CANVAS: case report on a novel repeat expansion disorder with late-onset ataxia

This article presents the case of a 74-year-old female patient who first developed a progressive disease with sensory neuropathy, cerebellar ataxia and bilateral vestibulopathy at the age of 60 years. The family history was unremarkable. Magnetic resonance imaging (MRI) showed atrophy of the cerebellum predominantly in the vermis and atrophy of the spinal cord. The patient was given the syndromic diagnosis of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In 2019 the underlying genetic cause of CANVAS was discovered to be an intronic repeat expansion in the RFC1 gene with autosomal recessive inheritance. The patient exhibited the full clinical picture of CANVAS and was tested positive for this repeat expansion on both alleles. The CANVAS is a relatively frequent cause of late-onset hereditary ataxia (estimated prevalence 5‑13/100,000). In contrast to the present patient, the full clinical picture is not always present. Therefore, testing for the RFC1 gene expansion is recommended in the work-up of patients with otherwise unexplained late-onset sporadic ataxia. As intronic repeat expansions cannot be identified by next generation sequencing methods, specific testing is necessary

Bridging intravenous thrombolysis in patients with atrial fibrillation.

Background and purpose 40% of acute ischemic stroke patients treated by mechanical thrombectomy (MT) have a clinical history of atrial fibrillation (AF). The safety of bridging intravenous thrombolysis (IVT) (MT + IVT) is currently being discussed. We aimed to analyze the interaction between oral anticoagulation (OAC) status or AF with bridging IVT, regarding the occurrence of symptomatic intracranial hemorrhage (sICH) and functional outcome. Materials and Methods Multicentric observational cohort study (BEYOND-SWIFT registry) of consecutive patients undergoing MT between 2010 and 2018 (n = 2,941). Multinomial regression models were adjusted for prespecified baseline and plausible pathophysiological covariates identified on a univariate analysis to assess the association of AF and OAC status with sICH and good outcomes (90-day modified Rankin Scale score 0-2). Results In the total cohort (median age 74, 50.6% women), 1,347 (45.8%) patients had AF. Higher admission National Institutes of Health Stroke Scale (NIHSS) score (aOR 1.04 [95% 1.02-1.06], per point of increase) and prior medication with Vitamin K antagonists (VKA) (aOR 2.19 [95% 1.27-3.66]) were associated with sICH. Neither AF itself (aOR 0.71 [95% 0.41-1.24]) nor bridging IVT (aOR 1.08 [0.67-1.75]) were significantly associated with increased sICH. Receiving bridging IVT (aOR 1.61 [95% 1.24-2.11]) was associated with good 90-day outcome, with no interaction between AF and IVT (p = 0.92). Conclusion Bridging IVT appears to be a reasonable clinical option in selected patients with AF. Given the increased sICH risk in patients with VKA, subgroup analysis of the randomized controlled trials should analyze whether patients with VKA might benefit from withholding bridging IVT. Registration clinicaltrials.gov; Unique identifier: NCT03496064

Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0-5.

Background and Purpose- If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0-5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0-5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods- Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration-URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0-3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0-2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results- Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0-5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363-12.961), functional independence (aOR, 5.583; 95% CI, 1.964-15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083-0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062-0.887). The mortality-reducing effect remained in patients with ASPECTS 0-4 (aOR, 0.167; 95% CI, 0.056-0.499). Sensitivity analyses did not change the primary results. Conclusions- In patients presenting with ASPECTS 0-5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted

Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry.

In acute ischaemic stroke (AIS) of the anterior circulation (AC) treated with mechanical thrombectomy (MT), data point to a decline of treatment effect with increasing time from symptom onset to treatment. However, the magnitude of the decline will depend on the clinical setting and imaging selection used. The aims of this study were (1) to evaluate the clinical effect of time to reperfusion (TTR); and (2) to assess the safety and technical efficacy of MT according to strata of TTR. Using the retrospective multicentre BEYOND-SWIFT registry data (ClinicalTrials.gov identifier: NCT03496064), we compared safety and efficacy of MT in 1461 patients between TTR strata of 0-180 min (n = 192), 180-360 min (n = 876) and >360 min (n = 393). Clinical effect of TTR was evaluated using multivariable logistic regression analyses adjusting for pre-specified confounders [adjusted odds ratios (aOR) and 95% confidence intervals (95% CI)]. Primary outcome was good functional outcome (modified Rankin Scale: mRS 0-2) at day 90. Every hour delay in TTR was a significant factor related to mRS 0-2 (aOR 0.933, 95% CI 0.887-0.981) with an estimated 1.5% decreased probability of good functional outcome per hour delay of reperfusion, and mRS 0-1 (aOR 0.929, 95% CI 0.877-0.985). Patients with late TTR had lower rates of successful and excellent reperfusion, higher complication rates and number of passes. TTR is an independent factor related to long-term functional outcome. With increasing TTR, interventional procedures become technically less effective. Efforts should be made to shorten TTR through optimized prehospital and in-hospital pathways

Thrombus Histology of Basilar Artery Occlusions : Are There Differences to the Anterior Circulation?

