Influence of including patients with pre-morbid disability in acute stroke trials : The HeadPoST experience

Background: Patients with premorbid functional impairment are generally excluded from acute stroke trials. We aimed to determine the impact of including such patients in the Head Positioning in acute Stroke Trial (HeadPoST) and early additional impairment on outcomes. Methods: Post hoc analyses of HeadPoST, an international, cluster-randomized crossover trial of lying-flat versus sitting-up head positioning in acute stroke. Associations of early additional impairment, defined as change in modified Rankin scale (mRS) scores from premorbid levels (estimated at baseline) to Day 7 (“early ΔmRS”), and poor outcome (mRS score 3–6) at Day 90 were determined with generalized linear mixed model. Heterogeneity of the trial treatment effect was tested according to premorbid mRS scores 0–1 versus 2–5. Results: Of 8,285 patients (38.9% female, mean age 68 ± 13 years) with complete data, there were 1,984 (23.9%) with premorbid functional impairment (mRS 2–5). A significant linear association was evident for early ∆mRS and poor outcome (per 1-point increase in ΔmRS, adjusted odds ratio 1.20, 95% confidence interval 1.14–1.27; p < 0.0001). Patients with greater premorbid functional impairment were less likely to develop additional impairment, but their risk of poor 90-day outcome significantly increased with increasing (worse) premorbid mRS scores (linear trend p < 0.0001). There was no heterogeneity of the trial treatment effect by level of premorbid function. Conclusions: Early poststroke functional impairment that exceeded premorbid levels was associated with worse 90-day outcome, and this association increased with greater premorbid functional impairment. Yet, including premorbid impaired patients in the HeadPoST did not materially affect the subsequent treatment effect. Clinical Trial Registration: HeadPoST is registered at http://www.ClinicalTrials.gov (NCT02162017)

Lipid-lowering pretreatment and outcome following intravenous thrombolysis for acute ischaemic stroke: a post hoc analysis of the enhanced control of hypertension and thrombolysis stroke study trial

Background: Debate exists as to whether statin pretreatment confers an increased risk of 90-day mortality and symptomatic intracranial haemorrhage (sICH) in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis. We assessed the effects of undifferentiated lipid-lowering pretreatment on outcomes and interaction with low-dose versus standard-dose alteplase in a post hoc subgroup ­analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study. Methods: In all, 3,284 thrombolysis-eligible AIS patients (mean age 66.6 years; 38% women), with information on lipid-lowering pretreatment, were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 h of symptom onset. Of the total number of patients, 615 (19%) received statin or other lipid-lowering pretreatment. The primary clinical outcome was combined endpoint of death or disability (modified Rankin Scale scores 2–6) at 90 days. Results: Compared with patients with no lipid-lowering pretreatment, those with lipid-lowering pretreatment were significantly older, more likely to be non-Asian and more likely to have a medical history including vascular co-morbidity. After propensity analysis assessment and adjustment for important baseline variables at the time of randomisation, as well as imbalances in management during the first 7 days of hospital admission, there were no significant differences in mortality (OR 0.85; 95% CI 0.58–1.25, p = 0.42), or in overall ­90-day death and disability (OR 0.85, 95% CI 0.67–1.09, p = 0.19), despite a significant decrease in sICH among those with ­lipid-lowering pretreatment according to the European Co-operative Acute Stroke Study 2 definition (OR 0.49, 95% CI 0.28–0.83, p = 0.009). No differences in key efficacy or safety outcomes were seen in patients with and without lipid-lowering pretreatment between low- and standard-dose alteplase arms. Conclusions: Lipid-lowering pretreatment is not associated with adverse outcome in AIS patients treated with intravenous alteplase, whether assessed by 90-day death and disability or death alone

Influence of Including Patients with Premorbid Disability in Acute Stroke Trials: The HeadPoST Experience

