Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis

OBJECTIVES Improvement of skin fibrosis is part of the natural course of diffuse cutaneous systemic sclerosis (dcSSc). Recognising those patients most likely to improve could help tailoring clinical management and cohort enrichment for clinical trials. In this study, we aimed to identify predictors for improvement of skin fibrosis in patients with dcSSc. METHODS We performed a longitudinal analysis of the European Scleroderma Trials And Research (EUSTAR) registry including patients with dcSSc, fulfilling American College of Rheumatology criteria, baseline modified Rodnan skin score (mRSS) ≥7 and follow-up mRSS at 12±2 months. The primary outcome was skin improvement (decrease in mRSS of >5 points and ≥25%) at 1 year follow-up. A respective increase in mRSS was considered progression. Candidate predictors for skin improvement were selected by expert opinion and logistic regression with bootstrap validation was applied. RESULTS From the 919 patients included, 218 (24%) improved and 95 (10%) progressed. Eleven candidate predictors for skin improvement were analysed. The final model identified high baseline mRSS and absence of tendon friction rubs as independent predictors of skin improvement. The baseline mRSS was the strongest predictor of skin improvement, independent of disease duration. An upper threshold between 18 and 25 performed best in enriching for progressors over regressors. CONCLUSIONS Patients with advanced skin fibrosis at baseline and absence of tendon friction rubs are more likely to regress in the next year than patients with milder skin fibrosis. These evidence-based data can be implemented in clinical trial design to minimise the inclusion of patients who would regress under standard of care.

Increased bone mineral density at the hypoxia prone site of the juxta-articular metacarpal bone in patients with limited systemic sclerosis: a cross-sectional study

OBJECTIVES Low levels of oxygen has been shown to be involved in the induction of osteogenesis, particularly in bone repair. It is unknown whether hypoxia leads to osteogenesis at the hypoxia prone skeletal sites in limited systemic sclerosis. This study determined the total and trabecular volumetric bone mineral density (vBMD) at the hypoxia prone site of the juxta-articular metacarpal bone. METHODS In this cross-sectional study, female patients with limited systemic sclerosis were included and compared to healthy controls. Peripheral quantitative computed tomography was used to measure cross-sectional area, total vBMD, and trabecular vBMD at the radius, the tibia and the third metacarpal bone. Disease severity was assessed by the modified Rodnan Skin Score. RESULTS Twenty consecutive patients were included in the sclerosis group and 20 in the control group. Mean age was 60 years (range 52-68 years), and mean disease duration was 45 months (range 4-156 months). Age, height, and weight were comparable between the groups. The mean modified Rodnan Skin Score was 1.78 (range 0 to 8). The sclerosis group showed both higher total and trabecular vBMD at the distal metacarpal bone (p=0.05 and 0.04, respectively). vBMD of the tibia and radius did not differ in both groups. CONCLUSIONS vBMD at the juxta-articular metacarpal bone in patients with limited systemic sclerosis is increased, possibly due to an alteration in local bone metabolism and hypoxia induced local osteogenesis.

Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database.

OBJECTIVES To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. METHODS 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan-Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors. RESULTS The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies. CONCLUSION Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening.

Validation of the DRAGON score in 12 stroke centers in anterior and posterior circulation

BACKGROUND AND PURPOSE The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. METHODS Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0-2) and miserable (modified Rankin scale score, 5-6) outcomes. RESULTS Area under the receiver operating characteristic curve was 0.84 (0.82-0.85) for miserable outcome and 0.82 (0.80-0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83-0.86) and 0.82 (0.78-0.87), respectively. No sex-related difference in performance was observed (P=0.25). CONCLUSIONS The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

What Is a Minor Stroke?

Background and Purpose— The term “minor stroke” is often used; however a consensus definition is lacking. We explored the relationship of 6 “minor stroke” definitions and outcome and tested their validity in subgroups of patients. Methods— A total of 760 consecutive patients with acute ischemic strokes were classified according to the following definitions: A, score ≤1 on every National Institutes of Health Stroke Scale (NIHSS) item and normal consciousness; B, lacunar-like syndrome; C, motor deficits with or without sensory deficits; D, NIHSS ≤9 excluding those with aphasia, neglect, or decreased consciousness; E, NIHSS ≤9; and F, NIHSS ≤3. Short-term outcome was considered favorable when patients were discharged home, and favorable medium-term outcome was defined as a modified Rankin Scale score of ≤2 at 3 months. The following subgroup analyses were performed by definition: sex, age, anterior versus posterior and right versus left hemispheric stroke, and early (0 to 6 hours) versus late admission (6 to 24 hours) to the hospital. Results— Short-term and medium-term outcomes were most favorable in patients with definition A (74% and 90%, respectively) and F (71% and 90%, respectively). Patients with definition C and anterior circulation strokes were more likely to be discharged home than patients with posterior circulation strokes (P=0.021). The medium-term outcome of older patients with definition E was less favorable compared with the outcome of younger ones (P=0.001), whereas patients with definition A, D, and F did not show different outcomes in any subgroup. Conclusions— Patients fulfilling definition A and F had best short-term and medium-term outcomes. They would be best suited to the definition of “minor stroke.”

