1. Intraarterial Thrombolysis
Intra-arterial thrombolysis should be given in stroke centres with the appropriate level of experience
In patients who fulfil the criteria for iv thrombolysis this should be given ASAP.
Potential indications for i.a. rather than iv or in addition to iv thrombolysis include:
Primary intraarterial thombolysis
Severe disabling neurological deficit and
Contraindications to iv thrombolysis (e.g. recent surgery), 3-6 h from symptom onset or
Dense artery sign on the CT head scan
Rescue thrombolysis
No improvement (or worsening without bleed) with iv thrombolysis
No recanalization or early reolclusion after iv thrombolysis
Brain stem stroke
treatment can be delivered within 12 h of symptom onset and
Occlusion of basilar artery documented on 4-vessel angiography
Eligible even if consciousness impaired and or patient ventilated
Shaltoni et al 2007, Arnold et al 2002, 2003, Hill et al 2002

2. Primary intraarterial thrombolysis (LIT) Arnold, Mattle et al, Bern (2002 n=100 MCA, 2003 n=40 basilar)
Equipment
high-resolution angiography system (Toshiba CAS 500) with a matrix of 1024x1024 pixels
5.5 F-JB2 catheter (Valavanis) was inserted into the femoral artery for 4-vessel angiography
LIT using a microcatheter, mostly a Fast Tracker 18 (Target Therapeutics) through the 5.5-F JB2 catheter, which was navigated into the occluded MCA
Thrombolytic agent
Urokinase (Urokinase HS Medac) in a mean dose of IU (range 20,000 to 1,250,000 IU)
[or alteplase 50% of standard iv dose (not in above papers, pers comm. 2004)]
Technique
Inject as near as possible to or into the thrombus over 60 to 90 minutes
Additional procedures
In patients occlusion due to soft thrombotic material, mechanical disruption of the clot was performed in addition using a very flexible hydrophilic guidewire catheter (Silver Speed MTI or inch). The tip of the guidewire was formed in a J shape to avoid perforation of the vessel walls. Penetration and fragmentation of the thrombus was achieved by gently advancing and rotating the convex border of the J-shaped guidewire (n=8).
In 2 patients without recanalization after injection of IU urokinase a percutaneous transluminal angioplasty was performed using a FasStealth balloon dilatation catheter (Target Therapeutics) with a balloon diameter of 2.00 mm (n=2)
Documentation of outcome
control angiography immediately after thombolysis [TIMI grade 0; minimal recanalization, TIMI grade 1; partial recanalization, TIMI grade 2; complete recanalization, TIMI grade 3].
Aftercare
heparin in a dose doubling the activated thromboplastin time immediately after LIT before IST n=18), after IST change to mg aspirin (n=82) iv immediately after LIT and then daily po/iv instead of heparin.
pts treated on neurological intensive care ward. Standard protocols for ward care and follow-up
Intraarterial thrombolysis (LIT) for middle cerebral artery occlusion using urokinase
(Mattle, Swizerland, 2002)
Inclusions/exclusions
(1) clinical diagnosis of ischemic stroke was established by a neurologist;
(2) baseline NIHSS score reached at least 4 points, except for isolated hemianopia or aphasia;
(3) CT (n=97) or MRI (n=3) excluded intracranial hemorrhage;
(4) 4-vessel cerebral angiography showed a vessel occlusion correlating to the neurological deficit;
(5) the expected interval from symptom onset to LIT was <6 hours;
(6) there were no individual clinical or laboratory findings advising against thrombolysis;
(7) for patients >75 years of age, their general condition before stroke was not advising against it.
IVT was performed within a 3-hour time window, when intra-arterial delivery of the thrombolytic agent into the MCA was not possible because of occlusion of the ipsilateral extracranial internal carotid artery (n=6).
Equipment
high-resolution angiography system (Toshiba CAS 500) with a matrix of 1024x1024 pixels
5.5 F-JB2 catheter (Valavanis) was inserted into the femoral artery for 4-vessel angiography
LIT using a microcatheter, mostly a Fast Tracker 18 (Target Therapeutics) through the 5.5-F JB2 catheter, which was navigated into the occluded MCA
Thrombolytic agent
Urokinase (Urokinase HS Medac) in a mean dose of IU (range to IU)
Technique
M1 or M2 occlusions: Infused directly into or near the proximal end of the occluding thrombus over 60 to 90 minutes
M3/M4 occlusion: urokinase was infused as close to the clot as possible, mostly in the M2 segment
Additional procedures
In 8 patients with M1 or M2 occlusion due to soft thrombotic material, mechanical disruption of the clot was performed in addition using a very flexible hydrophilic guidewire catheter (Silver Speed MTI or inch). The tip of the guidewire was formed in a J shape to avoid perforation of the vessel walls. Penetration and fragmentation of the thrombus was achieved by gently advancing and rotating the convex border of the J-shaped guidewire.
In 2 patients without recanalization after injection of IU urokinase a percutaneous transluminal angioplasty was performed using a FasStealth balloon dilatation catheter (Target Therapeutics) with a balloon diameter of 2.00 mm.
Documentation of outcome
Treatment effect was documented by control angiography immediately after administration of urokinase [no recanalization, TIMI grade 0; minimal recanalization, TIMI grade 1; partial recanalization, TIMI grade 2; complete recanalization, TIMI grade 3].
Aftercare
Eighteen patients who had been treated before publication of the International Stroke Trial results received heparin in a dose doubling the activated thromboplastin time immediately after LIT. After the International Stroke Trial results were published, 250 to 500 mg aspirin was given to all patients (n=82) instead of heparin.
Note: assumes pts treated on neurological intensive care ward. Standard protocols for ward care and follow-up
Intra-arterial thrombolysis in 100 patients with acute stroke due to middle cerebral artery occlusion. Arnold M, Schroth G, Nedeltchev K, Loher T, Remonda L, Stepper F, Sturzenegger M, Mattle HP. Stroke Jul;33(7):
N=100, 47% rankin <2 at 3 mo, 7% haemorrhages
Intraarterial thrombolysis for basilar artery thrombosis (Mattle 2003)
Exclusions
>12 h from sx onset
occlusion of ipsilateral VA and hypoplasia of contralat VA making access impossible
sp open heart surgery
Method
Fast Tracker 18 (Target Therapeutics) micro catheter
Urokinase (Urokinase HS Medac) in a mean dose of IU (range 20, 000 to 1, 250, 000 IU) as near to the clot as possible or into the clot over 60 to 90 min
21 pts aspirin , 19 full dose heparin
Arnold M, Nedeltchev K, Schroth G, Baumgartner RW, Remonda L, Loher TJ, Stepper F, Sturzenegger M, Schuknecht B, Mattle HP. Clinical and radiological predictors of recanalisation and outcome of 40 patients with acute basilar artery occlusion treated with intra-arterial thrombolysis. J Neurol Neurosurg Psychiatry Jun;75(6):