BACKGROUND For patients with acute vessel occlusions of the anterior circulation histopathology of retrieved cerebral thrombi has been reported to be associated to stroke etiology. Due to the relatively small incidence of posterior circulation stroke, exclusive histopathologic analyses are missing for this subgroup. The aim of the study was to investigate thrombus histology for patients with basilar artery occlusions and uncover differences to anterior circulation clots with respect to underlying etiology. METHODS A total of 59 basilar thrombi were collected during intracranial mechanical recanalization and quantitatively analyzed in terms of their relative fractions of the main constituents, e.g. fibrin/platelets (F/P), red (RBC) and white blood cells (WBC). Data were compared to histopathological analyses of 122 thrombi of the anterior circulation with respect to underlying pathogenesis. RESULTS The composition of basilar thrombi differed significantly to thrombi of the anterior circulation with an overall higher RBC amount (median fraction in % (interquartile range):0.48 (0.37-0.69) vs. 0.37 (0.28-0.50), p < 0.001) and lower F/P count (0.45 (0.21-0.58) vs. 0.57 (0.44-0.66), p < 0.001). Basilar thrombi composition did not differ between the different etiological stroke subgroups. CONCLUSION The results depict a differing thrombus composition of basilar thrombi in comparison to anterior circulation clots with an overall higher amount of RBC. This may reflect different pathophysiologic processes between anterior and posterior circulation thrombogenesis, e.g. a larger proportion of appositional thrombus growth in the posterior circulation

Intraprocedural Thrombus Fragmentation During Interventional Stroke Treatment: A Comparison of Direct Thrombus Aspiration and Stent Retriever Thrombectomy

Purpose The aim of this study was to compare the rates of intraprocedural thrombus fragmentation between the exclusive thrombus aspiration technique (ADAPT) and the use of stent retrievers. Materials and Methods Cases with successful recanalization of the primary occlusion site (POS) with either of the techniques were analyzed (n = 36 ADAPT, n = 61 stent retriever). The primary endpoint was the evaluation of intraprocedural thrombus fragmentation before applying additional maneuvers to enhance reperfusion success. Grading was performed using the modified thrombolysis in cerebral infarction (mTICI) perfusion scale grade with the implementation of an additional TICI 2c grade. Secondary endpoints were procedural complications and clinical data. Results After opening of the POS, 83.3% successful reperfusions were reached using the ADAPT technique and 88.5% using stent retrievers (p = 0.47). Subarachnoid hemorrhages (SAH) appeared only when using stent retrievers (16.4 vs. 0%, p = 0.010). The number of maneuvers was significantly higher (median 2 vs. 1, p = 0.006), and procedural time was longer in the stent retriever group (median 30 vs. 13 min, p < 0.0001). There was no significant difference between both techniques with regard to the occurrence of embolizations to new territories (2.8 vs. 8.2%, p = 0.28). Conclusion When retrieving of the primary thrombus is possible, ADAPT results in comparable reperfusion grades as do stent retrievers. This suggests that comparable distraction forces act on the thrombus and that both techniques possess a comparable risk of periprocedural thrombus fragmentation. SAH exclusively occurred after using stent retrievers, which may further promote ADAPT as safe and fast initial front-line approach

A short history of thrombectomy - Procedure and success analysis of different endovascular stroke treatment techniques.

BACKGROUND The historical development of interventional stroke treatment shows a wide variation of different techniques and materials used. Thus, the question of the present work is whether the technical and procedural differences of thrombectomy techniques lead to different technical and clinical results. METHODS AND RESULTS Analysis of a mixed retrospective/prospective database of all endovascular treated patients with an occlusion of the Carotid-T or M1 segment of the MCA at a single comprehensive stroke center since 2008. Patients were classified regarding the technical approach used. Six hundred sixty-eight patients were available for the final analysis. Reperfusion rates ranged between 56% and 100% depending on the technical approach. The use of balloon guide catheters and most recently the establishment of combination techniques using balloon guide catheters, aspiration catheters and stent retrievers have shown a further significant increase in the rates of successful recanalization, full recanalization and first-pass recanalization. Additionally, the technical development of interventional techniques has led to a subsequent drop in complications, embolization into previously unaffected territories in particular. CONCLUSION Technical success of MT has improved substantially over the past decade owing to improved materials and procedural innovations. Combination techniques including flow modulation have emerged to be the most effective approach and should be considered as a standard of care.Level of evidence: Level 3, retrospective study