Patients with premorbid functional impairment are generally excluded from acute stroke trials. We aimed to determine the impact of including such patients in the Head Positioning in acute Stroke Trial (HeadPoST) and early additional impairment on outcomes. Post hoc analyses of HeadPoST, an international, cluster-randomized crossover trial of lying-flat versus sitting-up head positioning in acute stroke. Associations of early additional impairment, defined as change in modified Rankin scale (mRS) scores from premorbid levels (estimated at baseline) to Day 7 ("early ΔmRS"), and poor outcome (mRS score 3-6) at Day 90 were determined with generalized linear mixed model. Heterogeneity of the trial treatment effect was tested according to premorbid mRS scores 0-1 versus 2-5. Of 8,285 patients (38.9% female, mean age 68 ± 13 years) with complete data, there were 1,984 (23.9%) with premorbid functional impairment (mRS 2-5). A significant linear association was evident for early ∆mRS and poor outcome (per 1-point increase in ΔmRS, adjusted odds ratio 1.20, 95% confidence interval 1.14-1.27; p < 0.0001). Patients with greater premorbid functional impairment were less likely to develop additional impairment, but their risk of poor 90-day outcome significantly increased with increasing (worse) premorbid mRS scores (linear trend p < 0.0001). There was no heterogeneity of the trial treatment effect by level of premorbid function. Early poststroke functional impairment that exceeded premorbid levels was associated with worse 90-day outcome, and this association increased with greater premorbid functional impairment. Yet, including premorbid impaired patients in the HeadPoST did not materially affect the subsequent treatment effect. HeadPoST is registered at http://www.ClinicalTrials.gov (NCT02162017). [Abstract copyright: © 2021 S. Karger AG, Basel.

Posterior circulation collaterals as predictors of outcome in basilar artery occlusion: a sub-analysis of the BASICS randomized trial

Introduction and purposeBasilar artery occlusion (BAO) is still one of the most devastating neurological conditions associated with high morbidity and mortality. In the present study, we aimed to assess the role of posterior circulation collaterals as predictors of outcome in the BASICS trial and to compare two grading systems (BATMAN score and PC-CS) in terms of prognostic value.MethodsWe performed a sub-analysis of the BASICS trial. Baseline clinical and imaging variables were analyzed. For the imaging analysis, baseline CT and CTA were analyzed by a central core lab. Only those patients with good or moderate quality of baseline CTA and with confirmed BAO were included. Multivariable binary logistic regression analysis was used to test the independent association of clinical and imaging characteristics with a favorable outcome at 3 months (defined as a modified Rankin Score of ≤3). ROC curve analysis was used to assess and compare accuracy between the two collateral grading systems.ResultsThe mean age was 67.0 (±12.5) years, 196 (65.3%) patients were males and the median NIHSS was 21.5 (IQR 11–35). Median NCCT pc-ASPECTS was 10 (IQR10-10) and median collateral scores for BATMAN and PC-CS were 8 (IQR 7–9) and 7 (IQR 6–8) respectively. Collateral scores were associated with favorable outcome at 3 months for both BATMAN and PC-CS but only with a modest accuracy on ROC curve analysis (AUC 0.62, 95% CI [0.55–0.69] and 0.67, 95% CI [0.60–0.74] respectively). Age (OR 0.97, 95% CI [0.95–1.00]), NIHSS (OR 0.91, 95% CI [0.89–0.94]) and collateral score (PC-CS – OR 1.2495% CI [1.02–1.51]) were independently associated with clinical outcome.ConclusionThe two collateral grading systems presented modest prognostic accuracy. Only the PC-CS was independently associated with a favorable outcome at 3 months

Leigh-like syndrome with the T8993G mutation in the mitochondrial ATPase 6 gene: long-term follow-up discloses a slowly progressive course

We describe the long-term clinical outcome of a patient with Leigh-like syndrome presenting as an early onset encephalopathy and peripheral neuropathy caused by the T8993G mutation in the mitochondrial DNA (mtDNA). Clinical follow-up for 20 years revealed a peculiar pattern of slow disease progression, characterized by the addition of new minor deficits, while worsening of previous symptoms was mild. Brain MRI revealed cerebellar atrophy, diffuse demyelination of corona radiata and parietal white matter, and bilateral and symmetrical putaminal lesions. The proportion of mutant mtDNAs in blood was 72% (+/- 0.02%) and in skeletal muscle was 81% (+/- 0.4%). Leigh-like syndrome caused by the T8993G mtDNA mutation is a progressive disease, although not necessarily associated with an aggressive clinical course. (C) 2009 Elsevier B.V. All rights reserved.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[98/14928-3

Predictors of quality of life after moderate to severe traumatic brain injury

ABSTRACT Objective To verify correlations between age, injury severity, length of stay (LOS), cognition, functional capacity and quality of life (QOL) six months after hospital discharge (HD) of victims of traumatic brain injury (TBI). Method 50 patients consecutively treated in a Brazilian emergency hospital were assessed at admission, HD and six months after HD. The assessment protocol consisted in Abbreviated Injury Scale, Injury Severity Score, Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), Mini Mental Test, Barthel Index and World Health Organization QOL - Brief. Results Strong negative correlation was observed between LOS and GCS and LOS and RTS. An almost maximal correlation was found between RTS and GCS and functional capacity and GCS at HD. Age and LOS were considered independent predictors of QOL. Conclusion Age and LOS are independent predictors of QOL after moderate to severe TBI