UvA-DARE (Digital Academic Repository) Optimizing thrombolysis in acute ischaemic stroke Zinkstok, S.M. Link to publication

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1 UvA-DARE (Digital Academic Repository) Optimizing thrombolysis in acute ischaemic stroke Zinkstok, S.M. Link to publication Citation for published version (APA): Zinkstok, S. M. (2014). Optimizing thrombolysis in acute ischaemic stroke General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 06 Feb 2018

2 CHAPTER 7 SAFETY AND FUNCTIONAL OUTCOME OF THROMBOLYSIS IN DISSECTION-RELATED STROKE: A META-ANALYSIS OF INDIVIDUAL PATIENT DATA Sanne M. Zinkstok Mervyn D. Vergouwen Stefan T. Engelter Philippe A. Lyrer Leo H. Bonati Marcel Arnold Heinrich P. Matttle Urs Fischer Hakan Sarikaya Ralf W. Baumgartner Dimitrios Georgiadis Céline Odier Patrik Michel Jukka Putaala Martin Griebe Nils Wahlgen Niaz Ahmed Nan van Geloven Rob J. de Haan Paul J. Nederkoorn Stroke 2011;42: PMID

3 ABSTRACT Background The safety and efficacy of thrombolysis in cervical artery dissection (CAD) is controversial. The aim of this meta-analysis was to provide a valid estimate of safety and outcome of thrombolysis in CAD by pooling all available individual patient data (IPD). Methods We performed a systematic literature search on intravenous thrombolysis (IVT) and intra-arterial thrombolysis (IAT) in CAD. The rates of pooled symptomatic intracranial haemorrhage (SICH) and mortality were calculated and indirectly compared to matched controls from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register (SITS- ISTR). We applied multivariate regression models to identify predictors of excellent (modified Rankin scale [mrs] score of 0 1) and favourable (mrs score 0 2) outcome. Results We obtained IPD of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%) with a mean age of 46 years. Median National Institutes of Health Stroke Scale score was 16. Treatment modality was IVT in 121 patients (67%) and IAT in 59 patients (33%). Median follow-up duration was 3 months. The pooled SICH rate was 3.1% (95% CI ). Overall mortality was 8.1% (95% CI ) and 41.0% (95% CI ) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of endpoints indicated no relevant differences with matched controls from SITS-ISTR. Conclusion Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.

4 Safety and outcome of thrombolysis in dissection-related stroke 97 INTRODUCTION Approximately 2% of all ischaemic strokes are caused by cervical artery dissection (CAD). In patients below the age of 50, CAD accounts for 10 25% of all ischaemic strokes. 1,2 CAD is characterized by the presence of an intramural haematoma due to an intimal tear in the carotid or vertebral artery wall. Subsequent ischaemic stroke is believed to be caused by thrombo-embolism in most cases rather than by haemodynamic factors. 3 Randomised controlled trials that investigated intravenous thrombolysis (IVT) in acute ischaemic stroke did not exclude patients with CAD, 4 although safety and efficacy have not been investigated for this particular group of patients. Therefore, it remains unknown whether IVT should be administered in acute ischaemic stroke attributable to CAD. The most serious complication of IVT is symptomatic intracranial haemorrhage (SICH), which occurs in 2 9%. 4 In patients with CAD an additional concern is the risk of enlargement of the intramural haematoma. Small retrospective case series suggested that thrombolysis in CAD patients is safe. 5,6 The aim of the current meta-analysis was to pool all available case reports and series using individual patient data (IPD) in order to provide a valid estimate of safety and outcome of thrombolytic treatment in patients with CAD-related stroke. In addition, predictors of outcome after thrombolysis in CAD-patients were evaluated. 7 METHODS Study selection We systematically searched the PUBMED and EMBASE database up to March 2010 for publications on thrombolysis in patients with CAD-related ischaemic stroke, using the following combination of variables: [ dissection ] AND [ carotid or vertebral or cervical or extracranial or stroke or brain ischaemia or brain infarction ] AND [ thrombolysis or recombinant tissue plasminogen activator or rtpa or tissue plasminogen activator or tpa or urokinase or pro-urokinase ]. In addition, we searched for relevant studies in the Cochrane Library and Cochrane Central Register of Controlled Trials, and hand searched