Lipid profiles and outcome in patients treated by intravenous thrombolysis for cerebral ischemia

OBJECTIVE:To determine whether low low-density lipoprotein cholesterol (LDL-C) but not high-density lipoprotein cholesterol (HDL-C) and triglyceride concentrations are associated with worse outcome in a large cohort of ischemic stroke patients treated with IV thrombolysis. METHODS:Observational multicenter post hoc analysis of prospectively collected data in stroke thrombolysis registries. Because of collinearity between total cholesterol (TC) and LDL-C, we used 2 different models with TC (model 1) and with LDL-C (model 2). RESULTS:Of the 2,485 consecutive patients, 1,847 (74%) had detailed lipid profiles available. Independent predictors of 3-month mortality were lower serum HDL-C (adjusted odds ratio [(adj)OR] 0.531, 95% confidence interval [CI] 0.321-0.877 in model 1; (adj)OR 0.570, 95% CI 0.348-0.933 in model 2), lower serum triglyceride levels ((adj)OR 0.549, 95% CI 0.341-0.883 in model 1; (adj)OR 0.560, 95% CI 0.353-0.888 in model 2), symptomatic ICH, and increasing NIH Stroke Scale score, age, C-reactive protein, and serum creatinine. TC, LDL-C, HDL-C, and triglycerides were not independently associated with symptomatic ICH. Increased HDL-C was associated with an excellent outcome (modified Rankin Scale score 0-1) in model 1 ((adj)OR 1.390, 95% CI 1.040-1.860). CONCLUSION:Lower HDL-C and triglycerides were independently associated with mortality. These findings were not due to an association of lipid concentrations with symptomatic ICH and may reflect differences in baseline comorbidities, nutritional state, or a protective effect of triglycerides and HDL-C on mortality following acute ischemic stroke.

Vertebral artery dissection: presenting findings and predictors of outcome

BACKGROUND AND PURPOSE: Few data exist about clinical, radiologic findings, clinical outcome, and its predictors in patients with spontaneous vertebral artery dissection (sVAD). METHODS: Clinical characteristics, imaging findings, 3-month outcomes, and its predictors were investigated in consecutive patients with sVAD. RESULTS: One hundred sixty-nine patients with 195 sVAD were identified. Brain ischemia occurred in 131 patients (77%; ischemic stroke, n=114, 67%; transient ischemic attack, n=17, 10%). Three patients with ischemic stroke showed also signs of subarachnoid hemorrhage (SAH); 3 (2%) had SAH without ischemia. The 134 patients with brain ischemia or SAH had head and/or neck pain in 118 (88%) and pulsatile tinnitus in seven (5%) patients. The remaining 35 patients (21%) had isolated head and/or neck pain in 21 (12%) cases, asymptomatic sVAD in 13 (8%), and cervical radiculopathy in one case (1%). Location of sVAD was more often in the pars transversaria (V2; 35%) or atlas loop (V3; 34%) than in the prevertebral (V1; 20%) or intracranial (V4; 11%) segment (P=0.0001). Outcome was favorable (modified Rankin scale score 0 or 1) in 88 (82%) of 107 ischemic stroke patients with follow up. Two (2%) patients died. Low baseline National Institutes of Health Stroke Scale score (P<0.0001) and younger age (P=0.007) were independent predictors of favorable outcome. CONCLUSIONS: sVAD is predominantly located in the pars transversaria (V2) or the atlas loop (V3). Most patients show posterior circulation ischemia. Favorable outcome is observed in most ischemic strokes and independently predicted by low National Institutes of Health Stroke Scale score and younger age.

