Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.
BACKGROUND AND PURPOSE: In certain clinical circumstances, dual-antiplatelet therapy can be problematic in patients with acute SAH. In some aneurysms, however, flow-diverting stents are the ideal therapeutic option. We report our experience with ruptured intracranial aneurysms treated with flow diverters with hydrophilic coating (p48 MW HPC and p64 MW HPC) under single-antiplatelet therapy.MATERIALS AND METHODS: Patients were treated with either flow-diverter placement alone or a flow diverter and additional coiling. Due to the severity of the hemorrhage, the potential for periprocedural rehemorrhage, and the potential for additional surgical interventions, a single-antiplatelet regimen was used in all patients.RESULTS: Thirteen aneurysms were treated in 10 patients. The median age was 62 years; 5 patients were male. All had acute SAH due to aneurysm rupture. Four blood-blister, 2 dissecting, and 7 berrylike aneurysms were treated. Seven aneurysms were adjunctively coiled. Eight of the 10 patients received a single-antiplatelet protocol of aspirin, 1 patient was treated with prasugrel only, and 1 patient was treated with tirofiban first and then switched to the aspirin single-antiplatelet protocol. One device-related complication occurred, a thrombosis of an overstented branch. All stents, however, remained open at DSA, CTA, or MRA follow-up. CONCLUSIONS:The implantation of flow diverters with reduced thrombogenicity due to hydrophilic surface coating under singleantiplatelet therapy seems to be an option in carefully selected cases of SAH due to aneurysm rupture.
Background and Purpose: Cell-free DNA (cfDNA) and endogenous deoxyribonuclease activity are opposing mediators and might influence the inflammatory response following acute ischemic stroke. In this cohort study, we investigated the relation between these markers, circulating inflammatory mediators and clinical course including occurrence of stroke-associated infections (SAI) in patients with acute stroke. Methods: Ninety-two patients with stroke due to large vessel occlusion undergoing mechanical thrombectomy were prospectively recruited at Hannover Medical School from March 2018 to August 2019. Deoxyribonuclease activity, cfDNA, damage-associated molecular patterns, and circulating cytokines were measured in venous blood collected immediately before mechanical thrombectomy and 7 days later. Reperfusion status was categorized (sufficient/insufficient). Clinical outcome was evaluated using the modified Rankin Scale after 90 days, where a score of 3 to 6 was considered unfavorable. To validate findings regarding SAI, another stroke cohort (n=92) was considered with blood taken within 24 hours after stroke onset. Results: Patients with unfavorable clinical outcome had higher cfDNA concentrations. After adjustment for confounders (Essen Stroke Risk Score, National Institutes of Health Stroke Scale, and sex), 7-day cfDNA was independently associated with clinical outcome and especially mortality (adjusted odds ratio: 3.485 [95% CI, 1.001–12.134] and adjusted odds ratio: 9.585 [95% CI, 2.006–45.790]). No association was found between reperfusion status and cfDNA or deoxyribonuclease activity. While cfDNA concentrations correlated positively, deoxyribonuclease activity inversely correlated with distinct biomarkers. Baseline deoxyribonuclease activity was lower in patients who developed SAI compared with patients without SAI. This association was confirmed after adjustment for confounding factors (adjusted odds ratio: 0.447 [95% CI, 0.237–0.844]). In cohort 2, differences of deoxyribonuclease activity between patients with and without SAI tended to be higher with higher stroke severity. Conclusions: The interplay of endogenous deoxyribonuclease activity and cfDNA in acute stroke entails interesting novel diagnostic and potential therapeutic approaches. We confirm an independent association of cfDNA with a detrimental clinical course after stroke due to large vessel occlusion. This study provides first evidence for lower endogenous deoxyribonuclease activity as risk factor for SAI after severe stroke.
Background and Purpose: Pre- and intra-hospital workflow in mechanical recanalization of large cervicocephalic arteries in patients with acute ischemic stroke still needs optimization. In this study, we analyze workflow and outcome in our routine care of stroke patients undergoing mechanical thrombectomy as a precondition for such optimization.Methods: Processes of pre- and intra-hospital management, causes of treatment delay, imaging results (Alberta Stroke Program Early Computed Tomography Score, localization of vessel occlusion), recanalization (modified thrombolysis in cerebral infarction score), and patient outcome (modified Rankin scale at discharge and at the end of inpatient rehabilitation) were analyzed for all patients who underwent mechanical thrombectomy between April 1, 2016, and September 30, 2018, at our site.Results: Finally, data of 282 patients were considered, of whom 150 (53%) had been referred from external hospitals. Recanalization success and patient outcome were similar to randomized controlled thrombectomy studies and registries. Delay in treatment occurred when medical treatment of a hypertensive crisis, epileptic fits, vomiting, or agitation was mandatory but also due to missing prenotification of the hospital emergency staff by the rescue service, multiple mode or repeated brain imaging, and transfer from another hospital. Even transfer from external hospitals located within a 10-km radius of our endovascular treatment center led to a median increase of the onset-to-groin time of ~60 min.Conclusion: The analysis revealed several starting points for an improvement in the workflow of thrombectomy in our center. Analyses of workflow and treatment results should be carried out regularly to identify the potential for optimization of operational procedures and selection criteria for patients who could benefit from endovascular treatment.
Background and purpose Recent studies suggest that endovascular treatment (EVT) in distal medium vessel occlusion (DMVO) stroke is beneficial even beyond middle cerebral artery (MCA) - M2 segment. However, data about aspiration thrombectomy of DMVOs is scarce since common state-of-the-art aspiration catheters are usually too large for small distal intracranial arteries. We report our initial experiences using the microcatheter aspiration thrombectomy (MAT) technique as frontline therapy for acute DMVOs in the MCA territory. Methods We retrospectively analyzed all acute ischemic stroke (AIS) patients that underwent MAT of a primary or secondary DMVO in the M3 or M4 segment between January 2019 and October 2021. Recanalization rates, procedural safety and outcome data were recorded. Results MAT of acute M3 and M4 occlusions was performed in 19 patients with AIS. Six had isolated DMVO strokes, 13 had secondary DMVOs during EVT of a proximal large vessel occlusion. Successful revascularization to DMVO TICI ≥ 2b was achieved in 58% (11/19) with a single pass in all of them. The median National Institutes of Health Strokes Scale (NIHSS) score at admission and discharge was 12 and 3, respectively. 68% (13/19) of the patients had a good clinical outcome at discharge (modified Rankin Scale 0-2). No symptomatic complications related to MAT occurred. Conclusions MAT of DMVOs in the MCA territory is technically feasible and effective. Compared to stent retriever-based thrombectomy in DMVOs the hemorrhagic complication rate appears notably lower. Further studies are needed to validate the benefit of mechanical thrombectomy in the distal intracranial vasculature.
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