5 98 Chapter 7 citations from the retrieved studies. Finally, experts in the field were consulted. We included studies that investigated thrombolysis in patients with CAD-related stroke, either as the main focus of research or as a subgroup analysis. Since the number of publications on this topic is scarce, we have not set a minimum to the number of patients per study. We included publications in English, German and French and other languages if an abstract in English, German or French was available. Patients with a dissection limited to the intracranial part of the vessel(s) only, or with an aortic dissection extending into the cervical arteries, were excluded. Diagnosis of CAD needed to be confirmed with appropriate imaging tests: color duplex sonography, computed tomography angiography, magnetic resonance angiography, or conventional angiography. Confirmation of the dissection after thrombolysis was allowed. Since most studies did not systematically assess the degree of both extracranial and intracranial stenosis before and after treatment, recanalization was not included in our analysis. We analysed two treatment groups: IVT and intra-arterial thrombolysis (IAT). IAT was defined as treatment with IAT only, IVT followed by IAT, or IAT in combination with any other endovascular procedure such as mechanical thrombectomy or stent placement. Thrombolytic therapy had to be administered within 24 hours after stroke symptom onset. Data extraction We collected the following baseline characteristics: sex, age, preceding trauma, stroke severity as assessed with the National Institutes of Health Stroke Scale (NIHSS), location of dissected artery (carotid or vertebral), vessel occlusion before treatment, intracranial extension, time from symptom onset to thrombolysis, treatment type (IVT or IAT), and duration of follow-up. As safety variables, symptomatic intracranial haemorrhage (SICH), mortality, and recurrent stroke were analysed. For the present study, SICH was defined as any intracranial haemorrhage documented on CT or MRI which was temporally related to a deterioration in the patients clinical condition. In the included studies different definitions were used for clinical deterioration. Additional relevant adverse events as reported by the authors were collected and described. Stroke progression was

6 Safety and outcome of thrombolysis in dissection-related stroke 99 defined as an increase of the NIHSS score as compared to baseline with intracranial haemorrhage excluded by imaging. We assessed functional outcome by means of the modified Rankin scale (mrs), with excellent outcome defined as a score of 0 1, and favourable functional as a score of 0 2. When the mrs was unavailable, the same observers reconstructed the score if this could clearly be deducted from the case description, according to the mrs criteria. 7 Two independent observers (SMZ, PJN) extracted all data. Disagreements were resolved by consensus. Individual patient data (IPD) We sent a uniform datasheet to the authors of all case series reporting aggregated data only. To prevent double counting of patients who were reported in case series only the IPD were used for analysis. Authors of case reports were contacted only if IPD needed for the analysis were incompletely described in the manuscript. Statistical analysis We used the IPD to construct mixed models with the lme4 package of R. 8 We adjusted for the heterogeneity across studies by including a random intercept per study in these models. Pooled proportions were calculated for SICH, mortality, recurrent stroke, excellent outcome, and favourable outcome. SICH and mortality rates were calculated for the subgroup treated within 3 and within 4.5 hours according to IVT guidelines. These proportions were also calculated for all patients treated with IVT. The following variables were included in univariate models as predictors for excellent and favourable outcome: sex, age, preceding trauma, location of dissection, onset to treatment time, NIHSS, and treatment modality. Onset to treatment time was analysed both as continuous and as categorical variable, the latter based on empirically defined cut-off values (<120 minutes, minutes and >180 minutes). In the multivariate analyses, we adjusted for predictors that were significantly (p<0.05) associated with excellent and favourable outcome in the univariate analyses. A subgroup analysis of data from case series only was performed in order to reduce the influence of potential publication bias. 7