Outcome of stroke with mild or rapidly improving symptoms

BACKGROUND AND PURPOSE: Acute ischemic stroke with mild or rapidly improving symptoms is expected to result in good functional outcome, whether treated or not. Therefore, thrombolysis with its potential risks does not seem to be justified in such patients. However, recent studies indicate that the outcome is not invariably benign. METHODS: We analyzed clinical and radiological data of patients with stroke who presented within 6 hours of stroke onset and did not receive thrombolysis because of mild or rapidly improving symptoms. Univariate and logistic regression analyses were performed to define predictors of clinical outcome. RESULTS: One hundred sixty-two consecutive patients (110 men and 52 women) aged 63+/-13 years were included. The median National Institutes of Health Stroke Scale score on admission was 2 (range, 1 to 14). All patients presented within 6 hours of symptom onset. After 3 months, modified Rankin Scale score was modified Rankin Scale 2 to 5) and 2 patients (1.3%) had died. Baseline National Institutes of Health Stroke Scale score >/=10 points increased the odds of unfavorable outcome or death 16.9-fold (95% CI: 1.8 to 159.5; P<0.013), and proximal vessel occlusion increased the odds 7.13-fold (95% CI: 1.1 to 45.5; P<0.038). CONCLUSIONS: Seventy-five percent of patients with mild or rapidly improving symptoms will have a favorable outcome after 3 months. Therefore, a decision against thrombolysis seems to be justified in the majority of patients. However, selected patients, especially those with proximal vessel occlusions and baseline National Institutes of Health Stroke Scale scores >/=10 points, might derive a benefit from thrombolysis.

Recanalization and outcome after intra-arterial thrombolysis in middle cerebral artery and internal carotid artery occlusion: does sex matter?

BACKGROUND AND PURPOSE: Recent studies have reported sex differences in recanalization and outcome after intravenous thrombolysis (IVT) in acute ischemic stroke. METHODS: We analyzed sex differences in outcome in consecutive patients with middle cerebral artery (MCA) M1 or M2 and internal carotid artery (ICA) occlusion treated with intra-arterial thrombolysis (IAT). Recanalization immediately after thrombolysis and outcome after 3 months were assessed. RESULTS: Two hundred five patients (111 men) with MCA and 43 (22 men) with ICA occlusion were identified. Baseline variables did not differ between the sexes except for a higher prevalence of smokers among men in the MCA group (31% vs 12%; P=0.001). Partial or complete recanalization (TIMI flow 2 or 3) of the MCA was observed in 71 (75%) women and 80 (72%) men (P=0.488). In the ICA group, 14 (67%) women and 11 men (50%) showed TIMI 2 or 3 recanalization (P=0.425). Favorable outcome (modified Rankin Scale score 0 to 2) was seen in 57 women (61%) and 63 men (57%) with MCA occlusion (P=0.512) and in 6 women (28%) and 4 men (18%) with ICA occlusion (P=0.656). After multiple-regression analyses, there was still no association between sex and outcome (P=0.763 for MCA and P=0.813 for ICA occlusion) or recanalization (P=0.488 for MCA and P=0.104 for ICA occlusion). CONCLUSIONS: There was no association between sex and recanalization or outcome after IAT. These findings are in contrast to previous studies reporting better recanalization and outcome after IVT in women and might have implications in the selection of patients for IAT or IVT.

Intra-arterial thrombolysis of acute iatrogenic intracranial arterial occlusion attributable to neuroendovascular procedures or coronary angiography

BACKGROUND AND PURPOSE: For selected stroke patients, intra-arterial thrombolysis (IAT) has been shown to be an effective treatment option. However, knowledge of safety and efficacy of IAT in patients with acute stroke as a complication of arterial catheter interventions is limited. METHODS: We analyzed clinical radiological findings and functional outcomes in consecutive patients 3 months after treatment with IAT for peri-procedural strokes occurring during neuroendovascular or cardiac catheter interventions. To measure outcome, the modified Rankin scale score was used. RESULTS: Of a total of 432 patients treated with IAT, 12 (4 women and 8 men; mean age, 60 years) were treated because of an ischemic stroke after a neuro-endovascular procedure (n=6) or coronary angiography (n=6). The median baseline National Institutes of Health Stroke Scale score was 15. Recanalization was complete (thrombolysis in myocardial infarction grade 3) in 6, partial (thrombolysis in myocardial infarction 2) in 5, and minimal (thrombolysis in myocardial infarction 1) in 1. Nine patients (75%) had a favorable outcome (modified Rankin scale score, 0 to 2), and 3 had a poor outcome (modified Rankin scale score, 3 or 4). All patients with complete recanalization had a favorable outcome, whereas only 3 of 6 patients with partial or minimal recanalization (P=0.18) had a favorable outcome. Follow-up brain imaging was normal in 2 and showed new ischemic lesions in 10 patients. Two patients (17%) had a symptomatic intracerebral hemorrhage. CONCLUSIONS: In acute stroke attributable to arterial catheter interventions, IAT is feasible and has the potential to improve outcome in these patients. A high recanalization rate could be achieved.

