission with three-month poor outcome (modified Rankin Scale 3-6), mortality and symptomatic intracranial haemorrhage (European Cooperative Acute Stroke Study II-criteria (ECASS-II-criteria)). Haemoglobin level was used as continuous and categorical variable distinguishing anaemia (female: 15.5 g/dl; male: >17 g/dl). Anaemia was subdivided into mild and moderate/severe (female/male:Peer reviewe

Prior Dual Antiplatelet Therapy and Thrombolysis in Acute Stroke

Non peer reviewe

Non-invasive electrical brain stimulation for vision restoration after stroke : An exploratory randomized trial (REVIS)

Background: Occipital strokes often cause permanent homonymous hemianopia leading to significant disability. In previous studies, non-invasive electrical brain stimulation (NIBS) has improved vision after optic nerve damage and in combination with training after stroke. Objective: We explored different NIBS modalities for rehabilitation of hemianopia after chronic stroke. Methods: In a randomized, double-blinded, sham-controlled, three-armed trial, altogether 56 patients with homonymous hemianopia were recruited. The three experiments were: i) repetitive transorbital alternating current stimulation (rtACS, n=8) vs. rtACS with prior cathodal transcranial direct current stimulation over the intact visual cortex (tDCS/rtACS, n=8) vs. sham (n = 8); ii) rtACS (n = 9) vs. sham (n = 9); and iii) tDCS of the visual cortex (n = 7) vs. sham (n = 7). Visual functions were evaluated before and after the intervention, and after eight weeks follow-up. The primary outcome was change in visual field assessed by high-resolution and standard perimetries. The individual modalities were compared within each experimental arm. Results: Primary outcomes in Experiments 1 and 2 were negative. Only significant between-group change was observed in Experiment 3, where tDCS increased visual field of the contralesional eye compared to sham. tDCS/rtACS improved dynamic vision, reading, and visual field of the contralesional eye, but was not superior to other groups. rtACS alone increased foveal sensitivity, but was otherwise ineffective. All trial-related procedures were tolerated well. Conclusions: This exploratory trial showed safety but no main effect of NIBS on vision restoration after stroke. However, tDCS and combined tDCS/rtACS induced improvements in visually guided performance that need to be confirmed in larger-sample trials.Peer reviewe

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial.

BACKGROUND We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER URL: https://www. CLINICALTRIALS gov ; Unique identifier: NCT03192332