7 100 Chapter 7 Comparison with SITS-ISTR We compared our findings with the results of the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR), an ongoing, prospective, international stroke register of patients treated with IVT. 9 Our pooled rates for SICH and functional outcome (including mortality) were indirectly compared with the same endpoints of selected controls from SITS-ISTR; that is, matched for age and NIHSS. If a complete match did not exist (allowing deviation of one year or one point in NIHSS) a control patient was recorded as missing. In SITS-ISTR, SICH was reported both according to the definition of National Institute of Neurological Diseases and Stroke (NINDS; any haemorrhage with any neurological deterioration <7 days after symptom onset) and to the European-Cooperative Acute Stroke Study II (ECASS II, any haemorrhage with 4 points increase on the NIHSS and likely to be the cause of the clinical deterioration). MRs scores in SITS-ISTR were assessed at 3 months, whereas followup duration in our meta-analysis differed between studies. For this comparison, we selected only patients who had their outcome assessed within 3 months of follow-up. RESULTS Studies Of the 186 citations identified by our search strategy, 36 publications including 190 patients fulfilled our predefined criteria. All studies were retrospective series or single case reports; no randomised controlled trials were identified. Fourteen case series (160 patients) presented data of thrombolysis in CAD-related stroke. 5,6,10-21 Nine series used data from stroke registries 10,14,18,21 or thrombolysis registries 5,11,16,22 and one was based on a non-defined hospital registry. 15 Of these, three studies were multicenter studies. 5,10,22 Table 7.1 gives an overview of the study characteristics of these case series. In addition, 22 case reports were retrieved describing another 24 patients IPD were available from 33 publications (72 patients). IPD from 108 patients were provided by the authors from the remaining three publications that contained aggregated data of 118 patients,

8 Safety and outcome of thrombolysis in dissection-related stroke 101 and from unpublished cases. In total, IPD from 180 patients were available for the analysis. Baseline characteristics Patients were predominantly female (68%) with a mean age of 46 years. The median NIHSS score was 16 and most patients (60%) presented with severe stroke symptoms (NIHSS 15). Median onset to treatment time was 165 minutes. Treatment modality was IVT in 121 patients (67%) and IAT in 59 patients (33%). Six percent of the IVT patients were treated beyond the therapeutic window of 4.5 hours after symptom onset (Table 7.2). Safety Survival status was not available in seven patients (4%). After correction for heterogeneity, The pooled mortality was 8.1% (95% confidence interval [CI] ). For the 121 patients treated with IVT, pooled mortality was 6.7% (95% CI ). SICH occurred in eight of 180 patients (3.1%, 95% CI ), of which two were fatal. In the IVT group, four patients experienced SICH (3.3%, 95% CI ). Recurrent stroke occurred in eight patients (4.5%, 95% CI ), whom were all treated with IVT (Table 7.3). Other complications after thrombolytic treatment were asymptomatic intracranial haemorrhage in 26 patients (14.4%, 95% CI ). One patient with vertebral artery dissection treated with IVT experienced haematoma expansion (unpublished data), with excellent recovery. Pseudo-aneurysm at follow-up was reported in eight of the 133 patients for whom this information was available. One patient had a asymptomatic subarachnoid bleeding. Progression of the infarct was reported in 13 of 161 patients. 7 Functional Outcome The mrs score was available for 156 patients and could additionally be deducted from the description of the functional status in 17 patients. After correction for heterogeneity, 41.0% (95% CI ) had an excellent outcome and 59.5% (95% CI ) had a favourable outcome. In the IVT group, 33.3% (95% CI ) had an excellent outcome and 60.8% (95% CI ) had a favourable outcome (Table 7.3). Median follow-up was 3 months (range 5 days and