Thrombolysis in childhood stroke: report of 2 cases and review of the literature

BACKGROUND AND PURPOSE: No controlled, randomized trial has investigated whether intravenous, intra-arterial (IAT), or mechanical thrombolysis is beneficial in children with ischemic stroke. We report 2 children who underwent IAT for acute ischemic stroke and include them in a review about intravenous thrombolysis, IAT, and mechanical thrombolysis for childhood stroke. METHODS: We searched in MEDLINE and EMBASE for studies that reported on treatment of childhood stroke with intravenous thrombolysis, IAT, or mechanical thrombolysis in the presence of occlusion of the basilar artery, sphenoidal, or insular middle cerebral artery. To be included in this review, the following findings had to be reported: (1) stroke severity at presentation; (2) cerebral imaging findings before thrombolysis; (3) time to treatment; (4) dose of the thrombolytic agent; (5) pre- and postinterventional angiographic findings in IAT; and (6) outcome assessed at hospital discharge or within 12 months after thrombolysis. RESULTS: Adequate data were available in 17 children (including our 2 own cases) who underwent intravenous thrombolysis (n=6), IAT (n=10), or mechanical thrombolysis (n=1). No symptomatic intracranial hemorrhage occurred, but 2 asymptomatic intracranial hemorrhages were present. Sixteen children (94%) survived, and 12 (71%) had a good outcome (modified Rankin Scale score 0 or 1). CONCLUSIONS: The available data about thrombolysis in pediatric stroke are limited. They suggest that this treatment may be beneficial in children with ischemic stroke. Controlled, randomized trials are needed to determine whether thrombolysis is useful in childhood stroke.

Subarachnoid hemorrhage and intracerebral hematoma: incidence, prognostic factors, and outcome

OBJECTIVE: To analyze the incidence and impact of an intracerebral hematoma (ICH) on treatment and outcome in patients with aneurysmal subarachnoid hemorrhage. METHODS: Data of 585 consecutive patients with subarachnoid hemorrhage from June 1999 to December 2005 were prospectively entered in a database. ICH was diagnosed and size was measured by computed tomographic scan before aneurysm occlusion. Fifty patients (8.5%) presented with an ICH larger than 50 cm3. The treatment decision (coil, clip, or hematoma evacuation) was based on an interdisciplinary approach. Patients were stratified into good (Hunt and Hess Grades I-III) versus poor (Hunt and Hess Grades IV and V) grade, and outcome was assessed according to the modified Rankin Scale at 6 months. RESULTS: Overall, 358 patients presented in good grade, with 4 of them having ICH (1.1%); and 227 patients presented in poor grade, with 46 of them having ICH (20.3%, P < 0.01). In good-grade patients with an ICH (n = 4), a favorable outcome (modified Rankin Scale score of 0-2) was achieved in 1 patient (25%), and in 246 patients (75%) without an ICH (P = 0.053; odds ratio, 0.11). A favorable outcome was achieved in 5 poor-grade patients (12.8%) with an ICH and in 40 patients (23.7%) without an ICH (P = 0.19; odds ratio, 0.47). Time to treatment was significantly shorter in patients with an ICH than without an ICH (median, 7 versus 26 h; P < 0.001) and shortest in patients with favorable outcome (3.5 hours; P < 0.01). CONCLUSION: The current data confirm that the presence of an ICH is a predictor of unfavorable outcome. However, despite large ICHs, a significant number of patients have a good outcome. To achieve a favorable outcome, ultra-early treatment with hematoma evacuation and aneurysm obliteration seems to be mandatory.

