Sodium and water perturbations in patients who had an acute stroke: clinical relevance and management strategies for the neurologist

Sodium and water perturbations, manifesting as hyponatraemia and hypernatraemia, are common in patients who had an acute stroke, and are associated with worse outcomes and increased mortality. Other non-stroke-related causes of sodium and water perturbations in these patients include underlying comorbidities and concomitant medications. Additionally, hospitalised patients who had an acute stroke may receive excessive intravenous hypotonic solutions, have poor fluid intake due to impaired neurocognition and consciousness, may develop sepsis or are administered drugs (eg, mannitol); factors that can further alter serum sodium levels. Sodium and water perturbations can also be exacerbated by the development of endocrine consequences after an acute stroke, including secondary adrenal insufficiency, syndrome of inappropriate antidiuretic hormone secretion and diabetes insipidus. Recently, COVID-19 infection has been reported to increase the risk of development of sodium and water perturbations that may further worsen the outcomes of patients who had an acute stroke. Because there are currently no accepted consensus guidelines on the management of sodium and water perturbations in patients who had an acute stroke, we conducted a systematic review of the literature published in English and in peer-reviewed journals between January 2000 and December 2020, according to PRISMA guidelines, to assess on the current knowledge and clinical practices of this condition. In this review, we discuss the signs and symptoms of hyponatraemia and hypernatraemia, the pathogenesis of hyponatraemia and hypernatraemia, their clinical relevance, and we provide our recommendations for effective treatment strategies for the neurologist in the management of sodium and water perturbations in commonly encountered aetiologies of patients who had an acute stroke.

Effect of haemodynamics on the risk of ischaemic stroke in patients with severe vertebral artery stenosis

ObjectivesEndovascular treatment strategies to optimise individualised care for patients with vertebral artery (VA) stenosis need to be revisited. This study aimed to investigate the relationship between net VA flow volume (NVAFV) and the risk of posterior circulation infarction (PCI) in a high-risk patient population.MethodsWe screened 1239 patients with extracranial VA stenosis, of whom 321 patients with severe VA V1 segment stenosis (≥70%) were enrolled in our study. We restratified the patients based on NVAFV and contralateral VA stenosis grades to analyse the proportion of each PCI mechanism—large artery atherosclerosis and branch artery occlusive disease. Furthermore, we estimated the incidence of recurrent ischaemic stroke between groups with different NVAFV over a follow-up period of 2 years.ResultsNVAFV was lower in the PCI group. Multiple logistic regression analysis showed that NVAFV is an independent risk factor for PCI and that the OR for PCI for the lowest NVAFV (<112.8 mL/min) was 4.19 (1.76 to 9.95, p=0.001). In patients with severe carotid artery disease, the OR for the lowest NVAFV was 14.03 (3.18 to 61.92, p<0.001). The lower NVAFV group had a higher incidence of recurrent ischaemic stroke events than the higher NVAFV group (HR 2.978, 95% CIs 1.414 to 6.272).ConclusionOur study demonstrated that NVAFV, as estimated by colour duplex ultrasonography, was associated with the incidence of PCI and subsequent ischaemic events and that a high-risk population could be identified for further posterior circulation revascularisation.

Mobile stroke care expedites intravenous thrombolysis and endovascular thrombectomy

BackgroundThe number of mobile stroke programmes has increased with evidence, showing they expedite intravenous thrombolysis. Outstanding questions include whether time savings extend to patients eligible for endovascular therapy and impact clinical outcomes.ObjectiveOur mobile stroke unit (MSU), based at an academic medical centre in upstate New York, launched in October 2018. We reviewed prospective observational data sets over 26 months to identify MSU and non-MSU emergency medical service (EMS) patients who underwent intravenous thrombolysis or endovascular thrombectomy for comparison of angiographic and clinical outcomes.ResultsOver 568 days in service, the MSU was dispatched 1489 times (2.6/day) and transported 300 patients (20% of dispatches). Intravenous tissue plasminogen activator (tPA) was administered to 57 MSU patients and the average time from 911 call-to-tPA was 42.5 min (±9.2), while EMS transported 73 patients who received tPA at 99.4 min (±35.7) (p<0.001). Seven MSU patients (12%) received tPA from 3.5 hours to 4.5 hours since last known well and would likely have been outside the window with EMS care. Endovascular thrombectomy was performed on 21 MSU patients with an average 911 call-to-groin puncture time of 99.9 min (±18.1), while EMS transported 54 patients who underwent endovascular thrombectomy (ET) at 133.0 min (±37.0) (p=0.0002). There was no difference between MSU and traditional EMS in modified Rankin score at 90-day clinic follow-up for patients undergoing intravenous thrombolysis or endovascular thrombectomy, whether assessed as a dichotomous or ordinal variable.ConclusionsMobile stroke care expedited both intravenous thrombolysis and endovascular thrombectomy. There is an ongoing need to show improved functional outcomes with MSU care.

Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion

Background and purposeIt remains controversial if endovascular treatment (EVT) can improve the outcome of patients with acute basilar artery occlusion (BAO). This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis (IVT) first in patients who had acute ischaemic stroke (AIS) due to BAO.MethodsPatients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study, and the efficacy and safety were compared between IVT+EVT and direct EVT. The primary outcome was 90-day functional independence. All outcomes were assessed with adjusted OR (aOR) from the multivariable logistic regression. In addition, a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO.ResultsOf 310 enrolled patients with BAO, 241 (78%) were treated with direct EVT and 69 (22%) with IVT+EVT. Direct EVT was associated with a worse functional outcome (aOR, 0.46 (95% CI 0.24 to 0.85), p=0.01). IVT+EVT was associated with a lower percentage of patients who needed ≥3 passes of stent retriever (10.14% vs 20.75%). The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence (r=0.14 (95% CI 0.05 to 0.24), p<0.01).ConclusionsThis study showed that compared with direct EVT, EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset. The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.

Incidence, prevalence and risk of stroke in patients with Takayasu arteritis: a nationwide population-based study in South Korea

BackgroundTakayasu arteritis (TAK) is a disease associated with increased risk of cardiovascular complications. We aimed to evaluate the incidence, prevalence and risk of stroke in patients with TAK.MethodsData from 1065 patients were obtained from a national database (2010–2018). The annual incidence and prevalence per 100 000 persons were estimated using the registration population in the midst of every year, and the standardised incidence ratio (SIR) of stroke was compared with the general population based on the data from the 2006 national report for cardiovascular and cerebrovascular diseases. Age-adjusted incidence rate ratio (IRR) of stroke based on the time interval after diagnosis was also calculated. A time-dependent Cox regression was conducted to investigate predictive factors of stroke.ResultsThe overall incidence rate of TAK ranged between 0.2 and 0.3/100 000 person-years annually; the prevalence of TAK gradually increased, reaching 3.25/100 000 person-years in 2018. Seventy-three (6.9%) patients experienced stroke during follow-up, and the risk of developing stroke was higher than the general population (overall SIR 7.39, 95% CI 5.79 to 9.29; men: SIR 5.70, 95% CI 2.84 to 10.20; women: SIR 7.06, 95% CI 5.41 to 9.05). Most stroke events (90.9%) were cerebral infarction for men, whereas the proportion of cerebral infarction was lower (62.9%) in women. Over half of stroke events occurred within 6 months after diagnosis, and stroke was more common within 6 months of diagnosis compared with after 3 years in women (IRR 13.46, 95% CI 6.86 to 26.40). In Cox regression analysis, age was the sole predictor of stroke (adjusted HR 1.02, 95% CI 1.00 to 1.04, p=0.043).ConclusionsThe annual incidence of TAK was similar to the previous studies from Asia, and the risk of stroke increased in TAK. Different patterns of subtype and incidence of stroke were found according to sex, although age was the only predictor.

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease

ObjectivesThe predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.MethodsUnrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis.ResultsAmong 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.ConclusionsOur GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

Childhood strokes in China describing clinical characteristics, risk factors and performance indicators: a case-series study

AimTo investigate clinical characteristics, risk factors (RFs), neurologic deficits and medical care provided in children who had a stroke in China.MethodsWe conducted a retrospective case-series study using the medical records of children aged 1 month to 18 years with arterial ischaemic stroke (AIS) or haemorrhagic stroke (HS) (with the entry codes I60, I61, I62, I63 (ICD-10)), who were admitted to different hospitals in Beijing, between January 2018 and December 2018. We obtained the following information from the charts: demographic characteristics, clinical presentations, RFs for paediatric stroke, laboratory examination, neuroimaging records and neurologic sequelae.ResultsWe identified 312 first admissions for stroke (172 AIS and 140 HS). The mean age at onset was 8.6±3.9 years for patients who had an AIS and 8 (5–13) years for patients who had an HS. There were more males than females in both groups (AIS: 59.88% vs 40.12%; HS: 52.14% vs 47.86%). A known aetiology was identified in 92.44% and 86.43% of patients who had an AIS and HS, respectively. The leading cause of AIS was cerebrovascular diseases including moyamoya (68.6%), while that for HS was arteriovenous malformation (51.43%). The most common initial clinical presentation was hemiplegia (86.05%) in patients who had an AIS and headache (67.86%) in patients who had an HS. The use of healthcare, including acute treatment (antithrombotic in 17.44%, anticoagulant in 5.23%) and secondary prevention (antithrombotic in 6.39%, anticoagulant in 1.16%), varied and was significantly lower among patients who had an AIS. The most common complications were epilepsy (22.09%) and pneumonia (4.65%) in patients who had an AIS and epilepsy (17.14%) and hydrocephalus (12.14%) in patients who had an HS. Neurological deficits occurred in 62.8% of patients who had an AIS and 72.86% of patients who had an HS.ConclusionCerebral arteriopathy was a major RF for both AIS and HS in children living in China. Large epidemiological studies are required to identify RFs to prevent stroke as well as appropriate interventions.

