Lipid-Lowering Therapy and Hemorrhagic Stroke Risk: Comparative Meta-Analysis of Statins and PCSK9 Inhibitors.

Background and Purpose: Statins were shown to increase hemorrhagic stroke (HS) in patients with a first cerebrovascular event in 2006 (SPARCL), likely due to off-target antithrombotic effects, but continued to sometimes be used in patients with elevated HS risk due to absence of alternative medications. Recently, the PCSK9Is (proprotein convertase subtilisin kexin 9 inhibitors) have become available as a potent lipid-lowering class with potentially less hemorrhagic propensity. Methods: We performed a systematic comparative meta-analysis assessing HS rates across all completed statin and PCSK9I randomized clinical trials with treatment >3 months, following PRISMA guidelines. In addition to HS rates across all trials, causal relation was probed by evaluating for dose-response relationships by medication (low versus high medication dose/potency) and by presence and type of preceding brain vascular events at inception (none versus ischemic stroke/transient ischemic attack versus HS). Results: The systematic review identified 36 statin randomized clinical trials (204 918 patients) and 5 PCSK9I randomized clinical trials (76 140 patients). Across all patient types and all medication doses/potencies, statins were associated with increased HS: relative risk 1.15, P=0.04; PCSK9Is were not (P=0.77). In the medication dose/potency analysis, higher dose/potency statins (7 trials, 62 204 patients) were associated with magnified HS risk: relative risk, 1.53; P=0.002; higher dose/potency PCSK9Is (1 trial, 27 564 patients) were not (P=0.99). In the type of index brain vascular injury analysis for statins (5 trials, 9772 patients), prior ischemic stroke/transient ischemic attack was associated with a magnified risk of HS: relative risk, 1.43; P=0.04; and index intracerebral hemorrhage was associated with an extremely high effect estimate of risk of recurrent HS: hazard ratio, 4.06. For PCSK9Is, prior ischemic stroke/transient ischemic attack (1 trial, 5337 patients) was not associated with increased HS risk (P=0.97). Conclusions: Statins increase the risk of HS in a medication dose- and type of index brain vascular injury-dependent manner; PCSK9Is do not increase HS risk. PCSK9Is may be a preferred lipid-lowering medication class in patients with elevated HS risk, including patients with prior HS.

Occipital Condyle Syndrome: A Red Flag for Malignancy. Comprehensive Literature Review and New Case Report.

OBJECTIVE: To perform a literature review of the epidemiology, clinical presentation, diagnostic evaluation, and clinical course of occipital condyle syndrome, including a new case report. BACKGROUND: Occipital condyle syndrome (OCS) is a rare clinical syndrome, consisting of unilateral occipital headache accompanied by ipsilateral hypoglossal palsy. This headache typically radiates to the temporal region, and is triggered by contralateral head rotation. It is usually associated with skull base metastasis, often unrevealed in basic neuroimaging studies. OCS might be the first manifestation of malignancy, and its unfamiliarity can lead to a delay in the diagnosis. METHODS: We performed a systematic literature review using PubMed and Embase for OCS, along with a new case report. RESULTS: A total of 35 cases (mean age 59 years, range 25-77), 24 (70%) men, presented typical unilateral headache followed by ipsilateral hypoglossal palsy from 0 to 150 days after headache presentation. In 16 patients (46%), initial neuroimaging studies were normal. OCS was due to skull base metastasis in 32 cases (91%). In 18 patients (51%), OCS was the first symptom of disease. CONCLUSIONS: OCS represents a warning sign and requires an exhaustive search for underlying neoplasm. An appropriate clinical evaluation can lead to an earlier diagnosis in patients with consistent headache.

DCE-MRI blood-brain barrier assessment in acute ischemic stroke.

OBJECTIVE: To quantitatively evaluate blood-brain barrier changes in ischemic stroke patients using dynamic contrast-enhanced (DCE) MRI. METHODS: We examined 54 stroke patients (clinicaltrials.gov NCT00715533, NCT02077582) in a 3T MRI scanner within 48 hours after symptom onset. Twenty-eight patients had a follow-up examination on day 5-7. DCE T1 mapping and Patlak analysis were employed to assess BBB permeability changes. RESULTS: Median stroke Ktrans values (0.7 × 10-3 min-1 [interquartile range (IQR) 0.4-1.8] × 10-3 min-1) were more than 3-fold higher compared to median mirror Ktrans values (0.2 × 10-3 min-1, IQR 0.1-0.7 × 10-3 min-1, p < 0.001) and further increased at follow-up (n = 28, 2.3 × 10-3 min-1, IQR 0.8-4.6 × 10-3 min-1, p < 0.001). By contrast, mirror Ktrans values decreased over time with a clear interaction of timepoint and stroke/mirror side (p < 0.001). Median stroke Ktrans values were 2.5 times lower than in hemorrhagic transformed regions (0.7 vs 1.8 × 10-3 min-1; p = 0.055). There was no association between stroke Ktrans values and the delay from symptom onset to baseline examination, age, and presence of hyperintense acute reperfusion marker. CONCLUSION: BBB in acute stroke patients can be successfully assessed quantitatively. The decrease of BBB permeability in unaffected regions at follow-up may be an indicator of global BBB leakage even in vessel territories remote from the index infarct.