3. Rescue i.a. thrombolysis after full dose iv thrombolysis (Shaltoni et al 2007)
N=69, age , NIHSS 18 (6-39)
Patients with persisting occlusion a/o lack of clinical improvement after iv thrombolysis
Iv rtPa started med 120 min, iaT med 288 min
Reteplase n=56, alteplase n=7, urokinase n=6
Symptomatic ICH n=4( 5.8%), 3 fatal
Recanalisation in 50%
Favourable outcome (H or IP rehab) 55%
Combination safe compared with iv alone. Higher rate of recanalisation and favourable outcome
Shaltoni et al , Stroke 2007;38:

4. Procedures for rescue i.a. thrombolysis (Shaltoni et al 2007)
Control angio every 10 min
Mechanical disruption of the clot via microcatheter premitted
Neuro function assesses every 15 min
Terminate IAT if TICI flow>2a or time >6h form onset (except for basilar artery where time was not limited) or maximum dose achieved (alteplase 24 mg, reteplase 6 u urokinase U)

5. Rescue ia thrombolysis after full dose IV thrombolysis (Hill et al, Calgary n=6, Stroke 2002;33: )
Indication
Disabling (severe) ischaemic stroke and persistent occlusion of the symptomatic artery or clinical and CT?MR evidence of basilar artery thrombosis
All patients had had standard full dose Alteplase within 3 h of symptom onset.
Procedure
Femoral approach
Alteplase 1 mg/ml diluted x2 with sterile water
Alteplase applied to the face of the thrombus, into the thrombus, and distal to the thrombus
Pulse spray technique, 3 cc per application, using 3 cc syringes
Combined with mechanical clot disruption, where possible
Max dose of Alteplase i.a. 20 mg
IV heparin was given as 2000 IU bolus at the beginning of the procedure and in a bolus fashion intermittently throughout to a maximum of 500 iu/h (???)
Angioplasty/stenitng not prospectively planned but available as ‘rescue’ procedures
Post procedure
No heparin/antithrombotics for 24 h
N=6, but more detailed description of procedure than in other papers.