Triple and quadruple spontaneous cervical artery dissection: presenting characteristics and long-term outcome

BACKGROUND: Spontaneous cervicocephalic artery dissection (sCAD) of more than two cervical arteries is rare. PATIENTS AND METHODS: Vascular and potential sCAD risk factors, triggering events, clinical and neuroimaging findings, and outcome of patients with multiple sCAD were studied. Patients were drawn from prospective hospital-based sCAD registries. RESULTS: Of 740 consecutive patients with sCAD, 11 (1.5%) had three, and one had four (0.1%) sCAD. Eight of these 12 patients were women. One patient had additional dissections of the celiac trunk and hepatic artery. Vascular risk factors included hypertension (n = 1), hypercholesterolaemia (n = 6), current smoking (n = 5) and migraine (n = 6). No patient had a family history of sCAD, fibromuscular dysplasia (FMD) or connective tissue disease. SCAD was preceded by a minor trauma in five and infection in four patients. Clinical manifestations included ischaemic stroke (n = 8), transient ischaemic attack (n = 3), headache (n = 9), neck pain (n = 4), Horner syndrome (n = 5), pulsatile tinnitus (n = 2) and dysgeusia (n = 1). Brain MRI revealed ischaemic infarcts that affected one vessel territory in seven and two territories in two patients. The 3-month outcome was favourable (modified Rankin scale score 0-1) in 10 patients (83%). No new recurrent stroke or sCAD occurred during a mean follow-up of 50 (SD 29) months. CONCLUSION: Multiple sCAD occurred preferentially in women and caused clinical symptoms and signs mainly in one vascular territory. In none of the patients was FMD or any other underlying arteriopathy apparent. The majority of multiple sCAD was preceded by a minor trauma or infection. Clinical outcome was favourable in most patients, and long-term prognosis benign. The data suggest that transient vasculopathy may be a major mechanism for multiple sCAD.

Outcome of acute stroke patients without visible occlusion on early arteriography

BACKGROUND: The aim of this study was to determine the clinical and radiological outcome of acute stroke patients who had no vessel occlusion on arteriography and to define predictors of clinical outcome. METHODS: We analyzed clinical and radiological data of stroke patients whose arteriography performed within 6 hours of symptom onset did not visualize any vessel occlusion. RESULTS: Twenty-eight of 283 consecutive patients (10%) who underwent arteriography with the intention to perform intraarterial thrombolysis did not show any arterial occlusion. Their median baseline National Institutes of Health Stroke Scale (NIHSS) score was 7. Time from symptom onset to arteriography ranged from 115 to 315 minutes; on average, it was 226 minutes. Presumed stroke cause was cardiac embolism in 11 patients (39%), small artery disease in 6 (21%), coronary angiography in 1 (4%), and undetermined in 10 patients (36%). After 3 months, modified Rankin Scale score (mRS) was < or =2 in 21 patients (75%), indicating a favorable outcome. Six patients (21%) had a poor outcome (mRS 3 or 4) and 1 patient (4%) had a myocardial infarction and died. Twenty-seven patients had follow-up brain imaging. It was normal in 5, showed a lacunar lesion in 8, a striatocapsular infarct in 2, a small or medium-sized anterior circulation infarct in 6, multiple small anterior circulation infarcts in 2, and multiple posterior circulation infarcts in 4. No predictors of clinical outcome were identified. CONCLUSIONS: Most acute stroke patients with normal early arteriography show infarcts on brain imaging; however, clinical outcome is usually favorable.

Intravenous thrombolysis in stroke attributable to cervical artery dissection

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Whether this is also true for cervical artery dissection (CAD) is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated patients with CAD with IVT-treated patients with other etiologies (non-CAD patients). Main outcome and complication measures were favorable 3-month outcome, intracranial cerebral hemorrhage, and recurrent ischemic stroke. Modified Rankin Scale score scores (14 versus 13) and time to treatment (152.5 versus 156 minutes) as non-CAD patients. In the CAD group, 36% (20 of 55) had a favorable 3-month outcome compared with 44% (447 of 1007) non-CAD patients (OR, 0.72; 95% CI, 0.41 to 1.26), which was less favorable after adjustment for age, gender, and National Institutes of Health Stroke Scale score (OR, 0.50; 95% CI, 0.27 to 0.95; P=0.03). Intracranial cerebral hemorrhages (asymptomatic, symptomatic, fatal) were equally frequent in CAD (14% [7%, 7%, 2%]) and non-CAD patients (14% [9%, 5%, 2%]; P=0.99). Recurrent ischemic stroke occurred in 1.8% of patients with CAD and in 3.7% of non-CAD-patients (P=0.71). CONCLUSIONS: IVT-treated patients with CAD do not recover as well as IVT-treated non-CAD patients. However, intracranial bleedings and recurrent ischemic strokes were equally frequent in both groups. They do not account for different outcomes and indicate that IVT should not be excluded in patients who may have CAD. Hemodynamic compromise or frequent tandem occlusions might explain the less favorable outcome of patients with CAD.