Risk factors for carotid plaque progression after optimising the risk factor treatment: substudy results of the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the carotid Bifurcation Plaque Study (ANTIQUE)

Background and aimCarotid plaque progression contributes to increasing stroke risk. The study aims to identify factors influencing carotid plaque thickness progression after changing the preventive treatment to the ‘treating arteries instead of risk factors’ strategy, that is, change in treatment depending on the progression of atherosclerosis.MethodsThe study participants who completed sonographic controls over the course of 3 years were enrolled to the analysis. Duplex sonography of cervical arteries was performed in 6-month intervals with measurement of carotid plaque thickness. Plaque thickness measurement error (σ) was set as 3 SD. Only evidently stable and progressive plaques (defined as plaque thickness difference between initial and final measurements of ˂σ and >2σ, respectively) were included to analysis. Univariate and multivariate logistic regression analysis was performed to identify factors influencing plaque progression.ResultsA total of 1391 patients (466 males, age 67.2±9.2 years) were enrolled in the study. Progressive plaque in at least one carotid artery was detected in 255 (18.3%) patients. Older age, male sex, greater plaque thickness, coronary heart disease, vascular surgery/stenting history and smoking were more frequently present in patients with progressive plaque (p˂0.05 in all cases). Multivariate logistic regression analysis identified only the plaque thickness (OR 1.850 for left side, 95% CI 1.398 to 2.449; and OR 1.376 for right side, 95% CI 1.070 to 1.770) as an independent factor influencing plaque progression.ConclusionCarotid plaque thickness corresponding to stenosis severity is the only independent risk factor for plaque thickness progression after optimising the prevention treatment.Trial registration numberNCT02360137.

Night-time diastolic blood pressure variability relates to stroke recurrence in patients who had ischaemic stroke with small artery occlusion

Background and purposeThe association between blood pressure variability (BPV) and stroke recurrence among patients who had ischaemic stroke (IS) remains unclear. This study aimed to investigate the association between BPV and stroke recurrence in patients who had IS of large artery atherosclerosis (LAA) subtype and small artery occlusion (SAO) subtype.MethodsData from the BOSS (Blood Pressure and Clinical Outcome in Transient Ischemic Attack or Ischemic Stroke) study were examined. IS subtypes were diagnosed according to the Trial of Org 10172 in Acute Stroke Treatment criteria. BPV was performed by 24-hour ambulatory blood pressure monitoring and defined through SD of blood pressure. The primary outcome was stroke recurrence within 90 days after discharge. Multivariable Cox regression model was used to assess the association between BPV and stroke recurrence in patients who had IS of LAA subtype and SAO subtype.ResultsA total of 1390 patients who had IS from the BOSS study were included in the present study. Multivariable analysis suggests that 24-hour systolic BPV (SBPV) and night-time diastolic BPV (DBPV) were significantly associated with stroke recurrence among all patients who had IS (HR, 2.50, 95% CI 1.07 to 5.84; HR, 1.85, 95% CI 1.07 to 3.21, respectively). Night-time SBPV and night-time DBPV were significantly associated with stroke recurrence in patients with SAO subtype (HR, 2.77, 95% CI 1.07 to 7.15; HR, 3.60, 95% CI 1.39 to 9.29, respectively). However, in the adjusted model, only night-time DBPV remained significant in patients with SAO subtype (HR, 3.87, 95% CI 1.40 to 10.71). Similar results were not found in patients who had IS of LAA subtype.ConclusionsHigh night-time DBPV was associated with increased risk of stroke recurrence among patients who had IS of SAO subtype. The results of this study have implications for the secondary prevention management and future research of patients who had IS of SAO subtype. The association between BPV and stroke recurrence in patients who had IS of LAA subtype and SAO subtype should be investigated in larger, population-based studies.

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

RationaleHaematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.Methods and designStopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.HypothesisIn patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimatesA sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.InterventionParticipants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.Primary efficacy measureThe primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.DiscussionWe describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.