6. Rescue Intraarterial Thrombolysis IMS II Investigators 2007
Recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg over 30 minutes)
For subjects with an arterial occlusion at angiography, additional rt-PA was administered via the EKOS micro-infusion catheter or a standard microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis.
Significantly better than no thrombolysis. Trial to compare iv with combined iv/ia therapy ongoing
BACKGROUND AND PURPOSE: The purpose of this study was to further investigate the feasibility and safety of a combined intravenous and intra-arterial approach to recanalization for ischemic stroke. METHODS: Subjects, ages 18 to 80, with a baseline NIHSS > or =10 had intravenous recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg over 30 minutes) within 3 hours of onset. For subjects with an arterial occlusion at angiography, additional rt-PA was administered via the EKOS micro-infusion catheter or a standard microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis.
RESULTS: The 81 subjects had a median baseline NIHSS score of 19. The median time to initiation of intravenous rt-PA was 142 minutes as compared with 108 minutes for placebo and 90 minutes for rt-PA-treated subjects in the NINDS rt-PA Stroke Trial (P<0.0001). The 3-month mortality in IMS II subjects was 16% as compared with the mortality of placebo (24%) and rt-PA-treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic intracerebral hemorrhage in IMS II subjects (9.9%) was not significantly different than that for rt-PA treated subjects in the NINDS t-PA Stroke Trial (6.6%). IMS II subjects had significantly better outcomes at 3 months than NINDS placebo-treated subjects for all end points (OR > or =2.7) and better outcomes than NINDS rt-PA-treated subjects as measured by the Barthel Index and Global Test Statistic.
CONCLUSIONS: A randomized trial of standard intravenous rt-PA as compared with a combined intravenous and intra-arterial approach is warranted and has begun.
IMS II Trial Investigators. The Interventional Management of Stroke (IMS) II Study. Stroke. 2007;38:

7. Ongoing IAT Research IMS III
RCT, n=900 planned, end date 2015
18-82 years, initiation of IV rt-PA within 3h, NIHSSS ≥ 10, occlusion seen in M1, ICA or basilar artery on CTA
Iv rt-PA alone (0.9 mg/kg) vs combined IV/IA (0.6 mg/kg over 30 min followed by immediate angiography. If clot is demonstrated, the neuro-interventionalist will then choose from currently available but trial defined intra-arterial treatment approaches. IAT will be given at maximum 2 mg bolus and 10 mg/hr, max 22 mg) using standard microcathether.
The IV

8. GA or sedation?
General anaesthesia (GA)
Patient does not retch
Airway secure
Head stable and access better
Sedation
Faster time to treatment
Avoids complications of GA
Preliminary Results From a Retrospective Multicenter Study.
N=980 with IAT
Only large vessel anterior circulation strokes included, GA was used in 44% No differences in intracranial hemorrhage rates compared with sedation
Poorer neurological outcome at 90 days (OR=2.33; 95% CI, ; P<0.0001) with GA
Higher mortality (odds ratio=1.68; 95% CI, ; P<0.0001) with GA
ABOU-CHEBL Stroke April 2010
ABOU-CHEBL A, Lin R, Hussain MS, Jovin TG, et al.
Conscious Sedation Versus General Anesthesia During Endovascular Therapy for
Acute Anterior Circulation Stroke. Preliminary Results From a Retrospective,
Multicenter Study.
Stroke
BACKGROUND AND PURPOSE: Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT. METHODS: A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death. RESULTS: The mean age was 66+/-15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13-20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, ; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, ; P<0.0001) compared with conscious sedation. CONCLUSIONS: Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences

9. Upper age limit for IA lysis?
<80?
<70 and fit for age?
Consider
anaesthetic risk
More difficult access with tortuous stiff vessels
Age in ia trials
66+/-13 (Shaltoni 2007)
<80 (IMS II investigators)
66+/-15 (Abou-Chebl 2010 large register)
Age <70 (and fit for age)
No recognized guidance on this, but increasing age makes carotids stiffer and access more difficult/risky
Also anaesthtitic risk greater with increasing age and frailty or multimorbidity
Use sedation in preference to GA if technically possible (AHA Stroke conference paper 2010 suggests lower risk with sedation)

10. Thrombectomy Karolinska Stroke Update meeting in November 2010 The consensus statement
There is still a controversy whether mechanical removal of thrombus should be used routinely or only within trials.
Large artery occlusion is associated with a high morbidity and mortality if left untreated
Mechanical thrombectomy achieves higher recanalization rates compared to historical controls with or without intravenous rt-PA
The odds for favourable outcome in general are significantly increased with early vessel recanalization
Due to the lack of evidence of randomized control trials for clinical efficacy, mechanical thrombectomy should not be used in clinical routine
However, in selected patients (e.g. with indication for iv-treatment but also contraindication), endovascular approaches may be considered as part of a institutional protocol
If treatment is done outside a RCT, data should be included in a multicenter registry including assessment of three months outcome
Future prospective randomized controlled trials of endovascular treatment should also evaluate the impact of sedation modality on safety of the intervention, technical success, time to recanalization, and clinical outcome
For full statement