9 102 Chapter 7 Characteristics of included series (case-reports are not listed) Engelter 5 (2010) retrospective, multicenter Vergouwen 21 (2009) retrospective, Putaala 19 (2009) retrospective, Huang 17 (2009) retrospective, Cerrato 14 (2008) retrospective, Baumgartner 12 (2008) retrospective, Lavallée 18 (2007) retrospective, Dabitz 15 (2007) retrospective, Georgiadis 22 (2005) retrospective, multicenter Arnold 10 (2002) retrospective, Bin Saeed 11 (2000) retrospective, Derex 12 (2000) retrospective, Ahmad 10 (1999) retrospective, multicenter Rudolf 20 (1999) retrospective, 55 consecutive patients with stroke due to cervical artery dissection treated with IVT 55 IVT 8 consecutive patients with stroke due to extracranial artery dissection 6 IVT, IAT 48 consecutive patients with stroke aged treated with IVT 12 IVT 73 patients with cervicocranial arterial dissection 1 IAT 3 patients with vertebral artery dissection and basilar artery occlusion treated with IAT 18 consecutive patients with internal carotid artery dissection and a symptomatic middle cerebral artery occlusion 10 patients with tandem internal carotid and middle cerebral artery occlusion with internal carotid dissection 10 consecutive patients with cerebral ischaemia associated with proximal carotid artery occlusion 33 consecutive patients with stroke due to spontaneous carotid dissection treated with IVT 3 IAT 18 IVT, IAT 5 IVT, IAT 3 IAT 33 IVT 9 patients with cervical artery dissection treated with thrombolysis 9 IVT, IAT 26 patients with vertebral artery dissection 2 IAT 11 consecutive patients with acute ischaemic stroke related to internal carotid artery dissection treated with IVT 11 IVT 18 patients with cervicocerebral artery dissections 2 IAT 15 consecutive patients with internal carotid artery occlusion treated with IVT 6 IVT IVT indicates intravenous thrombolysis; IAT, intra-arterial thrombolysis.

10 Safety and outcome of thrombolysis in dissection-related stroke 103 Baseline characteristics of all included cervical artery dissection patients treated with thrombolysis: individual patient data Age (years) 46 (11) Men 57 (32) Preceding trauma 31 (17) NIHSS 16 (11 20) Mild stroke (NIHSS 1 7) 21 (15) Moderate stroke (NIHSS 8 14) 42 (25) Severe stroke (NIHSS 15) 86 (60) Location of dissection Carotid artery 131 (73) Vertebral artery 48 (27) Both 1 (1) Occlusion before treatment 107 (83) Intracranial extension 16 (10) Onset-to-treatment time (minutes) 165 ( ) Treatment IVT 121 (67) IAT 59 (33) Duration of follow-up (months) 3.0 ( ) Data are number, number (%), mean (standard deviation) or median (interquartile range). NIHSS indicates National Institutes of Health Stroke Scale; IVT, intravenous thrombolysis; IAT, intra-arterial thrombolysis. 18 months) but 137 patients had their outcome assessment at 3 months exactly. Proportions per follow-up period are reported in Table Regression models Predictors of excellent and favourable outcome are presented in Table 7.5. In the univariate analysis, only stroke severity was inversely associated with both excellent and favourable outcome. The odds ratio (OR) for excellent outcome was 0.9 (95% CI ) for each point increase on the NIHSS. For favourable outcome this OR was also 0.9 (95% CI ). Vertebral artery dissection was significantly associated with excellent outcome compared to carotid artery dissection (OR 2.6, 95% CI ), but not with favourable outcome. Other variables were not associated with outcome. In the multivariate models, we adjusted for stroke severity only. In these models, vertebral artery dissection remained associated

11 104 Chapter 7 Safety and outcome in cervical artery dissection patients treated with thrombolysis and of the subgroup of patients treated with IVT SICH 8/ ( ) 3.1 ( ) 4/ ( ) 3.3 ( ) minutes* 3/ ( ) 3.1 ( ) 2/ ( ) 2.3 ( ) minutes* 5/ ( ) 3.6 ( ) 3/ ( ) 2.7 ( ) Mortality 14/ ( ) 8.1 ( ) 8/ ( ) 6.7 ( ) minutes* 8/ ( ) 8.3 ( ) 6/ ( ) 7.0 ( ) minutes* 9/ ( ) 6.7 ( ) 6/ ( ) 5.5 ( ) Recurrent stroke 8/ ( ) 4.5 ( ) 8/ ( ) 6.8 ( ) mrs score / ( ) 41.0 ( ) 40/ ( ) 33.3 ( ) mrs score / ( ) 59.5 ( ) 73/ ( ) 60.8 ( ) Minutes from symptom onset to start of thrombolytic treatment. CI indicates confidence interval; IVT, intravenous thrombolysis; SICH, symptomatic intracranial haemorrhage; mrs = modified Rankin scale.