Mechanical thrombectomy in patients with medical contraindications for intravenous thrombolysis: a prospective observational study.

BACKGROUND AND PURPOSE: The present study was conducted with the objective of evaluating the safety of primary mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke and comorbidities that preclude treatment with IV thrombolysis (IVT), compared with patients who received standard IVT treatment followed by MT. Secondary objectives were to analyse the recanalization rate and outcomes. METHODS: A prospective observational multicenter study (FUN-TPA) that recruited patients treated within 4.5 hours of symptom onset was performed. Treatments were IVT followed by MT if occlusion persisted, or primary MT when IVT was contraindicated. Outcome measures were procedural complications, symptomatic intracranial hemorrhage (SICH), recanalization rate, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, modified Rankin Scale (mRS) score and mortality at 90 days. RESULTS: Of 131 patients, 21 (16%) had medical contraindications for IVT and were treated primarily with MT whereas 110 (84%) underwent IVT, followed by MT in 53 cases (40%). The recanalization rate and procedural complications were similar in the two groups. There were no SICHs after primary MT vs 3 (6%) after IVT+MT. Nine patients (43%) in the primary MT group achieved independence (mRS 0-2) compared with 36 (68%) in the IVT+MT group (p=0.046). Mortality rates in the two groups were 14% (n=3) vs 4% (n=2) (p=0.13). Adjusted ORs for independence in patients receiving standard IVT+MT vs MT in patients with medical contraindications for IVT were 2.8 (95% CI 0.99 to 7.98) and 0.24 (95% CI 0.04 to 1.52) for mortality. CONCLUSIONS: MT is safe in patients with potential comorbidity-derived risks that preclude IVT. MT should be offered, aiming for prompt recanalization, to patients with LVO stroke unsuitable for IVT. TRIAL REGISTRATION NUMBER: NCT02164357; Results.

Alberta Stroke Program Early CT Score applied to CT angiography source images is a strong predictor of futile recanalization in acute ischemic stroke.

INTRODUCTION: Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization. METHODS: Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, time-lapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability). RESULTS: Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT + MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3-0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5-1.2). A score ≤5 in CTA-SI-ASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %). CONCLUSIONS: CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapies.

Acute ischemic stroke patients with diabetes should not be excluded from intravenous thrombolysis.

The benefit of intravenous thrombolysis (IVT) has been questioned for patients with diabetes mellitus (DM) in cases of acute ischemic stroke (IS). Our objective was to analyze the differences in outcome according to prior diagnosis of DM and the use or not of IVT. Observational study with inclusion of consecutive IS patients admitted to an stroke unit. Demographic data, vascular risk factors, comorbidity, stroke severity and 3-month follow-up outcome (modified Rankin Scale) were compared according to prior diagnosis of DM and the use or not of IVT. A total of 1,139 IS patients were admitted; 283 (24.8%) patients had a diagnosis of DM, and 261 were IVT treated (23.2% of the group without DM and 21.9% of the DM group). The IVT-treated patients with DM were older, had more comorbidities and had higher glucose levels on admission than those without DM and than IVT-treated patients. No significant differences in stroke severity, hemorrhagic transformation, in-hospital mortality or outcome at 3 months were found. The logistic regression analysis showed that stroke severity was associated with a higher risk of a poor outcome in IVT-treated patients, with no significant effect from DM after adjustment for confounders. Moreover, IVT was independently associated with a lower risk of poor outcome in DM patients (OR 0.49; 95% CI 0.31-0.76; P = .002). DM patients should not be excluded from IVT, because DM is not associated with a poor outcome after IVT and this treatment is clearly beneficial for DM patients as compared with DM patients not treated with IVT.

The effect of telestroke systems among neighboring hospitals: more and better? The Madrid Telestroke Project.

A telestroke system was established between a community hospital lacking an on-call neurologist and a comprehensive stroke center only 13 km away. Our goal was to analyze the impact of telestroke on the number of intravenous thrombolysis (IVT), door-to-needle times and stroke outcomes. An observational before-and-after study of patients with acute ischemic stroke (IS) who were attended in a community hospital during the 2 years before the telestroke system was implemented (pre-telestroke group) and the first 2 years after telestroke was established (telestroke group). The number of IVT, the door-to-needle time (min), the outcomes [modified Rankin Scale (mRS)] and the safety (mortality and hemorrhagic transformations) were compared between groups. During the pre-telestroke years, 259 patients with IS were attended (28 phone activations), 12 of whom received IVT (4.7 %). During the telestroke years, 225 patients with IS were attended (42 telestroke activations), of whom 18 (8 %) received IVT. The door-to-needle times were lower in the telestroke group [median interquartile range: 66 (54) vs. 143.5 (48) min, P < 0.0001]. The safety was similar in both groups; however, the 3-month mRS scores were lower in the telestroke group (P = 0.049). The multiple linear regression analysis showed a negative association between telestroke and door-to-needle time [ß-coefficient (SE) = -59.089 (14.461)], adjusted for confounders. In conclusion, telestroke systems are effective, even between nearby hospitals, shortening door-to-needle time and improving stroke outcomes.