12 Safety and outcome of thrombolysis in dissection-related stroke 105 Functional outcome of cervical artery dissection patients per time period of follow-up 0 10 days 4 2 (50.0) 2 (50.0) 2 (50) 1 0 (0.0) 0 (0.0) 1 (100.0) days 1 1 (100.0) 1 (100.0) 0 (0.0) 0 0 (0.0) 0 (0.0) 0 (0.0) 1 3 months 139* 42 (30.2) 77 (55.4) 11 (7.9) (30.9) 64 (58.2) 7 (6.4) >3 12 months (68.2) 17 (77.3) 1 ( (66.7) 8 (88.9) 0 (0.0) >12 18 months 3 1 (33.3) 2 (66.7) 0 (0.0) Duration or mrs unknown Data are number (%). * 137 patients had their outcome assessment at 3 months exactly; 107 patients had their outcome assessment at 3 months exactly. IVT indicates intravenous thrombolysis; mrs, modified Rankin scale. 7

13 106 Chapter 7 with an excellent outcome (OR 3.9, 95% CI ). None of the other variables examined were associated with outcome. Publication bias Leaving out the data from case reports did not alter the main findings. Apparently, there was no publication bias in favour of case reports compared to the results of the larger studies. Comparison with SITS-ISTR Selection of controls from SITS-ISTR, matched for age and NIHSS, resulted in 170 eligible cases. Point estimates for the main outcomes of our study compared with SITS-ISTR are presented in Table 7.6. Overlapping CIs indicated no relevant differences in SICH rates, mortality and functional outcome. DISCUSSION This meta-analysis of IPD comprises the largest published number of CAD patients treated with thrombolysis to date and suggests that thrombolysis in acute ischaemic stroke due to CAD is safe. The pooled SICH rate of 3% and overall mortality of 8% (3% and 7%, respectively, in IVT) in CAD patients are apparently similar to stroke from all causes. In particular, the indirect comparison between our population and matched controls from SITS-ISTR did not show relevant differences for these important endpoints. We did not perform statistical testing of differences between our population and SITS-ISTR, since both studies were not designed beforehand to be compared. We therefore presented this comparison only in a descriptive way. However, since placebo-controlled trials on thrombolysis in patients with CAD related stroke may not be ethical anymore, the presented data may be the best available evidence for clinical guidelines to date. Expansion of the intramural haematoma during thrombolysis seems to be a rather theoretical concern. In our study only one patient suffering from intramural haematoma expansion was described but had an excellent outcome. We realise that most studies did not systemically report on this direct complica-

14 Safety and outcome of thrombolysis in dissection-related stroke 107 Univariable and multivariable analysis: odds for excellent (mrs score 0 1) and favourable (mrs score 0 2) outcome in cervical artery dissection patients treated with thrombolysis Female sex 0.73 ( ) ( ) ( ) ( ) 0.83 Age 1.01 ( ) ( ) ( ) ( ) 0.97 Preceding trauma 1.79 ( ) ( ) ( ) ( ) 0.78 Vertebral artery 2.64 ( ) ( ) ( ) ( ) 0.19 Onset to treatment time Continuous 1.00 ( ) ( ) ( ) ( ) 0.15 <120 minutes reference reference minutes 0.75 ( ) ( ) ( ) ( ) 0.46 >180 minutes 0.63 ( ) ( ) ( ) ( ) 0.13 NIHSS 0.88 ( ) < ( ) < Treatment IVT reference reference IAT 1.66 ( ) ( ) ( ) ( ) 0.40 Adjusted for stroke severity by means of the NIHSS before start of treatment. mrs indicates modified Rankin scale; OR, odds ratio; CI, confidence interval; NIHSS, National Institutes of Health Stroke Scale; IVT, intravenous thrombolysis; IAT, intra-arterial thrombolysis. 7

15 108 Chapter 7 Indirect comparison of thrombolysis in patients with cervical artery dissection (current meta-analysis) with matched* patients with stroke from all causes treated with IVT (data from SITS-ISTR) 9 SICH ( ) ( ) SICH per NINDS ( ) SICH per ECASS-II ( ) Mortality ( 3 months) ( ) ( ) Mortality (3 months) ( ) mrs 0 1 ( 3 months) ( ) ( ) mrs 0 1 (3 months) ( ) mrs 0 2 ( 3 months) ( ) ( ) mrs 0 2 (3 months) ( ) Matched for age and stroke severity by means of the NIHSS before start of treatment; any haemorrhage plus any neurological deterioration; any haemorrhage plus 4 points increase on the NIHSS. CAD indicates cervical artery dissection; IVT, intravenous thrombolysis; SITS-ISTR, Safety Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register; CI, confidence interval; SICH, symptomatic intracranial haemorrhage; NINDS, National Institute of Neurological Disorders and Stroke; ECASS II, European-Cooperative Acute Stroke Study II; mrs, modified Rankin scale.

16 Safety and outcome of thrombolysis in dissection-related stroke 109 tion. However, given the overall safety endpoints and functional outcome, direct bleeding complications from thrombolysis are apparently not a major issue. In our population, 31% of all CAD patients had an excellent outcome compared to 37% in SITS-ISTR. However, favourable outcome seemed slightly higher in our population (58% versus 52% in SITS-ISTR). For both outcome measures, the CIs largely overlapped. Therefore, given the fact that we can only make an indirect comparison, the outcome after IVT in patients with stroke due to CAD is in the same range as is observed in IVT after stroke from all causes. Our study has some limitations. First, no randomised trials were available for this meta-analysis. The pooled estimates are based on retrospective - and mostly uncontrolled - series and case reports only. Although leaving out the case reports did not change our findings, the possibility of publication bias in the included series cannot be excluded and might still have influenced the results of this meta-analysis. Another limitation is that we used a pragmatic instead of a strict definition of SICH because the criteria for SICH in the studies contributing to our meta-analysis were heterogeneous. This makes a comparison of SICH rates with other studies difficult. However, our rate with mixed definitions of SICH falls within the rates from SITS-ISTR according to the NINDS and ECASS II definition. This strongly suggests that the risk of SICH is not increased in patients with CAD related stroke. Another point of concern in this study is diagnostic uncertainty in patients with presumed CAD. However, the largest published series included in our analysis excluded patients with possible CAD, thereby reducing the diagnostic uncertainty. 5 The type of antithrombotic agents used after thrombolysis was not assessed, which might influence the rate of SICH as well as the outcome. 45 One could argue that we applied a wide treatment window of 24 hours after symptom onset, which is beyond the current guidelines of 4.5 hours for IVT. Median treatment time in our study was 165 minutes (IQR ) after symptom onset, indicating that thrombolytic therapy was mostly administered in the very acute phase of the stroke, which was the focus of our study. In the subgroup analysis we showed that safety and outcome did not differ between patients treated within 3 and within 4.5 hours after symptom onset, in comparison with the entire study population. Finally, the follow-up duration varied among 7

17 110 Chapter 7 the included studies. Therefore we presented subgroups according to follow-up duration. Moreover, the majority of patients had their follow-up at 3 months exactly, which is similar to that in SITS-ISTR. CONCLUSIONS In conclusion, thrombolysis appears to be safe in acute ischaemic stroke due to CAD. Mortality and SICH rates as well as outcome after thrombolysis in these patients seem to be similar with the rates in stroke patients from all causes treated with thrombolysis. Although our analysis is based on retrospective data with small numbers of patients, our results give no evidence that thrombolysis should be withheld in patients with ischaemic stroke caused by CAD. ACKNOWLEDGMENT We gratefully acknowledge the final comments of Professor Jan Stam, Department of Neurology, Academic Medical Center, University of Amsterdam, the Netherlands. REFERENCES 1. Putaala J, Metso AJ, Metso TM, et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry. 2009;40: Schievink WI. Spontaneous dissection of the carotid and vertebral arteries. 2001; Lucas C, Moulin T, Deplanque D, Tatu L, Chavot D. Stroke patterns of internal carotid artery dissection in 40 patients. 1998;29: Wardlaw JM, Murray V, Berge E, del Zoppo. Thrombolysis for acute ischemic stroke. 2009;4:CD Engelter ST, Rutgers MP, Hatz F, Georgiadis D, Fluri F, Sekoranja L et al. Intravenous thrombolysis in stroke attributable to cervical artery dissection. 2009;40: Georgiadis D, Baumgartner RW. Thrombolysis in cervical artery dissection. 2005;20: van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver

18 Safety and outcome of thrombolysis in dissection-related stroke 111 agreement for the assessment of handicap in stroke patients. 1988;19: The comprehensive R archive network (CRAN). Institute for statistics and mathematics of the WU Wien. Assessed February 25, Ahmed N, Wahlgren N, Grond M, Hennerici M, Lees KR, Mikulik R et al. Implementation and outcome of thrombolysis with alteplase h after an acute stroke: an updated analysis from SITS-ISTR. 2010;9: Ahmad HA, Gerraty RP, Davis SM, Cameron PA. Cervicocerebral artery dissections. J 1999;16: Arnold M, Nedeltchev K, Sturzenegger M, Schroth G, Loher TJ, Stepper F et al. Thrombolysis in patients with acute stroke caused by cervical artery dissection: analysis of 9 patients and review of the literature. 2002;59: Baumgartner RW, Georgiadis D, Nedeltchev K, Schroth G, Sarikaya H, Arnold M. Stent-assisted endovascular thrombolysis versus intravenous thrombolysis in internal carotid artery dissection with tandem internal carotid and middle cerebral artery occlusion. 2008;39:e27 e Bin Saaed A, Shuaib A, Al-Sulaiti G, Emery D. Vertebral Artery Dissection: Warning symptoms, clinical features and prognosis in 26 patients. 2000;27: Cerrato P, Berardino M, Bottacchi E, Corso G, Lentini A, Bosco G et al. Vertebral artery dissection complicated by basilar artery occlusion successfully treated with intraarterial thrombolysis: three case reports. 2008;29: Dabitz R, Triebe S, Leppmeier U, Ochs G, Vorwerk D. Percutaneous recanalization of acute internal carotid artery occlusions in patients with severe stroke. 2007;30: Derex L, Nighoghossian N, Turjman F, Hermier M, Honnorat J, Neuschwander P et al. Intravenous tpa in acute ischemic stroke related to internal carotid artery dissection. 2000;54: Huang YC, Chen YF, Wang YH, Tu YK, Jeng JS, Liu HM. Cervicocranial arterial dissection: experience of 73 patients in a single center. 2009;72:S20 S Lavallee PC, Mazighi M, Saint-Maurice JP, Meseguer E, Abboud H, Klein IF et al. Stentassisted endovascular thrombolysis versus intravenous thrombolysis in internal carotid artery dissection with tandem internal carotid and middle cerebral artery occlusion. 2007;38: Putaala J, Metso TM, Metso AJ, Mäkelä E, Haapaniemi E, Salonen O et al. Thrombolysis in young adults with ischemic stroke. 2009;40: Rudolf J, Neveling M, Grond M, Schmulling S, Stenzel C, Heiss WD. Stroke following internal carotid artery occlusion - a contra-indication for intravenous thrombolysis? 1999;6: Vergouwen MD, Beentjes PA, Nederkoorn PJ. Thrombolysis in patients with acute ischemic stroke due to arterial extracranial dissection. 2009;16: Georgiadis D, Lanczik O, Schwab S, Engelter S, Sztajzel R, Arnold M et al. IV thrombolysis in patients with acute stroke due to spontaneous carotid dissection. 2005;64: Abboud H, Houdart E, Meseguer E, Amarenco P. Stent assisted endovascular thrombolysis of internal carotid artery dissection. 2005;76: Bissay F, Allard S, van Tussenbroek F, Stadnik T, Michotte A. Vertebral artery dissection complicated by a thrombosis of the basilar artery was successfully treated with endovascular thrombolysis. 2004;51: Cohen JE, Gomori JM, Grigoriadis S, et al. Intra-arterial thrombolysis and stent placement for traumatic carotid dissection with subsequent stroke: a combined, simultan- 7

19 112 Chapter 7 eous endovascular approach. 2008;269: Erlich VM, Newell DW. Successful treatment of basilar artery thrombosis with both heparin and tissue plasminogen activator in the setting of traumatic vertebral artery dissection. 2004;57: Fateri F, Groebli Y, Rufenacht DA. Intraarterial thrombolysis and stent placement in the acute phase of blunt internal carotid artery trauma with subocclusive dissection and thromboembolic complication: case report and review of the literature. 2005;19: Findlay JM, Ashforth R, Dean N. Malignant carotid artery dissection. 2002;29: Ichihashi T, Matsushita Y, Tsuji Y, Harano H, Nakagawa H. Spontaneous extracranial vertebral artery dissection accompanied with multiple cerebral infarctions due to re-canalization. 2003;31: Abstract 30. Izquierdo-Casas J, Soler-Singla L, Vivas- Diaz E, Balaguer-Martinez E, Sola-Martinez T, Guimaraens-Martinez L. Locked-in syndrome due to a vertebral dissection and therapeutic options with intraarterial fibrinolysis in acute phase. 2004;38: Abstract 31. Krieger D, Leibold M, Bruckmann H. Dissections of the vertebral artery following cervical chiropractic manipulations. 1990;115: Leistner S, Hartmann A, Marx P, Koennecke HC. Successful thrombolytic treatment of intracranial carotid occlusion due to dissection. 2001;45: Mader K, Gawenda M, Zahringer M, Lackner K, Brunkwall J. Internal carotid artery dissection at the carotid canal after blunt trauma: case report of endovascular repair and literature review. 2003;128: McIntosh A, Hungs M, Kostanian V, Yu W. Carotid artery dissection and middle cerebral artery stroke following methamphetamine use. 2006;67: Mourand I, Brunel H, Vendrell JF, Thouvenot E, Bonafe A. Endovascular stent-assisted thrombolysis in acute occlusive carotid artery dissection. 2009;52: Nishimura H, Uemura Y, Morikawi T. Local intra-arterial thrombolytic therapy for basilar artery occlusion caused by extracranial vertebral artery dissection: A case report. Japanese Journal of 2002;11: Abstract 37. Price RF, Sellar R, Leung C, O Sullivan MJ. Traumatic vertebral arterial dissection and vertebrobasilar arterial thrombosis successfully treated with endovascular thrombolysis and stenting. 1998;19: Restrepo L, Pradilla G, Llinas R, Beauchamp NJ. Perfusion- and diffusion-weighted MR imaging-guided therapy of vertebral artery dissection: intraarterial thrombolysis through an occipital vertebral anastomosis. 2003;24: Sampognaro G, Turgut T, Conners JJ 3rd, White C, Collins T, Ramee SR. Intra-arterial thrombolysis in a patient presenting with an ischemic stroke due to spontaneous internal carotid artery dissection. 1999;48: Shibata T, Ogiichi T, Miyake T, et al. A case of basilar artery occlusion of traumatic vertebral artery dissection successfully managed by endovascular treatment. 2003;31: Abstract 41. Sugrue PA, Hage ZA, Surdell DL, Foroohar M, Liu J, Bendok BR. Basilar Artery Occlusion Following C1 Lateral Mass Fracture Managed by Mechanical and Pharmacological Thrombolysis. 2008;11: Tinel D, Bliznakova E, Juhel C, Gallien P, Brissot R. Vertebrobasilar ischemia after cervical spine manipulation: a case report. 2008;51:

20 Safety and outcome of thrombolysis in dissection-related stroke Toyoda K, Hirano T, Kumai Y, Fujii K, Kiritoshi S, Ibayashi S. Bilateral deafness as a prodromal symptom of basilar artery occlusion. 2002;193: Zaidat OO, Fernandes Filho JA, Singh G, Suarez JI. Thrombolytic therapy for acute extra-cranial artery dissection: report of two cases. 2001;59: Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection. 2010;10:CD